Zoonotic helminths affecting the human eye - Parasites & Vectors

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Zoonotic helminths affecting the human eyeDomenico Otranto1 and Mark L Eberhard2

Abstract

Nowaday zoonoses are an important cause of human parasitic diseases worldwide and a major threat to thesocio-economic development mainly in developing countries Importantly zoonotic helminths that affect humaneyes (HIE) may cause blindness with severe socio-economic consequences to human communities Theseinfections include nematodes cestodes and trematodes which may be transmitted by vectors (dirofilariasisonchocerciasis thelaziasis) food consumption (sparganosis trichinellosis) and those acquired indirectly from theenvironment (ascariasis echinococcosis fascioliasis) Adult andor larval stages of HIE may localize into humanocular tissues externally (ie lachrymal glands eyelids conjunctival sacs) or into the ocular globe (ie intravitreousretina anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to theimmune reaction they elicit in the host Unfortunately data on HIE are scant and mostly limited to case reportsfrom different countries The biology and epidemiology of the most frequently reported HIE are discussed as wellas clinical description of the diseases diagnostic considerations and video clips on their presentation and surgicaltreatmentHomines amplius oculis quam auribus creduntSeneca Ep 65Men believe their eyes more than their ears

BackgroundBlindness and ocular diseases represent one of the mosttraumatic events for human patients as they have thepotential to severely impair both their quality of life andtheir psychological equilibrium Although it is highlyunusual blindness has always been of great interest inhuman medicine For example the evaluation of theemotional and quality of life impacts in patients withsome diseases causing blindness (eg macular degenera-tion) gave results similar to those found in diseases suchas AIDS chronic obstructive pulmonary disease cardiacdisorders and leukemia [1] In addition blindness hasprofound human and socio-economic consequenceswith high costs for the individual and society linked tolost productivity and rehabilitation estimated at $42USD billion per year in 2000 and predicted to reach ashigh as $110 USD billion per year in 2020 [2]There are many causes of blindness and those induced

by parasitic agents (ie Protozoa Helminths and Dip-tera) are of major public health concern in developed

and developing countries For example eye diseasecaused by river blindness (Onchocerca volvulus) affectsmore than 177 million people inducing visual impair-ment and blindness elicited by microfilariae that migrateto the eyes after being released by female adult wormsin the subcutaneous tissues [3] Several parasites localizein human eyes as an effect of a specific neurotropism(eg Toxoplasma gondii in the foetuses) larval migra-tion (eg ascarids Dirofilaria spp Trichinella spp)and in a few cases as a primary localization beingreleased directly into the eyes (eg Thelazia callipaedaeyeworm and some oestrid fly larvae causing myiasis) [4]The present article focuses on those zoonotic hel-

minths transmitted from animals to humans that affectthe human eye Undoubtedly the parasitic zoonotic dis-eases and their epidemiology have been changing as aresult of complex factors including abiotic (eg increas-ing temperatures) and biotic (eg demographicalchanges political upheaval and land- use practices) thatrender this topic of great interest for the scientific com-munity [5] In addition the impact of zoonotic diseasesmay vary in relationship to the socio-economic contextand to the public health systems in different geographi-cal areas [6] and for some infections a greater threat

Correspondence dotrantoveterinariaunibait1Dipartimento di Sanitagrave Pubblica e Zootecnia Universitagrave degli Studi di BariValenzano BA ItalyFull list of author information is available at the end of the article

Otranto and Eberhard Parasites amp Vectors 2011 441httpwwwparasitesandvectorscomcontent4141

copy 2011 Otranto and Eberhard licensee BioMed Central Ltd This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (httpcreativecommonsorglicensesby20) which permits unrestricted use distribution andreproduction in any medium provided the original work is properly cited

exists for populations in developing countries [7] Zoo-notic helminths infecting eyes (HIE) include those trans-mitted by vectors (ie vector borne zoonosis VbZ) byfood consumption (ie food-borne zoonosis FbZ) andthose at direct transmission from the environment (iewater soil etc) also known as environmentally-bornezoonosis (EbZ) A list of those helminths along withtheir route of transmission geographical distributionlocalization in the eye and definitive host species is pro-vided in Table 1 Unfortunately data on HIE are scantand mostly limited to case reports from different coun-tries Therefore a broad view of these infections on pub-lic health is lacking and ophthalmologists havedifficulties managing HIE caused diseases and providinga clear diagnosis and therapeutic option for them Thepresent article focuses on those zoonotic helminthsnaturally infecting animals but which occasionally aretransmitted to humans and affect the eye Recentadvances in the diagnosis and control of these parasiticinfestations are also discussed on the basis of their dis-tribution in different geographical areas and of interestin travel medicine

Biology and pathogenic effectsHelminths at the adult andor larval stages may infecthuman ocular tissues externally (ie eyelids conjunctivasacs subconjunctiva and lachrymal glands) or the ocularglobe (ie optical nerve intravitreous retina anterior andposterior chamber) Several parasitic helminths adapted atropism for animal eyes and related tissues when migrat-ing throughout the host body mainly during their imma-ture stages This is the case of ascarids and strongylidscausing ocular larva migrans filarioid species and larvaeof Trichinella as well of trematode and cestode parasitesNonetheless human ocular infestations by zoonotic hel-minths may also be caused by the parasitic adult stagesas in the case of thelaziids (eye worm infestation) andfilarioid species including those belonging to the generaDirofilaria and Onchocerca [8-10] Thus ocular localiza-tion of helminths is mainly caused by aberrant migrationin host tissues and only in one case (ie T callipaeda)by direct inoculation into the eyes What is equallyunclear is the route that most follow to gain entry intothe eye It is supposed that some migrate along and fol-low the optic nerve but others may enter the bloodstreamand be carried to the eye in that manner however it isnot known if these are the preferred or aberrant routesor even which is the most common route that helminthsfollow to reach the eye Once in the eye larvae likely findit to be a more protected site from host immuneresponses but it is not clear that a directed migrationinto the eye had occurredConsequently ocular alterations caused by zoonotic

helminths vary considerably causing mild to severe

clinical signs including lacrimation epiphora conjuncti-vitis keratitis corneal ulcers or retinal lesions resultingin vision loss (Table 2) For example in ascarid infec-tions visual impairment or blindness results from larvalmigration with destruction of the visual cortex In addi-tion larvae might develop inside the patientrsquos eye (egin baylisascariasis) progressively impairing the visionHowever blindness might be also an effect of theimmune reaction the parasites elicit in the host body orof a combined effect of both presence of the parasiteand antibody-mediated reaction This is the case ofascarids in which ocular signs are related to inflamma-tion because of the presence of larvae and a localimmune reaction to them in the retina [1112]

The most commonly reported HIENematodesThere are many nematode parasites that can be found inthe orbit or within the eye proper (Table 1) Althoughmost nematode infections of the eye are rare some aremore frequently reported than others In this sectionwe will discuss those zoonotic nematodes that are mostlikely to be encountered and reported by examiningtheir aetiology case reports and epidemiologyTrichuroidsTrichinellosis (Trichuroidea Trichinellidae) has a cos-mopolitan distribution but is generally less important asan infection of humans in the tropics than in more tem-perate regions of the world Once thought to be a singlespecies (Trichinella spiralis) there are now at least eightdistinct species recognized Each of these species has aslightly different geographical distribution and hostrange and only Trichinella zimbabwensis of crocodilesin Tanzania has not been reported from humans todate The most striking feature of this group of parasitesis their obligatory transmission by ingestion of infectedmeat containing larvae either in typical cysts or unen-capsulated in the case of several species [13] The clini-cal course is characterized by two phases the entericenteral phase when adult worms are present in theintestinal mucosa and the parenteral phase when thereleased larvae invade the host muscles [14] During theparenteral phase which follows the enteral a typicalsyndrome of fever myalgia periorbital edema and eosi-nophilia occur In addition to periorbital and facialedema conjunctivitis is also frequent The cause of theorbital and facial edema is not well known but probablyincludes some component of an allergic response Peri-orbital edema often appears early in the parenteralphase and typically begins to wane after several weeksLarvae also affect the macula and retina causing hemor-rhage and other damage as they migrate through andinto these ocular tissues [15] The diagnosis can be sug-gested from clinical history of ingesting raw or

Table 1 Classification (Order Family and Species) of zoonotic helminths causing human blindness divided accordingtheir route of transmission (Vector borne zoonosis VbZ food consumption FbZ and those at direct transmissionfrom the environment EbZ) geographical distribution localization in the eyes and zoonotic relevance

OrderOrder(Family)

Species (commonname)

Route of transmission Geographical distribution Localization Definitivehost

HELMINTHS

Strongylida

Angiostrongyluscantonensis (ratlungworm)

Ingestion of snailsslugs shellfish andcrustacean (FbZ)

Asia Australia Africa USAPacific Islands CaribbeanIslands and South America

Anterior chambervitreous

Rat 131137

Ascaridida(Ascarididae)

Toxocara canis (dogroundworm)

Dog faeces (EbZ) Worldwide Eyebrows andeyelds aqueoushumor andvitreous

Dog 11

Toxocara cati (felineroundworm)

Cat faeces (EbZ) Worldwide Aqueous humorand vitreous

Cat 11

Baylisascarisprocyonis (raccoon

roundworm)

Raccoon faeces (EbZ) North America Europe Japan Vitreous Raccoon 46

Spirurida SuborderSpirurina

GnathostomaspinigerumG hispidum

Ingestion of crustacean(cyclops)

Worldwide Anterior chambereye lid

Dog cat wildcarnivores

G doloresi andG nipponicum

infected fish frogs (FbZ) raccoonopossum

(Onchocercidae)

Dirofilaria repens Aedes Anopheles Culex(VbZ)

Europe Asia Africa Subconjunctival Dog 8 197

D immitis Aedes Anopheles Culex(VbZ)

Worldwide Anterior chamber Dog cat 876

D tenuis Aedes Anopheles (VbZ) Canada USA Subconjunctival Raccon 8

Acanthocheilonemaarbuta

Aedes Taeniorhynchus(VbZ)

