Perinatal Infections Engl

8/9/2019 Perinatal Infections Engl

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Congenital andCongenital and

PerinatalPerinatalInfectionsInfections

Department of Faculty andDepartment of Faculty and

Hospital PaediatricsHospital Paediatrics


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DenitionDenition

• Congenital (intrauterine) infection

Congenital (intrauterine) infection isisan infection acquired in utero thatan infection acquired in utero thatcausescauses fetal lossfetal loss or can result inor can result in

intrauterine growth restriction,intrauterine growth restriction,congenital anomalies, prematurity, orcongenital anomalies, prematurity, or postnatal infection postnatal infection any of which isany of which isobvious at birthobvious at birth

• Perinatal infectionPerinatal infection refers to therefers to theinfectious process which originatesinfectious process which originatesfrom intrapartum or postpartum periodfrom intrapartum or postpartum period


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DenitionDenition

• Vertical infectionVertical infection – any infection of a newborn – any infection of a newborn

acquired from a mother acquired from a mother • Congenital infections may be broadly summarizedCongenital infections may be broadly summarized

by acronymby acronym “TORCH” “TORCH” ! – !o"oplasmosis# $ – ! – !o"oplasmosis# $ –

$thers# % – %ubella# C – Cytomegalovirus ($thers# % – %ubella# C – Cytomegalovirus (CMV CMV )#)#

& – &erpes simple" viruses (& – &erpes simple" viruses (HSV HSV ) ' and '') ' and ''

• !he term !$%C& is a misnomer because!he term !$%C& is a misnomer because – the others category continues to e"pand*the others category continues to e"pand*

– several infections are rarely truly congenital + they areseveral infections are rarely truly congenital + they areusually perinatally acquired with clinical onset within theusually perinatally acquired with clinical onset within the

first month of age,first month of age,

– screening tests only assesses maternal e"posure# butscreening tests only assesses maternal e"posure# but

not necessarily antenatal or perinatal infection in thenot necessarily antenatal or perinatal infection in the

fetusfetus


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IncidenceIncidence• -ppro"imately ./ of newborn infants -ppro"imately ./ of newborn infants

e"cretee"crete CMVCMV• 0p to .1 / of infants are infected with0p to .1 / of infants are infected with

Chlamydia trachomatisChlamydia trachomatis

– about one third of these infants developabout one third of these infants developcon2unctivitis andcon2unctivitis and

– one si"th develop pneumoniaone si"th develop pneumonia

• . to 3 infants per .444 live births develop. to 3 infants per .444 live births develop

bacterial sepsisbacterial sepsis• %egional incidences of%egional incidences of congenital rubellacongenital rubella

and syphilisand syphilis very much depend on thevery much depend on the

prevention programsprevention programs


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IncidenceIncidence

• 'n utero a perinatal infection with'n utero a perinatal infection with HSV HSV ##Toxoplasma gondii Toxoplasma gondii andand VZV VZV occurs inoccurs in

about . infant per .444 live births (about . infant per .444 live births (1 ‰1 ‰)#)#

but the sequelae of infection are usuallybut the sequelae of infection are usuallyseveresevere

• !he incidence of perinatally &'V+infection!he incidence of perinatally &'V+infection

is still uncertain, 'n the absence of anyis still uncertain, 'n the absence of anyprevention measures about 51/ ofprevention measures about 51/ of

infants born to infected mothers developinfants born to infected mothers develop

this diseasethis disease


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ConsequencesConsequences

• 'nfection acquired in utero may result'nfection acquired in utero may resultin6in6 – resorption of the embryo#resorption of the embryo#

– abortion#abortion# – stillbirth#stillbirth#

– malformation#malformation#

– intrauterine growth retardationintrauterine growth retardation – prematurity andprematurity and

– the untoward sequelae of chronic postnatalthe untoward sequelae of chronic postnatalinfectioninfection


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• 'nfection acquired during the birth'nfection acquired during the birthprocess or soon after birth may result inprocess or soon after birth may result in

– severe systemic disease that leads tosevere systemic disease that leads to

death ordeath or

– persistent postnatal infectionpersistent postnatal infection

•7oth in utero infection and infection7oth in utero infection and infectionacquired during the birth process mayacquired during the birth process may

lead to late+onset diseaselead to late+onset disease


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• !he infection may be inapparent at birth!he infection may be inapparent at birthbut may present with signs of diseasebut may present with signs of disease

wee8s# months or years later# aswee8s# months or years later# as

e"emplified by the chorioretinitis ofe"emplified by the chorioretinitis of

T.T.

gonii,gonii, the hearing loss of C9V or rubellathe hearing loss of C9V or rubella

virus and the immunologic defects thatvirus and the immunologic defects that

result from &'Vresult from &'V

• !he immediate as well as the long+term!he immediate as well as the long+term

effects of these infections are a ma2oreffects of these infections are a ma2or

problem throughout the worldproblem throughout the world

R t F


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Re at ve Frequency oe a ve requency oCongenital and PerinatalCongenital and PerinatalInfections According toInfections According to

