Review ArticleLight and Darkness Prevalence of Hepatitis E Virus Infectionamong the General Population

Joseacute-Manuel Echevarriacutea

Department of Virology National Centre of Microbiology Instituto de Salud Carlos III Road Majadahonda-PozueloKm2 Majadahonda 28220 Madrid Spain

Correspondence should be addressed to Jose-Manuel Echevarrıa jmechevaisciiies

Received 7 November 2013 Accepted 25 December 2013 Published 10 February 2014

Academic Editors S Bofill-Mas M Ciccozzi M T Shata and F R Spilki

Copyright copy 2014 Jose-Manuel Echevarrıa This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Human hepatitis E virus (HHEV) spreads early in life among the population in areas endemic for genotype 1 and infects mainlyadults in areas endemic for genotype 3 where it would be responsible for about 10 of cases of suspected acute viral hepatitis ofunknown etiology and for a number of subclinical unrecognized infections The overall prevalence of antibody to HHEV is highin most of the former areas and low in most of the later ones but wide regional differences have been recorded in both cases ldquoHotspotsrdquo of HHEV infection would exist for both types of strains in particular regions or among particular populations of the worldStudies on pork derivatives shellfish bivalves and vegetables for HHEV contamination at the sale point need to be extended forevaluating the impact of the agent on food safety and the meaning of the finding of HHEV genotype 1 genomes in urban sewagefromdeveloped countries should be established through active surveillance Consensus about technical issues in regard to anti-HEVtesting would improve the knowledge of the HHEV epidemiology Studies in particular regions and populations and introductionof molecular diagnosis in the clinical setting as a routine tool would also be required

1 Introduction

One of the mysterious aspects of hepatitis E virus (HEV) isthe high seroprevalence of antibody to HEV (anti-HEV) IgGin developed countries where the infection is not endemicdespite the seldom reported cases of acute clinical hepatitiscaused by HEV in these countries

This sentence opened five years ago a review articleon the hepatitis E virus (HEV) seroprevalence in developedcountries a matter of mystery for the authors of the review[1] Though the infection by zoonotic HEV strains is actuallyendemic in these regions there are still reasons five yearslater to share with them some perception of mystery fromanalyzing the data available about the prevalence of antibodyto HEV (anti-HEV) in the different populations of the worldSuch reasons arise both from conceptual and technical issuesand from the data and set both light and darkness onthe epidemiology of HEV Next pages will try to show theenlighten areas and to suggest ways for illuminating the darkones

2 Taxonomic Status and General Proprietiesof Human HEV

The family Hepeviridae includes at present five separategroups of viruses of vertebrates Genomes from strains foundamong bats are the closest to the avian viruses [2] Virusesfrom ferrets and rats cluster separately from human-relatedviruses in phylogenetic trees Finally strains isolated fromtrout draw a group independent from the remainder [3]In a recent review of the information available a futureclassification of the family into two genera was proposedon the basis of these genetic relationships with the avianand mammal viruses drawing a single genus and the virusesfrom fish a second one [4] The former genus would consistof four separate species avian HEV bat HEV HEV fromrodent and ferret and human-relatedHEV (HHEV)This lastspecies would be further subdivided into six genotypes twoof them found among wild boars only Therefore all HEVstrains found among humans would belong to a single viralspecies consisting of four separate genotypes Some of these

Hindawi Publishing CorporationScientificaVolume 2014 Article ID 481016 14 pageshttpdxdoiorg1011552014481016

2 Scientifica

genotypes are exclusive of the human beings and some areshared with other mammal species as explained below

The HHEV virion is a spherical-shaped particle about30 nm in diameter whose structure resembles the structureof the calicivirus particle under the electron microscopeThe viral core protein is the single structural protein of thevirion but arranges in different ways to generate a series ofstructural unitsThe genome consists of a single linear speciesof single-stranded 31015840-capped RNA of positive polarity andof 73 kilobases (kb) in length which is organized in threeopen reading frames (ORFs) [11] ORF1 extends for 51 kband encodes at least four functional nonstructural proteinsdisplaying activities of methyl-transferase protease heli-case and RNA-dependent RNA polymerase ORF2 encodesthe core protein which builds the capsid of the virionand is responsible for attachment and entry into the hostcell and for the main stimulation of the specific immuneresponse ORF3 encodes a small antigenic phosphoproteinof unknown function HHEV is difficult to replicate in cellculture to a high titer and laboratory assays for specificantibody testing are commonly developed with differentrecombinant antigens from the core protein though someinclude also recombinant antigens from the ORF3-encodedprotein Assays for molecular diagnosis are usually based onamplification of sequences from theORF1 region Sequencingof the products may render the identification of the HHEVgenotype present in the sample but further characterizationrequires amplification of sequences from the ORF2 region orbetter full genome sequencing

Though comparative analysis of genomes is winning anincreasing relevance in biological taxonomy other meaning-ful considerations must also be taken in mind for classifyingviruses In addition to the traditional criteria of virionmorphology and antigenic proprieties the survival strategyrepresents a trait intimately linked to the evolution of viruspopulations that may involve important epidemiologicalconsequences In the particular case of HHEV this trait isrelevant and should not be ignored by taxonomists

3 Is HHEV a Single Virus

Cross-neutralization gave herpes simplex virus (HSV) theformer consideration of a single virus species consisting oftwo types After some years HSV types 1 and 2 (HSV1HSV2) were classified into two separate species sharing mostneutralizing epitopes but lacking cross-protective immunitySuch distinction recognized among other differential fea-tures the radically different survival strategies of these twoagents which determine a totally different epidemiologyHSV1 spreads widely among the population very early in lifeand is transmitted mainly by the respiratory route amongchildren In contrast HSV2 is a sexually transmitted agentwhose spreading among adolescents and adults dependson the sexual behavior Anti-HSV1 prevalence is almostuniformly high everywhere The prevalence of anti-HSV2is lower and displays wide differences between regionsbut also in regard to the subset of population considered

within a given region Formerly performance of antibodysurveys specific for each of these two viruses was impairedby an important technical limitation Detection of type-specific antibody required the measurement of the kineticsof the neutralization observed after mixing the sample withcarefully titrated preparations of infectious virus from eachtype a cumbersome approach almost unaffordable for testinghundred or thousand samples Later on novel and friendliertype specific tests were developed and these antibody surveyscould be achieved In a study from Spain almost 80 ofan adult female population tested positive for anti-HSV1 byimmunoblot but only 35 tested positive for anti-HSV2 [12]In the USA a study performed at the national level found18 of white adult women positive for anti-HSV2 but therate increased to 46 among black women [13] Thereforeboth significant regional and population-based differencesexisted in the epidemiology of the HSV2 infection andsuch knowledge was relevant for improving the preventionof genital herpes and of the devastating neonatal diseaseresulting from mother-to-child virus transmission

The present taxonomic status of HHEV as a single viralspecies reminds the former status of HSV No evidenceof cross-protective immunity between the different HHEVgenotypes exists and they can also be meaningfully groupedinto two groups in regard to their survival strategies andtheir epidemiological features Genotypes 1 and 2 (HHEV1HHEV2) are exclusive of human beings though HHEV1may accidentally or artificially infect other species Theyare restricted to particular geographical areas and spreadoften among the population as waterborne open epidemicoutbreaks In contrast genotypes 3 and 4 (HHEV3 HHEV4)are adapted to mammals from different orders from swineand deer to mongoose and rat and are distributed worldwideand infect humans sporadically through zoonotic transmis-sion or by consumption of contaminated aliments Thesebehaviors most likely reflect two sharply separated evolu-tionary lineages representing two different survival strategiesthat evolved independently since long time ago From anevolutionary point of view wider than the strict considera-tion of the genetic relationships these two HHEV lineageswould perhaps merit the consideration of two different viralspecies and such consideration would fit the epidemiologicalfindings

Diseases caused by theseHHEVgenotypes share identicalclinical features between them and with other acute viralhepatitis But for the high mortality recorded sometimesamong pregnant women infected by HHEV1 hepatitis E canbe indeed taken by clinicians as hepatitis A in the regions ofthe World where hepatitis A virus (HAV) remains endemicThis lack of specific symptoms and signs is characteristic ofacute viral hepatitis in general and the disease is classified asA B C D E or non-AndashE after performing laboratory studiesIf HEV was divided into two species acute hepatitis E wouldalso be divided into two different diseases and virologistswould learn that they should try to separate them in thelaboratory as they do for the rest

The investigation of the HEV epidemiology is thereforeinfluenced by these conceptual issues since we are actually

Scientifica 3

mixing two different viral infections and two different dis-eases into the same pot In addition testing samples for anti-HEV with epidemiological purposes is limited by the lack ofgenotype-specific assays a limitation that researchers of theHSV epidemiology suffered from for many years in the pastDevelopment of genotype-specific tests would therefore bean important requirement to enlighten the mysteries of theanti-HEV prevalence in the future

4 Hepatitis E Infection and Disease

The actual rate between disease and infection is unknownfor HHEV but the general thought is that asymptomaticinfection is a common event [14] Most diagnosis wasachieved among patients suffering icteric hepatitis and mostdata regarding other symptoms and signs came from thestudy of epidemic outbreaks due to HHEV1 In addition tojaundice anorexia abdominal pain and hepatomegaly wereconsistently found among patients from the main studiesother symptoms like fever nausea or vomiting were lessfrequent Fulminant hepatic failure was uncommon but inpregnant women and the case fatality rate ranged from 05 to4 among patients requiring hospitalization who are likely asmall minority Persistent viral infection was never reportedin these studies

Clinical data from patients with acute hepatitis infectedwith HHEV3 are scarcer Most cases reported were ictericand displayed elevated ALT levels in serum very muchlike cases of acute hepatitis A when the comparison wasperformed [15] Jaundice and biochemical alterations weremore pronounced among cases confirmed by detection ofviremia and the duration of the disease was also longeramong them than among patients testing negative for viralRNA in serum However these differences might just reflectan earlier sampling among the former Complications werenot frequent and fatal outcome was always associated tounnoticed prior alcoholic cirrhosis

A careful investigation performed on people involvedin an outbreak of HHEV3 infection among the passengersof a cruise ship found 11 cases of acute hepatitis and 22asymptomatic infections (rate up to 33) [16] Disease wassignificantly associated with excessive alcohol intake andanorexia malaise nausea and dark urine were the mostfrequent symptoms and signs Jaundicewas observed in sevencases Liver enzyme levels were often high among the patientsbut were always normal among the people experiencingasymptomatic infections A common source of infectioncould not be identified for the outbreak but shellfish intakewas likely involved In agreement with the usual male tofemale rate found in collections of sporadic cases of acutehepatitis due to HHEV3 the likelihood of infection wassignificantly higher among men than among women

Though hepatitis E is always a self-limited disease amongimmune competent patients HHEV3 persistency resultingin chronic hepatitis has been reported among patients withimmune impairment [17] Reports included transplant recip-ients haematological patients receiving chemotherapy andpatients infected by human immunodeficiency virus Rapid

progression to liver cirrhosis was often observed Ribavirintherapy and lowering immunosuppression lead efficiently tovirus clearance in most cases

In summary hepatitis E is amild disease that may presentboth as epidemics and sporadic cases Symptoms and singsresemble hepatitis A and the rate of asymptomatic infectionmight be as high as two additional infections for each case ofdisease Otherwise than acute liver failure among pregnantwomen infected by HHEV1 complications are infrequentViral persistency is not rare among immunosuppressedpatients and may result in rapid progression to cirrhosisbut the outcome can be efficiently prevented by the antiviraltherapy

5 Considerations about the Frequency andthe Acquisition of the Disease

Hepatitis E is the most frequent acute viral hepatitis indeveloping countries and is recorded both as sporadic casesand as epidemic outbreaks in these settings [18] It is causedbyHHEV1 in Southern andCentral Asia the Far East and theCaribbean and by HHEV1 and -2 in Africa Most cases fromoutbreaks are recorded among children Sporadic hepatitisE caused by HHEV3 or -4 is also common in China JapanKorea and Taiwan and HHEV4 has been detected amongswine livestock from India and Indonesia [18]Molecular test-ing is still uncommon in clinical laboratories worldwide andthe genotype responsible for the disease is rarely identifiedTherefore a participation of HHEV3 and -4 in sporadic casesat India and South-east Asia cannot be ruled out

Though HHEV4 may cause locally acquired hepatitis Ein Western Europe HHEV3 is responsible for the majorityof autochthonous cases recorded in the continent [19] Inrecent studies HHEV was involved in 44 of 1027 casesof acute hepatitis tested in The Netherlands for three years[20] 33 of 838 cases tested in Southwest England fortwo years [15] 105 of 97 cases tested in Finland for nineyears [21] 96 of 1203 cases tested in Hungary for sixyears [22] 108 of 277 cases tested in Spain for six years[23] and exceptionally 557 of 52 cases tested in Italy forseven years [24] Imported infections byHEV1 predominatedin studies from Finland and in special from Italy Locallyacquired infections due to HEV3 were the most frequentin the remaining series These local infections were morecommon among men aged over 40 than among women oramong younger men and were almost never found amongchildren and adolescents In addition some studies recordedregional differences in frequency rates within a given countrythough the data must be confirmed by population-basedprospective studies before these differences can be acceptedas a matter of fact Updated data from Spain suggest that theprevalence of locally acquired hepatitis E could be up to 20-fold higher in the northern regions of the country than inthe south increasing gradually from south to north (authorrsquosunpublished observations)

A report from the Centers for Disease Control andPrevention recorded 26 confirmed cases of hepatitis E among154 US patients tested in a period of seven years [25]

4 Scientifica

Fifteen patients did not travel abroad recently Thus thefrequency of locally acquired hepatitis E in the series was97 Genotyping was performed in eight of the 15 casesand HHEV3 was found in all samples Communicationsreporting autochthonous cases of hepatitis E due to HHEV3in other American countries were previously published fromArgentina Bolivia Brazil Mexico Venezuela and Uruguay[26ndash31] Frequency of HHEV diagnosis among patients withlocally acquired acute hepatitis of unknown origin rangedfrom 16 in Brazil to 30 in Venezuela though HHEV1strains were also detected in the last country HHEV1 was theonly genotype responsible for sporadic cases and epidemicoutbreaks of hepatitis E in Cuba [32] and has been recentlyinvolved in an autochthonous case presented in Uruguay(Arbiza J personal communication)

HHEVwould therefore respond to about 10 of cases ofnon-AndashD suspected acute viral hepatitis presenting in west-ern countries among nontravelers and collecting a significantnumber of cases has taken years of work from the authorsof these reports Since results from different investigationssuggest a likely involvement of the consumption of porkderivatives shellfish bivalves or crude vegetables in virustransmission [33ndash36] autochthonous hepatitis E is consid-ered at present a food-borne low-incidence zoonosis inEurope NorthAmerica and the SouthCone of this continentin addition to an imported disease Such consideration couldbe likely extended to other temperate regions such Australiaor New Zealand where specific data are still scarce

6 Laboratory Diagnosis of the Acute Infection

The dynamics of virus shedding viremia and antibodyresponse in the acute HHEV infection displays the usualevents in other systemic viral infections acquired by the fecal-oral route The antibody window period extends for twoweeks and viremia persists at detectable levels for a variableperiod of time after the window closing Virus is shed in stoolfrom the beginning of this period and fecal shedding persistsfor several weeks after the viremia is cleared Moleculartesting of stool samples provides therefore an excellentchance for laboratory diagnosis but it is seldom performed atclinical laboratories because of technical issues regarding theextraction of viral RNA from stool which requires experiencefor a suitable yield

Viremia levels are lower than in other viral acute hepatitiswith the yield of serum testing being highly dependent ofthe analytical sensitivity of the assay used Since commercialtests for HHEV genome detection are still scarce in themarket most laboratories performing molecular diagnosisare testing samples by in-house conventional techniquesof RNA amplification by reverse transcription polymerasechain reaction (RT-PCR) However commercial sensitivemethods of real-time PCRwill likely replace them in the shortterm Retrospective testing of samples after long storage mayreduce significantly the yield of molecular testing becauseof viral RNA degradation which underlines that clinicallaboratories must always test fresh samples

Early serological diagnosis is based on detection of theanti-HHEV IgM response which precedes in most cases therising of anti-HHEV IgG Testing is performed by indirectenzyme-immunoassay (EIA) using recombinant antigensfrom the core protein Most commercial tests use antigensmatching HHEV1 sequences which are thought less sensitivefor diagnosing infections caused by the remaining genotypesHowever such thoughts are not always fully supported bydata Like in other viral infections samples reactive in EIAtesting can be retested by recombinant immunoblot (RIB)for confirmatory purposes A commercial test is availablefor such confirmation and includes recombinant antigenscorresponding to HHEV1 and -3 core and ORF3 proteinsequences Confirmed reactivity for anti-HHEV IgM is con-sidered diagnostic for acute infection Since a segment ofthe healthy population from any geographical region of theWorld considered displays residual anti-HHEV IgG in serumreflecting a prior contact with the virus the finding of thismarker alone has no diagnostic value unless seroconversionis demonstrated after testing serial samples from the patient

In agreement with these considerations diagnostic cri-teria for acute HHEV infection among patients with acutehepatitis would be as follows (1) IgM negative RNA positive(window period) (2) IgM positive RNA positive (earlyseroconversion stage) (3) IgM positive RNA negative (post-seroconversion stage) and (4) Seroconversion to IgG anti-body on follow-up When specific IgM is the only diagnosticmarker found exclusion of acute primary infection by humancytomegalovirus and Epstein-Barr virus by specific testing issuitable because these agents may rise up a false diagnosis ofhepatitis E through polyclonal stimulation of HHEV-specificB cell subsets

7 Technical Issues Would InfluenceAnti-HHEV IgG Testing

Though the data available support the reasonable robustnessof the current assays for anti-HHEV IgM testing in thediagnosis of acute hepatitis E doubts about the specificityandor sensitivity of these reagents in recognizing residualimmunity to HHEV among the general population by anti-HHEV IgG testing emerged in the last years On one handtesting enzyme immunoassay (EIA-) reactive samples byrecombinant immunoblot (RIB) classified 28ndash50 of them asanti-HHEVnegative if RIBwas used as a confirmatory test [820 37] On the other hand comparison of the performanceof current EIA assays using a standard preparation of anti-HHEV showed considerable differences that were claimedto reflect the insensitivity of most of them leading tosuggest that results from all seroprevalence studies on HHEVperformed in the World would have largely underestimatedthe reality [38]

In a report from France a new testing of samples by thetest claimed the most sensitive one rose up by three times theprevalence of anti-HHEV found formerly among the blooddonors from Toulouse (166 versus 525) [39] The verysame discrepancy between this particular test and anotherone was observed among a group of samples from transplant