Canada USA Anterior chamber Porcupine 198

A sprenti Mosquitoes (VbZ) Canada Oregon USA Anterior chamber Beaver 8

A reconditum Fleas louses (VbZ) Worldwide Subconjunctival Dog 79

Onchocercagutturosa

Simulium spp (VbZ) Worldwide Subconjunctivalcornea

Cattle 8

O cervicalis Culicoides spp (VbZ) Worldwide Subconjunctivalcornea

Horse 169

Onchocercajakutensis

Culicoides spp (VbZ) Europe Austria Subconjunctivalcornea

Red deer 199

O reticulata Culicoides spp (VbZ) Europe Asia Africa Subconjunctivalcornea

Horse 170

O dewittei japonica Simulium spp (VbZ) Japan Subconjunctivalcornea

Bear 167

O lupi Simulium spp (VbZ) Europe Subconjunctival Dog 172

Loaina uniformis Aedes Anopheles Culex North America Subconjunctival Lagomorphs 8626483

P (Loaina)scapiceps

Aedes Mansonia North America Subconjunctival Lagomorphs 86283

(Thelaziidae)

Thelazia callipaedaT californiensis

Phortica spp (VbZ) China Southeastern AsiaEurope USA

Subconjunctivalintraocular

Dogs catsrabbits and

wildcarnivores

inadequately cooked meat and the ophthalmologist isoften the first contact because of the swollen eyelids andconjunctivitis Demonstration of larvae in muscle biop-sies of patients or in frozen sample of the ingestedmeat if available is still standard procedure to confirminfection Good serological tests exist and are also veryuseful in confirming infection especially in cases withlow-level infection where symptoms may be minimaland the number of larvae in muscle may be low Someareas of the world such as the United States andEurope have effectively controlled the infection inhumans by removing the parasite from the domestic pigcycle through heightened food safety regulations regard-ing inspection and feeding practices In other areas of

the world the domestic pig cycle continues to beresponsible for human infection and in all areas humaninfection continues to occur when infected wild gamemeat is ingested without proper cooking Because of thewide range of animals that can harbour infection withTrichinella larvae proper handling and cooking of allmeats is recommendedAscaridsAscarids (Ascaridida Ascaridiidae) occur worldwideinfecting various mammals including humans [1617]Many of these nematodes are causative agents of zoo-noses transmitted to humans via contaminated soilWithin the ascarids Toxocara canis Toxocara cati andBaylisascaris procyonis are zoonotic parasites of dogs

Table 1 Classification (Order Family and Species) of zoonotic helminths causing human blindness divided accordingtheir route of transmission (Vector borne zoonosis VbZ food consumption FbZ and those at direct transmissionfrom the environment EbZ) geographical distribution localization in the eyes and zoonotic relevance (Continued)

Enoplida

(Trichuridae) Trichinella spp Ingestion of raw meat(FbZ)

Worldwide Orbit Ocularmuscles

Numerousdomestic andwild animals

CESTODA

Pseudophyllidea(Diphyllobothriidae)

Spirometraerinaceieuropaei(Sparganosis)

Ingestion of crustaceanfrogs birds snakes

Middle East Australia Subconjunctival Carnivores 102109

Spargana (otherspecies)

South America Asia Subconjunctival Carnivores 102109

Cyclophyllidea(Teniidae)

Taenia crassiceps Food contaminated bydog faeces (EbZ)

USA and Europe Anteriorchamber

Carnivores 89

Echinococcusgranulosus

Food contaminated bydog faeces (EbZ)

Worldwide Intraocular Dog 112

E multilocularis Food contaminated bywild carnivores dog

faeces (EbZ)

Worldwide Intraocular Wolf jackalcoyote

E oligharthrus Food contaminated bywild carnivores dog

faeces (EbZ)

South and Central America Orbit Wild felids Wildfelids

Coenurus cerebralis(Multicepsmulticeps)

dog faeces (EbZ) Worldwide Intraocular Dog 95

TREMATODA

(Fluke)

Fasciola hepatica water plants (FbZ) Worldwide Anterior chamber Domestic andwild

ruminantshorse

Alaria mesocercariaA americana

Frogs (FbZ) Asia USA Canada Intraocular Canids 122

Philophthalmuslacrimosus

Contaminated food ordirect contact with the

eye mucosa (EbZ)

Europe Asia and America Conjunctival Birds 124

cats and raccoons respectively and they are among themost widespread causes of neural and ocular larvamigrans Indeed larvae of T canis are probably themost common nematode infection of the human eyealso known as ocular larva migrans (OLM) and infec-tion in humans occurs worldwide [11] Infection occursthrough the ingestion of infective eggs most often fromsoil or other environmental surfaces that have been con-taminated with faeces from infected animals Examina-tion of soil or sand from parks and playgrounds oftendemonstrates infective Toxocara eggs which mightremain infectious for long periods of time (even years)in the environment [18] When ingested the eggs hatchand larvae migrate in the tissues most often to the liverbut on occasion to other sites such as the eye and cen-tral nervous system (CNS) The wandering larvae causea syndrome called visceral larva migrans (VLM) of

marked eosinophilia hepatomegaly fever cough andpulmonary infiltrates The severity of symptoms is oftenrelated to the number of larvae acquired and can rangefrom asymptomatic to acute with a fatal outcome Theability of Toxocara larvae to cause OLM was recognizedabout 60 years ago [1920] OLM occurs most typicallyin older children (mean 8 yr versus 2 yr for VLM) gen-erally have no other evidence of organ involvement andhypereosinophilia hepatomegaly and pulmonary symp-toms are absent there is no history of pica and evi-dence suggests that OLM is caused by a single larvaentering the eye Antibodies to Toxocara tend to belower in cases of OLM possibly as a result of fewerinfective larvae and there is experimental evidence thatsomewhat different immune responses occur betweenOLM and VLM [21] Hundreds of cases have beenreported and described and untold thousands of cases

Table 2 Ocular tissue affected and symptoms caused by zoonotic helminths (Genus andor Species) at differentstage [4163]

Ocular tissueaffected

Signs Helminths involved

Eyebrows andeyelids

Eye lid edema Taenia solium (cysticercus) Spirometra Ancyclostoma A Americana Gnathostoma ToxocaraTrichinella Dirofilaria

Lacrimal duts andglands

Lacrymation Mammomonogamus Thelazia

Orbit Exophthalmos Echinococcus coenurus Taenia solium (cysticercus) spargana Trichinella DirofilariaGnathostoma

Ocular muscles Diplopia Trichinella Angiostrongylus Ancyclostoma sparganaTaenia

Conjunctiva Subconjunctival cysts Taenia Dirofilaria Acanthocheilonema Habronema Mansonella spargana Philophthalmus

Chemosis and conjunctivitis Thelazia Trichinella Onchocerca

Hemorrhages Trichinella

Cornea Keratitis scleritis Onchocerca Toxocara Ancylostoma

Anterior chamber Parasites in the anteriorChamber

Onchocerca Schistosoma Taenia spargana Angiostrongylus Gnathostoma Toxocara DirofilariaThelazia Acanthocheilonema

Cysts in the anterior chamber Taenia

Hypopyon Taenia Gnathostoma Toxocara

Secondary glaucoma Taenia Echinococcus Angiostrongylus Dirofilaria Onchocerca spp Gnathostoma Toxocara

Iris Mydriasis Trichinella

Miosis

Distortion of the pupil Onchocerca

Iritis and iridocyclitis Taenia Angiostrongylus Ancyclostoma Trichinella Toxocara Onchocerca Pelecitus

Vitreous body Hemorrhages Trichinella cysticercus Gnathostoma

Cysts Cysticercus Echinococcus coenurus

Parasites in the vitreous Cyclitis spargana Acanthocheilonema Dirofilaria Onchocerca Gnathostoma Onchocerca ToxocaraTrichinella

Optic nerve Papilledema papillitis andoptic atrophy

Taenia Ancylostyoma Toxocyara Trichinella Onchocerca

Retina andchorioidea

Hemorrhages Ancylostoma Gnathostoma Toxocara Trichinella

Retinal detachment Taenia

Cysts Echinococcus

Retinitis and choroiditis Baylisascaris Taenia Toxocara Trichinella Onchocerca

have probably occurred even in developed countries asevidenced by seropositivity in population-based surveys[2223] Worldwide cases continue to be reported in theliterature including descriptions of lesions effectivetreatments and newmodified methods to observe theinfection in the eye [24-37] Visual observation of motilelarvae in the eye is possible although accurate diagnosisis difficult serodiagnosis continues to be very useful indetecting and confirming cases [3839] Toxocara larvaeare approximately 400 by 20 μm and a larva of this sizein the eye is highly suggestive In this presentationdestruction of the larva by photocoagulation is recom-mended and prognosis is favourable when recognizedearly and prompt treatment is provided [40] After anundefined period of wandering in the tissues but prob-ably for several weeks or longer larvae become encapsu-lated including those in the eye These cases typicallypresent with unilateral visual deficits with or withoutocular pain and a raised white retinal mass that pre-sents difficulty in distinguishing from retinoblastomaUnfortunately in these situations loss of visual acuityblindness and even enucleation of the eye may resultToxocara larva seen in biopsy specimens or surgicallyresected tissues are rather easily identified based on sizeand morphological features Generally the larva will beenclosed in a granuloma coiled and one or more sec-tions of the larva evident In tissue sections larvae mea-sure 15-21 μm in diameter and are characterized by asingle prominent lateral ala non- patent gut and largeexcretory columns [41] The prevention of toxocariasisincluding OLM is based on good personal hygieneincluding washing hands and the proper disposal of petwaste including and specifically not letting pets andstray animals defecate in public places where childrenand others play and could come in contact with infec-tive eggs Rubinsky-Elefant and colleagues [11] recentlyreviewed the subjectOcular disease in baylisascariasis occurs in association

with severe neural and VLM and only rarely aloneAmong the ascarids Baylisascaris species are most oftenimplicated in serious cases of neural and OLM [42-45]Baylisascaris procyonis a common ascarid of raccoons inmany parts of the United States Europe and Japan hasdemonstrated potential for extensive larval migration inrodents and birds or other accidental hosts where it canproduce a fatal eosinophilic meningoencephalitis Thisnematode different from other causes of larva migranshas an aggressive somatic migration with larval invasionof the central nervous system and capability for contin-ued larval growth within intermediate hosts [46] Recentserological studies have indicated that significantly moreexposure to this parasite is occurring than previouslythought and consequently low level infections may alsobe more common than believed [46] As we recognize