PathogenPathogenPathogenPathogen CongenitalCongenital PerinatalPerinatal

ToxoplasmaToxoplasma :::::: ::

TreponemaTreponema :::::: ::VVVV :::: ::::

H!V Type !H!V Type ! :: ::::::

"ubella #irus"ubella #irus :::::: ::

CMVCMV :::: ::::

H$VH$V

:: ::::::


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Pathogenesis of haematogenousPathogenesis of haematogenous

transplacental infectionstransplacental infections


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Pathogenetic mechanismsPathogenetic mechanisms

• 7ecause of their relatively low virulence# the7ecause of their relatively low virulence# the

organisms involved seldom lead to fetal deathorganisms involved seldom lead to fetal deathbeyond the earliest stages of embryogenesisbeyond the earliest stages of embryogenesis

• ;ince the fetus is essentially a graft of foreign;ince the fetus is essentially a graft of foreign

tissue in the uterus# the placenta constitutes atissue in the uterus# the placenta constitutes aprotective immunologic barrier that shields theprotective immunologic barrier that shields thefetus from the mother


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Pathogenetic mechanismsPathogenetic mechanisms

• =arly in pregnancy the most comple" events=arly in pregnancy the most comple" eventsin embryogenesis ta8e place# ma8ing sensoryin embryogenesis ta8e place# ma8ing sensoryorgans such as the eyes and ears vulnerable,organs such as the eyes and ears vulnerable,

• !he immature fetus lac8s the immunologic!he immature fetus lac8s the immunologic

mechanisms necessary to completelymechanisms necessary to completelyeliminate an infecting organismeliminate an infecting organism

• !herefore# a state of immunologic tolerance is!herefore# a state of immunologic tolerance is

often established# which results in persistenceoften established# which results in persistenceof organisms that ordinarily would beof organisms that ordinarily would beeliminated by a normal child or adulteliminated by a normal child or adult


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The degree of severity isThe degree of severity is

dependent ondependent on ......

• >estational age of the fetus when>estational age of the fetus when

infectedinfected

• Virulence of the organism#Virulence of the organism#

• ?amage to the placenta#?amage to the placenta#

• ;everity of maternal disease;everity of maternal disease• Primary maternal infection (thePrimary maternal infection (the

highest ris8 of fetal in2ury)highest ris8 of fetal in2ury)


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Clues to the diagnosis ofClues to the diagnosis ofpossile infection!possile infection!

• Congenital growth retardationCongenital growth retardationsymmetrical typesymmetrical type

• 9icrocephaly9icrocephaly• @ABDEFBGAHEIAJGKL@ABDEFBGAHEIAJGKL

MJABDNDM OEDLHNQLMJABDNDM OEDLHNQL• PetechiaeM purpura M bluePetechiaeM purpura M blue

berry muffinsberry muffins• Cranial calcificates# NLGAHKCranial calcificates# NLGAHK

H RAHDJAHEJRIK SE BKT UFH RAHDJAHEJRIK SE BKT UFGWDRXYEEJEGWDRXYEEJETEFGKTOAHHL IEXYTEFGKTOAHHL IEXY

• 7rain edema# IZLXE7rain edema# IZLXEJKBEDEHKL# FTEIN# AHQA[GKDJKBEDEHKL# FTEIN# AHQA[GKD

• &ydrops foetalis&ydrops foetalis

• Congenital heart diseaseCongenital heart disease• \DRYDN# IKYRE[DGWIKL#\DRYDN# IKYRE[DGWIKL#

]ERKERADNHKD]ERKERADNHKD• ^YXAIDEXHKMAXNYGLRHK^YXAIDEXHKMAXNYGLRHK

NFNBHHL H _YKRKNFNBHHL H _YKRK• `ROAHHL _YKRN K FGNXEN]`ROAHHL _YKRN K FGNXEN]

ESEGEHEY (FEBKHHL)ESEGEHEY (FEBKHHL)• HEIGK YKFDEY H HEIGK YKFDEY H

RAHDJAHEJRIKRAHDJAHEJRIK• KI[TAHEBDKLKI[TAHEBDKL• @G]ED@G]ED• HAIKL# AEXNHE[KGKL# HAIKL# AEXNHE[KGKL#

DREISEQNDEBAHKLDREISEQNDEBAHKL


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Congenital syphilisCongenital syphilis

• ;yphilis is a se"ually transmitted disease;yphilis is a se"ually transmitted disease

caused bycaused by Treponema pallium.Treponema pallium.