Scientifica 5

recipients from Marseille two years later (109 versus 313)[40] Aiming at knowing whether the apparently moresensitive test (Wantai China) was actually more sensitive orless specific than the other one (Adaltis Italy) the authorsof this last study tested by RIB six samples reacting in bothassays and 14 reacting only in Wantai These six samples and10 of the last 14 samples tested positive but the remaining foursamples tested negative If any conclusion can be drawn fromthe data it would either be that theWantai test provides false-positive results for anti-HEV IgG or that the RIB test is notsatisfactory for the purpose of confirmation It was certainlyshown however that the Adaltis test was rather insensitivebut this would only affect the results from seroprevalencestudies performed with this particular reagent

There are therefore reasons to pursuit efforts in stan-dardizing the HHEV serology and to agree about collab-orative studies which can lead to a consensus about thetechnology suitable for performing serosurveys and about thevalidity of the data collected during the last two decades inthe different regions Until these objectives are achieved whatcan be done is just to look at these data and try to understandwhat they may mean

8 A Look on the Data

Tables 1 2 3 and 4 summarize the results reported fromstudies involving collections of samples more or less repre-sentative of the general population of countries or regionsfrom Europe South Asia the Far East the Middle East andthe Americas

South Asia and the Far East displayed often high preva-lence rates India Malaysia and Southern China displayedthe highest rates among children (up to 20ndash50) Rateshigher than 50 were found also among adults from HongKong and other regions of China and low rates (less than 10among adults) were consistently reported from Japan Thiswould roughly match the impact of HHEV1 (and of subtypes1a and 1b in particular) on epidemic hepatitis E HHEV1 -3and -4 overlap however widely in the region and rates higherthan reported would have been expected from countries likeThailand Indonesia or Vietnam

In the Middle East the prevalence was low everywherebut in Egypt With this single exception anti-HHEV wasalmost absent among children and did not reach 20 amongadults However most reports are from Turkey and Iranwhich can be considered countries of low endemicity forHHEV

In regard to Europe and the Americas the rates reportedwere low and pretty much the same for all studies but forthree performed in the UK the US and Bolivia In the UKthe prevalence was sixfold lower among the adult populationof London sampled in 1988-89 than among the populationof England and Wales sampled throughout 1991 and 2004(39 versus 27) [9 41] In the US anti-HHEV rose withage up to 45 among adult men aged over 60 years in asurvey performed by the National Institutes of Health andthe Centers for Disease Control at the national level The rateamong adults would have been expected higher in areas close

0102030405060708090

Ant

i-HEV

pos

itive

()

0 20 40 60 80Age (years)

EgyptBangladeshChina (east)

USAEnglandNetherlands

Figure 1 Examples of the patterns of acquisition of anti-HHEVwithage among the population from regions endemic forHHEV1 (EgyptBangladesh and East China) [5ndash7] or HHEV3 (USA England andThe Netherlands) [8ndash10]

to the Mexican border than in the rest of the country butthe data available show actually the very opposite (16 versus42) [10 42]ThoughMexico is usually included in the list ofhighly endemic countries for hepatitis E this is just based onthe report of an epidemics developing 26 years ago that wasattributed to a uniqueHHEV2 strain (genotype 2a) [43] neverfound again As for other areas of Latin America formerlythought as highly endemic for HHEV the data available orbetter the scarcity of them in the case of Mexico do notsupport the assertion [44]

As a complement to these data Table 5 summarizes theresults from representative studies performed among blooddonors worldwide Most of them agree with the data fromthe general population of adults and significant discrepanciesbetween studies performed within a given country are againnoticed In the US results from the two studies availablewould suggest that the prevalence of anti-HHEV is 13-foldhigher in Washington DC than in Northern California [4546] In the United Kingdom donors from Bristol displayeda prevalence almost fourfold higher than the one foundrecently among Scottish donors [38 47] In France theprevalence would be more than 16-fold higher at MidiPyrenees than at Ile de France or Pays de Loire [39 48]Differences might respond in some cases but not always tothe technical issues discussed above

Comparison of data shows that the greatest regionaldifferences are seen among children and indicates thatHHEVspreads earlier in life among the population of Asia and Egyptthan of the rest of the World (Table 6) Among the adultsthe differences do not look so sharp when only the rangesare considered Independently of the overall prevalence anti-HHEV is acquired earliest in life in regions endemic forHHEV1 in comparison with the regions endemic for HHEV3(Figure 1) However the prevalence of anti-HHEV reportedfor the oldest population groups was almost the same in theUS than in Bangladesh and was lower in East China than in

6 Scientifica

Table 1 Prevalence of anti-HHEV among the general population of Europe

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

United Kingdom 710 mdash 39 mdash [41]1591 20-30 5ndash27 13 [9]

Italy 1889 mdash 26 mdash [64]3511 mdash 29 mdash [65]

San Marino 2233 mdash 15 mdash [66]

Spain 2529 46 73 60 [67 68]2305a 05 21 11 [37]

Germany 4422a mdash 17 mdash [69]The Netherlands 7072a 0ndash03 14ndash64 19 [8]aAnti-HHEV screened or confirmed by RIBT

Table 2 Prevalence of anti-HHEV among the general population of South Asia and the Far East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

India (north) 2070 24ndash29 mdash mdash [70]India (Andaman) 814 13ndash40 16ndash77 15ndash73 [57]India (Chennai) 185 53ndash17 mdash mdash [71]India (south) 2279 06ndash89 92ndash36 91ndash23 [72]Bangladesh 1134 mdash 23 mdash [5]Pakistan 540 14 mdash mdash [73]Thailand 513 mdash 23 mdash [74]Malaysia 132 40ndash50 43ndash67 44ndash50 [75]Indonesia 1115 mdash 05ndash20 mdash [76]Vietnam 646 30ndash50 11ndash19 90 [58]China 8762 54ndash42 98ndash46 18 [59]China (south) 3844 10ndash21 40ndash66 44 [77]China (east) 12052 67ndash13 14ndash23 17 [6]China (Fujian) 1151 mdash 23 mdash [78]China (Han) 7376 52ndash12 20ndash57 24 [79]China (Hui) 2258 31ndash40 21ndash68 36

Hong Kong 934 mdash 19 mdash [60]450 60ndash80 18ndash60 28 [80]

Taiwan984 03 11 44 [81]997 15ndash96 88ndash13 64ndash88 [82]2538 34 mdash mdash [83]

Japan 1253 mdash 46ndash67 mdash [84]22027 mdash 27ndash66 mdash [85]

Korea 147 mdash 14ndash23 mdash [86]

England The low-prevalence pattern found in The Nether-lands is representative for other Western European countrieslike Spain or San Marino but also for Asiatic countrieslike Japan where both HHEV1 and HHEV3 autochthonousinfections are reported

The significance of this overview is however limitedby the finding of some very significant variations of theanti-HHEV prevalence when different populations from asingle country or region are compared (Table 7) Particularethnic groups and some rural populations of South Asiaand of the Far and the Middle East seem to represent

true ldquohot spotsrdquo of the HHEV epidemiology Just Egyptwould constitute such a hot spot as a full country since theprevalence keeps high among rural populations from boththe Lower and the Upper Nile River Whether this fact ischaracteristic of the Egyptian rural setting or is also sharedby the population from great cities like Cairo or Alexandriais unknown

In Latin America [44] the rate of anti-HHEV found 15years ago among homeless children fromCochabamba (66)[49] remains more than threefold higher than the highestever reported for any other population group in the region

Scientifica 7

Table 3 Prevalence of anti-HHEV among the general population of the Middle East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

Turkey 1374 mdash 59 mdash [87]Turkey (Istanbul) 909 21 mdash mdash [88]Turkey (Antalya) 338 09 mdash mdash [89]Turkey (Anatolia) 321 mdash 12-13 mdash [90]Turkey (Aydin) 386 mdash 70 mdash [91]Turkey (Duzce) 589 03 mdash mdash [92]Turkey (Trace) 580 mdash 24 mdash [93]Iran (Nahavand) 304 mdash 93 mdash [94]Iran (Isfahan) 816 09 81 38 [95]Iran (Sari) 1080 12 73 23 [96]Iran (west) 400 mdash 78 mdash [97]Iran (Teheran) 551 mdash 79ndash15 mdash [98]Yemen 356 80 15 11 [99]Israel 1416 mdash 18ndash28 mdash [100]

Egypt10026 36ndash76 48ndash76 68 [101]100 26 mdash mdash [102]2428 mdash 84 mdash [7]

Table 4 Prevalence of anti-HHEV among the general population of the Americas

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

USA 18695 10ndash50 39ndash42 21 [10]USA (Texas) 864 mdash 04ndash16 mdash [42]Canada (Inuit) 393 26 31 30 [103]Greenland (Inuit) 503 mdash 30 mdash [104]Venezuela (urban) 184 mdash 16 mdashVenezuela (rural) 204 mdash mdash 39 [50]

Venezuela (Amerindians) 223 mdash 54 mdash463 mdash 97 mdash [51]

Nicaragua 399 mdash 46ndash80 mdash [105]Argentina 1304 015 mdash mdash [106]Chile 168 12 mdash mdash [107]Chile (Amerindians) 100 mdash 170 mdash [108]Bolivia (rural) 490 mdash 73 mdash [109]Bolivia (rural) 186 mdash 20 mdashBolivia (urban) 193 66 31 49 [49]Bolivia (Amazon) 318 0ndash14 70ndash30 20Mexico 3549 11 14 10 [110]Brazil 1196 45 mdash mdash [111]

Cuba 209 mdash 53 mdash [61]469 mdash 100 mdash [112]

However reagents used to perform the study were primitiveand further studies are required before qualifying this regionof Bolivia as highly endemic for HHEV Rates recorded in theBolivian Amazon in the same report (up to 26 among theYurakare Amerindians) were also higher than the rates foundbefore among Amerindian populations from tropical forestsof Venezuela outside theAmazon (54 and 97) [50 51] New

data obtainedwith updated reagents will eventually enlightenthe epidemiology of HHEV in the tropical woodlands ofSouth America and confirm the differences they may display

The anti-HHEV prevalence rate reported for blooddonors aged 58 to 65 years from the French region of MidiPyrenees (70) [39] is a single and unexpected Europeanspot in Table 6 It seems unlikely that a rate of 25 to 4-fold

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Volume 2014

Zoology

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

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BioinformaticsAdvances in

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Signal TransductionJournal of

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Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Microbiology

2 Scientifica

genotypes are exclusive of the human beings and some areshared with other mammal species as explained below

The HHEV virion is a spherical-shaped particle about30 nm in diameter whose structure resembles the structureof the calicivirus particle under the electron microscopeThe viral core protein is the single structural protein of thevirion but arranges in different ways to generate a series ofstructural unitsThe genome consists of a single linear speciesof single-stranded 31015840-capped RNA of positive polarity andof 73 kilobases (kb) in length which is organized in threeopen reading frames (ORFs) [11] ORF1 extends for 51 kband encodes at least four functional nonstructural proteinsdisplaying activities of methyl-transferase protease heli-case and RNA-dependent RNA polymerase ORF2 encodesthe core protein which builds the capsid of the virionand is responsible for attachment and entry into the hostcell and for the main stimulation of the specific immuneresponse ORF3 encodes a small antigenic phosphoproteinof unknown function HHEV is difficult to replicate in cellculture to a high titer and laboratory assays for specificantibody testing are commonly developed with differentrecombinant antigens from the core protein though someinclude also recombinant antigens from the ORF3-encodedprotein Assays for molecular diagnosis are usually based onamplification of sequences from theORF1 region Sequencingof the products may render the identification of the HHEVgenotype present in the sample but further characterizationrequires amplification of sequences from the ORF2 region orbetter full genome sequencing

Though comparative analysis of genomes is winning anincreasing relevance in biological taxonomy other meaning-ful considerations must also be taken in mind for classifyingviruses In addition to the traditional criteria of virionmorphology and antigenic proprieties the survival strategyrepresents a trait intimately linked to the evolution of viruspopulations that may involve important epidemiologicalconsequences In the particular case of HHEV this trait isrelevant and should not be ignored by taxonomists

3 Is HHEV a Single Virus

Cross-neutralization gave herpes simplex virus (HSV) theformer consideration of a single virus species consisting oftwo types After some years HSV types 1 and 2 (HSV1HSV2) were classified into two separate species sharing mostneutralizing epitopes but lacking cross-protective immunitySuch distinction recognized among other differential fea-tures the radically different survival strategies of these twoagents which determine a totally different epidemiologyHSV1 spreads widely among the population very early in lifeand is transmitted mainly by the respiratory route amongchildren In contrast HSV2 is a sexually transmitted agentwhose spreading among adolescents and adults dependson the sexual behavior Anti-HSV1 prevalence is almostuniformly high everywhere The prevalence of anti-HSV2is lower and displays wide differences between regionsbut also in regard to the subset of population considered

within a given region Formerly performance of antibodysurveys specific for each of these two viruses was impairedby an important technical limitation Detection of type-specific antibody required the measurement of the kineticsof the neutralization observed after mixing the sample withcarefully titrated preparations of infectious virus from eachtype a cumbersome approach almost unaffordable for testinghundred or thousand samples Later on novel and friendliertype specific tests were developed and these antibody surveyscould be achieved In a study from Spain almost 80 ofan adult female population tested positive for anti-HSV1 byimmunoblot but only 35 tested positive for anti-HSV2 [12]In the USA a study performed at the national level found18 of white adult women positive for anti-HSV2 but therate increased to 46 among black women [13] Thereforeboth significant regional and population-based differencesexisted in the epidemiology of the HSV2 infection andsuch knowledge was relevant for improving the preventionof genital herpes and of the devastating neonatal diseaseresulting from mother-to-child virus transmission

The present taxonomic status of HHEV as a single viralspecies reminds the former status of HSV No evidenceof cross-protective immunity between the different HHEVgenotypes exists and they can also be meaningfully groupedinto two groups in regard to their survival strategies andtheir epidemiological features Genotypes 1 and 2 (HHEV1HHEV2) are exclusive of human beings though HHEV1may accidentally or artificially infect other species Theyare restricted to particular geographical areas and spreadoften among the population as waterborne open epidemicoutbreaks In contrast genotypes 3 and 4 (HHEV3 HHEV4)are adapted to mammals from different orders from swineand deer to mongoose and rat and are distributed worldwideand infect humans sporadically through zoonotic transmis-sion or by consumption of contaminated aliments Thesebehaviors most likely reflect two sharply separated evolu-tionary lineages representing two different survival strategiesthat evolved independently since long time ago From anevolutionary point of view wider than the strict considera-tion of the genetic relationships these two HHEV lineageswould perhaps merit the consideration of two different viralspecies and such consideration would fit the epidemiologicalfindings

Diseases caused by theseHHEVgenotypes share identicalclinical features between them and with other acute viralhepatitis But for the high mortality recorded sometimesamong pregnant women infected by HHEV1 hepatitis E canbe indeed taken by clinicians as hepatitis A in the regions ofthe World where hepatitis A virus (HAV) remains endemicThis lack of specific symptoms and signs is characteristic ofacute viral hepatitis in general and the disease is classified asA B C D E or non-AndashE after performing laboratory studiesIf HEV was divided into two species acute hepatitis E wouldalso be divided into two different diseases and virologistswould learn that they should try to separate them in thelaboratory as they do for the rest

The investigation of the HEV epidemiology is thereforeinfluenced by these conceptual issues since we are actually

Scientifica 3

mixing two different viral infections and two different dis-eases into the same pot In addition testing samples for anti-HEV with epidemiological purposes is limited by the lack ofgenotype-specific assays a limitation that researchers of theHSV epidemiology suffered from for many years in the pastDevelopment of genotype-specific tests would therefore bean important requirement to enlighten the mysteries of theanti-HEV prevalence in the future

4 Hepatitis E Infection and Disease

The actual rate between disease and infection is unknownfor HHEV but the general thought is that asymptomaticinfection is a common event [14] Most diagnosis wasachieved among patients suffering icteric hepatitis and mostdata regarding other symptoms and signs came from thestudy of epidemic outbreaks due to HHEV1 In addition tojaundice anorexia abdominal pain and hepatomegaly wereconsistently found among patients from the main studiesother symptoms like fever nausea or vomiting were lessfrequent Fulminant hepatic failure was uncommon but inpregnant women and the case fatality rate ranged from 05 to4 among patients requiring hospitalization who are likely asmall minority Persistent viral infection was never reportedin these studies

Clinical data from patients with acute hepatitis infectedwith HHEV3 are scarcer Most cases reported were ictericand displayed elevated ALT levels in serum very muchlike cases of acute hepatitis A when the comparison wasperformed [15] Jaundice and biochemical alterations weremore pronounced among cases confirmed by detection ofviremia and the duration of the disease was also longeramong them than among patients testing negative for viralRNA in serum However these differences might just reflectan earlier sampling among the former Complications werenot frequent and fatal outcome was always associated tounnoticed prior alcoholic cirrhosis

A careful investigation performed on people involvedin an outbreak of HHEV3 infection among the passengersof a cruise ship found 11 cases of acute hepatitis and 22asymptomatic infections (rate up to 33) [16] Disease wassignificantly associated with excessive alcohol intake andanorexia malaise nausea and dark urine were the mostfrequent symptoms and signs Jaundicewas observed in sevencases Liver enzyme levels were often high among the patientsbut were always normal among the people experiencingasymptomatic infections A common source of infectioncould not be identified for the outbreak but shellfish intakewas likely involved In agreement with the usual male tofemale rate found in collections of sporadic cases of acutehepatitis due to HHEV3 the likelihood of infection wassignificantly higher among men than among women

Though hepatitis E is always a self-limited disease amongimmune competent patients HHEV3 persistency resultingin chronic hepatitis has been reported among patients withimmune impairment [17] Reports included transplant recip-ients haematological patients receiving chemotherapy andpatients infected by human immunodeficiency virus Rapid

progression to liver cirrhosis was often observed Ribavirintherapy and lowering immunosuppression lead efficiently tovirus clearance in most cases

In summary hepatitis E is amild disease that may presentboth as epidemics and sporadic cases Symptoms and singsresemble hepatitis A and the rate of asymptomatic infectionmight be as high as two additional infections for each case ofdisease Otherwise than acute liver failure among pregnantwomen infected by HHEV1 complications are infrequentViral persistency is not rare among immunosuppressedpatients and may result in rapid progression to cirrhosisbut the outcome can be efficiently prevented by the antiviraltherapy

5 Considerations about the Frequency andthe Acquisition of the Disease

Hepatitis E is the most frequent acute viral hepatitis indeveloping countries and is recorded both as sporadic casesand as epidemic outbreaks in these settings [18] It is causedbyHHEV1 in Southern andCentral Asia the Far East and theCaribbean and by HHEV1 and -2 in Africa Most cases fromoutbreaks are recorded among children Sporadic hepatitisE caused by HHEV3 or -4 is also common in China JapanKorea and Taiwan and HHEV4 has been detected amongswine livestock from India and Indonesia [18]Molecular test-ing is still uncommon in clinical laboratories worldwide andthe genotype responsible for the disease is rarely identifiedTherefore a participation of HHEV3 and -4 in sporadic casesat India and South-east Asia cannot be ruled out