increased exposure the potential exists for more cases ofserious visceral and CNS disease including migrationinto the eye (Figure 1) Baylisascariasis is acquired in thesame manner as other ascarids through the ingestion ofinfective eggs from the soil or other environmentalsources that have been contaminated by raccoon faecesSimilar to other visceral or OLM cases of baylisascariasisundoubtedly span the spectra of asymptomatic to seriousoften fatal infections Baylisascaris spp differ from Toxo-cara spp in that the larvae continue to grow oftenreaching 1-2 mm in length (by 50 - 60 μm in diameter)in the tissues including the eye The migration of suchrelatively large larvae can result in significantly morepathology than that of Toxocara The main symptomsare represented by chorioretinitis optic neuritis or opticnerve atrophy (Table 2) and examination occasionallymay reveal motile larvae migrating within the retina[1147] and vitreous humour [48] Ocular signs arerelated to the inflammation and local immune reaction ofthe retina retinal vasculature and optic nerve to the lar-vae Prevention of baylisascariasis is directed at avoidingingestion of infective eggs This is best accomplished byreducing the environmental contamination with raccoonfaeces through not feeding wild animals and not encoura-ging them to live in close proximity to humans promptand safe clean up of raccoon faeceslatrines and not let-ting children play in areas that have been contaminatedwith raccoon faeces [46]SpiruridsGnathostoma spp Another form of larva migrans iscaused by spirurid worms in the genus Gnathostoma(Spirurida Gnathostomatidae) [49] The definitive hostsinclude dogs cats wild carnivores raccoons and ottersDue to the large range of intermediate (eg fish frogschickens and other birds snakes pigs lizards somecrabs monkeys hamsters rats mice squirrels and gui-nea pigs) and paratenic (birds snakes and frogs) hoststhe control of this parasitic infection is particularly

Figure 1 Nematode larva in the retinal fundus Larvapresumably of Baylisascaris procyonis in the retinal fundus of apatient The infection was presumed to have been acquired inConnecticut USA Larva measures approximately 14 mm and wastreated with retinal lasar (Original courtesy of Drs CaplivskiBhatnagar and Goldberg Mount Sinai School of Medicine)

difficult The zoonotic infections occur much morecommonly as cutaneous larva migrans (CLM) or VLMbut on rare occasions can invade the eye [50-59] Oculargnathostomiasis can involve both invasion of surround-ing tissues or the eye itself by a wandering larva In theformer edema and hemorrhage of the eyelid or inflam-mation of the orbit may occur When a larva enters thetissue of the eye corneal ulceration iris perforation orretinal artery occlusion may occur with pronounceduveitis vitritis vitreal hemorrhage or secondary glau-coma Infections are acquired through accidental inges-tion of infected copepods that harbour 2nd stage larvaebut more often through the ingestion of poorly-cookedinfected fish or other paratenic hosts such as frogssnakes birds or even other mammals Migration of lar-vae directly from infected animal tissues used as poul-tices may also occur and place the larvae in theimmediate vicinity of the eye Four species of Gnathos-toma have been reported from humans includingGnathostoma spinigerum Gnathostoma hispidumGnathostoma doloresi and Gnathostoma nipponicumHowever many other species occur in nature and maypose a threat of zoonotic infection to man These arerelatively stout larvae and the 3rd stage larva in humantissue can measure between 1 and 5 mm or more inlength by 200-600 μm in diameter The larval stageshave many morphological features in common withadult worms including the prominent head bulb andcuticular spines In sectioned tissue the size of the larvais again distinguishing and occasionally both the headbulb and cuticular spines may be seen but are absent inmany sections The cuticle can vary between thin andthick and the muscle cells are numerous and welldefined the lateral chords tend to be large and very pro-minent and the gut is distinctive in nature being com-posed of many cuboidal cells each with multiple nucleiand a luminal brush border microvilli [41] The intestineand its lumen can be round or variously shaped but isgenerally a prominent structure noted inside the larvaSerology has proven useful in diagnosing cases[496061] Because of the size of the larva and theirability to migrate readily in the tissue its location withinthe eye is generally of concern although there arereports of successful recovery of larva from the eye withrestoration of visual acuity (Figure 2) [50] Prevention isprimarily through the avoidance of eating poorly-cookedfoods or use of raw flesh as poulticeFilarioidsThere are a number of different filarioids that have beenreported infecting the eye or the conjunctiva and thosereports date back several hundred years making themone of the oldest groups of parasites known to occur inor on the eye Indeed besides the well-known (but notzoonotic) Wuchereria bancrofti Brugia malayi and Loa

loa some filarioids from domestic and wild mammals(eg Dirofilaria spp Onchocerca spp Acanthocheilo-nema (Dipetalonema) spp Brugia spp and Loaina spp)have a zoonotic origin and may infect human eyes[86263] In addition a number of yet incompletely iden-tified filarioids have been described in human eyes in theAmazon forest regions [6465] For many of them the lifecycle and animal reservoir hosts are poorly known Ani-mal filarioids occur globally in many different forms andall filarioid infections are transmitted by various blood-sucking arthropods the majority of them including zoo-notic infections by mosquitoes although blackfliesculicoids and others may be involved Most personsworldwide are at some risk and those who are morelikely to be exposed to the vectors may be at increasedrisk but given the worldwide occurrence of animal filariathere are probably other undefined risk factorsThe largest number of filarioid eye infections is caused

by species of Dirofilaria and these result in a worm thatmigrates across the conjunctiva or is encapsulated in anodule on the conjunctiva or eyelid These cases werereferred to as Filaria conjunctivae [66] for decadesuntil they were properly aligned with known animal spe-cies [67] Hundreds of these cases have been reportedand new cases continue to be reported from wide geo-graphic areas including areas that have not previouslyreported such cases [68-76] Undoubtedly many morecases occur and are either not recognized or reportedIn the United States these are most often caused byDirofilaria tenuis a common parasite of raccoons and

Figure 2 Gnathostoma spinigerum larva in the anteriorchamber of the eye Gnathostoma spinigerum larva in the anteriorchamber of the eye of patient in Thailand (From Teekhasaenee CRicht R Kanchanaranya Ocular parasitic infection in Thailand RevInf Dis 1986 8350-356)

in Europe and other parts of the world by D repens acommon parasite of dogs and other canids (See addi-tional file 1 Movie1 Surgical removal of Dirofilariarepens from patientrsquos conjunctiva) [77] Other Dirofilariaspecies such as Dirofilaria ursi of bears Dirofilaria sub-dermata of porcupines Dirofilaria striata of wild catsand others have been isolated from humans on occasion[8] These species have not been reported to involve theeye but they certainly could in the future In wormsremoved intact or broken from the conjunctiva or seenin histological sections of nodules the morphologic fea-tures of most Dirofilaria make them relatively easy toidentify to genus level [8] They tend to be large robustworms and they have distinctive longitudinal and circularcuticular ridging that gives the external cuticle a beadedor corn-row appearance This can be seen easily in grossspecimens that have been removed intact and is one ofthe more prominent features noted in histological sectionas well Additionally in sections the worms have numer-ous strong muscle cells (polymyarian and coelomyarian)giving a strong body wall Determining the species ismore difficult especially if a male worm is not presentand final diagnosis is often based on the presumed loca-tion of acquisition (ie D tenuis if in the United StatesD repens elsewhere) Once removed clinical signsquickly resolve and there are no residual sequelaeWorms identified as Dirofilaria have also been reported

from within the eye either the anterior chamber or vitr-eous Some of these cases have been attributed toD immitis the dog heartworm D repens or Dirofilariaroemeri of kangaroos [8] A small number of them weresuccessfully removed and identified based on morphol-ogy A case of intravitreal dirofilariasis was recentlyreported from Turkey [78] and a case of human intraocu-lar dirofilariasis has been reported from northern Brazil(See additional file 2 Movie2 Surgical removal of Dirofi-laria immitis like nematode) [65] The nematode fromBrazil was morphologically and phylogenetically close toD immitis but genetically distinct from referencesequences including those of D immitis collected frominfected dogs in the same area The possible existence ofa closely related zoonotic Dirofilaria species in Brazil andits implications have been discussed and serve to high-light the high number of yet unknown species infectingwild mammals that have potential to cause zoonoticinfections Different from the above reported case wormswere generally of modest size making removal ratherthan photocoagulation the preferred method of treat-ment Dirofilaria spp worms are often motile andnoticed by the patient because of interference with visionRemoval is curative and full visual acuity is generallyrestored with no long term sequelaeIn addition to Dirofilaria several cases of small

Acanthocheilonema -like worms within the eye have also

been reported (Figure 3) [63] Although removed andexamined it was not possible to positively identify theseworms to species In a single case report Acanthocheilo-nema (Dipetalonema) reconditum a subcutaneous filar-ial infection in dogs worldwide was removed from thesubconjunctiva in a patient from Australia [79] Twoother unusual infections caused by Macacanema aparasite of monkeys have been reported where wormswere removed from the conjunctiva of humans [8081]The zoonotic role of filarial infection in humans in some

regions is far from understood Recently a mature malefilaria extracted from the iris fibers of a man from theAmazon region of Brazil was identified as belonging to thegenus Loaina or Pelecitus (See additional file 3 Movie 3Surgical removal of Pelecitus sp from the iris fibers of apatient) [64] This human case and a previous one fromColombia [62] were of unknown origin and both occurredin the tropical Amazon region but little is known aboutthe source of the infection Vectors of species of Loainaand Pelecitus are mosquitoes mallophagans or tabanids asshown with the three cycles elucidated [82-84] Unfortu-nately despite some studies on these genera [8586] infor-mation on these taxa is scant In the same manner wormsremoved from the eye and identified as Brugia are oftenhard to identify as B malayi of human origin or Brugiaspp of animal origin [87]

CestodesTaenia crassicepsHuman ocular infection by Taenia crassiceps occurswhen individuals accidentally ingest eggs in contaminatedfood or water Indeed T crassiceps is a tapeworm closelyrelated to Taenia saginata and Taenia solium and adult