• %arly congenital syphilis%arly congenital syphilis is when clinicalis when clinical

manifestations occur beforemanifestations occur before

5 years of age5 years of age

• &ate congenital syphilis&ate congenital syphilis is whenis when

manifestations occur at 5manifestations occur at 5

years of ageyears of age


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• 0ntreated maternal syphilis can result in0ntreated maternal syphilis can result in

– stillbirthM perinatal deathM premature deliverystillbirthM perinatal deathM premature delivery

– congenital infectioncongenital infection

– about half of survivors have long+termabout half of survivors have long+term

neurological sequelaeneurological sequelae

• 0ntreated infection in the first and second0ntreated infection in the first and second

trimesters often leads to significant fetaltrimesters often leads to significant fetal

morbiditymorbidity

• ith third+trimester infection many infantsith third+trimester infection many infants

are asymptomaticare asymptomatic


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• 'nfection can also be acquired via contact of'nfection can also be acquired via contact ofinfectious lesions during passage through theinfectious lesions during passage through thebirth canalbirth canal

• Virtually all infants born to untreated womenVirtually all infants born to untreated women

with primary and secondary syphilis havewith primary and secondary syphilis havecongenital infectioncongenital infection

• 14/ are clinically symptomatic14/ are clinically symptomatic

• !he infection rate is only 4/ with early latent!he infection rate is only 4/ with early latentdisease and +./ with late latent stages,disease and +./ with late latent stages,

• !he mortality rate may be as high as 1/ in!he mortality rate may be as high as 1/ ininfected infantsinfected infants


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Clinical presentationClinical presentation

• !he most common findings in the!he most common findings in theneonatal period include hepatospleno+neonatal period include hepatospleno+megaly# 2aundice# and osteochondritismegaly# 2aundice# and osteochondritis

• $ther signs include generalized lymph+$ther signs include generalized lymph+adenopathy# pneumonitis# myocarditis#adenopathy# pneumonitis# myocarditis#nephrosis# pseudoparalysis (atypicalnephrosis# pseudoparalysis (atypical=rb


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• ate congenital syphilis manifests byate congenital syphilis manifests by&utchinson


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DiagnosisDiagnosis

•&aboratory studies&aboratory studies ++ 'onspecific'onspecificreagin antibody testsreagin antibody tests

– Venereal ?isease %esearch aboratoryVenereal ?isease %esearch aboratory(V?%) slide test(V?%) slide test

• - V?% titer at least 5 dilutions (+fold) - V?% titer at least 5 dilutions (+fold)higher in the infant than in the motherhigher in the infant than in the mothersignifies probable active infectionsignifies probable active infection

• !iters should be monitored and repeated,!iters should be monitored and repeated,• 'f liters decrease in the first 3 months of life#'f liters decrease in the first 3 months of life#

the infant is probably not infectedthe infant is probably not infected


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DiagnosisDiagnosis

• &aboratory studies&aboratory studies ++ 'onspecific'onspecificreagin antibody testsreagin antibody tests

– %apid plasma reagin test%apid plasma reagin test

• !his is an !- test that detects antibodies to!his is an !- test that detects antibodies tocardiolipin and is a screening test for syphiliscardiolipin and is a screening test for syphilis

• 't should not be used on spinal fluid't should not be used on spinal fluid

• - normal test result is negative# and any - normal test result is negative# and any

positive test should be followed up with apositive test should be followed up with aspecific treponemal testspecific treponemal test

• !iters can also be reported as for the V?%!iters can also be reported as for the V?%testtest


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DiagnosisDiagnosis

•&aboratory studies&aboratory studies ++ $pecific$pecifictreponemal teststreponemal tests ((FT()(*$ testFT()(*$ test## Micro)Micro)hemagglutination test forhemagglutination test for T. pallidumT. pallidum +MHTP(,+MHTP(,

– ;pecific ;!- tests verify a diagnosis of current;pecific ;!- tests verify a diagnosis of current

or past infectionor past infection – !hese tests should be performed if !- test!hese tests should be performed if !- test

results are positiveresults are positive

– !hese antibody tests do not correlate with!hese antibody tests do not correlate withdisease activity and are not quantifieddisease activity and are not quantified

– !hey are useful for diagnosing a first episode of!hey are useful for diagnosing a first episode ofsyphilis and for distinguishing a false+positivesyphilis and for distinguishing a false+positiveresult of !- testsresult of !- tests


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DiagnosisDiagnosis

• ?irect antigen tests for?irect antigen tests for T. pallium,T. pallium, includingincludingan =';- that uses monoclonal antibody toan =';- that uses monoclonal antibody tothe organism


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DiagnosisDiagnosis

•umbar puncture, C; disease may beumbar puncture, C; disease may bedetected by positive serologic tests# dar8+detected by positive serologic tests# dar8+field e"amination positive for spirochetes#field e"amination positive for spirochetes#elevated monocyte count# or elevated spinalelevated monocyte count# or elevated spinalfluid protein levelsfluid protein levels

•!he V?% test is the only one approved for!he V?% test is the only one approved foruse on C;juse on C;j

•PC%s on C;j may prove usefulPC%s on C;j may prove useful

•-)ray studies of the long bones-)ray studies of the long bones may showmay showsclerotic changes of the metaphysis andsclerotic changes of the metaphysis anddiaphysis# with widespread osteitis anddiaphysis# with widespread osteitis andperiostitisperiostitis


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"anagement"anagement

•;ymptomatic infant should be treated;ymptomatic infant should be treated• !he infant should be treated if6!he infant should be treated if6