Though HHEV4 may cause locally acquired hepatitis Ein Western Europe HHEV3 is responsible for the majorityof autochthonous cases recorded in the continent [19] Inrecent studies HHEV was involved in 44 of 1027 casesof acute hepatitis tested in The Netherlands for three years[20] 33 of 838 cases tested in Southwest England fortwo years [15] 105 of 97 cases tested in Finland for nineyears [21] 96 of 1203 cases tested in Hungary for sixyears [22] 108 of 277 cases tested in Spain for six years[23] and exceptionally 557 of 52 cases tested in Italy forseven years [24] Imported infections byHEV1 predominatedin studies from Finland and in special from Italy Locallyacquired infections due to HEV3 were the most frequentin the remaining series These local infections were morecommon among men aged over 40 than among women oramong younger men and were almost never found amongchildren and adolescents In addition some studies recordedregional differences in frequency rates within a given countrythough the data must be confirmed by population-basedprospective studies before these differences can be acceptedas a matter of fact Updated data from Spain suggest that theprevalence of locally acquired hepatitis E could be up to 20-fold higher in the northern regions of the country than inthe south increasing gradually from south to north (authorrsquosunpublished observations)

A report from the Centers for Disease Control andPrevention recorded 26 confirmed cases of hepatitis E among154 US patients tested in a period of seven years [25]

4 Scientifica

Fifteen patients did not travel abroad recently Thus thefrequency of locally acquired hepatitis E in the series was97 Genotyping was performed in eight of the 15 casesand HHEV3 was found in all samples Communicationsreporting autochthonous cases of hepatitis E due to HHEV3in other American countries were previously published fromArgentina Bolivia Brazil Mexico Venezuela and Uruguay[26ndash31] Frequency of HHEV diagnosis among patients withlocally acquired acute hepatitis of unknown origin rangedfrom 16 in Brazil to 30 in Venezuela though HHEV1strains were also detected in the last country HHEV1 was theonly genotype responsible for sporadic cases and epidemicoutbreaks of hepatitis E in Cuba [32] and has been recentlyinvolved in an autochthonous case presented in Uruguay(Arbiza J personal communication)

HHEVwould therefore respond to about 10 of cases ofnon-AndashD suspected acute viral hepatitis presenting in west-ern countries among nontravelers and collecting a significantnumber of cases has taken years of work from the authorsof these reports Since results from different investigationssuggest a likely involvement of the consumption of porkderivatives shellfish bivalves or crude vegetables in virustransmission [33ndash36] autochthonous hepatitis E is consid-ered at present a food-borne low-incidence zoonosis inEurope NorthAmerica and the SouthCone of this continentin addition to an imported disease Such consideration couldbe likely extended to other temperate regions such Australiaor New Zealand where specific data are still scarce

6 Laboratory Diagnosis of the Acute Infection

The dynamics of virus shedding viremia and antibodyresponse in the acute HHEV infection displays the usualevents in other systemic viral infections acquired by the fecal-oral route The antibody window period extends for twoweeks and viremia persists at detectable levels for a variableperiod of time after the window closing Virus is shed in stoolfrom the beginning of this period and fecal shedding persistsfor several weeks after the viremia is cleared Moleculartesting of stool samples provides therefore an excellentchance for laboratory diagnosis but it is seldom performed atclinical laboratories because of technical issues regarding theextraction of viral RNA from stool which requires experiencefor a suitable yield

Viremia levels are lower than in other viral acute hepatitiswith the yield of serum testing being highly dependent ofthe analytical sensitivity of the assay used Since commercialtests for HHEV genome detection are still scarce in themarket most laboratories performing molecular diagnosisare testing samples by in-house conventional techniquesof RNA amplification by reverse transcription polymerasechain reaction (RT-PCR) However commercial sensitivemethods of real-time PCRwill likely replace them in the shortterm Retrospective testing of samples after long storage mayreduce significantly the yield of molecular testing becauseof viral RNA degradation which underlines that clinicallaboratories must always test fresh samples

Early serological diagnosis is based on detection of theanti-HHEV IgM response which precedes in most cases therising of anti-HHEV IgG Testing is performed by indirectenzyme-immunoassay (EIA) using recombinant antigensfrom the core protein Most commercial tests use antigensmatching HHEV1 sequences which are thought less sensitivefor diagnosing infections caused by the remaining genotypesHowever such thoughts are not always fully supported bydata Like in other viral infections samples reactive in EIAtesting can be retested by recombinant immunoblot (RIB)for confirmatory purposes A commercial test is availablefor such confirmation and includes recombinant antigenscorresponding to HHEV1 and -3 core and ORF3 proteinsequences Confirmed reactivity for anti-HHEV IgM is con-sidered diagnostic for acute infection Since a segment ofthe healthy population from any geographical region of theWorld considered displays residual anti-HHEV IgG in serumreflecting a prior contact with the virus the finding of thismarker alone has no diagnostic value unless seroconversionis demonstrated after testing serial samples from the patient

In agreement with these considerations diagnostic cri-teria for acute HHEV infection among patients with acutehepatitis would be as follows (1) IgM negative RNA positive(window period) (2) IgM positive RNA positive (earlyseroconversion stage) (3) IgM positive RNA negative (post-seroconversion stage) and (4) Seroconversion to IgG anti-body on follow-up When specific IgM is the only diagnosticmarker found exclusion of acute primary infection by humancytomegalovirus and Epstein-Barr virus by specific testing issuitable because these agents may rise up a false diagnosis ofhepatitis E through polyclonal stimulation of HHEV-specificB cell subsets

7 Technical Issues Would InfluenceAnti-HHEV IgG Testing

Though the data available support the reasonable robustnessof the current assays for anti-HHEV IgM testing in thediagnosis of acute hepatitis E doubts about the specificityandor sensitivity of these reagents in recognizing residualimmunity to HHEV among the general population by anti-HHEV IgG testing emerged in the last years On one handtesting enzyme immunoassay (EIA-) reactive samples byrecombinant immunoblot (RIB) classified 28ndash50 of them asanti-HHEVnegative if RIBwas used as a confirmatory test [820 37] On the other hand comparison of the performanceof current EIA assays using a standard preparation of anti-HHEV showed considerable differences that were claimedto reflect the insensitivity of most of them leading tosuggest that results from all seroprevalence studies on HHEVperformed in the World would have largely underestimatedthe reality [38]

In a report from France a new testing of samples by thetest claimed the most sensitive one rose up by three times theprevalence of anti-HHEV found formerly among the blooddonors from Toulouse (166 versus 525) [39] The verysame discrepancy between this particular test and anotherone was observed among a group of samples from transplant

Scientifica 5

recipients from Marseille two years later (109 versus 313)[40] Aiming at knowing whether the apparently moresensitive test (Wantai China) was actually more sensitive orless specific than the other one (Adaltis Italy) the authorsof this last study tested by RIB six samples reacting in bothassays and 14 reacting only in Wantai These six samples and10 of the last 14 samples tested positive but the remaining foursamples tested negative If any conclusion can be drawn fromthe data it would either be that theWantai test provides false-positive results for anti-HEV IgG or that the RIB test is notsatisfactory for the purpose of confirmation It was certainlyshown however that the Adaltis test was rather insensitivebut this would only affect the results from seroprevalencestudies performed with this particular reagent

There are therefore reasons to pursuit efforts in stan-dardizing the HHEV serology and to agree about collab-orative studies which can lead to a consensus about thetechnology suitable for performing serosurveys and about thevalidity of the data collected during the last two decades inthe different regions Until these objectives are achieved whatcan be done is just to look at these data and try to understandwhat they may mean

8 A Look on the Data

Tables 1 2 3 and 4 summarize the results reported fromstudies involving collections of samples more or less repre-sentative of the general population of countries or regionsfrom Europe South Asia the Far East the Middle East andthe Americas

South Asia and the Far East displayed often high preva-lence rates India Malaysia and Southern China displayedthe highest rates among children (up to 20ndash50) Rateshigher than 50 were found also among adults from HongKong and other regions of China and low rates (less than 10among adults) were consistently reported from Japan Thiswould roughly match the impact of HHEV1 (and of subtypes1a and 1b in particular) on epidemic hepatitis E HHEV1 -3and -4 overlap however widely in the region and rates higherthan reported would have been expected from countries likeThailand Indonesia or Vietnam

In the Middle East the prevalence was low everywherebut in Egypt With this single exception anti-HHEV wasalmost absent among children and did not reach 20 amongadults However most reports are from Turkey and Iranwhich can be considered countries of low endemicity forHHEV

In regard to Europe and the Americas the rates reportedwere low and pretty much the same for all studies but forthree performed in the UK the US and Bolivia In the UKthe prevalence was sixfold lower among the adult populationof London sampled in 1988-89 than among the populationof England and Wales sampled throughout 1991 and 2004(39 versus 27) [9 41] In the US anti-HHEV rose withage up to 45 among adult men aged over 60 years in asurvey performed by the National Institutes of Health andthe Centers for Disease Control at the national level The rateamong adults would have been expected higher in areas close

0102030405060708090

Ant

i-HEV

pos

itive

()

0 20 40 60 80Age (years)

EgyptBangladeshChina (east)

USAEnglandNetherlands

Figure 1 Examples of the patterns of acquisition of anti-HHEVwithage among the population from regions endemic forHHEV1 (EgyptBangladesh and East China) [5ndash7] or HHEV3 (USA England andThe Netherlands) [8ndash10]

to the Mexican border than in the rest of the country butthe data available show actually the very opposite (16 versus42) [10 42]ThoughMexico is usually included in the list ofhighly endemic countries for hepatitis E this is just based onthe report of an epidemics developing 26 years ago that wasattributed to a uniqueHHEV2 strain (genotype 2a) [43] neverfound again As for other areas of Latin America formerlythought as highly endemic for HHEV the data available orbetter the scarcity of them in the case of Mexico do notsupport the assertion [44]

As a complement to these data Table 5 summarizes theresults from representative studies performed among blooddonors worldwide Most of them agree with the data fromthe general population of adults and significant discrepanciesbetween studies performed within a given country are againnoticed In the US results from the two studies availablewould suggest that the prevalence of anti-HHEV is 13-foldhigher in Washington DC than in Northern California [4546] In the United Kingdom donors from Bristol displayeda prevalence almost fourfold higher than the one foundrecently among Scottish donors [38 47] In France theprevalence would be more than 16-fold higher at MidiPyrenees than at Ile de France or Pays de Loire [39 48]Differences might respond in some cases but not always tothe technical issues discussed above

Comparison of data shows that the greatest regionaldifferences are seen among children and indicates thatHHEVspreads earlier in life among the population of Asia and Egyptthan of the rest of the World (Table 6) Among the adultsthe differences do not look so sharp when only the rangesare considered Independently of the overall prevalence anti-HHEV is acquired earliest in life in regions endemic forHHEV1 in comparison with the regions endemic for HHEV3(Figure 1) However the prevalence of anti-HHEV reportedfor the oldest population groups was almost the same in theUS than in Bangladesh and was lower in East China than in

6 Scientifica

Table 1 Prevalence of anti-HHEV among the general population of Europe

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

United Kingdom 710 mdash 39 mdash [41]1591 20-30 5ndash27 13 [9]

Italy 1889 mdash 26 mdash [64]3511 mdash 29 mdash [65]

San Marino 2233 mdash 15 mdash [66]

Spain 2529 46 73 60 [67 68]2305a 05 21 11 [37]

Germany 4422a mdash 17 mdash [69]The Netherlands 7072a 0ndash03 14ndash64 19 [8]aAnti-HHEV screened or confirmed by RIBT

Table 2 Prevalence of anti-HHEV among the general population of South Asia and the Far East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

India (north) 2070 24ndash29 mdash mdash [70]India (Andaman) 814 13ndash40 16ndash77 15ndash73 [57]India (Chennai) 185 53ndash17 mdash mdash [71]India (south) 2279 06ndash89 92ndash36 91ndash23 [72]Bangladesh 1134 mdash 23 mdash [5]Pakistan 540 14 mdash mdash [73]Thailand 513 mdash 23 mdash [74]Malaysia 132 40ndash50 43ndash67 44ndash50 [75]Indonesia 1115 mdash 05ndash20 mdash [76]Vietnam 646 30ndash50 11ndash19 90 [58]China 8762 54ndash42 98ndash46 18 [59]China (south) 3844 10ndash21 40ndash66 44 [77]China (east) 12052 67ndash13 14ndash23 17 [6]China (Fujian) 1151 mdash 23 mdash [78]China (Han) 7376 52ndash12 20ndash57 24 [79]China (Hui) 2258 31ndash40 21ndash68 36

Hong Kong 934 mdash 19 mdash [60]450 60ndash80 18ndash60 28 [80]

Taiwan984 03 11 44 [81]997 15ndash96 88ndash13 64ndash88 [82]2538 34 mdash mdash [83]

Japan 1253 mdash 46ndash67 mdash [84]22027 mdash 27ndash66 mdash [85]

Korea 147 mdash 14ndash23 mdash [86]

England The low-prevalence pattern found in The Nether-lands is representative for other Western European countrieslike Spain or San Marino but also for Asiatic countrieslike Japan where both HHEV1 and HHEV3 autochthonousinfections are reported

The significance of this overview is however limitedby the finding of some very significant variations of theanti-HHEV prevalence when different populations from asingle country or region are compared (Table 7) Particularethnic groups and some rural populations of South Asiaand of the Far and the Middle East seem to represent

true ldquohot spotsrdquo of the HHEV epidemiology Just Egyptwould constitute such a hot spot as a full country since theprevalence keeps high among rural populations from boththe Lower and the Upper Nile River Whether this fact ischaracteristic of the Egyptian rural setting or is also sharedby the population from great cities like Cairo or Alexandriais unknown

In Latin America [44] the rate of anti-HHEV found 15years ago among homeless children fromCochabamba (66)[49] remains more than threefold higher than the highestever reported for any other population group in the region

Scientifica 7

Table 3 Prevalence of anti-HHEV among the general population of the Middle East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

Turkey 1374 mdash 59 mdash [87]Turkey (Istanbul) 909 21 mdash mdash [88]Turkey (Antalya) 338 09 mdash mdash [89]Turkey (Anatolia) 321 mdash 12-13 mdash [90]Turkey (Aydin) 386 mdash 70 mdash [91]Turkey (Duzce) 589 03 mdash mdash [92]Turkey (Trace) 580 mdash 24 mdash [93]Iran (Nahavand) 304 mdash 93 mdash [94]Iran (Isfahan) 816 09 81 38 [95]Iran (Sari) 1080 12 73 23 [96]Iran (west) 400 mdash 78 mdash [97]Iran (Teheran) 551 mdash 79ndash15 mdash [98]Yemen 356 80 15 11 [99]Israel 1416 mdash 18ndash28 mdash [100]

Egypt10026 36ndash76 48ndash76 68 [101]100 26 mdash mdash [102]2428 mdash 84 mdash [7]

Table 4 Prevalence of anti-HHEV among the general population of the Americas

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

USA 18695 10ndash50 39ndash42 21 [10]USA (Texas) 864 mdash 04ndash16 mdash [42]Canada (Inuit) 393 26 31 30 [103]Greenland (Inuit) 503 mdash 30 mdash [104]Venezuela (urban) 184 mdash 16 mdashVenezuela (rural) 204 mdash mdash 39 [50]

Venezuela (Amerindians) 223 mdash 54 mdash463 mdash 97 mdash [51]

Nicaragua 399 mdash 46ndash80 mdash [105]Argentina 1304 015 mdash mdash [106]Chile 168 12 mdash mdash [107]Chile (Amerindians) 100 mdash 170 mdash [108]Bolivia (rural) 490 mdash 73 mdash [109]Bolivia (rural) 186 mdash 20 mdashBolivia (urban) 193 66 31 49 [49]Bolivia (Amazon) 318 0ndash14 70ndash30 20Mexico 3549 11 14 10 [110]Brazil 1196 45 mdash mdash [111]

Cuba 209 mdash 53 mdash [61]469 mdash 100 mdash [112]

However reagents used to perform the study were primitiveand further studies are required before qualifying this regionof Bolivia as highly endemic for HHEV Rates recorded in theBolivian Amazon in the same report (up to 26 among theYurakare Amerindians) were also higher than the rates foundbefore among Amerindian populations from tropical forestsof Venezuela outside theAmazon (54 and 97) [50 51] New

data obtainedwith updated reagents will eventually enlightenthe epidemiology of HHEV in the tropical woodlands ofSouth America and confirm the differences they may display

The anti-HHEV prevalence rate reported for blooddonors aged 58 to 65 years from the French region of MidiPyrenees (70) [39] is a single and unexpected Europeanspot in Table 6 It seems unlikely that a rate of 25 to 4-fold

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

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BioinformaticsAdvances in

Marine BiologyJournal of

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Signal TransductionJournal of

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Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Microbiology

Scientifica 3

mixing two different viral infections and two different dis-eases into the same pot In addition testing samples for anti-HEV with epidemiological purposes is limited by the lack ofgenotype-specific assays a limitation that researchers of theHSV epidemiology suffered from for many years in the pastDevelopment of genotype-specific tests would therefore bean important requirement to enlighten the mysteries of theanti-HEV prevalence in the future

4 Hepatitis E Infection and Disease

The actual rate between disease and infection is unknownfor HHEV but the general thought is that asymptomaticinfection is a common event [14] Most diagnosis wasachieved among patients suffering icteric hepatitis and mostdata regarding other symptoms and signs came from thestudy of epidemic outbreaks due to HHEV1 In addition tojaundice anorexia abdominal pain and hepatomegaly wereconsistently found among patients from the main studiesother symptoms like fever nausea or vomiting were lessfrequent Fulminant hepatic failure was uncommon but inpregnant women and the case fatality rate ranged from 05 to4 among patients requiring hospitalization who are likely asmall minority Persistent viral infection was never reportedin these studies

Clinical data from patients with acute hepatitis infectedwith HHEV3 are scarcer Most cases reported were ictericand displayed elevated ALT levels in serum very muchlike cases of acute hepatitis A when the comparison wasperformed [15] Jaundice and biochemical alterations weremore pronounced among cases confirmed by detection ofviremia and the duration of the disease was also longeramong them than among patients testing negative for viralRNA in serum However these differences might just reflectan earlier sampling among the former Complications werenot frequent and fatal outcome was always associated tounnoticed prior alcoholic cirrhosis