Figure 3 Acanthocheilonema - Mansonella -like worm Anteriorend of an Acanthocheilonema - Mansonella -like worm removedfrom the posterior chamber of the vitreous of a patient in KansasUSA Scale bar = 500 μm Original courtesy of DPDx CDC

stages live in the intestine of carnivores and pass eggswith the faeces In the intermediate hosts primarilyrodents the immature cestodes (ie cysticerci) develop inthe peritoneal cavity [88] In humans larvae invade thebloodstream and reach subcutaneous and muscular tis-sues of immune- compromised individuals [8889] Inter-estingly larval T crassiceps in the anterior eye chamberor subretinally (Figure 4) have been reported in immuno-competent humans in the United States [9091] andEurope [92] The infection by cysticerci of T crassicepsmay be asymptomatic or cause iridocyclitis andor retini-tis [8892] Surgical intervention on the anterior chamberor the subretinal space is successful in curing the infec-tion [8892] Although not a zoonosis cysticercosiscaused by Taenia solium has been reported from thehuman eye [93]Coenurus cerebralisCoenurus cerebralis is the larval stage of the tapewormT multiceps (syn Multiceps multiceps) which developsin the small intestine of dogs foxes and other canids(definitive hosts) After ingestion by the intermediatehosts the oncospheres penetrate the intestinal mucosaenter the bloodstream and reach the brain where theydevelop into the infective cystic coenuri [9495] Coe-nurosis rarely occurs in humans through accidentalingestion of eggs causing mainly cerebral lesions butalso localizing in the eyes [92] C cerebralis ocularlesions cause severe anterior uveitis retrolental or

orbital cystic tumor-like masses and subretinal lesions(Figure 5) Subconjunctival localization may also occurafter accidental direct inoculation with infective eggsThe onset of inflammatory responses result in a red andpainful eye followed by development of glaucoma ret-inal fibrosis and ultimately blindness as the final resultof the infection [9697] Surgical removal of accessiblecysts (Figure 6) is the only choice to cure the infection[9698]Spirometra sppAnalogously adult Spirometra cestodes live in the smallintestine of carnivores where they release eggs whichreach the environment with the host faeces Larvae ofSpirometra spp tapeworms infect domestic animals andhumans Humans are dead-end hosts given that theybecome infected mostly by drinking polluted water (viaingesting the immature procercoid) or eating inectedintermediate hosts (ie frogs birds snakes that alongwith rats and mice are infected with the larval stages)and assuming the plerocercoid larvae Once ingestedthe larvae (sparganardquo) may invade muscles subcuta-neous tissue urogenital and abdominal viscera andsometimes the central nervous system and the eyes[99] Human ocular sparganosis has been reported fromSouth America [100] Central Europe [101] and Asia[102-105] Spargana usually infect subconjunctival andconjunctival tissues causing symptoms varying fromsimple itching due to local granulomata to more serioussigns represented by local pain epiphora chemosis andptosis [105106] Conjunctival infection may also be

Figure 4 Cysticercus cyst of Taenia crassiceps in situ Retinalphotograph showing budding cysticercus of Taenia crassiceps insitu (From the collection of Herman Zaiman ldquoA Presentation ofPictorial Parasitesrdquo)

Figure 5 Coenurus cyst behind displaced retina Sagittal sectionof eye from Ghanaian showing coenurus cyst with multipleprotoscoleces lying behind displaced retina (From Parasites InHuman Tissues Orihel and Ash ASCP Press 1995)

characterized by irritation continued foreign body sen-sation redness [104] and mimic signs and symptoms oforbital cellulitis with exophthalmia and corneal ulcersWhen the immature cestode invades the orbit it maycause acute anterior uveitis and iridocyclitis [101] andsevere inflammation with blindness [107] Unfortunatelysurgery is the only effective treatment [104105]Echinococcus granulosus Echinococcus multilocularis andEchinococcus oligarthrusEchinococcus granulosus Echinococcus multilocularisand Echinococcus oligarthrus are tapeworms that occurworldwide Adult stages of E granulosus and E multilo-cularis infect mainly dogs or wild canids (eg wolvesjackals coyotes and foxes) while E oligarthrus adultsinfect wild felines [108-111] Along with several otheranimal species human may act as (accidental) inter-mediate hosts of these cestodes by ingesting food con-taminated by their eggs [110111] When a human beinginadvertently ingests eggs the larvae hatch and dissemi-nate via the bloodstream into different organs and vis-cera (mostly liver or lungs but also heart) where theyproduce a typical hydatid cyst (E granulosus E oligar-thrus) or many alveolar small cysts (E multilocularis)causing a major zoonotic disease [108-111]Although not very common ocular infection by larval

Echinococcus spp may thus occur as a consequence ofbloodborne dissemination of the oncospheres Ocularlocalization by the larval form of E granulosus accountsfor 1 to 2 of all reports Intra-orbital hydatid cysts byE granulosus may cause severe exophthalmia [112] pain

and blindness as the hydatids have the ability to fill thevitreous cavity [113] or severe inflammation of orbitalstructures and acute eyesight loss due to the rupture ofintraorbital hydatids [114] Ocular alveolar hydatidosiscaused by E multilocularis may occur after spreading ofthe larval cestodes to other sites For instance a choroi-dal eye mass has been reported in a patient with historyof visceral alveolar hydatid disease with cerebral metas-tasis [115] Human infection by E oligarthrus is veryrare with only a few cases published in the internationalliterature two of which involve the eye [116] Nonethe-less the ocular localization of E oligarthrus has a rele-vant clinical impact since it causes the presence of asingle orbital retro-ocular cyst in the orbit [117] or theoccurrence of a retroocular cystic tumor-like mass indu-cing exophthalmia chemosis palpebral ptosis andblindness [108]

TrematodesFascioliasis also known as liver fluke is caused by Fas-ciola hepatica and Fasciola gigantica trematodes whichlocalize in the biliary ducts of the definitive hosts grass-grazing domestic and wild ruminants (ie cattle sheepgoats buffaloes) and also horses and rabbits This para-site develops through various larval stages in watersnails of the genus Limnaea which release cercariae thatencyst as metacercariae on aquatic vegetation Infectionoccurs when animals ingest freshwater plants or watercontaining encysted metacercariae [118] Within the lastdecade reports of human cases of fascioliasis haveincreased [119] Although migrating immature F hepa-tica flukes in humans have been mainly reported inblood vessels lung subcutaneous tissue and ventriclesof the brain [119] they have also been recovered fromthe anterior chamber of a patient in Iran [120]Alaria americana (syn canis) is a three-host trema-

tode that lives as adults in the intestine of the dog defi-nitive host Eggs are passed in faeces and hatch inwater releasing miracidia which penetrate the helisomidsnails (first intermediate host) and develop through thesporocyst stage into cercariae [121] Cercariae releasedfrom snails actively penetrate the second intermediatehost (tadpoles) becoming infective mesocercariae inabout two weeks In the tadpole or in the frogs (follow-ing the metamorphosis) mesocercariae accumulate andmay be ingested by a number of paratenic hosts (egother frogs snakes) or directly by the definitive hostCases of human intraocular infection with mesocercariaeof A americana and other Alaria mesocercariae havebeen recorded in patients who had ingested under-cooked contaminated frogs legs [122] Both patients pre-sented with pigmentary tracks in the retina areas ofactive or healed retinitis and signs of diffuse unilateralsubacute neuroretinitis (Figure 7)

Figure 6 Coenurus cyst after surgical removing from the eyeIntact coenurus cyst removed from subconjunctival tissue anUgandan child showing multiple protoscoleces (Original by PaulBeaver)

The trematode Philophthalmus lacrimosus (Phi-lophthalmidae) as adults parasitize the eyes of birds(definitive host) Eggs containing miracidia hatch in thewater miracidia penetrate snails (intermediate hosts)and develop into redia and cercariae When the meta-cercariae encyst on surfaces of food for birds the infec-tion of a new definitive host can take place by enteringthe eye or by oral intake [123] Human cases of phi-lophthalmosis have been reported in Europe (Yugosla-via) Israel Asia (Thailand Sri Lanka Japan) andAmerica (ie Mexico and the United States) [124]

New or reemerging zoonotic helminths infectinghuman eyesOver the last decade parasitological knowledge has beenconsiderably refined and enhanced by the use of sophis-ticated technologies and molecular tools and by theinterdisciplinary approach in many fields of the humanand veterinary medical sciences Increasing awareness ofphysicians on previously poorly known diseases likely isan important part of this process Reports of several ofthese infections of the eye have been increasing butwhether this is due to a higher awareness or increasingrates of infection is unclear Possible reasons for the

highest number of reports may include changing epide-miological patterns in the natural definitive hostsleading to increased exposure of humans and new geo-graphic range because of spreading into new areasThree key examples namely infections by Angiostrongy-lus cantonensis Thelazia callipaeda and Onchocercaspp are discussed below

AngiostrongylusMetastrongylids encompass a large group of nematodes(Strongylida Metastrongyloidae) infecting organs andtissues of different vertebrates [125] A cantonensis alsoknown as rat lungworm is a well recognized zoonoticinfection and as such is the primary cause of eosino-philic meningitis in Southeast Asia The infection hasspread widely to many other areas of the world includ-ing the Caribbean and Americas [126-130] The parasitealso enters the eye with some frequency In a review of484 cases of eosinophilic meningitis Punyagupta andcolleagues [131] noted that 47 (16) of the cases hadreported ocular involvement and in 7 cases an activelymotile worm (most probably A cantonensis) was visua-lized and removed from the anterior chamber of vitr-eous of the eye [132133] Human ocular infections bylarval rat lungworm have been reported in several coun-tries in Southeast Asia [134-143] and they likely willcontinue to be reported wherever the parasite occursincluding in new geographical areas such as the Carib-bean [144] Ocular lesions by A cantonensis may eitheroccur alone or may accompany other symptoms such asmeningitis [142145] Often these long and slenderworms reach considerable size in the eye and are up toa centimeter or more in length [141] The female wormhas a distinctive helical pattern of dark intestine inter-twined with light coloured reproductive tubes maleworms have a copulatory bursa and very long (gt 1 mm)spicules These features make it fairly simple to recog-nize and identify a large worm removed from the eye asA cantonensisInfections are acquired through the ingestion of

infected intermediate snail or slug hosts or a variety ofparatenic hosts such as amphibians reptiles and somecrustaceans that have become infected by ingestion ofsnails andor slugs Migrating larvae in the human hostmake their way to the CNS and occasionally into theeye possibly along the optic nerve Caution in handlingand not eating raw or poorly cooked intermediate orparatenic hosts should prevent most human infectionsThere is some evidence that people can also be infectedby ingestion of produce that has been contaminatedwith slime trails of snails or slugs into which infectivelarvae have been shed Washing produce may helpreduce the risk of infection but probably does notremove all risk in endemic areas with high level of