– maternal treatment was inadequate# un8nown#maternal treatment was inadequate# un8nown#

or given during the last wee8s of pregnancyor given during the last wee8s of pregnancy

oror – if a drug other than penicillin (eg#if a drug other than penicillin (eg#

erythromycin) was usederythromycin) was used

• 'nfants with positive V?% tests# even if this'nfants with positive V?% tests# even if thisis only an indication of maternal transfer ofis only an indication of maternal transfer of

'g># should be treated if adequate follow+up'g># should be treated if adequate follow+up

cannot be obtainedcannot be obtained


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TreatmentTreatment

• -queous crystalline penicillin > + .44#444+ -queous crystalline penicillin > + .44#444+.14#444 unitsM8gM5 h 'V# or alternately.14#444 unitsM8gM5 h 'V# or alternately

14#444 unitsM8gMday of procaine penicillin '9*14#444 unitsM8gMday of procaine penicillin '9*

• !he duration of therapy should be .4+.!he duration of therapy should be .4+.

days in both instancesdays in both instances

• -symptomatic infants born to mothers -symptomatic infants born to mothers

whose treatment for syphilis may have beenwhose treatment for syphilis may have been

inadequate should be fully evaluated#inadequate should be fully evaluated#including C;j e"aminationincluding C;j e"amination


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TreatmentTreatment

•;ome e"perts would treat them with;ome e"perts would treat them withaqueous crystalline or procaine penicillin >aqueous crystalline or procaine penicillin >

• &owever# if C;j is normal# as well as&owever# if C;j is normal# as well as

normal k+ray films of long bones# plateletnormal k+ray films of long bones# platelet

count# and liver functions# many e"pertscount# and liver functions# many e"pertswould treat with a single '9 dose of 14#444would treat with a single '9 dose of 14#444

unitsM8g of penicillin > benzathineunitsM8g of penicillin > benzathine

• &owever# if the mother is infected with &'V+&owever# if the mother is infected with &'V+.# a complete .4+ to .+day course of.# a complete .4+ to .+day course of

therapy is recommendedtherapy is recommended


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PreventionPrevention

• ;creening at the initial antenatal visit is;creening at the initial antenatal visit ispart of routine obstetric care since womenpart of routine obstetric care since women

may have asymptomatic latent diseasemay have asymptomatic latent disease

(53 w8s# before birth)(53 w8s# before birth)• Prevention of vertical transmissionPrevention of vertical transmission

• -ny newborn should not be discharged -ny newborn should not be discharged

without the result of motherZs investigationwithout the result of motherZs investigation


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To#oplasmosisTo#oplasmosis

• Congenital !o"oplasmosis occurs inCongenital !o"oplasmosis occurs inbetween 4#5 to .4 per thousand pregnanciesbetween 4#5 to .4 per thousand pregnancies

• !, gondii is a parasitic organism, !he!, gondii is a parasitic organism, !he

domestic cat is the primary host, 'nfectiondomestic cat is the primary host, 'nfectioncan be contracted bycan be contracted by – ingesting oocytes present in faecal material of infectedingesting oocytes present in faecal material of infected

hostshosts

– eating pseudocysts present in undercoo8ed meateating pseudocysts present in undercoo8ed meat

• 9ost women have no symptoms, -lthough9ost women have no symptoms, -lthough

.1/ of women report acute flu+li8e illness.1/ of women report acute flu+li8e illness

with lymphadenopathywith lymphadenopathy


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To#oplasmosisTo#oplasmosis

• %is8 of fetal infection is%is8 of fetal infection is lo.estlo.est in earlyin earlypregnancy but most fetuses infected early havepregnancy but most fetuses infected early have

severe consequencessevere consequences

%is8 of fetal%is8 of fetalinfectioninfection

;evere;evereconsequences ofconsequences of

infectioninfection

1st trimester1st trimester 1/01/0 /0/0

2rd trimester 2rd trimester 3/03/0 410410


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Clinical featuresClinical features

• 'nfants congenitally infected with'nfants congenitally infected with

!o"oplasmosis can be!o"oplasmosis can be

– completely asymptomaticcompletely asymptomatic – unaffected at birth and manifestunaffected at birth and manifest

problems laterproblems later

– severely affected in+utero and at birthseverely affected in+utero and at birth

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Clinical featuresClinical features

• 'nfection usually affects the neurological'nfection usually affects the neurological

and haemopoietic systems, !he classicaland haemopoietic systems, !he classicaltetrad described by ;abin in .5 includestetrad described by ;abin in .5 includes – hydrocephalusMmicrocephalyhydrocephalusMmicrocephaly – chorioretinitischorioretinitis

– convulsionsconvulsions – other evidence of C; involvement (includingother evidence of C; involvement (including

calcification)calcification)

• 5 clinical forms infection of the C; or the5 clinical forms infection of the C; or theeyes# or infection of the C; and eyes witheyes# or infection of the C; and eyes withdisseminated infectiondisseminated infection

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Clinical featuresClinical features• &aematological&aematological