A careful investigation performed on people involvedin an outbreak of HHEV3 infection among the passengersof a cruise ship found 11 cases of acute hepatitis and 22asymptomatic infections (rate up to 33) [16] Disease wassignificantly associated with excessive alcohol intake andanorexia malaise nausea and dark urine were the mostfrequent symptoms and signs Jaundicewas observed in sevencases Liver enzyme levels were often high among the patientsbut were always normal among the people experiencingasymptomatic infections A common source of infectioncould not be identified for the outbreak but shellfish intakewas likely involved In agreement with the usual male tofemale rate found in collections of sporadic cases of acutehepatitis due to HHEV3 the likelihood of infection wassignificantly higher among men than among women

Though hepatitis E is always a self-limited disease amongimmune competent patients HHEV3 persistency resultingin chronic hepatitis has been reported among patients withimmune impairment [17] Reports included transplant recip-ients haematological patients receiving chemotherapy andpatients infected by human immunodeficiency virus Rapid

progression to liver cirrhosis was often observed Ribavirintherapy and lowering immunosuppression lead efficiently tovirus clearance in most cases

In summary hepatitis E is amild disease that may presentboth as epidemics and sporadic cases Symptoms and singsresemble hepatitis A and the rate of asymptomatic infectionmight be as high as two additional infections for each case ofdisease Otherwise than acute liver failure among pregnantwomen infected by HHEV1 complications are infrequentViral persistency is not rare among immunosuppressedpatients and may result in rapid progression to cirrhosisbut the outcome can be efficiently prevented by the antiviraltherapy

5 Considerations about the Frequency andthe Acquisition of the Disease

Hepatitis E is the most frequent acute viral hepatitis indeveloping countries and is recorded both as sporadic casesand as epidemic outbreaks in these settings [18] It is causedbyHHEV1 in Southern andCentral Asia the Far East and theCaribbean and by HHEV1 and -2 in Africa Most cases fromoutbreaks are recorded among children Sporadic hepatitisE caused by HHEV3 or -4 is also common in China JapanKorea and Taiwan and HHEV4 has been detected amongswine livestock from India and Indonesia [18]Molecular test-ing is still uncommon in clinical laboratories worldwide andthe genotype responsible for the disease is rarely identifiedTherefore a participation of HHEV3 and -4 in sporadic casesat India and South-east Asia cannot be ruled out

Though HHEV4 may cause locally acquired hepatitis Ein Western Europe HHEV3 is responsible for the majorityof autochthonous cases recorded in the continent [19] Inrecent studies HHEV was involved in 44 of 1027 casesof acute hepatitis tested in The Netherlands for three years[20] 33 of 838 cases tested in Southwest England fortwo years [15] 105 of 97 cases tested in Finland for nineyears [21] 96 of 1203 cases tested in Hungary for sixyears [22] 108 of 277 cases tested in Spain for six years[23] and exceptionally 557 of 52 cases tested in Italy forseven years [24] Imported infections byHEV1 predominatedin studies from Finland and in special from Italy Locallyacquired infections due to HEV3 were the most frequentin the remaining series These local infections were morecommon among men aged over 40 than among women oramong younger men and were almost never found amongchildren and adolescents In addition some studies recordedregional differences in frequency rates within a given countrythough the data must be confirmed by population-basedprospective studies before these differences can be acceptedas a matter of fact Updated data from Spain suggest that theprevalence of locally acquired hepatitis E could be up to 20-fold higher in the northern regions of the country than inthe south increasing gradually from south to north (authorrsquosunpublished observations)

A report from the Centers for Disease Control andPrevention recorded 26 confirmed cases of hepatitis E among154 US patients tested in a period of seven years [25]

4 Scientifica

Fifteen patients did not travel abroad recently Thus thefrequency of locally acquired hepatitis E in the series was97 Genotyping was performed in eight of the 15 casesand HHEV3 was found in all samples Communicationsreporting autochthonous cases of hepatitis E due to HHEV3in other American countries were previously published fromArgentina Bolivia Brazil Mexico Venezuela and Uruguay[26ndash31] Frequency of HHEV diagnosis among patients withlocally acquired acute hepatitis of unknown origin rangedfrom 16 in Brazil to 30 in Venezuela though HHEV1strains were also detected in the last country HHEV1 was theonly genotype responsible for sporadic cases and epidemicoutbreaks of hepatitis E in Cuba [32] and has been recentlyinvolved in an autochthonous case presented in Uruguay(Arbiza J personal communication)

HHEVwould therefore respond to about 10 of cases ofnon-AndashD suspected acute viral hepatitis presenting in west-ern countries among nontravelers and collecting a significantnumber of cases has taken years of work from the authorsof these reports Since results from different investigationssuggest a likely involvement of the consumption of porkderivatives shellfish bivalves or crude vegetables in virustransmission [33ndash36] autochthonous hepatitis E is consid-ered at present a food-borne low-incidence zoonosis inEurope NorthAmerica and the SouthCone of this continentin addition to an imported disease Such consideration couldbe likely extended to other temperate regions such Australiaor New Zealand where specific data are still scarce

6 Laboratory Diagnosis of the Acute Infection

The dynamics of virus shedding viremia and antibodyresponse in the acute HHEV infection displays the usualevents in other systemic viral infections acquired by the fecal-oral route The antibody window period extends for twoweeks and viremia persists at detectable levels for a variableperiod of time after the window closing Virus is shed in stoolfrom the beginning of this period and fecal shedding persistsfor several weeks after the viremia is cleared Moleculartesting of stool samples provides therefore an excellentchance for laboratory diagnosis but it is seldom performed atclinical laboratories because of technical issues regarding theextraction of viral RNA from stool which requires experiencefor a suitable yield

Viremia levels are lower than in other viral acute hepatitiswith the yield of serum testing being highly dependent ofthe analytical sensitivity of the assay used Since commercialtests for HHEV genome detection are still scarce in themarket most laboratories performing molecular diagnosisare testing samples by in-house conventional techniquesof RNA amplification by reverse transcription polymerasechain reaction (RT-PCR) However commercial sensitivemethods of real-time PCRwill likely replace them in the shortterm Retrospective testing of samples after long storage mayreduce significantly the yield of molecular testing becauseof viral RNA degradation which underlines that clinicallaboratories must always test fresh samples

Early serological diagnosis is based on detection of theanti-HHEV IgM response which precedes in most cases therising of anti-HHEV IgG Testing is performed by indirectenzyme-immunoassay (EIA) using recombinant antigensfrom the core protein Most commercial tests use antigensmatching HHEV1 sequences which are thought less sensitivefor diagnosing infections caused by the remaining genotypesHowever such thoughts are not always fully supported bydata Like in other viral infections samples reactive in EIAtesting can be retested by recombinant immunoblot (RIB)for confirmatory purposes A commercial test is availablefor such confirmation and includes recombinant antigenscorresponding to HHEV1 and -3 core and ORF3 proteinsequences Confirmed reactivity for anti-HHEV IgM is con-sidered diagnostic for acute infection Since a segment ofthe healthy population from any geographical region of theWorld considered displays residual anti-HHEV IgG in serumreflecting a prior contact with the virus the finding of thismarker alone has no diagnostic value unless seroconversionis demonstrated after testing serial samples from the patient

In agreement with these considerations diagnostic cri-teria for acute HHEV infection among patients with acutehepatitis would be as follows (1) IgM negative RNA positive(window period) (2) IgM positive RNA positive (earlyseroconversion stage) (3) IgM positive RNA negative (post-seroconversion stage) and (4) Seroconversion to IgG anti-body on follow-up When specific IgM is the only diagnosticmarker found exclusion of acute primary infection by humancytomegalovirus and Epstein-Barr virus by specific testing issuitable because these agents may rise up a false diagnosis ofhepatitis E through polyclonal stimulation of HHEV-specificB cell subsets

7 Technical Issues Would InfluenceAnti-HHEV IgG Testing

Though the data available support the reasonable robustnessof the current assays for anti-HHEV IgM testing in thediagnosis of acute hepatitis E doubts about the specificityandor sensitivity of these reagents in recognizing residualimmunity to HHEV among the general population by anti-HHEV IgG testing emerged in the last years On one handtesting enzyme immunoassay (EIA-) reactive samples byrecombinant immunoblot (RIB) classified 28ndash50 of them asanti-HHEVnegative if RIBwas used as a confirmatory test [820 37] On the other hand comparison of the performanceof current EIA assays using a standard preparation of anti-HHEV showed considerable differences that were claimedto reflect the insensitivity of most of them leading tosuggest that results from all seroprevalence studies on HHEVperformed in the World would have largely underestimatedthe reality [38]

In a report from France a new testing of samples by thetest claimed the most sensitive one rose up by three times theprevalence of anti-HHEV found formerly among the blooddonors from Toulouse (166 versus 525) [39] The verysame discrepancy between this particular test and anotherone was observed among a group of samples from transplant

Scientifica 5

recipients from Marseille two years later (109 versus 313)[40] Aiming at knowing whether the apparently moresensitive test (Wantai China) was actually more sensitive orless specific than the other one (Adaltis Italy) the authorsof this last study tested by RIB six samples reacting in bothassays and 14 reacting only in Wantai These six samples and10 of the last 14 samples tested positive but the remaining foursamples tested negative If any conclusion can be drawn fromthe data it would either be that theWantai test provides false-positive results for anti-HEV IgG or that the RIB test is notsatisfactory for the purpose of confirmation It was certainlyshown however that the Adaltis test was rather insensitivebut this would only affect the results from seroprevalencestudies performed with this particular reagent

There are therefore reasons to pursuit efforts in stan-dardizing the HHEV serology and to agree about collab-orative studies which can lead to a consensus about thetechnology suitable for performing serosurveys and about thevalidity of the data collected during the last two decades inthe different regions Until these objectives are achieved whatcan be done is just to look at these data and try to understandwhat they may mean

8 A Look on the Data

Tables 1 2 3 and 4 summarize the results reported fromstudies involving collections of samples more or less repre-sentative of the general population of countries or regionsfrom Europe South Asia the Far East the Middle East andthe Americas

South Asia and the Far East displayed often high preva-lence rates India Malaysia and Southern China displayedthe highest rates among children (up to 20ndash50) Rateshigher than 50 were found also among adults from HongKong and other regions of China and low rates (less than 10among adults) were consistently reported from Japan Thiswould roughly match the impact of HHEV1 (and of subtypes1a and 1b in particular) on epidemic hepatitis E HHEV1 -3and -4 overlap however widely in the region and rates higherthan reported would have been expected from countries likeThailand Indonesia or Vietnam

In the Middle East the prevalence was low everywherebut in Egypt With this single exception anti-HHEV wasalmost absent among children and did not reach 20 amongadults However most reports are from Turkey and Iranwhich can be considered countries of low endemicity forHHEV

In regard to Europe and the Americas the rates reportedwere low and pretty much the same for all studies but forthree performed in the UK the US and Bolivia In the UKthe prevalence was sixfold lower among the adult populationof London sampled in 1988-89 than among the populationof England and Wales sampled throughout 1991 and 2004(39 versus 27) [9 41] In the US anti-HHEV rose withage up to 45 among adult men aged over 60 years in asurvey performed by the National Institutes of Health andthe Centers for Disease Control at the national level The rateamong adults would have been expected higher in areas close

0102030405060708090

Ant

i-HEV

pos

itive

()

0 20 40 60 80Age (years)

EgyptBangladeshChina (east)

USAEnglandNetherlands

Figure 1 Examples of the patterns of acquisition of anti-HHEVwithage among the population from regions endemic forHHEV1 (EgyptBangladesh and East China) [5ndash7] or HHEV3 (USA England andThe Netherlands) [8ndash10]

to the Mexican border than in the rest of the country butthe data available show actually the very opposite (16 versus42) [10 42]ThoughMexico is usually included in the list ofhighly endemic countries for hepatitis E this is just based onthe report of an epidemics developing 26 years ago that wasattributed to a uniqueHHEV2 strain (genotype 2a) [43] neverfound again As for other areas of Latin America formerlythought as highly endemic for HHEV the data available orbetter the scarcity of them in the case of Mexico do notsupport the assertion [44]

As a complement to these data Table 5 summarizes theresults from representative studies performed among blooddonors worldwide Most of them agree with the data fromthe general population of adults and significant discrepanciesbetween studies performed within a given country are againnoticed In the US results from the two studies availablewould suggest that the prevalence of anti-HHEV is 13-foldhigher in Washington DC than in Northern California [4546] In the United Kingdom donors from Bristol displayeda prevalence almost fourfold higher than the one foundrecently among Scottish donors [38 47] In France theprevalence would be more than 16-fold higher at MidiPyrenees than at Ile de France or Pays de Loire [39 48]Differences might respond in some cases but not always tothe technical issues discussed above

Comparison of data shows that the greatest regionaldifferences are seen among children and indicates thatHHEVspreads earlier in life among the population of Asia and Egyptthan of the rest of the World (Table 6) Among the adultsthe differences do not look so sharp when only the rangesare considered Independently of the overall prevalence anti-HHEV is acquired earliest in life in regions endemic forHHEV1 in comparison with the regions endemic for HHEV3(Figure 1) However the prevalence of anti-HHEV reportedfor the oldest population groups was almost the same in theUS than in Bangladesh and was lower in East China than in

6 Scientifica

Table 1 Prevalence of anti-HHEV among the general population of Europe

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

United Kingdom 710 mdash 39 mdash [41]1591 20-30 5ndash27 13 [9]

Italy 1889 mdash 26 mdash [64]3511 mdash 29 mdash [65]

San Marino 2233 mdash 15 mdash [66]

Spain 2529 46 73 60 [67 68]2305a 05 21 11 [37]

Germany 4422a mdash 17 mdash [69]The Netherlands 7072a 0ndash03 14ndash64 19 [8]aAnti-HHEV screened or confirmed by RIBT

Table 2 Prevalence of anti-HHEV among the general population of South Asia and the Far East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

India (north) 2070 24ndash29 mdash mdash [70]India (Andaman) 814 13ndash40 16ndash77 15ndash73 [57]India (Chennai) 185 53ndash17 mdash mdash [71]India (south) 2279 06ndash89 92ndash36 91ndash23 [72]Bangladesh 1134 mdash 23 mdash [5]Pakistan 540 14 mdash mdash [73]Thailand 513 mdash 23 mdash [74]Malaysia 132 40ndash50 43ndash67 44ndash50 [75]Indonesia 1115 mdash 05ndash20 mdash [76]Vietnam 646 30ndash50 11ndash19 90 [58]China 8762 54ndash42 98ndash46 18 [59]China (south) 3844 10ndash21 40ndash66 44 [77]China (east) 12052 67ndash13 14ndash23 17 [6]China (Fujian) 1151 mdash 23 mdash [78]China (Han) 7376 52ndash12 20ndash57 24 [79]China (Hui) 2258 31ndash40 21ndash68 36

Hong Kong 934 mdash 19 mdash [60]450 60ndash80 18ndash60 28 [80]

Taiwan984 03 11 44 [81]997 15ndash96 88ndash13 64ndash88 [82]2538 34 mdash mdash [83]

Japan 1253 mdash 46ndash67 mdash [84]22027 mdash 27ndash66 mdash [85]

Korea 147 mdash 14ndash23 mdash [86]

England The low-prevalence pattern found in The Nether-lands is representative for other Western European countrieslike Spain or San Marino but also for Asiatic countrieslike Japan where both HHEV1 and HHEV3 autochthonousinfections are reported

The significance of this overview is however limitedby the finding of some very significant variations of theanti-HHEV prevalence when different populations from asingle country or region are compared (Table 7) Particularethnic groups and some rural populations of South Asiaand of the Far and the Middle East seem to represent

true ldquohot spotsrdquo of the HHEV epidemiology Just Egyptwould constitute such a hot spot as a full country since theprevalence keeps high among rural populations from boththe Lower and the Upper Nile River Whether this fact ischaracteristic of the Egyptian rural setting or is also sharedby the population from great cities like Cairo or Alexandriais unknown

In Latin America [44] the rate of anti-HHEV found 15years ago among homeless children fromCochabamba (66)[49] remains more than threefold higher than the highestever reported for any other population group in the region

Scientifica 7

Table 3 Prevalence of anti-HHEV among the general population of the Middle East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

Turkey 1374 mdash 59 mdash [87]Turkey (Istanbul) 909 21 mdash mdash [88]Turkey (Antalya) 338 09 mdash mdash [89]Turkey (Anatolia) 321 mdash 12-13 mdash [90]Turkey (Aydin) 386 mdash 70 mdash [91]Turkey (Duzce) 589 03 mdash mdash [92]Turkey (Trace) 580 mdash 24 mdash [93]Iran (Nahavand) 304 mdash 93 mdash [94]Iran (Isfahan) 816 09 81 38 [95]Iran (Sari) 1080 12 73 23 [96]Iran (west) 400 mdash 78 mdash [97]Iran (Teheran) 551 mdash 79ndash15 mdash [98]Yemen 356 80 15 11 [99]Israel 1416 mdash 18ndash28 mdash [100]

Egypt10026 36ndash76 48ndash76 68 [101]100 26 mdash mdash [102]2428 mdash 84 mdash [7]

Table 4 Prevalence of anti-HHEV among the general population of the Americas

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

USA 18695 10ndash50 39ndash42 21 [10]USA (Texas) 864 mdash 04ndash16 mdash [42]Canada (Inuit) 393 26 31 30 [103]Greenland (Inuit) 503 mdash 30 mdash [104]Venezuela (urban) 184 mdash 16 mdashVenezuela (rural) 204 mdash mdash 39 [50]

Venezuela (Amerindians) 223 mdash 54 mdash463 mdash 97 mdash [51]

Nicaragua 399 mdash 46ndash80 mdash [105]Argentina 1304 015 mdash mdash [106]Chile 168 12 mdash mdash [107]Chile (Amerindians) 100 mdash 170 mdash [108]Bolivia (rural) 490 mdash 73 mdash [109]Bolivia (rural) 186 mdash 20 mdashBolivia (urban) 193 66 31 49 [49]Bolivia (Amazon) 318 0ndash14 70ndash30 20Mexico 3549 11 14 10 [110]Brazil 1196 45 mdash mdash [111]

Cuba 209 mdash 53 mdash [61]469 mdash 100 mdash [112]

However reagents used to perform the study were primitiveand further studies are required before qualifying this regionof Bolivia as highly endemic for HHEV Rates recorded in theBolivian Amazon in the same report (up to 26 among theYurakare Amerindians) were also higher than the rates foundbefore among Amerindian populations from tropical forestsof Venezuela outside theAmazon (54 and 97) [50 51] New

data obtainedwith updated reagents will eventually enlightenthe epidemiology of HHEV in the tropical woodlands ofSouth America and confirm the differences they may display