Figure 7 Alaria sp in the eye Freely moving Alaria mesocercariaon the retina of the eye The anterior sucker is evident on the leftside of the organism (From the collection of Herman ZaimanldquoA Presentation of Pictorial Parasitesrdquo)

transmission Although in a number of cases worms aresuccessfully removed ocular disease caused by larvalA cantonensis may vary from blurred vision due tointraretinal haemorrhage [144] to severe optic neuritisdue to the presence of the nematode in the vitreous cav-ity [143] Other signs include visual disturbances andimpairments extraocular muscular paralysis and a widerange of ocular inflammatory conditions [141146147]Diagnosis is based on the identification of a (usuallysingle) living worm in any eye localization (eg anteriorchamber vitreous cavity and subretinal space) (Figure 8)The treatment regimen relies on the surgical removal orlaser therapy accompanied by oral benzimidazole (egmebendazole) and corticosteroids in the case of inflam-matory manifestatios such as retinitis or optic neuritis[147] Ocular damage caused by A cantonensis can besevere and may be permanent thus in some patientsthe outcome is poor and depends on the initial visualacuity [141147]

ThelaziasisThelazia callipaeda (Spirurida Thelaziidae) represents agood example of HIE that is both spreading and new tothe scientific community in western countries Along withThelazia californiensis that has been reported to infecthumans occasionally in the United States [148] T calli-paeda is the only helminth transmitted by secretophagousflies directly into the orbit of humans [149] This nema-tode primarily affects the eyes of domestic dogs and catsand wild carnivores (eg foxes wolves beech martens andwild cats) (See additional file 4 Thelazia callipaeda infect-ing the eye of a dog) [150] Since its first description at thebeginning of the previous century this nematode has beenknown as the ldquooriental eye-wormrdquo for its distribution in

the former Soviet Union [151] and the Asian continentincluding China [10] Korea [152] Japan [153] Indonesia[154] Thailand [155] Taiwan [156] and India [157]Human thelaziasis may cause mild to severe clinical signs(including lachrymation epiphora conjunctivitis keratitisandor even corneal ulcers) [125] The worm is trans-mitted by various secretophagous flies which feed onlachrymal secretions of infected animals andor humansthus ingesting Thelazia 1st stage larvae and after obligatedevelopment in the fly depositing 3rd stage larvae directlyback into the orbit The competence of drosophilid flies ofthe genus Phortica (Diptera Drosophilidae) as vectors ofT callipaeda has recently been elucidated under bothlaboratory and natural conditions [158159] We nowrecognize that T callipaeda infection is widespreadthroughout Italy with infection prevalence as high as 60in dogs from some municipalities (Figure 9) [160] and alsoin southwestern France (Dordogne area) [161162] andSwitzerland [163] In addition four cases of human thela-ziasis have been diagnosed in patients coming from anarea of north-western Italy and south-eastern France[164] Infected patients present with exudative conjunctivi-tis follicular hypertrophy of the conjunctiva foreign bodysensation excessive lachrymation itchiness congestionhypersensitivity to light and keratitis depending on thenumber of nematodes present in the eye [10] Childrenand the elderly seem to be at higher risk Thelazia wormsare generally removed intact from the eye and there areseveral morphological features that assist in identifyingthem from other worms that might occur in the orbitincluding filaria such as Loa or Dirofilaria The morpholo-gical identification of T callipaeda has been reviewed[165] The adult worms measure from 5 to 20 mm inlength by 250 - 800 μm in diameter (males are smallerthan females) They have a distinct buccal capsule andthe cuticle has typical regularly spaced distinct transverse

Figure 9 Thelazia calllipaeda in a heavily infected dog Heavyinfection by Thelazia callipaeda nematodes in the conjunctiva of adog from Italy

Figure 8 Angiostrongylus cantonensis in the anterior chamberof the eye Angiostrongylus cantonensis in the anterior chamber(Original by John Cross courtesy of Lawrence Ash)

striations giving the cuticle a ridged appearance (Figure 10)In addition adult females of T callipaeda are character-ized by the position of the vulva located anterior to theoesophagus-intestinal junction and the males possess fivepairs of postcloacal papillae Poor living conditions andlow socio-economic standards seem to be risk factors foracquiring infection and better hygiene would probablycontribute to prevention The adults and larvae of T calli-paeda can be removed mechanically by rinsing the con-junctival sac with sterile physiological saline whereasadults can also be isolated with forceps or cotton swabs[10]

OnchocercaAs previously noted the vast majority of filarioid infec-tions of the eye occur on the conjunctiva and arecaused by species of Dirofilaria However there is anincreasing number of reports of zoonotic Onchocercainfections and several of these have been either within

the eye or associated with the conjunctiva or connectivetissue of the orbit (See additional file 5 Onchocerca spinfecting the anterior chamber of a human patient) Ofthe 15 clinical cases reported to date [166167] five havebeen associated with the eye 3 involved the conjunctivaand 2 involved the cornea These have been reportedfrom Crimea the United States Albania Hungary andTurkey [168-172] The species causing infections of theeye have tentatively been attributed to Onchocerca gut-turosa or Onchocerca cervicalis [169173] Onchocercareticulata [170] Onchocerca spp [171] and Oncho-cerca lupi [172] This last species O lupi is of particu-lar interest because it affects dogs and it induces acuteor chronic ocular disease characterized by conjunctivitisphotophobia lacrimation ocular discharge andexophthalmia [166] In most cases zoonotic Onchocercaspp are encased in a nodular granuloma are resectedand sectioned and the worms identified morphologically(Figure 11a) In section of Onchocerca the distinctivemuscle anatomy composed of few low poorly devel-oped cells and the characteristic structures of the cuti-cle are often apparent including the circular ridges andinner cuticular striae making the identification straight-forward The distances between the prominent undu-lated annular ridges and the number of transverse striaein the internal layer represent the morphological charac-ters for differentiating filarioids belonging to the Oncho-cerca genus (Figure 11a) The apparent increase innumber and range of zoonotic Onchocerca infectionsincluding those affecting the eye is noteworthy but diffi-cult to fully explain Recent cases in both the US andEurope highlight this trend Case reports of canine ocu-lar onchocerciasis by O lupi [166] have also increasedin Europe including in Greece Portugal GermanyHungary and Switzerland [174-177] The number ofcases of canine ocular onchocerciasis have also increasedin the United States but the species of parasite in theUnited States has not been established [178-180] Therole played by dogs as reservoir of this zoonotic agentdeserves to be investigated further to establish both theprimary definitive hosts as well as the vectors that serveto transmit the infection naturally and to humans

Diagnosis and cureThe diagnosis of the causative agent is usually only pos-sible after surgery and extraction of the worm or tissuecontaining the worm and often requires the assistanceof a specialist with an appreciation of the microscopicfeatures of helminths Generally in those cases wherethe parasite is amenable to obliteration with photocoa-gulation or laser surgery only a tentative diagnosis ispossible However surgery remains the only optionavailable for treating a number of the HIE Althoughinvasive and often requiring sophisticated devices and

Figure 10 Thelazia californiensis from a human patient Posteriorend of a female Thelazia californiensis from the conjunctiva of ahuman patient in New Hampshire USA showing cuticle serrationScale bar = 50 μm Original courtesy of DPDx CDC

advanced medical expertise (not always available indeveloping countries) ocular surgery is often curativeand also allows the recovery of helminths to identifythem (Table 3) At the time of ophthalmological exami-nation observation of motile larvae in the eye is

occasionally possible although a diagnosis at specieslevel can be difficult Indeed in some cases it is possibleto tentatively identify helminths by measuring larvae inthe retina This is the case with B procyonis larvaewhich are larger (1 to 2 mm by 50 to 60 μm) than those

Figure 11 Zoonotic Onchocerca from human ocular connective tissue Zoonotic Onchocerca sp from a nodular granuloma of the eye in apatient from Ohio USA a) Transverse section of female worm shown in Fig 5a encased in a nodular granuloma Low cuticular ridges and innerstriae 2 per ridge are evident Hematoxylin and eosin stain Scale bar = 50 μm (Original courtesy of Drs Yassin and Hariri University of PittsburgMedical Center) b) Short piece of female Onchocerca sp removed from granuloma tissue before fixation showing characteristic diagnosticstructures of the cuticle with circular ridges and inner cuticular striae Scale bar = 150 μm (Original courtesy of Drs Yassin and Hariri Universityof Pittsburg Medical Center)

Table 3 Informative morphological characters and measurements of different stage of helminths infecting humaneyes [4163]

Parasite Location Size Comments Stage

Toxocara canis Intraocular le 400 μm times 15-21 μm Smallest of the nematode larvae encountered in the eye ML

Baylisascaris spp Intraocular 1-2 mm times 50-60 μm Relatively small but easily recognized as being larger thanToxocara larvae

Gnathostoma spp Intraocular 1-5 mm times 200-600 μm Much more robust than other nematode larva presence ofcuticular spines and head bulb distinctive

Angiostrongylusspp

Intraocular le1-2 cm times 200-300 μm One of the larger more robust worms found in intraocularlocation

Thelazia callipaeda Eye socket 5-20 mm times 250-800 μm Distinct morphologic features free in orbit A L

Philophthalmus Intraocular 2-3 mm times 600-800 μm Ovoid to oblong flat solid body ML SA