– hydrops due tohydrops due toanaemiaanaemia

– rash due torash due tothrombocytopeniathrombocytopenia+purpura+purpura

– blueberry muffinblueberry muffinappearance (seen inappearance (seen in51/ of generalised51/ of generalisedinfection)infection)

– lymphadenopathylymphadenopathy

– hepatosplenomegalyhepatosplenomegaly • eurologicaleurological

– convulsionsconvulsions – hydrocephalus withhydrocephalus with

bulging fontanellebulging fontanelle

– microcephalymicrocephaly

– chorioretinitis can bechorioretinitis can bepresent early orpresent early ordevelop laterdevelop later

• >eneralised features>eneralised features

includeinclude – lethargy and malaiselethargy and malaise – poor feedingpoor feeding – vomitingvomiting – diarrhoeadiarrhoea

– temperature instabilitytemperature instability – 2aundice 2aundice


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Diagnosis $Diagnosis $ Serologic testsSerologic tests• !o"oplasma+specific 'g9 antibodies can be measured by!o"oplasma+specific 'g9 antibodies can be measured by

indirect fluorescent antibody ('j-) test# =';-# or 'g9indirect fluorescent antibody ('j-) test# =';-# or 'g9immunosorbent agglutination assay ('g9+';->-)immunosorbent agglutination assay ('g9+';->-)

• 0sually become positive within .+5 wee8s of infection* and0sually become positive within .+5 wee8s of infection* andpersist for months or years# especially when very sensitivepersist for months or years# especially when very sensitiveassays such as double+sandwich 'g9 enzymeassays such as double+sandwich 'g9 enzymeimmunoassay (?;+'g9 ='-) or 'g9+';->- are used,immunoassay (?;+'g9 ='-) or 'g9+';->- are used,

• 'f 'g9 titers are high and accompanied by high specific 'g>'f 'g9 titers are high and accompanied by high specific 'g>titers of .1.5# as measured by 'j- or ;abin+jeldman dyetiters of .1.5# as measured by 'j- or ;abin+jeldman dyetest# this suggests acute infectiontest# this suggests acute infection

• 'g- antibodies are found in 1/ of patients with acute'g- antibodies are found in 1/ of patients with acuteinfectionsinfections

• !o"oplasma+specific 'g= antibodies are found!o"oplasma+specific 'g= antibodies are foundin almost all women who seroconvert during pregnancyin almost all women who seroconvert during pregnancy


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DiagnosisDiagnosis• Perinatal diagnosisPerinatal diagnosis can be made by usingcan be made by using

polymerase chain reaction (PC%) amplification ofpolymerase chain reaction (PC%) amplification ofthe 7 gene ofthe 7 gene of T. goniiT. gonii in a sample of amnioticin a sample of amniotic

fluid, ?;+'g9 ='- and ';->- detectfluid, ?;+'g9 ='- and ';->- detect To!oplasmaTo!oplasma

'g9 in 1+34/ of infants with congenital'g9 in 1+34/ of infants with congenital

infectioninfection

• C$F examinationC$F examination should be performed inshould be performed in

suspected cases, !he most characteristicsuspected cases, !he most characteristic

abnormalities are "anthochromia# mononuclearabnormalities are "anthochromia# mononuclearpleocytosis# and a very high protein level,pleocytosis# and a very high protein level,

• !ests for C;j 'g9 to to"oplasmosis may also!ests for C;j 'g9 to to"oplasmosis may also

be performedbe performed


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DiagnosisDiagnosis• - cranial ultrasonogram or C! scan of the head - cranial ultrasonogram or C! scan of the head

may demonstrate characteristic intracranialmay demonstrate characteristic intracranialcalcifications (spec8led throughout the C;#calcifications (spec8led throughout the C;#

including the meninges)including the meninges)

• ong+bone films may show abnormalities#ong+bone films may show abnormalities#specifically# metaphyseal lucency and irregularityspecifically# metaphyseal lucency and irregularity

of the line of calcification at the epiphyseal platesof the line of calcification at the epiphyseal plates

without periosteal reaction,without periosteal reaction,

• $ther studies, $phthalmologic e"amination$ther studies, $phthalmologic e"aminationcharacteristically shows chorioretinitis, $thercharacteristically shows chorioretinitis, $ther

ocular features are often present at some stagesocular features are often present at some stages


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• 'n cases of an'n cases of an infected child withinfected child withsymptomssymptoms# spiramycin .44 mgM8gMday# spiramycin .44 mgM8gMdayfor 5 wee8s# followed by alternating .for 5 wee8s# followed by alternating .

month of pyrimethamine . mgM8gMdaymonth of pyrimethamine . mgM8gMdayand sulfadiazine .44 mgM8gMday# andand sulfadiazine .44 mgM8gMday# and. month of spiramycin .44 mgM8gMday. month of spiramycin .44 mgM8gMdayis recommended,is recommended,