The anti-HHEV prevalence rate reported for blooddonors aged 58 to 65 years from the French region of MidiPyrenees (70) [39] is a single and unexpected Europeanspot in Table 6 It seems unlikely that a rate of 25 to 4-fold

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Volume 2014

Zoology

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Microbiology

4 Scientifica

Fifteen patients did not travel abroad recently Thus thefrequency of locally acquired hepatitis E in the series was97 Genotyping was performed in eight of the 15 casesand HHEV3 was found in all samples Communicationsreporting autochthonous cases of hepatitis E due to HHEV3in other American countries were previously published fromArgentina Bolivia Brazil Mexico Venezuela and Uruguay[26ndash31] Frequency of HHEV diagnosis among patients withlocally acquired acute hepatitis of unknown origin rangedfrom 16 in Brazil to 30 in Venezuela though HHEV1strains were also detected in the last country HHEV1 was theonly genotype responsible for sporadic cases and epidemicoutbreaks of hepatitis E in Cuba [32] and has been recentlyinvolved in an autochthonous case presented in Uruguay(Arbiza J personal communication)

HHEVwould therefore respond to about 10 of cases ofnon-AndashD suspected acute viral hepatitis presenting in west-ern countries among nontravelers and collecting a significantnumber of cases has taken years of work from the authorsof these reports Since results from different investigationssuggest a likely involvement of the consumption of porkderivatives shellfish bivalves or crude vegetables in virustransmission [33ndash36] autochthonous hepatitis E is consid-ered at present a food-borne low-incidence zoonosis inEurope NorthAmerica and the SouthCone of this continentin addition to an imported disease Such consideration couldbe likely extended to other temperate regions such Australiaor New Zealand where specific data are still scarce

6 Laboratory Diagnosis of the Acute Infection

The dynamics of virus shedding viremia and antibodyresponse in the acute HHEV infection displays the usualevents in other systemic viral infections acquired by the fecal-oral route The antibody window period extends for twoweeks and viremia persists at detectable levels for a variableperiod of time after the window closing Virus is shed in stoolfrom the beginning of this period and fecal shedding persistsfor several weeks after the viremia is cleared Moleculartesting of stool samples provides therefore an excellentchance for laboratory diagnosis but it is seldom performed atclinical laboratories because of technical issues regarding theextraction of viral RNA from stool which requires experiencefor a suitable yield

Viremia levels are lower than in other viral acute hepatitiswith the yield of serum testing being highly dependent ofthe analytical sensitivity of the assay used Since commercialtests for HHEV genome detection are still scarce in themarket most laboratories performing molecular diagnosisare testing samples by in-house conventional techniquesof RNA amplification by reverse transcription polymerasechain reaction (RT-PCR) However commercial sensitivemethods of real-time PCRwill likely replace them in the shortterm Retrospective testing of samples after long storage mayreduce significantly the yield of molecular testing becauseof viral RNA degradation which underlines that clinicallaboratories must always test fresh samples

Early serological diagnosis is based on detection of theanti-HHEV IgM response which precedes in most cases therising of anti-HHEV IgG Testing is performed by indirectenzyme-immunoassay (EIA) using recombinant antigensfrom the core protein Most commercial tests use antigensmatching HHEV1 sequences which are thought less sensitivefor diagnosing infections caused by the remaining genotypesHowever such thoughts are not always fully supported bydata Like in other viral infections samples reactive in EIAtesting can be retested by recombinant immunoblot (RIB)for confirmatory purposes A commercial test is availablefor such confirmation and includes recombinant antigenscorresponding to HHEV1 and -3 core and ORF3 proteinsequences Confirmed reactivity for anti-HHEV IgM is con-sidered diagnostic for acute infection Since a segment ofthe healthy population from any geographical region of theWorld considered displays residual anti-HHEV IgG in serumreflecting a prior contact with the virus the finding of thismarker alone has no diagnostic value unless seroconversionis demonstrated after testing serial samples from the patient

In agreement with these considerations diagnostic cri-teria for acute HHEV infection among patients with acutehepatitis would be as follows (1) IgM negative RNA positive(window period) (2) IgM positive RNA positive (earlyseroconversion stage) (3) IgM positive RNA negative (post-seroconversion stage) and (4) Seroconversion to IgG anti-body on follow-up When specific IgM is the only diagnosticmarker found exclusion of acute primary infection by humancytomegalovirus and Epstein-Barr virus by specific testing issuitable because these agents may rise up a false diagnosis ofhepatitis E through polyclonal stimulation of HHEV-specificB cell subsets

7 Technical Issues Would InfluenceAnti-HHEV IgG Testing

Though the data available support the reasonable robustnessof the current assays for anti-HHEV IgM testing in thediagnosis of acute hepatitis E doubts about the specificityandor sensitivity of these reagents in recognizing residualimmunity to HHEV among the general population by anti-HHEV IgG testing emerged in the last years On one handtesting enzyme immunoassay (EIA-) reactive samples byrecombinant immunoblot (RIB) classified 28ndash50 of them asanti-HHEVnegative if RIBwas used as a confirmatory test [820 37] On the other hand comparison of the performanceof current EIA assays using a standard preparation of anti-HHEV showed considerable differences that were claimedto reflect the insensitivity of most of them leading tosuggest that results from all seroprevalence studies on HHEVperformed in the World would have largely underestimatedthe reality [38]

In a report from France a new testing of samples by thetest claimed the most sensitive one rose up by three times theprevalence of anti-HHEV found formerly among the blooddonors from Toulouse (166 versus 525) [39] The verysame discrepancy between this particular test and anotherone was observed among a group of samples from transplant

Scientifica 5

recipients from Marseille two years later (109 versus 313)[40] Aiming at knowing whether the apparently moresensitive test (Wantai China) was actually more sensitive orless specific than the other one (Adaltis Italy) the authorsof this last study tested by RIB six samples reacting in bothassays and 14 reacting only in Wantai These six samples and10 of the last 14 samples tested positive but the remaining foursamples tested negative If any conclusion can be drawn fromthe data it would either be that theWantai test provides false-positive results for anti-HEV IgG or that the RIB test is notsatisfactory for the purpose of confirmation It was certainlyshown however that the Adaltis test was rather insensitivebut this would only affect the results from seroprevalencestudies performed with this particular reagent

There are therefore reasons to pursuit efforts in stan-dardizing the HHEV serology and to agree about collab-orative studies which can lead to a consensus about thetechnology suitable for performing serosurveys and about thevalidity of the data collected during the last two decades inthe different regions Until these objectives are achieved whatcan be done is just to look at these data and try to understandwhat they may mean

8 A Look on the Data

Tables 1 2 3 and 4 summarize the results reported fromstudies involving collections of samples more or less repre-sentative of the general population of countries or regionsfrom Europe South Asia the Far East the Middle East andthe Americas

South Asia and the Far East displayed often high preva-lence rates India Malaysia and Southern China displayedthe highest rates among children (up to 20ndash50) Rateshigher than 50 were found also among adults from HongKong and other regions of China and low rates (less than 10among adults) were consistently reported from Japan Thiswould roughly match the impact of HHEV1 (and of subtypes1a and 1b in particular) on epidemic hepatitis E HHEV1 -3and -4 overlap however widely in the region and rates higherthan reported would have been expected from countries likeThailand Indonesia or Vietnam

In the Middle East the prevalence was low everywherebut in Egypt With this single exception anti-HHEV wasalmost absent among children and did not reach 20 amongadults However most reports are from Turkey and Iranwhich can be considered countries of low endemicity forHHEV

In regard to Europe and the Americas the rates reportedwere low and pretty much the same for all studies but forthree performed in the UK the US and Bolivia In the UKthe prevalence was sixfold lower among the adult populationof London sampled in 1988-89 than among the populationof England and Wales sampled throughout 1991 and 2004(39 versus 27) [9 41] In the US anti-HHEV rose withage up to 45 among adult men aged over 60 years in asurvey performed by the National Institutes of Health andthe Centers for Disease Control at the national level The rateamong adults would have been expected higher in areas close

0102030405060708090

Ant

i-HEV

pos

itive

()

0 20 40 60 80Age (years)

EgyptBangladeshChina (east)

USAEnglandNetherlands

Figure 1 Examples of the patterns of acquisition of anti-HHEVwithage among the population from regions endemic forHHEV1 (EgyptBangladesh and East China) [5ndash7] or HHEV3 (USA England andThe Netherlands) [8ndash10]

to the Mexican border than in the rest of the country butthe data available show actually the very opposite (16 versus42) [10 42]ThoughMexico is usually included in the list ofhighly endemic countries for hepatitis E this is just based onthe report of an epidemics developing 26 years ago that wasattributed to a uniqueHHEV2 strain (genotype 2a) [43] neverfound again As for other areas of Latin America formerlythought as highly endemic for HHEV the data available orbetter the scarcity of them in the case of Mexico do notsupport the assertion [44]

As a complement to these data Table 5 summarizes theresults from representative studies performed among blooddonors worldwide Most of them agree with the data fromthe general population of adults and significant discrepanciesbetween studies performed within a given country are againnoticed In the US results from the two studies availablewould suggest that the prevalence of anti-HHEV is 13-foldhigher in Washington DC than in Northern California [4546] In the United Kingdom donors from Bristol displayeda prevalence almost fourfold higher than the one foundrecently among Scottish donors [38 47] In France theprevalence would be more than 16-fold higher at MidiPyrenees than at Ile de France or Pays de Loire [39 48]Differences might respond in some cases but not always tothe technical issues discussed above

Comparison of data shows that the greatest regionaldifferences are seen among children and indicates thatHHEVspreads earlier in life among the population of Asia and Egyptthan of the rest of the World (Table 6) Among the adultsthe differences do not look so sharp when only the rangesare considered Independently of the overall prevalence anti-HHEV is acquired earliest in life in regions endemic forHHEV1 in comparison with the regions endemic for HHEV3(Figure 1) However the prevalence of anti-HHEV reportedfor the oldest population groups was almost the same in theUS than in Bangladesh and was lower in East China than in

6 Scientifica

Table 1 Prevalence of anti-HHEV among the general population of Europe

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

United Kingdom 710 mdash 39 mdash [41]1591 20-30 5ndash27 13 [9]

Italy 1889 mdash 26 mdash [64]3511 mdash 29 mdash [65]

San Marino 2233 mdash 15 mdash [66]

Spain 2529 46 73 60 [67 68]2305a 05 21 11 [37]

Germany 4422a mdash 17 mdash [69]The Netherlands 7072a 0ndash03 14ndash64 19 [8]aAnti-HHEV screened or confirmed by RIBT

Table 2 Prevalence of anti-HHEV among the general population of South Asia and the Far East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

India (north) 2070 24ndash29 mdash mdash [70]India (Andaman) 814 13ndash40 16ndash77 15ndash73 [57]India (Chennai) 185 53ndash17 mdash mdash [71]India (south) 2279 06ndash89 92ndash36 91ndash23 [72]Bangladesh 1134 mdash 23 mdash [5]Pakistan 540 14 mdash mdash [73]Thailand 513 mdash 23 mdash [74]Malaysia 132 40ndash50 43ndash67 44ndash50 [75]Indonesia 1115 mdash 05ndash20 mdash [76]Vietnam 646 30ndash50 11ndash19 90 [58]China 8762 54ndash42 98ndash46 18 [59]China (south) 3844 10ndash21 40ndash66 44 [77]China (east) 12052 67ndash13 14ndash23 17 [6]China (Fujian) 1151 mdash 23 mdash [78]China (Han) 7376 52ndash12 20ndash57 24 [79]China (Hui) 2258 31ndash40 21ndash68 36

Hong Kong 934 mdash 19 mdash [60]450 60ndash80 18ndash60 28 [80]

Taiwan984 03 11 44 [81]997 15ndash96 88ndash13 64ndash88 [82]2538 34 mdash mdash [83]

Japan 1253 mdash 46ndash67 mdash [84]22027 mdash 27ndash66 mdash [85]

Korea 147 mdash 14ndash23 mdash [86]

England The low-prevalence pattern found in The Nether-lands is representative for other Western European countrieslike Spain or San Marino but also for Asiatic countrieslike Japan where both HHEV1 and HHEV3 autochthonousinfections are reported

The significance of this overview is however limitedby the finding of some very significant variations of theanti-HHEV prevalence when different populations from asingle country or region are compared (Table 7) Particularethnic groups and some rural populations of South Asiaand of the Far and the Middle East seem to represent

true ldquohot spotsrdquo of the HHEV epidemiology Just Egyptwould constitute such a hot spot as a full country since theprevalence keeps high among rural populations from boththe Lower and the Upper Nile River Whether this fact ischaracteristic of the Egyptian rural setting or is also sharedby the population from great cities like Cairo or Alexandriais unknown

In Latin America [44] the rate of anti-HHEV found 15years ago among homeless children fromCochabamba (66)[49] remains more than threefold higher than the highestever reported for any other population group in the region

Scientifica 7

Table 3 Prevalence of anti-HHEV among the general population of the Middle East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

Turkey 1374 mdash 59 mdash [87]Turkey (Istanbul) 909 21 mdash mdash [88]Turkey (Antalya) 338 09 mdash mdash [89]Turkey (Anatolia) 321 mdash 12-13 mdash [90]Turkey (Aydin) 386 mdash 70 mdash [91]Turkey (Duzce) 589 03 mdash mdash [92]Turkey (Trace) 580 mdash 24 mdash [93]Iran (Nahavand) 304 mdash 93 mdash [94]Iran (Isfahan) 816 09 81 38 [95]Iran (Sari) 1080 12 73 23 [96]Iran (west) 400 mdash 78 mdash [97]Iran (Teheran) 551 mdash 79ndash15 mdash [98]Yemen 356 80 15 11 [99]Israel 1416 mdash 18ndash28 mdash [100]

Egypt10026 36ndash76 48ndash76 68 [101]100 26 mdash mdash [102]2428 mdash 84 mdash [7]

Table 4 Prevalence of anti-HHEV among the general population of the Americas

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

USA 18695 10ndash50 39ndash42 21 [10]USA (Texas) 864 mdash 04ndash16 mdash [42]Canada (Inuit) 393 26 31 30 [103]Greenland (Inuit) 503 mdash 30 mdash [104]Venezuela (urban) 184 mdash 16 mdashVenezuela (rural) 204 mdash mdash 39 [50]

Venezuela (Amerindians) 223 mdash 54 mdash463 mdash 97 mdash [51]

Nicaragua 399 mdash 46ndash80 mdash [105]Argentina 1304 015 mdash mdash [106]Chile 168 12 mdash mdash [107]Chile (Amerindians) 100 mdash 170 mdash [108]Bolivia (rural) 490 mdash 73 mdash [109]Bolivia (rural) 186 mdash 20 mdashBolivia (urban) 193 66 31 49 [49]Bolivia (Amazon) 318 0ndash14 70ndash30 20Mexico 3549 11 14 10 [110]Brazil 1196 45 mdash mdash [111]

Cuba 209 mdash 53 mdash [61]469 mdash 100 mdash [112]

However reagents used to perform the study were primitiveand further studies are required before qualifying this regionof Bolivia as highly endemic for HHEV Rates recorded in theBolivian Amazon in the same report (up to 26 among theYurakare Amerindians) were also higher than the rates foundbefore among Amerindian populations from tropical forestsof Venezuela outside theAmazon (54 and 97) [50 51] New

data obtainedwith updated reagents will eventually enlightenthe epidemiology of HHEV in the tropical woodlands ofSouth America and confirm the differences they may display

The anti-HHEV prevalence rate reported for blooddonors aged 58 to 65 years from the French region of MidiPyrenees (70) [39] is a single and unexpected Europeanspot in Table 6 It seems unlikely that a rate of 25 to 4-fold

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Scientifica 5

recipients from Marseille two years later (109 versus 313)[40] Aiming at knowing whether the apparently moresensitive test (Wantai China) was actually more sensitive orless specific than the other one (Adaltis Italy) the authorsof this last study tested by RIB six samples reacting in bothassays and 14 reacting only in Wantai These six samples and10 of the last 14 samples tested positive but the remaining foursamples tested negative If any conclusion can be drawn fromthe data it would either be that theWantai test provides false-positive results for anti-HEV IgG or that the RIB test is notsatisfactory for the purpose of confirmation It was certainlyshown however that the Adaltis test was rather insensitivebut this would only affect the results from seroprevalencestudies performed with this particular reagent

There are therefore reasons to pursuit efforts in stan-dardizing the HHEV serology and to agree about collab-orative studies which can lead to a consensus about thetechnology suitable for performing serosurveys and about thevalidity of the data collected during the last two decades inthe different regions Until these objectives are achieved whatcan be done is just to look at these data and try to understandwhat they may mean

8 A Look on the Data

Tables 1 2 3 and 4 summarize the results reported fromstudies involving collections of samples more or less repre-sentative of the general population of countries or regionsfrom Europe South Asia the Far East the Middle East andthe Americas

South Asia and the Far East displayed often high preva-lence rates India Malaysia and Southern China displayedthe highest rates among children (up to 20ndash50) Rateshigher than 50 were found also among adults from HongKong and other regions of China and low rates (less than 10among adults) were consistently reported from Japan Thiswould roughly match the impact of HHEV1 (and of subtypes1a and 1b in particular) on epidemic hepatitis E HHEV1 -3and -4 overlap however widely in the region and rates higherthan reported would have been expected from countries likeThailand Indonesia or Vietnam

In the Middle East the prevalence was low everywherebut in Egypt With this single exception anti-HHEV wasalmost absent among children and did not reach 20 amongadults However most reports are from Turkey and Iranwhich can be considered countries of low endemicity forHHEV

In regard to Europe and the Americas the rates reportedwere low and pretty much the same for all studies but forthree performed in the UK the US and Bolivia In the UKthe prevalence was sixfold lower among the adult populationof London sampled in 1988-89 than among the populationof England and Wales sampled throughout 1991 and 2004(39 versus 27) [9 41] In the US anti-HHEV rose withage up to 45 among adult men aged over 60 years in asurvey performed by the National Institutes of Health andthe Centers for Disease Control at the national level The rateamong adults would have been expected higher in areas close

0102030405060708090

Ant

i-HEV

pos

itive

()

0 20 40 60 80Age (years)

EgyptBangladeshChina (east)

USAEnglandNetherlands

Figure 1 Examples of the patterns of acquisition of anti-HHEVwithage among the population from regions endemic forHHEV1 (EgyptBangladesh and East China) [5ndash7] or HHEV3 (USA England andThe Netherlands) [8ndash10]

to the Mexican border than in the rest of the country butthe data available show actually the very opposite (16 versus42) [10 42]ThoughMexico is usually included in the list ofhighly endemic countries for hepatitis E this is just based onthe report of an epidemics developing 26 years ago that wasattributed to a uniqueHHEV2 strain (genotype 2a) [43] neverfound again As for other areas of Latin America formerlythought as highly endemic for HHEV the data available orbetter the scarcity of them in the case of Mexico do notsupport the assertion [44]