Spargana Intraocularor eyelid

5-20 mm times 1-2 mm Long flat solid body with pseudosegmentation ML

Coenurus Intraocular lt 1 cm Fluid filled cyst ovoid in shape and of variable size L

Dirofilaria tenuisDirofilaria repens

Conjunctiva 2-15 cm times 150-400 μm Males smaller than females most often closely associated withconjunctiva worms in the eye are appreciably smaller than those

on conjunctiva

Dirofilaria immitis Intraocular 1-165 cm times 160-400 μm Not a common location for this worm and very few confirmedcases exist

Conjunctiva 10 cm times 300 μm SA

Onchocerca spp Intraocular 3-5 cm times 80-100 μm L

Conjunctiva total length unknown but severalcm or more times 150-250 μm

Acanthocheilonemaspp

Intraocular 16 - 21 cm times lt100 μm Accurate identification to species has been L SA

Conjunctiva 32 cm times lt150 μm

Larva = L Migrating larva = ML SA = Subadult A = Adult

of Toxocara spp (lt 400 by 15 to 20 μm) [47] This lar-ger size often allows a quick differentiation betweenToxocara and Baylisascaris larvae when seen either intissue sections or within the eye Although Baylisascarislarvae share several morphologic features in commonwith Toxocara including single lateral cuticular alae andpaired excretory columns they differ markedly not onlyin size but in the fact that the gut is patent (has a dis-tinct lumen) in Baylisascaris spp Other types of nema-tode larvae such as those of Gnathostoma spp arerelatively easy to identify because of their stout robustsize and distinctive head bulb whether they are visua-lized in the eye or removed Similarly A cantonensisworms often reach considerable size in the eye but arelong and slender worms up to a centimetre or more inlength and are not easily confused with ascarid orGnathostoma larvae being more likely mistaken for afilarioid Microscopic examination however wouldquickly allow separation of Angiostrongylus from afilaria Other HIE such as Alaria mesocercaria couldbe distinguished on the basis of its shape size (500 times150 μm) and movement [122] Their localization on theconjunctiva surface size and morphologic featureswould allow a relatively easy diagnosis of T callipaedaOn the other hand when HIE are enclosed in a gran-

uloma or within the subconjunctiva the identification ismore difficult Furthermore in certain situationsremoval may increase the risk to the patient as in thecase of the cystic forms of Echinococcus spp whichcould induce anaphylactic immunoreactions when dis-turbed Indeed although rare the localization of Echino-coccus spp cysts in the eye are always cause of severedisease thus the careful surgical removal of the cysts isthe only optionWhere appropriate tests exist serological diagnosis

can often contribute to a definitive diagnosis of infec-tion such as in the case of some ascarids for which ser-ological testing using a sensitive specific enzymeimmunoassay (EIA or ELISA) is available Serologicaltesting is available for baylisascariasis and can be veryhelpful in identifying and confirming infection and likefor toxocariasis in conducting serosurveys to documentthe degree of exposure in different populations Unfor-tunately individuals may not mount a measurableimmune response during the early phases of acute infec-tion and serologic testing will not provide conclusiveevidence to help guide treatment hence the need foraggressive presumptive treatment in cases with solidexposure history [46] Serologic assays can be very help-ful to confirm infections caused by Gnathostoma espe-cially in cases where no larva or tissue is available toexamine Conversely seropositivity to spargana in IFATor ELISA tests always needs to be confirmed by histolo-gical examination [104105]

Unfortunately surgery is often the only effective treat-ment for many HIE (eg ocular sparganosis A canto-nensis) and this is one of the reasons why theseinfections represent a traumatic event for the patientsand treatment is not a particularly cost-effective mannerin which to manage the infection In some cases suchas the typical zoonotic filarial infection only a singleworm is present and the surgical removal is both thera-peutic and curative In other instances most notablyOLM or larval tapeworms there is some likelihood thatadditional larval stages may exist and chemotherapymay be indicated with corticosteroids in the case ofinflammatory conditions such as retinitis or optic neuri-tis [147]It should be noted that the use of photocoaggulation

and laser ablation continue to prove useful in a numberof cases infection with HIE eg ascarid larvae Alariamesocercaria and often result in improved visual out-come while at the same time destroying the invadinghelminth in situ [122]

Concerns ignorance and new avenues linkedto HIEOphthalmologists and physicians often lack an in- depthknowledge of parasites rendering it difficult for them tocorrectly address the etiological identification treat-ments and control strategies for many HIE In additionthe scientific information on HIE available in the inter-national literature is scarce and limited to single casereports in which a clear comparative differentiationamong helminth infections is not considered The mainlimitation for correctly identifying the etiological agentis that often helminths are not removed or they areseriously damaged during the surgical procedures thusrendering an accurate morphological identification diffi-cult if not impossible The microscopic identification ofhelminths at the species level often relies on the exami-nation of key morphological characters not all of whichare present on any given specimen or not recognized bythe person making the examination sometimes resultingin an incorrect diagnosis Accurate identification iscrucial to understanding both the source of infectionand environmental risks as well as prescribing correcttreatment optionsThere are several cases in the literature in which hel-

minths were erroneously identified for example casesof Trichinella sp in the vitreous of a woman and Toxo-cara sp in the retina of a man both from Germany anda case Angiostrongylus sp recovered from the anteriorchamber of a man from Sri Lanka were all incorrectlyidentified as filaria (reviewed in [63]) Twenty-eightcases of human dirofilariasis from the Old World wereerroneously attributed to D immitis subsequentlyreviewed and correctly attributed to D repens [181]

Recently the helminth causing a case of human intrao-cular infestation in Japan was erroneously identified asT callipaeda although the picture published in the arti-cle portrayed a filarioid [182] In the same article theauthors stated that the life cycle of T callipaedaremains unclear and discussed the possibility of humaninfection through the skin or by drinking untreatedwater This somewhat implausible hypothesis wasalready dispelled in the late 1990s [183] The scantattention of medical researchers towards human thela-ziasis may also be attributable to the difficulties in itsclinical diagnosis and differentiation from allergic con-junctivitis particularly when small numbers of adult orlarval stages are present in affected patients Morerecently the advent of molecular biological techniqueshas largely supplemented and enhanced knowledge ofparasitologists in areas such as systematics (taxonomyand phylogeny) population genetics and molecular iden-tification diagnosis and control of some HIE [184]Indeed the advent of PCR made it possible to studydamaged and incomplete specimens or fragments ofspecimens encysted in tissues which otherwise wouldnot be morphologically identifiable [185] The impor-tance of molecular identification and barcodingapproach (by the specific PCR-amplification of the cox1and 12S genes) for the rapid identification of specimenshas been emphasized including for either recognized oryet unknown species Recently an integrated DNA bar-coding of cox1 and 12S markers and morphologyapproaches was shown to be a powerful tool for the tax-onomical identification of many filarioid species even ifsmall nematode fragments were available [184] In addi-tion the delineation of Molecular Operational Taxono-mical Units (MOUTS) was useful to infer potential newspecies [184]Basic parasitological research in this field is often frag-

mentary due to the fact that experimental human infec-tions are rarely done and the retrieval of helminthsfrom the patientsrsquo eyes may be an infrequent occurrenceduring the ophthalmologic examination For a numberof these helminths poor experimental models exist orif good models exist the infections generally do notaffect the eye in the same way that occurs in aberranthuman infections Thus scientific knowledge in thisfield as well the information on helminth migration pat-terns is limited and often has been gained from studiesof the same parasites in other animal models All theabove concerns need to be addressed through basic andapplied research For example many nematode specieshave not yet been described and even those that areknown are often poorly studied such that there is a lackof basic information on the helminth fauna of wild ani-mals (eg O lupi) This is particularly true but notrestricted to regions of the world such as the Brazilian

Amazon forest where there is wide biodiversity and alarge amount of animal and plant species yet to bedescribed [186] Consequently species identification ofsome groups of HIE such as filarial nematodes can bedifficult if not impossible Another example of insuffi-cient information is represented by the unknown risk ofzoonotic infection such as other species of Baylisascaris(in addition to B procyonis) that may be considered aspotential zoonotic agents [46] For example Baylisascaristransfuga infecting bears worldwide [45187] has beenreported to produce visceral neural or OLM syndromesin mice [188-190] gerbils [45191] and guinea pigs[192] In addition cases of fatal neurological diseaseshave been reported in a colony of Japanese macaques(Macaca fuscata fuscata) housed with American blackbears in a safari-zoo in Japan [193] However the zoo-notic role of this parasite for humans has never beendemonstrated Since bears are frequently kept in zoosand game parks and often have high prevalence of theinfection in the population (up to 50-100 of bears har-bour this parasite) studies on the zoonotic capacity ofthis parasitic species would be pivotal for a betterunderstanding of the public health risk [194] Overall abetter understanding of the biology of a number of HIEis crucial for addressing their preventionBetter awareness among physicians (including

ophthalmologists) in the field of parasitology and moreactive collaboration with parasitologists would be veryhelpful in proper diagnosis control and prevention ofHIE This would also allow a better knowledge of thepotential risks for being infected by an HIE agent in agiven area as well as exposure when travelling in ende-mic areas Physicians and ophthalmologists needincreased awareness about the existence of a range ofzoonotic helminths other than those natural parasites ofhumans that might be expected to be found in patientsrsquoeyesUnfortunately there is a lack of knowledge about

many parasites in the local fauna and limited basicresearch studies are carried out Monitoring and peri-odic surveillance for the infections of both domestic andwild animals is important to provide a better under-standing of what potential pathogens exist locally andto prevent the HIE This is the case with B procyoniswhich is an emerging infection in raccoons in the south-eastern United States an area traditionally considered tobe at low risk [195196] An increasing appreciation ofonchocerciasis in domestic and wild animals in Europeand the United States is needed to accurately under-stand what species exist what the natural definitive hostis and ultimately what the risks for human infectionare Veterinarians physicians and public health officialsall share the need to be alert to the possibility of zoono-tic infections inside and outside of traditional high-risk

areas Lastly we need a better understanding of whysome parasites migrate to and occasionally enter theeye especially given that none of these helminths typi-cally resides in or around the eye