• !his regimen should continue for .!his regimen should continue for .year year


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• -symptomatic neonates with sero+ -symptomatic neonates with sero+logically+proven infection should alsologically+proven infection should also

be treated for the first 5 wee8s withbe treated for the first 5 wee8s with

spiramycin and then by sulfado"ine+spiramycin and then by sulfado"ine+pyrimethamine . : 54 mgM8gMwee8 forpyrimethamine . : 54 mgM8gMwee8 for

the first year of lifethe first year of life

• 'n all cases close clinical observation'n all cases close clinical observation

is suggestedis suggested


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PreventionPrevention

• 9any =uropean countries have instituted9any =uropean countries have institutedcompulsory testing for anti+!,compulsory testing for anti+!, goniigoniiantibody during pregnancy# and others areantibody during pregnancy# and others arepreparing the legislature for such tests,preparing the legislature for such tests,

• -voidance of contact with cat feces and -voidance of contact with cat feces andconsumption of only coo8ed or pic8ledconsumption of only coo8ed or pic8ledmeat# and careful handling of raw meat andmeat# and careful handling of raw meat and

meat products should be part of healthmeat products should be part of healtheducation preceding pregnancyeducation preceding pregnancy


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CytomegalovirusCytomegalovirus infectioninfection

C"% is a D&A virus and aC"% is a D&A virus and a

memer of the herpes virusmemer of the herpes virus

familyfamily


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C"% infectionC"% infection


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'pidemiology'pidemiology

• C9V is a ubiquitous virus that may beC9V is a ubiquitous virus that may betransmitted in secretions# including saliva#transmitted in secretions# including saliva#tears# semen# urine# cervical secretions#tears# semen# urine# cervical secretions#blood (white blood cells)# and breast mil8blood (white blood cells)# and breast mil8

• 7oth primary and recurrent maternal C9V7oth primary and recurrent maternal C9Vcan lead to transmission of virus to thecan lead to transmission of virus to thefetusfetus

• hen primary maternal infection occurshen primary maternal infection occursduring pregnancy# virus is transmitted toduring pregnancy# virus is transmitted tothe fetus in about 1/ of casesthe fetus in about 1/ of cases


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• !he ris8 does not appear to vary!he ris8 does not appear to varysignificantly with gestational age at time ofsignificantly with gestational age at time ofmaternal infectionmaternal infection

• ?uring recurrent infection# transmission?uring recurrent infection# transmissionrate is only 4#5+.#3/rate is only 4#5+.#3/

• 9ore than 4/ of infants born with C9V9ore than 4/ of infants born with C9Vhave subclinical infectionhave subclinical infection

• ;ymptomatic infants are usually born to;ymptomatic infants are usually born towomen with primary infection,women with primary infection,


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• $ubclinical infection$ubclinical infection is .4 timesis .4 timesmore common than clinical illnessmore common than clinical illness

•&o. birth .eight5&o. birth .eight5

9aternal C9V9aternal C9V

infection is associated with low birthinfection is associated with low birthweight and small for gestational ageweight and small for gestational ageinfants even when the infant is notinfants even when the infant is not

infectedinfected

Classic C"% inclusionClassic C"% inclusion


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Classic C"% inclusionClassic C"% inclusion

diseasedisease • 'ntrauterine growth retardation# hepatosplenomegaly'ntrauterine growth retardation# hepatosplenomegaly

with 2aundice# abnormal liver function tests# thrombo+with 2aundice# abnormal liver function tests# thrombo+cytopenia with or without purpura# and severe C;cytopenia with or without purpura# and severe C;disease (C; and sensory impairments are seen indisease (C; and sensory impairments are seen in14+4/ of symptomatic newborns)# including14+4/ of symptomatic newborns)# including

microcephaly# intracerebral calcifications# chorioreti+microcephaly# intracerebral calcifications# chorioreti+nitis# and progressive sensorineural hearing loss (.4+nitis# and progressive sensorineural hearing loss (.4+54/ of cases)54/ of cases)

• $ther symptoms include hemolytic anemia and$ther symptoms include hemolytic anemia and

pneumonitispneumonitis• 7y 5 years of age# 1+.1/ of infants who are7y 5 years of age# 1+.1/ of infants who areasymptomatic at birth may e"perience seriousasymptomatic at birth may e"perience serioussequelae# such as hearing loss or ocular abnormalitiessequelae# such as hearing loss or ocular abnormalities

( t l( t l


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(ate sequelae(ate sequelae

• ith subclinical infection# late sequelae such asith subclinical infection# late sequelae such as

mental retardation# learning disability# andmental retardation# learning disability# andsensorineural hearing loss have been attributed tosensorineural hearing loss have been attributed toC9VC9V

• ;tudies have now shown for children with;tudies have now shown for children with

asymptomatic congenital C9V infection aasymptomatic congenital C9V infection aprevalence of sensorineural hearing loss of +.1/prevalence of sensorineural hearing loss of +.1/

• -ppro"imately one half had bilateral loss# and 14/ -ppro"imately one half had bilateral loss# and 14/of affected children had progressive deteriorationof affected children had progressive deterioration

• %epeated auditory evaluation during the first %epeated auditory evaluation during the first years is strongly recommendedyears is strongly recommended