As a complement to these data Table 5 summarizes theresults from representative studies performed among blooddonors worldwide Most of them agree with the data fromthe general population of adults and significant discrepanciesbetween studies performed within a given country are againnoticed In the US results from the two studies availablewould suggest that the prevalence of anti-HHEV is 13-foldhigher in Washington DC than in Northern California [4546] In the United Kingdom donors from Bristol displayeda prevalence almost fourfold higher than the one foundrecently among Scottish donors [38 47] In France theprevalence would be more than 16-fold higher at MidiPyrenees than at Ile de France or Pays de Loire [39 48]Differences might respond in some cases but not always tothe technical issues discussed above

Comparison of data shows that the greatest regionaldifferences are seen among children and indicates thatHHEVspreads earlier in life among the population of Asia and Egyptthan of the rest of the World (Table 6) Among the adultsthe differences do not look so sharp when only the rangesare considered Independently of the overall prevalence anti-HHEV is acquired earliest in life in regions endemic forHHEV1 in comparison with the regions endemic for HHEV3(Figure 1) However the prevalence of anti-HHEV reportedfor the oldest population groups was almost the same in theUS than in Bangladesh and was lower in East China than in

6 Scientifica

Table 1 Prevalence of anti-HHEV among the general population of Europe

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

United Kingdom 710 mdash 39 mdash [41]1591 20-30 5ndash27 13 [9]

Italy 1889 mdash 26 mdash [64]3511 mdash 29 mdash [65]

San Marino 2233 mdash 15 mdash [66]

Spain 2529 46 73 60 [67 68]2305a 05 21 11 [37]

Germany 4422a mdash 17 mdash [69]The Netherlands 7072a 0ndash03 14ndash64 19 [8]aAnti-HHEV screened or confirmed by RIBT

Table 2 Prevalence of anti-HHEV among the general population of South Asia and the Far East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

India (north) 2070 24ndash29 mdash mdash [70]India (Andaman) 814 13ndash40 16ndash77 15ndash73 [57]India (Chennai) 185 53ndash17 mdash mdash [71]India (south) 2279 06ndash89 92ndash36 91ndash23 [72]Bangladesh 1134 mdash 23 mdash [5]Pakistan 540 14 mdash mdash [73]Thailand 513 mdash 23 mdash [74]Malaysia 132 40ndash50 43ndash67 44ndash50 [75]Indonesia 1115 mdash 05ndash20 mdash [76]Vietnam 646 30ndash50 11ndash19 90 [58]China 8762 54ndash42 98ndash46 18 [59]China (south) 3844 10ndash21 40ndash66 44 [77]China (east) 12052 67ndash13 14ndash23 17 [6]China (Fujian) 1151 mdash 23 mdash [78]China (Han) 7376 52ndash12 20ndash57 24 [79]China (Hui) 2258 31ndash40 21ndash68 36

Hong Kong 934 mdash 19 mdash [60]450 60ndash80 18ndash60 28 [80]

Taiwan984 03 11 44 [81]997 15ndash96 88ndash13 64ndash88 [82]2538 34 mdash mdash [83]

Japan 1253 mdash 46ndash67 mdash [84]22027 mdash 27ndash66 mdash [85]

Korea 147 mdash 14ndash23 mdash [86]

England The low-prevalence pattern found in The Nether-lands is representative for other Western European countrieslike Spain or San Marino but also for Asiatic countrieslike Japan where both HHEV1 and HHEV3 autochthonousinfections are reported

The significance of this overview is however limitedby the finding of some very significant variations of theanti-HHEV prevalence when different populations from asingle country or region are compared (Table 7) Particularethnic groups and some rural populations of South Asiaand of the Far and the Middle East seem to represent

true ldquohot spotsrdquo of the HHEV epidemiology Just Egyptwould constitute such a hot spot as a full country since theprevalence keeps high among rural populations from boththe Lower and the Upper Nile River Whether this fact ischaracteristic of the Egyptian rural setting or is also sharedby the population from great cities like Cairo or Alexandriais unknown

In Latin America [44] the rate of anti-HHEV found 15years ago among homeless children fromCochabamba (66)[49] remains more than threefold higher than the highestever reported for any other population group in the region

Scientifica 7

Table 3 Prevalence of anti-HHEV among the general population of the Middle East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

Turkey 1374 mdash 59 mdash [87]Turkey (Istanbul) 909 21 mdash mdash [88]Turkey (Antalya) 338 09 mdash mdash [89]Turkey (Anatolia) 321 mdash 12-13 mdash [90]Turkey (Aydin) 386 mdash 70 mdash [91]Turkey (Duzce) 589 03 mdash mdash [92]Turkey (Trace) 580 mdash 24 mdash [93]Iran (Nahavand) 304 mdash 93 mdash [94]Iran (Isfahan) 816 09 81 38 [95]Iran (Sari) 1080 12 73 23 [96]Iran (west) 400 mdash 78 mdash [97]Iran (Teheran) 551 mdash 79ndash15 mdash [98]Yemen 356 80 15 11 [99]Israel 1416 mdash 18ndash28 mdash [100]

Egypt10026 36ndash76 48ndash76 68 [101]100 26 mdash mdash [102]2428 mdash 84 mdash [7]

Table 4 Prevalence of anti-HHEV among the general population of the Americas

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

USA 18695 10ndash50 39ndash42 21 [10]USA (Texas) 864 mdash 04ndash16 mdash [42]Canada (Inuit) 393 26 31 30 [103]Greenland (Inuit) 503 mdash 30 mdash [104]Venezuela (urban) 184 mdash 16 mdashVenezuela (rural) 204 mdash mdash 39 [50]

Venezuela (Amerindians) 223 mdash 54 mdash463 mdash 97 mdash [51]

Nicaragua 399 mdash 46ndash80 mdash [105]Argentina 1304 015 mdash mdash [106]Chile 168 12 mdash mdash [107]Chile (Amerindians) 100 mdash 170 mdash [108]Bolivia (rural) 490 mdash 73 mdash [109]Bolivia (rural) 186 mdash 20 mdashBolivia (urban) 193 66 31 49 [49]Bolivia (Amazon) 318 0ndash14 70ndash30 20Mexico 3549 11 14 10 [110]Brazil 1196 45 mdash mdash [111]

Cuba 209 mdash 53 mdash [61]469 mdash 100 mdash [112]

However reagents used to perform the study were primitiveand further studies are required before qualifying this regionof Bolivia as highly endemic for HHEV Rates recorded in theBolivian Amazon in the same report (up to 26 among theYurakare Amerindians) were also higher than the rates foundbefore among Amerindian populations from tropical forestsof Venezuela outside theAmazon (54 and 97) [50 51] New

data obtainedwith updated reagents will eventually enlightenthe epidemiology of HHEV in the tropical woodlands ofSouth America and confirm the differences they may display

The anti-HHEV prevalence rate reported for blooddonors aged 58 to 65 years from the French region of MidiPyrenees (70) [39] is a single and unexpected Europeanspot in Table 6 It seems unlikely that a rate of 25 to 4-fold

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

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Signal TransductionJournal of

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Evolutionary BiologyInternational Journal of

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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Microbiology

6 Scientifica

Table 1 Prevalence of anti-HHEV among the general population of Europe

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

United Kingdom 710 mdash 39 mdash [41]1591 20-30 5ndash27 13 [9]

Italy 1889 mdash 26 mdash [64]3511 mdash 29 mdash [65]

San Marino 2233 mdash 15 mdash [66]

Spain 2529 46 73 60 [67 68]2305a 05 21 11 [37]

Germany 4422a mdash 17 mdash [69]The Netherlands 7072a 0ndash03 14ndash64 19 [8]aAnti-HHEV screened or confirmed by RIBT

Table 2 Prevalence of anti-HHEV among the general population of South Asia and the Far East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

India (north) 2070 24ndash29 mdash mdash [70]India (Andaman) 814 13ndash40 16ndash77 15ndash73 [57]India (Chennai) 185 53ndash17 mdash mdash [71]India (south) 2279 06ndash89 92ndash36 91ndash23 [72]Bangladesh 1134 mdash 23 mdash [5]Pakistan 540 14 mdash mdash [73]Thailand 513 mdash 23 mdash [74]Malaysia 132 40ndash50 43ndash67 44ndash50 [75]Indonesia 1115 mdash 05ndash20 mdash [76]Vietnam 646 30ndash50 11ndash19 90 [58]China 8762 54ndash42 98ndash46 18 [59]China (south) 3844 10ndash21 40ndash66 44 [77]China (east) 12052 67ndash13 14ndash23 17 [6]China (Fujian) 1151 mdash 23 mdash [78]China (Han) 7376 52ndash12 20ndash57 24 [79]China (Hui) 2258 31ndash40 21ndash68 36

Hong Kong 934 mdash 19 mdash [60]450 60ndash80 18ndash60 28 [80]

Taiwan984 03 11 44 [81]997 15ndash96 88ndash13 64ndash88 [82]2538 34 mdash mdash [83]

Japan 1253 mdash 46ndash67 mdash [84]22027 mdash 27ndash66 mdash [85]

Korea 147 mdash 14ndash23 mdash [86]

England The low-prevalence pattern found in The Nether-lands is representative for other Western European countrieslike Spain or San Marino but also for Asiatic countrieslike Japan where both HHEV1 and HHEV3 autochthonousinfections are reported

The significance of this overview is however limitedby the finding of some very significant variations of theanti-HHEV prevalence when different populations from asingle country or region are compared (Table 7) Particularethnic groups and some rural populations of South Asiaand of the Far and the Middle East seem to represent

true ldquohot spotsrdquo of the HHEV epidemiology Just Egyptwould constitute such a hot spot as a full country since theprevalence keeps high among rural populations from boththe Lower and the Upper Nile River Whether this fact ischaracteristic of the Egyptian rural setting or is also sharedby the population from great cities like Cairo or Alexandriais unknown

In Latin America [44] the rate of anti-HHEV found 15years ago among homeless children fromCochabamba (66)[49] remains more than threefold higher than the highestever reported for any other population group in the region

Scientifica 7

Table 3 Prevalence of anti-HHEV among the general population of the Middle East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

Turkey 1374 mdash 59 mdash [87]Turkey (Istanbul) 909 21 mdash mdash [88]Turkey (Antalya) 338 09 mdash mdash [89]Turkey (Anatolia) 321 mdash 12-13 mdash [90]Turkey (Aydin) 386 mdash 70 mdash [91]Turkey (Duzce) 589 03 mdash mdash [92]Turkey (Trace) 580 mdash 24 mdash [93]Iran (Nahavand) 304 mdash 93 mdash [94]Iran (Isfahan) 816 09 81 38 [95]Iran (Sari) 1080 12 73 23 [96]Iran (west) 400 mdash 78 mdash [97]Iran (Teheran) 551 mdash 79ndash15 mdash [98]Yemen 356 80 15 11 [99]Israel 1416 mdash 18ndash28 mdash [100]

Egypt10026 36ndash76 48ndash76 68 [101]100 26 mdash mdash [102]2428 mdash 84 mdash [7]

Table 4 Prevalence of anti-HHEV among the general population of the Americas

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

USA 18695 10ndash50 39ndash42 21 [10]USA (Texas) 864 mdash 04ndash16 mdash [42]Canada (Inuit) 393 26 31 30 [103]Greenland (Inuit) 503 mdash 30 mdash [104]Venezuela (urban) 184 mdash 16 mdashVenezuela (rural) 204 mdash mdash 39 [50]

Venezuela (Amerindians) 223 mdash 54 mdash463 mdash 97 mdash [51]

Nicaragua 399 mdash 46ndash80 mdash [105]Argentina 1304 015 mdash mdash [106]Chile 168 12 mdash mdash [107]Chile (Amerindians) 100 mdash 170 mdash [108]Bolivia (rural) 490 mdash 73 mdash [109]Bolivia (rural) 186 mdash 20 mdashBolivia (urban) 193 66 31 49 [49]Bolivia (Amazon) 318 0ndash14 70ndash30 20Mexico 3549 11 14 10 [110]Brazil 1196 45 mdash mdash [111]

Cuba 209 mdash 53 mdash [61]469 mdash 100 mdash [112]

However reagents used to perform the study were primitiveand further studies are required before qualifying this regionof Bolivia as highly endemic for HHEV Rates recorded in theBolivian Amazon in the same report (up to 26 among theYurakare Amerindians) were also higher than the rates foundbefore among Amerindian populations from tropical forestsof Venezuela outside theAmazon (54 and 97) [50 51] New

data obtainedwith updated reagents will eventually enlightenthe epidemiology of HHEV in the tropical woodlands ofSouth America and confirm the differences they may display

The anti-HHEV prevalence rate reported for blooddonors aged 58 to 65 years from the French region of MidiPyrenees (70) [39] is a single and unexpected Europeanspot in Table 6 It seems unlikely that a rate of 25 to 4-fold

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Volume 2014

Zoology

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Signal TransductionJournal of

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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Microbiology

Scientifica 7

Table 3 Prevalence of anti-HHEV among the general population of the Middle East

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

Turkey 1374 mdash 59 mdash [87]Turkey (Istanbul) 909 21 mdash mdash [88]Turkey (Antalya) 338 09 mdash mdash [89]Turkey (Anatolia) 321 mdash 12-13 mdash [90]Turkey (Aydin) 386 mdash 70 mdash [91]Turkey (Duzce) 589 03 mdash mdash [92]Turkey (Trace) 580 mdash 24 mdash [93]Iran (Nahavand) 304 mdash 93 mdash [94]Iran (Isfahan) 816 09 81 38 [95]Iran (Sari) 1080 12 73 23 [96]Iran (west) 400 mdash 78 mdash [97]Iran (Teheran) 551 mdash 79ndash15 mdash [98]Yemen 356 80 15 11 [99]Israel 1416 mdash 18ndash28 mdash [100]

Egypt10026 36ndash76 48ndash76 68 [101]100 26 mdash mdash [102]2428 mdash 84 mdash [7]

Table 4 Prevalence of anti-HHEV among the general population of the Americas

Country Number of samples Anti-HHEV rate () ReferenceChildren Adults Overall

USA 18695 10ndash50 39ndash42 21 [10]USA (Texas) 864 mdash 04ndash16 mdash [42]Canada (Inuit) 393 26 31 30 [103]Greenland (Inuit) 503 mdash 30 mdash [104]Venezuela (urban) 184 mdash 16 mdashVenezuela (rural) 204 mdash mdash 39 [50]

Venezuela (Amerindians) 223 mdash 54 mdash463 mdash 97 mdash [51]

Nicaragua 399 mdash 46ndash80 mdash [105]Argentina 1304 015 mdash mdash [106]Chile 168 12 mdash mdash [107]Chile (Amerindians) 100 mdash 170 mdash [108]Bolivia (rural) 490 mdash 73 mdash [109]Bolivia (rural) 186 mdash 20 mdashBolivia (urban) 193 66 31 49 [49]Bolivia (Amazon) 318 0ndash14 70ndash30 20Mexico 3549 11 14 10 [110]Brazil 1196 45 mdash mdash [111]

Cuba 209 mdash 53 mdash [61]469 mdash 100 mdash [112]

However reagents used to perform the study were primitiveand further studies are required before qualifying this regionof Bolivia as highly endemic for HHEV Rates recorded in theBolivian Amazon in the same report (up to 26 among theYurakare Amerindians) were also higher than the rates foundbefore among Amerindian populations from tropical forestsof Venezuela outside theAmazon (54 and 97) [50 51] New

data obtainedwith updated reagents will eventually enlightenthe epidemiology of HHEV in the tropical woodlands ofSouth America and confirm the differences they may display

The anti-HHEV prevalence rate reported for blooddonors aged 58 to 65 years from the French region of MidiPyrenees (70) [39] is a single and unexpected Europeanspot in Table 6 It seems unlikely that a rate of 25 to 4-fold

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

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Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

8 Scientifica

Table 5 Results from selected studies reporting the prevalence ofanti-HHEV among blood donors in the World

Country Donors tested Anti-HHEV rate () Reference

USA 5000 13 [45]1939 19 [46]

Chile 1360 80 [113]Argentina 2157 18 [114]Cuba 1149 14 [115]Brazil 996 23 [116]

France 1998 32 [48]512 53 [39]

Portugal 1473 25 [117]Spain 863 28 [118]

United Kingdom 500 16 [38]1559 47 [47]

Germany 1019 68 [119]China 44816 33 [120]Japan 12600 34 [121]

Table 6 Summary of the anti-HHEV prevalence reported fromdifferent regions of the World

Region Anti-HHEV rate ()Children Adults Overall Blood donors

Far East 03ndash21 2ndash75 4ndash44 3ndash33Southsoutheast Asia 06ndash50 05ndash67 9ndash73 mdashMiddle East 03ndash76 2ndash84 2ndash68 mdashUSACanada 0ndash5 04ndash42 3ndash21 1ndash19Latin America 0ndash14 0ndash30 10ndash49 1ndash8Western Europe 0ndash5 1ndash27 1ndash13 3ndash53

higher than the highest age-specific rate ever reported inEurope may merely respond to technical issues and it addsreasons to think that the southwest of France might also bea ldquohot spotrdquo of the HHEV epidemiology The existence ofparticular regions displaying a comparatively high incidenceof HHEV infections has been also suggested for otherEuropean countries [52 53]

9 Sources of HHEV and Routes ofTransmission

Sources for new human infections by HHEV1 and -2 shouldalways be infected people shedding the virus in stool fora short period of time during the acute self-limited infec-tion since no animal reservoir has yet been consistentlydemonstrated for these genotypes Drinking water wouldbe the main vehicle for transmission and crude vegetablesand shellfish bivalves contaminated by sewage would playsome role Hepatitis E due to these viral genotypes istherefore epidemiologically similar to hepatitis A and thelesser stability of the infectiousHHEVparticle [54ndash56] wouldexplain why the disease is no longer present in settings of

high sanitation standards but from importation Surveys per-forming comparison of anti-HHEVand anti-HAVprevalencein countries endemic for HHEV1 showed that the formerspreads among the populationmuch less than the second oneand suggested that the lesser stability of the HHEV particlematters very much for the epidemiology [5 57ndash61] Casesof HHEV1 infection secondary to importation have not yetbeen reported from European countries However HHEV1RNA has been reported twice from sewage samples from thecity of Barcelona which might allow the contamination ofshellfish bivalves and lead eventually to the local acquisitionof HHEV1 infection by consumption of seafood as suspectedfor a small outbreak of HHEV4 infection reported fromItaly [36] Whether the detection of HEV RNA in sewagereflects always and everywhere the presence of infectiousviral particles is unknown