ConclusionsDespite scientific advances and new methods for treat-ing helminth infections in the human eye therapiesavailable to patients are somewhat limited and can onlybe applied in specific cases This will lead to improve-ments in the clinical outcome in some cases but for theforeseeable future a number of these HIE have complexclinical presentations that still hold potential for seriousoutcome including blindness or death such as in thecase of B procyonis infections where despite treatmentneurological outcome is dismal in the overwhelmingmajority of documented cases [46] However manycases of these zoonotic helminth infections are preventa-ble by relatively simple measures of improved healthand sanitation conditions and awareness on the part ofboth public and health care providers Risks for toxocar-iasis and baylisascariasis could be significantly reducedthrough better hygiene and reduction of the amount ofanimal waste in areas where people especially childrenmight come in contact with it For the foodborne zoo-noses such as angiostrongyliasis gnathostomiasis andothers proper handling and preparation of foods wouldminimize the risk of infection For the vector-borne zoo-notic infections control and prevention is likely going tobe much harder as it involves not only the control ofthe infection in the definitive animal host but a con-certed control of vectors which is often outside the con-trol of any individual but almost always done at thecommunity or regional level

Additional material

Additional file 1 Surgical removal of Dirofilaria repens frompatientrsquos conjunctiva This video shows the surgical removal ofDirofilaria repens from the patientrsquos conjunctiva after topical anaesthesiaThe palpebral fissure was maintained open by using the blefarostat thenematode was extracted after incision of the conjunctiva membranesand it was collected A shortened version of a video in Otranto D BriantiE Gaglio G Dantas-Torres F Azzaro S Giannetto S Human ocularinfestation by Dirofilaria repens (Ralliet and Henry 1911) in acanine dirofilariosis-endemic area Am Jour Trop Med Hyg 2011 (inpress)

Additional file 2 Surgical removal of a Dirofilaria immitis -likenematode This video shows the surgical removal of a Dirofilaria immitis-like female nematode from the anterior eye chamber of a patient fromParagrave Brasil Eye was clipped and the cornea incised with a crescentBeaver corneal knife The nematode was extracted alive with forceps andFukasacu hook The patient recovered without complications after thesurgery A shortened version of a video in Otranto D Diniz DG Dantas-Torres F Casiraghi M de Almeida INF de Almeida LNF Nascimento dosSantos J Penha Furtado A de Almeida Sobrinho AF Bain O Humanintraocular filariasis caused by Dirofilaria sp Brazil Emerg Infect Dis2011 (in press)

Additional file 3 Surgical removal of Pelecitus sp from the irisfibers of a patient This video shows the surgical removal of a Pelecitussp male nematode (approximately 4 mm in length) from the iris fibersof a patient from the Amazon region Brasil After peribulbar anesthesiaand corneal incision of 2 mm The nematode was extracted by aspirationand the surgery had no complication A shortened version of a video inBain O Otranto D Diniz DG Nascimento dos Santos J Pinto de OliveiraN Negratildeo Frota de Almeida I Negratildeo Frota de Almeida R Negratildeo Frotade Almeida L Dantas-Torres F Frota de Almeida Sobrinho E Humanintraocular filariasis caused by Pelecitus sp Brazil Emerg Infect Dis2011 (in press)

Additional file 4 Thelazia callipaeda infecting the eye of a dog inBasilicata region (southern Italy) This video shows Thelazia callipaedanematodes floating in the eye of an infected dog in an endemic area ofItaly Conjunctivitis and lacrymation were the main symptoms observedIn the second part numerous T callipaeda specimens have beencollected by an ocular swab

Additional file 5 Onchocerca sp infecting the anterior eye chamberof a human patient This video shows the occurrence of Onchocerca spin the anterior chamber of a patient from Colorado United States Thenematode was surgically removed extracted alive and identified asOnchocerca The patient recovered without complications after thesurgery A video from the case presented in Burr WE Brown MFEberhard ML Zoonotic Onchocerca (Nematoda Filarioidea) in thecornea of a Colorado resident Ophthalmology 1051494-1497 1998Video courtesy of Dr WE Burr

AcknowledgementsThe authors are grateful to Alessio Giannelli (University of Bari Italy) andDonato Traversa (University of Teramo Italy) for their support during thepreparation of the manuscript We are grateful to Emanuele Brianti(University of Messina Italy) and Riccardo Paolo Lia (University of Bari Italy)for their assistance with the video editing and figure preparation Theauthors thank Susan Montgomery CDC and of two anonymous reviewersfor their helpful suggestions DO and MLE would like to thank their wivesIrene Canfora and Sandra Eberhard for their continuous support andassistance during the preparation of this article

Author details1Dipartimento di Sanitagrave Pubblica e Zootecnia Universitagrave degli Studi di BariValenzano BA Italy 2Division of Parasitic Diseases and Malaria Centers forDisease Control and Prevention Atlanta Georgia 30341-3724 USA

Authorsrsquo contributionsDO and MLE equally contributed in writing the article

Competing interestsThe authors declare that they have no competing interests

Received 31 January 2011 Accepted 23 March 2011Published 23 March 2011

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144 Mattis A Mowatt L Lue A Lindo J Vaughan H Ocular angiostrongyliasis-first case report from Jamaica West Indian Med J 2009 58383-385

145 Ramirez-Avila L Eosinophilic Meningitis due to Angiostrongylus andGnathostoma Species Emerging Infections 2009 48322-327

146 Koo J Pien F Kliks MM Angiostrongylus (Parastrongylus) eosinophilicmeningitis Rev Infect Dis 1988 101155-1162

147 Sawanyawisuth K Sawanyawisuth K Treatment of angiostrongyliasis TransR Soc Trop Med Hyg 2008 102990-996

148 Doezie AM Lucius RW Aldeen W Hale DV Smith DR Mamalis N Thelaziacaliforniensis conjunctival infestation Ophthalmic Surgery and Lasers 199627716-771

149 Otranto D Traversa D Thelazia eyeworm an original endo- and ecto-parasitic nematode Trends Parasitol 2005 211-4

150 Otranto D Dantas-Torres F Mallia E DiGeronimo PM Brianti E Testini GTraversa D Lia P Thelazia callipaeda (Spirurida Thelaziidae) in wildanimals report of new host species and ecological implications VetParasitol 2009 166262-267

151 Miroshnichenko VA Desiaterik MP Novik AP Gorbach AP Papernova N Acase of ocular thelaziasis in a 3-year-old child in Russian Vestn Oftalmol1988 104-64

152 Min S Jae RY Hyun YP Enzooticity of the dogs the reservoir host ofThelazia callipaeda in Korea Kor J Parasitol 2002 40101-103

153 Koyama Y Ohira A Kono T Yoneyama T Shiwaku K Five cases ofthelaziasis Br J Ophthalmol 2000 84(4)441

154 Kosin E Kosman ML Depary AA First case of human Thelaziasis inIndonesia Southeast Asian J Trop Med Public Health 1989 20233-236

155 Yospaiboon Y Sithithavorn P Maleewong V Ukosanakarn U Bhaibulaya MOcular thelaziasis in Thailand a case report J Med Assoc Thai 198972469-473

156 Cheung WK Lu HL Liang CH Peng ML Lee HH Conjunctivitis caused byThelazia callipaeda infestation in a woman J Formos Med Assoc 199897425-427

157 Singh TS Singh KN Thelaziasis report of two cases Br J Ophthalmol 199377528

158 Otranto D Lia RP Cantacessi C Testini G Troccoli A Shen JL Wang ZXNematode biology and larval development of Thelazia callipaeda(Spirurida Thelaziidae) in the drosophilid intermediate host in Europeand China Parasitology 2005 131847-855

159 Otranto D Cantacessi C Testini G Lia RP Phortica variegata is anintermediate host of Thelazia callipaeda under natural conditionsevidence for pathogen transmission by a male arthropod vector Int JParasitol 2006 36(10-11)1167-1173

160 Otranto D Ferroglio E Lia RP Traversa D Rossi L Current status andepidemiological observation of Thelazia callipaeda (SpiruridaThelaziidae) in dogs cats and foxes in Italy a ldquocoincidencerdquo or aparasitic disease of the Old Continent Vet Parasitol 2003 116315-325

161 Dorchies P Chaudieu G Simeacuteon LA Cazalot G Cantacessi C Otranto DFirst reports of autochthonous eyeworm infection by Thelazia callipaeda(Spirurida Thelaziidae) in dogs and cat from France Vet Parasitol 2007149294-297

162 Ruytoor P Deacutean E Pennant O Dorchies P Chermette R Otranto DGuillot J Ocular thelaziosis in dogs Emerg Infect Dis 2010 161943-1945

163 Malacrida F Hegglin D Bacciarini L Otranto D Naumlgeli F Naumlgeli CBernasconi C Scheu U Balli A Marengo M Togni L Deplazes PSchnyder M Emergence of canine ocular thelaziosis caused by Thelaziacallipaeda in southern Switzerland Vet Parasitol 2008 157321-327

164 Otranto D Dutto M Human thelaziasis Europe Emerg Infect Dis 20084647-649

165 Otranto D Lia RP Traversa D Giannetto S Thelazia callipaeda (SpiruridaThelaziidae) of carnivores and humans morphological study by lightand scanning electron microscopy Parassitologia 2003 45125-133

166 Sreacuteter T Szeacutell Z Onchocercosis a newly recognized disease in dogs VetParasitol 2008 1511-13

167 Uni S Boda T Daisaku K Ikura Y Maruyama H Hasegawa H Fukuda MTakaoka H Bain O Zoonotic filariasis caused by Onchocerca dewitteijaponica in a resident of Hiroshima Prefecture Honshu Japan ParasitolInt 2010 59477-80

168 Azarova NS Miretski OI Sonin MD 1st case of human infection by thenematode Onchocerca Diesing 1841 in the USSR Med Parazitol 196534(2)156-158

169 Burr WE Brown MF Eberhard ML Zoonotic Onchocerca (NematodaFilarioidea) in the cornea of a Colorado resident Ophthalmology 19981051494-1497

170 Pampiglione S Vakalis N Lyssimachou A Kouppari G Orihel TCSubconjunctival zoonotic Onchocerca in an Albanian man Ann Trop MedParasitol 2001 95827-832