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DiagnosisDiagnosis

• Culture for demonstration of the #irus5Culture for demonstration of the #irus5The 6gold standard6The 6gold standard6 for C9Vfor C9Vdiagnosis is urine or saliva culturediagnosis is urine or saliva culture

• 9ost urine specimens from infants with9ost urine specimens from infants withcongenital C9V are positive within 3+5 hcongenital C9V are positive within 3+5 h

• ;hell vial tissue culture technique –;hell vial tissue culture technique –detection of C9V+induced antigensdetection of C9V+induced antigens

by monoclonal antibodies# allowing forby monoclonal antibodies# allowing foridentification of the virus withinidentification of the virus within.3 h,.3 h,


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DiagnosisDiagnosis

• PC% may also be used* however# it doesPC% may also be used* however# it doesnot appear to offer any advantage overnot appear to offer any advantage overculture+based methodsculture+based methods

• $erologic tests$erologic tests based on detection of 'g9based on detection of 'g9

should not be used to diagnose congenitalshould not be used to diagnose congenitalC9V because they are less sensitive andC9V because they are less sensitive andmore sub2ect to false+positive results thanmore sub2ect to false+positive results than

culture or PC%culture or PC%• "adiological studies5"adiological studies5 ;8ull films or C!;8ull films or C!scans of the head may demonstratescans of the head may demonstratecharacteristic intracranial calcificationscharacteristic intracranial calcifications


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Postdiagnosis evaluationPostdiagnosis evaluation

• C! scan of the brain# ophthalmologicC! scan of the brain# ophthalmologice"amination# brainstem evo8ed responsese"amination# brainstem evo8ed responses

(7=%) hearing evaluation# complete blood(7=%) hearing evaluation# complete blood

cell count# platelet count# liver enzymecell count# platelet count# liver enzymelevels# bilirubin level# C;j for celllevels# bilirubin level# C;j for cell

count# protein and glucose# C;j C9Vcount# protein and glucose# C;j C9V

culture# or test for C9V ?-culture# or test for C9V ?-


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Treatment and preventionTreatment and prevention

• 0nder life+threatening circumstances0nder life+threatening circumstances >anciclovir >anciclovir – mgM8gMdose every .5 hrs – mgM8gMdose every .5 hrs w8s w8s

• ;pecific intravenous immunoglobulin;pecific intravenous immunoglobulin• Pre#entionPre#ention

– - phase '' clinical trial of a recombinant - phase '' clinical trial of a recombinantsubunit vaccine in young womensubunit vaccine in young women

is underwayis underway – ;tandard precautions# especially good hand;tandard precautions# especially good hand

washing after diaper changes# is particularlywashing after diaper changes# is particularlyimportant for pregnant personnelimportant for pregnant personnel


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Perinatal )erpesPerinatal )erpes

InfectionInfection


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)*%$II infection)*%$II infection


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• !wo serologic subtypes can be distingui+!wo serologic subtypes can be distingui+shed by antigenic and serologic testsshed by antigenic and serologic tests

&;V+. (orolabial) and &;V+5 (genital)&;V+. (orolabial) and &;V+5 (genital)

•!hree quarters of neonatal herpes!hree quarters of neonatal herpesinfections are secondary to &;V+5*infections are secondary to &;V+5*

• &;V+.# however# is the cause of +14/ of&;V+.# however# is the cause of +14/ of

primary genital herpes infections,primary genital herpes infections,

• &;V infection of the neonate can be&;V infection of the neonate can be

acquired at one of three times intrauterine#acquired at one of three times intrauterine#

intrapartum# or postnatalintrapartum# or postnatal


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• 9ost infections (34/) are acquired in the9ost infections (34/) are acquired in the

intrapartum period as ascending infectionsintrapartum period as ascending infections

with ruptured membranes (+ h iswith ruptured membranes (+ h is

considered a critical period for this toconsidered a critical period for this to

occur) or by delivery through an infectedoccur) or by delivery through an infectedcervi" or vaginacervi" or vagina

• $nly 51+/ of cases have signs or$nly 51+/ of cases have signs or

symptoms of genital herpes at the time ofsymptoms of genital herpes at the time oflabor and delivery despite having activelabor and delivery despite having active

infectioninfection


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• !he primary infection may be active for!he primary infection may be active foras long as 5 months,as long as 5 months,

• 9any neonatal infections occur because of9any neonatal infections occur because of

asymptomatic cervical shedding of virus#asymptomatic cervical shedding of virus#usually after a primary episode of &;Vusually after a primary episode of &;V

infectioninfection

• !he usual portals of entry for the virus are!he usual portals of entry for the virus are

the s8in# eyes# mouth# and respiratory tractthe s8in# eyes# mouth# and respiratory tract

id i l


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• 'nfection in a newborn'nfection in a newborn –// because of primary maternalbecause of primary maternal

infectioninfection

–/ +/ + because of recurrent infectionbecause of recurrent infection

((virus load#virus load# longer viral e"cretion#longer viral e"cretion#

lower antibody level)lower antibody level)