HHEV1 strains involved in locally acquired hepatitis Ein Latin America are highly related and are also geneticallyclose to some strains circulating in India These findingssuggest amore or less recent episode of secondary spread afterimportation Reporting of outbreaks of acute hepatitis involv-ing dual infections by HHEV1 and HAV from Caribbeancountries (Cuba Venezuela) would in addition mean thatsuch episodes may result in naturalization of the importedstrains when the sanitation conditions are favorable for thespread of the virus among the population Extending studiesabout the circulation of HHEV1 in Uruguay and in theneighbor temperate countries of the South Cone of SouthAmerica and investigation of viral strains responsible for thehigh anti-HHEV prevalence reported among the members ofsome isolated Amerindian communities from the Amazonbasin would enlighten the origin and the role of this epidemicgenotype in the continent

Main virus sources and routes of transmission arehowever less known for human HHEV3 and -4 infectionsStudies involving investigation of risk factors on a significantnumber of patients with locally acquired HHEV3 infectionand a control group have been reported only from Germany[62] Among 45 patients studied consumption of raw orundercooked beef and wild boar meat pig offal or piginternal organs other than liver were the only factors thatcould be recorded in at least 20 of cases with an OR gt2in comparison with controls Patients reported from Englandand Wales did not however share these features with theGerman patients [63] In addition no significant risk factorscommon to at least 50 of these German patients werefound Consumption of raw or undercooked pork productsis commonly thought as a relevant risk factor for acquisitionof HHEV in Europe However it was almost as commonamong the German patients as among the matched controls(786 versus 664 OR = 20) and was not recognized byany of the 28 British patients investigated The link betweenpork meat consumption and acquisition of hepatitis E is nottherefore so clearly established as it has been often stated inthe literature

Pork derivatives include sausage and this is a singleEnglish word for describing a wide diversity of productsprepared by Europeans in many different ways from air orsmoke-drying to boiling and cooking They enjoy a wide

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

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BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

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Stem CellsInternational

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Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Scientifica 9

Table 7 Studies reporting anti-HHEV prevalence higher than 50 among specific population groups

Region Population group Anti-HHEV rate () Reference

South Asia and the Far East

Orang Asli population older than 11 years (central Malaysia) 50ndash67 [75]Tribes from Andaman Islands (India) 50ndash100 [57]Guangxi rural population older than 60 years (China) 70ndash80 [77]Bangladeshi rural population older than 80 years 67 [5]Chinese Han older than 60 years 57 [59]Hong Kong population older than 80 years 52ndash60 [80]

Middle East Pregnant women from the Nile Delta 84 [7]Lower and Upper Egyptian rural population older than four years 51ndash78 [101]

South America Cochabamba city homeless children (Bolivia) 66 [49]Western Europe Blood donors older than 58 years from Toulouse France 70 [39]

range of specific names in other European languages whichshould be taken into account for a proper identificationConsumption of air-dried pork derivatives (ie Spanishserrano ham chorizo and salchichon Italian prosciutto etc)is traditional in Spain and Italy and is likely much morecommon than in any other region of the World Hepatitis Eis however not especially frequent in these countries and theprevalence of anti-HHEV among the population is lower inthem than in England or Germany (21ndash73 versus 39ndash27see Table 1) If sausage was involved in HHEV3 transmissionit remains therefore to be identified what kind of sausageis relevant and what is not since the procedure followed forpreparation might perhaps matter a lot when infectious virusis present in the pork meat at the beginning of the processThe finding of HHEV3 genome in some unidentified kind ofsausage purchased at a few sale points in Spain [35] suggeststhat extending studies in aliments would be important tounderstand better the epidemiology of HHEV in developedcountries

In summary improving the knowledge about the sourcesand routes of transmission of HHEV will require a mul-tidisciplinary strategy Specialists in public health virologyepidemiology veterinary medicine environmental healthand alimentary safety should coordinate research efforts andshare information in order to draw the full picture of theproblem

10 Light and Darkness

HHEV1 shares with HAV many epidemiological similari-ties but is less prevalent among the population because ofthe lesser stability of its particle Since the opportunity ofbecoming infected by HHEV1 is lesser than by HAV theprevalence of anti-HHEV increases more slowly with ageand primary infections among adults are more commonThese circumstances explain why HHEV1 became just animported agent in the developedWorld and may also explainregional and population-based differences of the prevalencein endemic areas It should be expected that improvementof the sanitation of drinking water and vegetables will helpthe control of HHEV1 in a shorter time than of HAV in theseareas but cocirculation of HHEV3 and -4 which are thought

less prevalent will interfere the evaluation of the impactof these improvements unless genotype-specific diagnosisof clinical cases are performed on a routine basis andgenotype-specific anti-HHEV tests can be used to performserial population-based surveys Such conclusions couldlikely be extended toHHEV2 but the scarcity of studies abouthepatitis E in Africa is a limitation In addition prospectivestudies in Mexico and neighbor countries would be requiredto enlighten the role that the missing subgenotype HHEV2acould play in the Americas

There is however much more darkness in the epidemi-ology of HHEV3 On one hand the high prevalence of anti-HHEV found among adults from somewestern countries likethe US and France would not be at all expected from a low-incidence zoonosis transmitted by food in regions where ali-ments are produced and commercialized under rather strictregulations On the other hand the similarities displayed inFigure 1 by the curves of anti-HHEVacquisition for the oldestpopulation groups from Bangladesh the US and the UKare also difficult to understand provided that they wouldrespond to agents of so dissimilar epidemiological propertieslike HHEV1 and HHEV3 A relatively high prevalence wouldnot be contradictory with a low incidence of the disease ifthe acute infection was very often symptomless as reportedfor HHEV3 [16] but the high prevalence seems surprisingin particular areas In the US study the prevalence washigher at the Middle West and the west than at the southor the Northeast and did not display major differences inregard to sex or ethnicity [10] However it always increasedslowly with age with the rate recorded among children beinglow everywhere Investigation of these likely ldquohot spotsrdquo ofHHEV3 prevalence would be a priority for understanding theepidemiology of HHEV in temperate countries In additiontechnical issues concerning anti-HHEV testing must beclarified and it seems likely that development of genotype-specific tests would also be of some help if such achievementbecomes possible

11 Conclusion

In conclusion the prevalence of anti-HEV in theWorld is nolonger a matter of mystery but some mysteries still remain

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Volume 2014

Zoology

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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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International Journal of

Microbiology

10 Scientifica

to reveal Among the 2146 articles displayed by the Pub-Meddata base under the search term ldquohepatitis E virusrdquo since 1990to the time of writing this conclusion 40 was publishedduring the past five years and year 2013 would likely breakagain the record number of 209 articles set during the pastone By following that way mysteries will for sure becomerevealed sooner best than later

Disclosure

The author is a member of the Iberian-American Networkfor Research on Hepatitis E (Red Iberoamericana para laInvestigacion de la Hepatitis E RIHEPE)

Conflict of Interests

The author declares the lack of any potential conflict (finan-cial professional or personal) that is relevant to the paperwithin the past two years including consultancies owner-ship equity patent-licensing agreements research supportand major honoraria from a company whose product ismentioned in the paper

References

[1] M T Shata and U Navaneethan ldquoThe mystery of hepatitisE seroprevalence in developed countries is there subclinicalinfection due to hepatitis E virusrdquo Clinical Infectious Diseasesvol 47 no 8 pp 1032ndash1034 2008

[2] J F Drexler A Seelen V M Corman et al ldquoBats worldwidecarry hepatitis E virus-related viruses that form a putative novelgenus within the family Hepeviridaerdquo Journal of Virology vol86 pp 9134ndash9147 2012

[3] W Batts S Yun R Hedrick and J Winton ldquoA novel memberof the family Hepeviridae from cutthroat trout (Oncorhynchusclarkii)rdquo Virus Research vol 158 no 1-2 pp 116ndash123 2011

[4] D B Smith M A Purdy and P Simmonds ldquoGenetic variabilityand the classification of hepatitis E virusrdquo Journal of Virologyvol 87 pp 4161ndash4169 2013

[5] A B Labrique K Zaman Z Hossain et al ldquoPopulation sero-prevalence of hepatitis E virus antibodies in rural BangladeshrdquoThe American Journal of Tropical Medicine and Hygiene vol 81no 5 pp 875ndash881 2009

[6] C Dong X Dai J-S Shao K Hu and J-H Meng ldquoIden-tification of genetic diversity of hepatitis E virus (HEV) anddetermination of the seroprevalence of HEV in eastern ChinardquoArchives of Virology vol 152 no 4 pp 739ndash746 2007

[7] S K Stoszek M Abdel-Hamid D A Saleh et al ldquoHighprevalence of hepatitis E antibodies in pregnant Egyptianwomenrdquo Transactions of the Royal Society of Tropical Medicineand Hygiene vol 100 no 2 pp 95ndash101 2006

[8] FVerhoefMKoopmans EDuizer J Bakker J Reimerink andW van Pelt ldquoSeroprevalence of hepatitis E antibodies and riskprofile of HEV seropositivity in The Netherlands 2006-2007rdquoEpidemiology and Infection vol 140 pp 1838ndash1847 2012

[9] S Ijaz A J Vyse D Morgan R G Pebody R S Tedder andD Brown ldquoIndigenous hepatitis E virus infection in Englandmore common than it seemsrdquo Journal of Clinical Virology vol44 no 4 pp 272ndash276 2009

[10] M H Kuniholm R H Pureell G M McQuillan R E EngleA Wasley and K E Nelson ldquoEpidemiology of hepatitis E virusin the United States results from the third national health andnutrition examination survey 1988ndash1994rdquo Journal of InfectiousDiseases vol 200 no 1 pp 48ndash56 2009

[11] R P Holla I Ahmad z Ahmad and S Jameel ldquoMolecularvirology of hepatitis E virusrdquo Seminars in Liver Disease vol 33pp 3ndash14 2013

[12] F De Ory I Pachon J M Echevarrıa and R RamırezldquoSeroepidemiological study of herpes simplex virus in thefemale population in the autonomous region of Madrid SpainrdquoEuropean Journal of Clinical Microbiology and Infectious Dis-eases vol 18 no 9 pp 678ndash680 1999

[13] D T Fleming G M Mcquillan R E Johnson et al ldquoHerpessimplex virus type 2 in the United States 1976 to 1994rdquoTheNewEngland Journal of Medicine vol 337 no 16 pp 1105ndash1111 1997

[14] R A Aggarwal ldquoHepatitis E clinical presentation in disease-endemic areas and diagnosisrdquo Seminars in Liver Disease vol 33pp 30ndash40 2013

[15] H RDaltonW Stableforth SHazeldine et al ldquoAutochthonoushepatitis E in Southwest England a comparison with hepatitisArdquo European Journal of Clinical Microbiology and InfectiousDiseases vol 27 no 7 pp 579ndash585 2008

[16] B Said S Ijaz G Kafatos et al ldquoHepatitis E outbreak on cruiseshiprdquo Emerging Infectious Diseases vol 15 no 11 pp 1738ndash17442009

[17] N Kamar L Rostaing and J Izopet ldquoHepatitis E virus infectionin immunossupressed patients natural history and therapyrdquoSeminars in Liver Disease vol 33 pp 62ndash70 2013

[18] B Kmush T Wierzba L Krain K Nelson and A B LabriqueldquoEpidemiology of hepatitis E in low- and middle-incomecountries of Asia and Africardquo Seminars in Liver Disease vol 33pp 15ndash29 2013

[19] A Jeblaoui S Haim-Boukobza E Marchadier C Mokhtariand A-M Roque-Afonso ldquoGenotype 4 hepatitis E virus inFrance an autochthonous infection with a more severe presen-tationrdquo Clinical Infectious Diseases vol 57 no 4 pp e122ndashe1262013

[20] M Herremans H Vennema J Bakker et al ldquoSwine-likehepatitis E viruses are a cause of unexplained hepatitis in theNetherlandsrdquo Journal of Viral Hepatitis vol 14 no 2 pp 140ndash146 2007

[21] T Kantala L Maunula C-H von Bonsdorff J Peltomaa andM Lappalainen ldquoHepatitis E virus in patients with unexplainedhepatitis in Finlandrdquo Journal of Clinical Virology vol 45 no 2pp 109ndash113 2009

[22] G Reuter D Fodor P Forgach A Katai and G SzucsldquoCharacterization and zoonotic potential of endemic hepatitisE virus (HEV) strains in humans and animals in HungaryrdquoJournal of Clinical Virology vol 44 no 4 pp 277ndash281 2009

[23] JM EchevarrıaM Fogeda andAAvellon ldquoDiagnosis of acutehepatitis E by antibody and molecular testing a study on 277suspected casesrdquo Journal of Clinical Virology vol 50 pp 69ndash712011

[24] A Candido S Taffon P Chionne et al ldquoDiagnosis of HEVinfection by serological and real-time PCR assays a study onacute non-A-C hepatitis collected from 2004 to 2010 in ItalyrdquoBMC Research Notes vol 5 pp 297ndash303 2012

[25] J Drobeniuc T Greene-Montfort N-T Le et al ldquoLaboratory-based surveillance for hepatitis E virus infection United States2005ndash2012rdquo Emerging Infectious Diseases vol 19 pp 218ndash2222013

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Scientifica 11

[26] M S Munne N R Altabert S N Vladimirsky et al ldquoIdenti-fications of polyphyletic variants in acute hepatitis suggest anunderdiagnosed circulation of hepatitis E virus in ArgentinardquoJournal of Clinical Virology vol 52 no 2 pp 138ndash141 2011

[27] M C DellrsquoAmico A Cavallo J L Gonzales et al ldquoHepatitisE virus genotype 3 in humans and swine Boliviardquo EmergingInfectious Diseases vol 17 no 8 pp 1488ndash1490 2011

[28] D R Lopes dos Santos L L Lewis-Ximenez M F M da SilvaP S F de Sousa A M C Gaspar and M A Pinto ldquoFirst reportof a human autochthonous hepatitis E virus infection in BrazilrdquoJournal of Clinical Virology vol 47 no 3 pp 276ndash279 2010

[29] J Drobeniuc R Novak L Ganova-Raeva et al ldquoGeneticdiversity of the epidemic hepatitis E virus in Mexico 1986ndash1987rdquo in Proceedings of the 13th International Symposium onViral Hepatitis and Liver Disease (ISVHLD rsquo09) WashingtonDC USA Abstract P161 March 2009

[30] C Gutierrez D Sanchez M C Villalba et al ldquoMolecularcharacterization of hepatitis E virus in patients with acutehepatitis in Venezuelardquo Journal of Medical Virology vol 84 pp1025ndash1029 2012

[31] S Mirazo N Ramos J C Russi G Gagliano and J ArbizaldquoDetection and molecular characterization of sporadic cases ofacute human hepatitis E virus infection in UruguayrdquoArchives ofVirology vol 156 no 8 pp 1451ndash1454 2011

[32] M C Montalvo L A R Lay V Chandra et al ldquoHepatitis Evirus genotype 1 Cubardquo Emerging Infectious Diseases vol 14no 8 pp 1320ndash1322 2008

[33] C Crossan P J Baker J Craft Y Takeuchi H R Dalton andL Scobie ldquoHepatitis E virus genotype 3 in shellfish UnitedKingdomrdquo Emerging Infectious Diseases vol 18 pp 2085ndash20872012

[34] M Dıez-Valcarce P Kokkinos K Soderberg et al ldquoOccurrenceof human enteric viruses in commercial mussels at retail levelin three European countriesrdquo Food and Environmental Virologyvol 4 pp 73ndash80 2012

[35] I Di Bartolo M Dıez-Valcarce P Vasickova et al ldquoHepatitisE virus in pork production chain in Czech Republic Italy andSpain 2010rdquo Emerging Infectious Diseases vol 18 pp 1282ndash12892012

[36] A R Garbuglia P Scognamiglio N Petrosillo et al ldquoHepatitisE virus genotype 4 outbreak Italy 2011rdquo Emerging InfectiousDiseases vol 19 pp 110ndash114 2013

[37] M Fogeda A Avellon and JM Echevarrıa ldquoPrevalence of spe-cific antibody to hepatitis E virus in the general population ofthe community of Madrid Spainrdquo Journal of Medical Virologyvol 84 no 1 pp 71ndash74 2012

[38] R Bendall V Ellis S Ijaz R Ali and H Dalton ldquoA comparisonof two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developedcountriesrdquo Journal of Medical Virology vol 82 no 5 pp 799ndash805 2010

[39] J-MMansuy R Bendall F Legrand-Abravanel et al ldquoHepatitisE virus antibodies in blood donors Francerdquo Emerging InfectiousDiseases vol 17 no 12 pp 2309ndash2312 2011

[40] M Rossi-Tamisier V Moal R Gerolami and P Colson ldquoDis-crepancy between anti-hepatitis E virus immunoglobulin Gprevalence assessed by two assays in kidney and liver transplantrecipientsrdquo Journal of Clinical Virology vol 56 pp 62ndash64 2013

[41] W Bernal H M Smith and R Williams ldquoA communityprevalence study on antibodies to hepatitis A and E in inerr-city Londonrdquo Journal of Medical Virology vol 49 pp 230ndash2341996

[42] T Redlinger KOrsquoRourke LNickey andGMartinez ldquoElevatedhepatitis A and E seroprevalence rates in a TexasMexico bordercommunityrdquo Texas Medicine vol 94 no 5 pp 68ndash71 1998

[43] C-C Huang D Nguyen J Fernandez et al ldquoMolecular cloningand sequencing of the Mexico isolate of hepatitis E virus(HEV)rdquo Virology vol 191 no 2 pp 550ndash558 1992

[44] J M Echevarrıa J E Gonzalez L L Lewis-Ximenez et alldquoHepatitis E virus infection in Latin America a reviewrdquo Journalof Medical Virology vol 85 pp 1037ndash1045 2013

[45] E EMast I Ken KuramotoMO Favorov et al ldquoPrevalence ofand risk factors for antibody to hepatitis E virus seroreactivityamong blood donors in Northern Californiardquo Journal of Infec-tious Diseases vol 176 no 1 pp 34ndash40 1997

[46] C Xu R Y Wang C A Schechterly et al ldquoassessment ofhepatitis E virus (HEV) in US blood donors and recipients nodetectable HEV RNA in 1939 donors tested and no evidencefor HEV transmission to 362 prospectively followed recipientsrdquoTransfusion vol 53 no 10 pp 2505ndash2511 2013

[47] A Cleland L Smith C Crossan et al ldquoHepatitis E virus inScottish blood donorsrdquo Vox Sanguinis vol 105 no 4 pp 283ndash289 2013

[48] A Boutrouille L Bakkali-Kassimi C Cruciere and N PavioldquoPrevalence of anti-hepatitis E virus antibodies in French blooddonorsrdquo Journal of Clinical Microbiology vol 45 no 6 pp2009ndash2010 2007