171 Sallo F Eberhard ML Fok E Baska F Hatvani I Zoonotic intravitrealOnchocerca in Hungary Ophthalmology 2005 112(3)502-504

172 Otranto D Sakru N Testini G Guumlrluuml VP Yakar K Lia RP Dantas-Torres FBain O First Evidence of Human Zoonotic Infestation by Onchocerca lupi(Spirurida Onchocercidae) Am J Trop Med Hyg 2011 84(1)55-8

173 Beaver PC Horner GS Bilos JZ Zoonotic onchocercosis in a resident ofIllinois and observations on the identification of Onchocerca species AmJ Trop Med Hyg 1974 23(4)595-607

174 Szeacutell Z Erdeacutelyi I Sreacuteter T Albert M Varga I Canine ocular onchocercosis inHungary Vet Parasitol 2001 97245-251

175 Komnenou A Eberhard ML Kaldrymidou E Tsalie E Dessiris ASubconjunctival filariasis due to Onchocerca sp in dogs report of 23cases in Greece Vet Ophthalmol 2002 5119-126

176 Hermosilla A Hetzel U Bausch M Gruumlbl J Bauer C First autochthonouscase of canine ocular onchocercosis in Germany Vet Rec 2005154450-452

177 Sreacuteter-Lancz Z Szeacutell Z Sreacuteter T Molecular genetic comparison ofOnchocerca sp infecting dogs in Europe with other spirurid nematodesincluding Onchocerca lienalis Vet Parasitol 2007 148365-370

178 Orihel TC Ash LR Holshuh HJ Santenelli S Onchocerciasis in a Californiadog Am J Trop Med Hyg 1991 44513-517

179 Eberhard ML Ortega Y Dial S Schiller CA Sears W Greiner E OcularOnchocerca infections in western United States Vet Parasitol 200090333-338

180 Zarfoss MK Dubielzig RR Eberhard ML Schmidt KS Canine ocularonchocerciasis in the United States two new cases and a review of theliterature Vet Ophthalmol 2005 851-57

181 Pampiglione S Rivasi F Gustinelli A Dirofilarial human cases in the OldWorld attributed to Dirofilaria immitis a critical analysis Histopathology2009 54(2)192-204

182 Kim HW Kim JL Kho WG Hwang SY Yun IH Intraocular infestation withThelazia callipaeda Jpn J Ophthalmol 2010 54(4)370-372

183 Zakir R Zhong-Xia Z Chiodini P Canning CR Intraocular infestation withthe worm Thelazia callipaeda Br J Ophthalmol 1999 831194-1195

184 Ferri E Barbuto M Bain O Galimberti A Uni S Guerrero R Ferteacute H Bandi CMartin C Casiraghi M Integrated taxonomy traditional approach andDNA barcoding for the identification of filarioid worms and relatedparasites (Nematoda) Front Zool 2009 61

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186 Barlow J Gardner TA Araujo IS Avila-Pires TC Bonaldo AB Costa JEEsposito MC Ferreira LV Hawes J Hernandez MI Hoogmoed MS Leite RNLo-Man-Hung NF Malcolm JR Martins MB Mestre LA Miranda-Santos RNunes-Gutjahr AL Overal WL Parry L Peters SL Ribeiro-Junior MA daSilva MN da Silva Motta C Peres CA Quantifying the biodiversity value of

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doi1011861756-3305-4-41Cite this article as Otranto and Eberhard Zoonotic helminths affectingthe human eye Parasites amp Vectors 2011 441

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Abstract

Background

Biology and pathogenic effects

The most commonly reported HIE

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp

Echinococcus granulosus Echinococcus multilocularis and Echinococcus oligarthrus

Trematodes

New or reemerging zoonotic helminths infecting human eyes

Thelaziasis

Diagnosis and cure

Concerns ignorance and new avenues linked to HIE

Conclusions

Acknowledgements

Author details

Authors contributions

Competing interests

References

exists for populations in developing countries [7] Zoo-notic helminths infecting eyes (HIE) include those trans-mitted by vectors (ie vector borne zoonosis VbZ) byfood consumption (ie food-borne zoonosis FbZ) andthose at direct transmission from the environment (iewater soil etc) also known as environmentally-bornezoonosis (EbZ) A list of those helminths along withtheir route of transmission geographical distributionlocalization in the eye and definitive host species is pro-vided in Table 1 Unfortunately data on HIE are scantand mostly limited to case reports from different coun-tries Therefore a broad view of these infections on pub-lic health is lacking and ophthalmologists havedifficulties managing HIE caused diseases and providinga clear diagnosis and therapeutic option for them Thepresent article focuses on those zoonotic helminthsnaturally infecting animals but which occasionally aretransmitted to humans and affect the eye Recentadvances in the diagnosis and control of these parasiticinfestations are also discussed on the basis of their dis-tribution in different geographical areas and of interestin travel medicine

Biology and pathogenic effectsHelminths at the adult andor larval stages may infecthuman ocular tissues externally (ie eyelids conjunctivasacs subconjunctiva and lachrymal glands) or the ocularglobe (ie optical nerve intravitreous retina anterior andposterior chamber) Several parasitic helminths adapted atropism for animal eyes and related tissues when migrat-ing throughout the host body mainly during their imma-ture stages This is the case of ascarids and strongylidscausing ocular larva migrans filarioid species and larvaeof Trichinella as well of trematode and cestode parasitesNonetheless human ocular infestations by zoonotic hel-minths may also be caused by the parasitic adult stagesas in the case of thelaziids (eye worm infestation) andfilarioid species including those belonging to the generaDirofilaria and Onchocerca [8-10] Thus ocular localiza-tion of helminths is mainly caused by aberrant migrationin host tissues and only in one case (ie T callipaeda)by direct inoculation into the eyes What is equallyunclear is the route that most follow to gain entry intothe eye It is supposed that some migrate along and fol-low the optic nerve but others may enter the bloodstreamand be carried to the eye in that manner however it isnot known if these are the preferred or aberrant routesor even which is the most common route that helminthsfollow to reach the eye Once in the eye larvae likely findit to be a more protected site from host immuneresponses but it is not clear that a directed migrationinto the eye had occurredConsequently ocular alterations caused by zoonotic

helminths vary considerably causing mild to severe

clinical signs including lacrimation epiphora conjuncti-vitis keratitis corneal ulcers or retinal lesions resultingin vision loss (Table 2) For example in ascarid infec-tions visual impairment or blindness results from larvalmigration with destruction of the visual cortex In addi-tion larvae might develop inside the patientrsquos eye (egin baylisascariasis) progressively impairing the visionHowever blindness might be also an effect of theimmune reaction the parasites elicit in the host body orof a combined effect of both presence of the parasiteand antibody-mediated reaction This is the case ofascarids in which ocular signs are related to inflamma-tion because of the presence of larvae and a localimmune reaction to them in the retina [1112]

The most commonly reported HIENematodesThere are many nematode parasites that can be found inthe orbit or within the eye proper (Table 1) Althoughmost nematode infections of the eye are rare some aremore frequently reported than others In this sectionwe will discuss those zoonotic nematodes that are mostlikely to be encountered and reported by examiningtheir aetiology case reports and epidemiologyTrichuroidsTrichinellosis (Trichuroidea Trichinellidae) has a cos-mopolitan distribution but is generally less important asan infection of humans in the tropics than in more tem-perate regions of the world Once thought to be a singlespecies (Trichinella spiralis) there are now at least eightdistinct species recognized Each of these species has aslightly different geographical distribution and hostrange and only Trichinella zimbabwensis of crocodilesin Tanzania has not been reported from humans todate The most striking feature of this group of parasitesis their obligatory transmission by ingestion of infectedmeat containing larvae either in typical cysts or unen-capsulated in the case of several species [13] The clini-cal course is characterized by two phases the entericenteral phase when adult worms are present in theintestinal mucosa and the parenteral phase when thereleased larvae invade the host muscles [14] During theparenteral phase which follows the enteral a typicalsyndrome of fever myalgia periorbital edema and eosi-nophilia occur In addition to periorbital and facialedema conjunctivitis is also frequent The cause of theorbital and facial edema is not well known but probablyincludes some component of an allergic response Peri-orbital edema often appears early in the parenteralphase and typically begins to wane after several weeksLarvae also affect the macula and retina causing hemor-rhage and other damage as they migrate through andinto these ocular tissues [15] The diagnosis can be sug-gested from clinical history of ingesting raw or

OrderOrder(Family)

HELMINTHS

Strongylida

Rat 131137

Dog 11

Cat 11

roundworm)

(Onchocercidae)

Onchocercagutturosa

Cattle 8

Horse 169

Red deer 199

Horse 170

Bear 167

P (Loaina)scapiceps

(Thelaziidae)

wildcarnivores

Enoplida

CESTODA

Carnivores 89

faeces (EbZ)

TREMATODA

(Fluke)

ruminantshorse

eye mucosa (EbZ)

Eyebrows andeyelids

Miosis

Cysts Echinococcus

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

OrderOrder(Family)

HELMINTHS

Strongylida

Rat 131137

Dog 11

Cat 11

roundworm)

(Onchocercidae)

Onchocercagutturosa

Cattle 8

Horse 169

Red deer 199

Horse 170

Bear 167

P (Loaina)scapiceps

(Thelaziidae)

wildcarnivores

Enoplida

CESTODA

Carnivores 89

faeces (EbZ)

TREMATODA

(Fluke)

ruminantshorse

eye mucosa (EbZ)

Eyebrows andeyelids

Miosis

Cysts Echinococcus

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Enoplida

CESTODA

Carnivores 89

faeces (EbZ)

TREMATODA

(Fluke)

ruminantshorse

eye mucosa (EbZ)

Eyebrows andeyelids

Miosis

Cysts Echinococcus

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Eyebrows andeyelids

Miosis

Cysts Echinococcus

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Angiostrongylusspp

on conjunctiva

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Additional material

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Abstract

Background

Nematodes

Trichuroids

Ascarids

Spirurids

Filarioids

Cestodes

Spirometra spp


Trematodes


Thelaziasis

Diagnosis and cure


Conclusions

Acknowledgements

Author details


Competing interests

References

Documents

Zoonotic helminths affecting the human eye - Parasites & Vectors