[49] P Leon E Venegas L Bengoechea et al ldquoPrevalencia de lasinfecciones producidas por los virus de la hepatitis B C D y Een distintas poblaciones de Boliviardquo Revista Panamericana deSalud Publica vol 5 pp 144ndash151 1999

[50] F H Pujol M O Favorov T Marcano et al ldquoPrevalence ofantibodies against hepatitis E virus among urban and ruralpopulations in Venezuelardquo Journal of Medical Virology vol 42no 3 pp 234ndash236 1994

[51] L Blitz-Dorfman F Monsalve R Atencio et al ldquoSerologicalsurvey of markers of infection with viral hepatitis amongthe Yukpa Amerindians from western Venezuelardquo Annals ofTropical Medicine and Parasitology vol 90 no 6 pp 655ndash6571996

[52] A N De Silva A K Muddu J P Iredale N Sheron SI Khakoo and E Pelosi ldquoUnexpectedly high incidence ofindigenous acute hepatitis E within South Hampshire time forroutine testingrdquo Journal of Medical Virology vol 80 no 2 pp283ndash288 2008

[53] J M Echevarrıa M Fogeda and A Avellon ldquoUpdate of casesof acute hepatitis E confirmed by the National Centre ofMicrobiology (Spain 2004ndash2011)rdquo Enfermedades Infecciosas yMicrobiologıa Clınica vol 31 pp 57ndash61 2013

[54] S U Emerson V A Arankalle and R H Purcell ldquoThermalstability of hepatitis E virusrdquo Journal of Infectious Diseases vol192 no 5 pp 930ndash933 2005

[55] A Schielke M Filter B Appel and R Johne ldquoThermal stabilityof hepatitis e virus assessed by amolecular biological approachrdquoVirology Journal vol 8 pp 487ndash495 2011

[56] E Barnaud S Rogee P Garry N Rose and N Pavio ldquoThermalinactivation of infectious hepatitis E virus in experimentallycontaminated foodrdquo Applied and Environmental Microbiologyvol 78 pp 5153ndash5159 2012

[57] M V Murhekar S C Sehgal K M Murhekar S P PadbhidriS D Chitambar and V A Arankalle ldquoChanging scenario ofhepatitis A virus and hepatitis E virus exposure among theprimitive tribes of Andaman and Nicobar Islands India over

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

12 Scientifica

the 10-year period 1989-99rdquo Journal of Viral Hepatitis vol 9 no4 pp 315ndash321 2002

[58] C H Hau T T Hien N T K Tien et al ldquoPrevalence of enterichepatitis A and E viruses in the Mekong River delta regionof Vietnamrdquo The American Journal of Tropical Medicine andHygiene vol 60 no 2 pp 277ndash280 1999

[59] J Lu Y Zhou X Lin et al ldquoGeneral epidemiological parametersof viral hepatitis A B C and E in six regions of China a cross-sectional study in 2007rdquo PLoS ONE vol 4 no 12 Article IDe8467 2009

[60] K H Wong Y M Liu P S P Ng B W Y Young and S SLee ldquoEpidemiology of hepatitis A and hepatitis E infection andtheir determinants in adult Chinese community inHongKongrdquoJournal of Medical Virology vol 72 no 4 pp 538ndash544 2004

[61] A Quintana L Sanchez O Larralde and D Anderson ldquoPreva-lence of antibodies to hepatitis E virus in residents of a districtin Havana Cubardquo Journal of Medical Virology vol 76 no 1 pp69ndash70 2005

[62] O Wichmann S Schimanski J Koch et al ldquoPhylogenetic andcase-control study on hepatitis E virus infection in GermanyrdquoJournal of Infectious Diseases vol 198 no 12 pp 1732ndash17412008

[63] H C Lewis S Boisson S Ijaz et al ldquoHepatitis E in England andWalesrdquo Emerging Infectious Diseases vol 14 no 1 pp 165ndash1672008

[64] G Gessoni and FManoni ldquoHepatitis E virus infection in north-east Italy serological study in the open population and groupsat riskrdquo Journal of Viral Hepatitis vol 3 no 4 pp 197ndash202 1996

[65] A Vulcano M Angelucci E Candelori et al ldquoHEV prevalencein the general population and among workers at zoonotic riskin Latium Regionrdquo Annali di igiene vol 19 no 3 pp 181ndash1862007

[66] M Rapicetta L A Kondili S Pretolani et al ldquoSeroprevalenceand anti-HEV persistence in the general population of theRepublic of San Marinordquo Journal of Medical Virology vol 58pp 49ndash53 1999

[67] M Buti A Domınguez P Plans et al ldquoCommunity-basedseroepidemiological survey of hepatitis E virus infection inCatalonia Spainrdquo Clinical and Vaccine Immunology vol 13 pp1328ndash1332 2006

[68] M Buti P Plans A Domınguez et al ldquoPrevalence of hepatitisE virus infection in children in the northeast of Spainrdquo Clinicaland Vaccine Immunology vol 15 no 4 pp 732ndash734 2008

[69] M S Faber J J Wenzel W Jilg M Thamm M Hohleand K Stark ldquoHepatitis E virus seroprevalence among adultsGermanyrdquo Emerging Infectious Diseases vol 18 pp 1654ndash16572012

[70] PMathur N K Arora S K Panda S K Kapoor B L Jailkhaniand M Irshad ldquoSero-epidemiology of Hepatitis E virus (HEV)in urban and rural children of North Indiardquo Indian Pediatricsvol 38 no 5 pp 461ndash475 2001

[71] B Mohanavalli E Dhevahi T Menon S Malathi and SP Thyagarajan ldquoPrevalence of antibodies to Hepatitis A andHepatitis E virus in urban school children in Chennairdquo IndianPediatrics vol 40 no 4 pp 328ndash331 2003

[72] R Vivek G M Chandy D W Brown and G Kang ldquoSero-prevalence of IgG antibodies to hepatitis E in urban and ruralsouthern Indiardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 4 pp 307ndash308 2010

[73] W Jafri J Yakoob S Abid et al ldquoSeroprevalence of hepatitisE and Helicobacter pylori in a low socioeconomic area of a

metropolitan city in a developing countryrdquo British Journal ofBiomedical Science vol 70 pp 27ndash30 2013

[74] S Hinjoy K E Nelson R V Gibbons et al ldquoA cross-sectionalstudy of hepatitis E virus infection in healthy people directlyexposed and unexposed to pigs in a rural community inNorthern Thailandrdquo Zoonoses and Public Health vol 60 no 8pp 555ndash562 2013

[75] H F Seow N M B Mahomed J-W Mak M A RiddellF Li and D A Anderson ldquoSeroprevalence of antibodies tohepatitis E virus in the normal blood donor population andtwo aboriginal communities in Malaysiardquo Journal of MedicalVirology vol 59 pp 164ndash168 1999

[76] I D NWibawa D HMuljonoMMulyanto et al ldquoPrevalenceof antibodies to hepatitis E virus among apparently healthyhumans and pigs in Bali Indonesia identification of A piginfected with A genotype 4 hepatitis E virusrdquo Journal of MedicalVirology vol 73 no 1 pp 38ndash44 2004

[77] R-C Li S-X Ge Y-P Li et al ldquoSeroprevalence of hepatitisE virus infection rural southern Peoplersquos Republic of ChinardquoEmerging Infectious Diseases vol 12 no 11 pp 1682ndash1688 2006

[78] Y-S Yan H-R Wang L-L Wang et al ldquoA sero-epidemiologystudy on hepatitis E virus infection in Fujian provincerdquoZhonghua liu xing bing xue za zhi vol 28 no 2 pp 105ndash1082007

[79] B Lu H L Zhao R G Tian et al ldquoAntibody detection ofhepatitis E virus in human population of different national inChinardquo Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhivol 26 pp 46ndash47 2012

[80] D M Y Chiu M C W Chan A C M Yeung K L K Ngaiand P K S Chan ldquoSeroprevalence of hepatitis E virus in HongKong 2008-2009rdquo Journal of Medical Virology vol 85 pp 459ndash461 2013

[81] S-D Lee Y-J Wang R-H Lu C-Y Chan K-J Lo andR Moeckli ldquoSeroprevalence of antibody to hepatitis E virusamong Chinese subjects in Taiwanrdquo Hepatology vol 19 no 4pp 866ndash870 1994

[82] C-F Peng M-R Lin P-Y Chue et al ldquoPrevalence of antibodyto hepatitis E virus among healthy individuals in SouthernTaiwanrdquo Microbiology and Immunology vol 39 no 9 pp 733ndash736 1995

[83] D-B Lin J-B Lin S-C Chen C-C YangW-K Chen andC-J Chen ldquoSeroepidemiology of hepatitis E virus infection amongpreschool children in Taiwanrdquo Journal of Medical Virology vol74 no 3 pp 414ndash418 2004

[84] E Tanaka N Takeda T-C Li et al ldquoSeroepidemiological studyof hepatitis E virus infection in Japan using a newly developedantibody assayrdquo Journal of Gastroenterology vol 36 no 5 pp317ndash321 2001

[85] M Takahashi K Tamura Y Hoshino et al ldquoA nationwidesurvey of hepatitis E virus infection in the general populationof Japanrdquo Journal of Medical Virology vol 82 no 2 pp 271ndash2812010

[86] H K Park S-H Jeong J-W Kim B-H Woo D H Lee andH Y Kim ldquoSeroprevalence of anti-hepatitis E virus (HEV) ina Korean population comparison of two commercial anti-HEVassaysrdquo BMC Infectious Diseases vol 12 pp 142ndash147 2012

[87] D L Thomas R W Mahley S Badur E Palaoglu and T CQuinn ldquoThe epidemiology of hepatitis C in Turkeyrdquo Infectionvol 22 no 6 pp 411ndash414 1994

[88] M Sidal E Unuvar F Ouz C Cihan D Onel and SBadur ldquoAge-specific seroepidemiology of hepatitis A B and

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Scientifica 13

E infections among children in Istanbul Turkeyrdquo EuropeanJournal of Epidemiology vol 17 no 2 pp 141ndash144 2001

[89] D Colak D Ogunc F Gunseren S Velipasaoglu M RAktekin and M Gultekin ldquoSeroprevalence of antibodies tohepatitis A and E viruses in pediatric aGe groups in TurkeyrdquoActa Microbiologica et Immunologica Hungarica vol 49 no 1pp 93ndash97 2002

[90] A S Cevrioglu M Altindis H M Tanir and F AksoyldquoInvestigation of the incidence of hepatitis E virus among preg-nant women in Turkeyrdquo Journal of Obstetrics and GynaecologyResearch vol 30 no 1 pp 48ndash52 2004

[91] S Oncu S Oncu POkyay S Ertug and S Sakarya ldquoPrevalenceand risk factors for HEV infection in pregnant womenrdquoMedicalScience Monitor vol 12 no 1 pp CR36ndashCR39 2006

[92] ADKaya C EOzturk T Yavuz COzaydin andT BahcebasildquoChanging patterns of hepatitis A and E sero-prevalences inchildren after the 1999 earthquakes in Duzce Turkeyrdquo Journalof Paediatrics and Child Health vol 44 no 4 pp 205ndash207 2008

[93] A Eker O Tansel H Kunduracilar B Tokuc Z Yulugkuraland P Yuksel ldquoHepatitis e virus epidemiology in adult popula-tion in edirne province Turkeyrdquo Mikrobiyoloji Bulteni vol 43no 2 pp 251ndash258 2009

[94] M Taremi A H Mohammad Alizadeh A Ardalan S Ansariand M R Zali ldquoSeroprevalence of hepatitis E in NahavandIslamic Republic of Iran a population-based studyrdquo EasternMediterranean Health Journal vol 14 no 1 pp 157ndash162 2008

[95] B Ataei Z Nokhodian A A Javadi et al ldquoHepatitis E virusin Isfahan Province a population-based studyrdquo InternationalJournal of Infectious Diseases vol 13 no 1 pp 67ndash71 2009

[96] M J Saffar R Farhadi A Ajami A R Khalilian F Babamah-modi and H Saffar ldquoSeroepidemiology of hepatitis E virusinfection in 2-25-year-olds in Sari district Islamic Republic ofIranrdquo Eastern Mediterranean Health Journal vol 15 no 1 pp136ndash142 2009

[97] RH RaoofiM R Nazer andY Pournia ldquoSeroepidemiology ofhepatitis E virus inWestern Iranrdquo Brazilian Journal of InfectiousDiseases vol 16 pp 302ndash303 2012

[98] S R Mohebbia M R Nejada S M E Tahaeia et al ldquoSeroepi-demiology of hepatitis A and E virus infections in Tehran Irana population based Studyrdquo Transactions of the Royal Society ofTropica Medicine and Hygiene vol 106 pp 528ndash531 2012

[99] A A Bawazir C A Hart T A Sallam C M Parry N JBeeching and L E Cuevas ldquoSeroepidemiology of hepatitis Aand hepatitis E viruses in Aden Yemenrdquo Transactions of theRoyal Society of Tropical Medicine and Hygiene vol 104 no 12pp 801ndash805 2010

[100] Y V Karetnyi M O Favorov N S Khudyakova et al ldquoSerolog-ical evidence for hepatitis E virus infection in Israelrdquo Journal ofMedical Virology vol 45 no 3 pp 316ndash320 1995

[101] A D Fix M Abdel-Hamid R H Purcell et al ldquoPrevalence ofantibodies to hepatitis E in two rural Egyptian communitiesrdquoTheAmerican Journal of Tropical Medicine and Hygiene vol 62no 4 pp 519ndash523 2000

[102] A A Aboulata M S Ahmad M M A Shaban K M S Zaydand A M Abd El-Moktader ldquoPrevalence of hepatitis E virus inEgyptian children presented with minor hepatic disordersrdquoTheEgyptian Journal of Immunology vol 12 no 2 pp 71ndash76 2005

[103] G Y Minuk A Sun D F Sun et al ldquoSerological evidence ofhepatitis E virus infection in an indigenous North Americanpopulationrdquo Canadian Journal of Gastroenterology vol 21 no7 pp 439ndash442 2007

[104] B C A Langer G G Frosner and A Von Brunn ldquoEpidemi-ological study of viral hepatitis types A B C D and E amongInuits in West Greenlandrdquo Journal of Viral Hepatitis vol 4 no5 pp 339ndash349 1997

[105] O M Perez W Morales M Paniagua and O StrannegardldquoPrevalence of antibodies to hepatitis A B C and E viruses in ahealthy population in Leon Nicaraguardquo The American Journalof Tropical Medicine and Hygiene vol 55 no 1 pp 17ndash21 1996

[106] J A Rey J A Findor J R Daruich et al ldquoPrevalence of IgGanti-HEV in Buenos Aires a nonendemic area for hepatitis ErdquoJournal of Travel Medicine vol 4 no 2 pp 100ndash101 1997

[107] H Ibarra S Riedemann G Reinhardt et al ldquoHepatitis A andE virus antibodies in Chilean children of low socioeconomicstatus a one year follow-up studyrdquo Revista Medica de Chile vol134 no 2 pp 139ndash144 2006

[108] H Ibarra S Riedemann G Reinhardt et al ldquoAnti-HEVmarkerin blood donors and other population groups in SouthernChilerdquo RevistaMedica de Chile vol 125 no 3 pp 275ndash278 1997

[109] A Bartoloni F Bartalesi M Roselli et al ldquoPrevalence ofantibodies against hepatitis A and E viruses among rural pop-ulations of the Chaco region south-eastern Boliviardquo TropicalMedicine and International Health vol 4 no 9 pp 596ndash6011999

[110] M T Alvarez-Munoz J Torres L Damasio A Gomez RTapia-Conyer and O unoz ldquoSeroepidemiology of hepatitis Evirus infection inMexican subjects 1 to 29 years of agerdquoArchivesof Medical Research vol 30 pp 251ndash254 1999

[111] S B Assis F J D Souto C J F Fontes and A M C GasparldquoPrevalence of hepatitis A and E virus infection in schoolchildren of an Amazonian municipality in Mato Grosso StaterdquoRevista da Sociedade Brasileira deMedicina Tropical vol 35 no2 pp 155ndash158 2002

[112] M C M Villalba M Guan A Perez et al ldquoSeroprevalenceof antibodies to hepatitis E virus in two large communities inHavana Cubardquo Transactions of the Royal Society of TropicalMedicine and Hygiene vol 104 no 12 pp 772ndash776 2010

[113] H Ibarra G S Riedemann V G Reinhardt and A M CalvoldquoPresence of anti hepatitis E virus antibodies in swine is it ananimal reservoir for hepatitis Erdquo Revista Medica de Chile vol135 no 8 pp 997ndash1001 2007

[114] H Fainboim J Gonzalez E Fassio et al ldquoPrevalence of hepati-tis viruses in an anti-human immunodeficiency virus-positivepopulation from Argentina A multicentre studyrdquo Journal ofViral Hepatitis vol 6 no 1 pp 53ndash57 1999

[115] G Lemos S Jameel S Panda L Rivera L Rodrıguez and JV Gavilondo ldquoHepatitis E virus in Cubardquo Journal of ClinicalVirology vol 16 no 1 pp 71ndash75 2000

[116] A L Bortoliero A M Bonametti H K Morimoto T MatsuoandEMV Reiche ldquoSeroprevalence for hepatitis E virus (HEV)infection among volunteer blood donors of the Regional BloodBank of Londrina State of Parana BrazilrdquoRevista do Instituto deMedicina Tropical de Sao Paulo vol 48 no 2 pp 87ndash92 2006

[117] L Queiros J Condeco A Tender M Mateus A Teixeiraand H Pascoal ldquoThe seroprevalence for hepatitis E viralantibodies in the northern region of Portugal (among the donorpopulation)rdquoActaMedica Portuguesa vol 10 pp 447ndash453 1997

[118] M L Mateos C Camarero E Lasa J L Teruel N Mir and FBaquero ldquoHepatitis E virus relevance in blood donors and riskgroupsrdquo Vox Sanguinis vol 76 no 2 pp 78ndash80 1999

[119] D Juhl S A Baylis J Blumel S Gorg and H HennigldquoSeroprevalence and incidence of hepatitis E virus infection in

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

14 Scientifica

German blood donorsrdquo Transfusion vol 54 no 1 pp 49ndash562014

[120] Q-S Guo Q Yan J H Xiong et al ldquoPrevalence of hepatitis Evirus in Chinese blood donorsrdquo Journal of ClinicalMicrobiologyvol 48 pp 317ndash318 2010

[121] H Takeda K Matsubayashi H Sakata et al ldquoA nationwidesurvey for prevalence of hepatitis E virus antibody in qualifiedblood donors in Japanrdquo Vox Sanguinis vol 99 no 4 pp 307ndash313 2010

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Molecular Biology International

GenomicsInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Signal TransductionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Evolutionary BiologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Genetics Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Enzyme Research

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

Microbiology