Cli i l i


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• &ocali7ed infections&ocali7ed infections involving the s8in#involving the s8in#

eyes# or oral cavity usually manifest at .4+eyes# or oral cavity usually manifest at .4+

.. days of age and account for 4/ of.. days of age and account for 4/ of

neonatal herpesneonatal herpes

• 'nfants with'nfants with disseminated H$Vdisseminated H$V infectioninfectionaccount for 51/ of all neonatal herpesaccount for 51/ of all neonatal herpes

patients, 0sually# they present at +.. dayspatients, 0sually# they present at +.. days

of ageof age• 'nfants with'nfants with encephalitisencephalitis usually present atusually present at

.1+. days of age (4+4/ will have no.1+. days of age (4+4/ will have no

herpetic s8in lesions)herpetic s8in lesions)

Di i d diDi i t d di


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Disseminated diseaseDisseminated disease• ;igns and symptoms of localized disease as well;igns and symptoms of localized disease as well

as anore"ia# vomiting# lethargy# fever# 2aundiceas anore"ia# vomiting# lethargy# fever# 2aundice(with abnormal j!s)# rash or purpura# apnea#(with abnormal j!s)# rash or purpura# apnea#respiratory distress# bleeding# and shoc8respiratory distress# bleeding# and shoc8

• Presentation with bleeding and cardiovascularPresentation with bleeding and cardiovascular

collapse may be sudden and rapidly fatalcollapse may be sudden and rapidly fatal• C; involvement is present in two thirds of theseC; involvement is present in two thirds of these

patientspatients

•ithout antiviral therapy# 34/ or more die# andithout antiviral therapy# 34/ or more die# andmost go on to have serious neurologic sequelaemost go on to have serious neurologic sequelae

• !he mortality rate remains as high as 11/# even!he mortality rate remains as high as 11/# evenwith appropriate treatment* however# 4+11/ ofwith appropriate treatment* however# 4+11/ of

survivors suffer longterm neurologic impairmentsurvivors suffer longterm neurologic impairment

DiagnosisDiagnosis


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DiagnosisDiagnosis

• Viral cultures5Viral cultures5 !he virus grows readily# with!he virus grows readily# with

preliminary results available in 5+5 h,preliminary results available in 5+5 h,Cultures are usually obtained from con2unctiva#Cultures are usually obtained from con2unctiva#throat# feces# urine# nasal pharyn"# and C;jthroat# feces# urine# nasal pharyn"# and C;j

• !mmunologic assays!mmunologic assays to detect &;V antigen into detect &;V antigen inlesion scrapings# usually using monoclonal anti+lesion scrapings# usually using monoclonal anti+&;V antibodies in either an =';- or&;V antibodies in either an =';- orfluorescent microscopy assay# are very specificfluorescent microscopy assay# are very specific

and 34+4/ sensitiveand 34+4/ sensitive• $erologic tests$erologic tests are not helpful in the diagnosisare not helpful in the diagnosisof neonatal infection# until a test for &;V 'g9 isof neonatal infection# until a test for &;V 'g9 isreadily availablereadily available

DiagnosisDiagnosis


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DiagnosisDiagnosis

• PC% to detect &;V ?- is a very sensitivePC% to detect &;V ?- is a very sensitivemethod# as high as .44/ in diagnosingmethod# as high as .44/ in diagnosing&;V within C;j, Contamination# however#&;V within C;j, Contamination# however#can frequently occur with this techniquecan frequently occur with this technique

• &umbar puncture&umbar puncture should be performed inshould be performed inall suspected cases, =vidence ofall suspected cases, =vidence ofhemorrhagic C; infection with increasedhemorrhagic C; infection with increasedwhite and red blood cells and protein iswhite and red blood cells and protein isfound, PC% should also be performed onfound, PC% should also be performed onC;jC;j

DiagnosisDiagnosis


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DiagnosisDiagnosis

• C! scan of the head may be useful in theC! scan of the head may be useful in thediagnosis of C; disease# but magneticdiagnosis of C; disease# but magneticresonance imaging (9%') and an electroenresonance imaging (9%') and an electroencephalogram (multiple independent foci ofcephalogram (multiple independent foci of

periodic slow and sharp wave discharge) areperiodic slow and sharp wave discharge) areprobably better for detecting earlier disease,probably better for detecting earlier disease,'n the neonate# C; disease is more diffuse'n the neonate# C; disease is more diffusethan in older patientsthan in older patients

• *rain biopsy*rain biopsy may be needed in certainmay be needed in certaincases to confirm the diagnosis* however#cases to confirm the diagnosis* however#PC% testing of C;j may ma8e this obsoletePC% testing of C;j may ma8e this obsolete



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• $tudies are ongoing to determine$tudies are ongoing to determine whether acyclovirwhether acyclovir

therapy should be given to pregnant women who havetherapy should be given to pregnant women who havea primary episode of genital &;V as well as to womena primary episode of genital &;V as well as to womenwith active infection (primary or secondary) near or atwith active infection (primary or secondary) near or attime of deliverytime of delivery

• !f there are no #isible lesions!f there are no #isible lesions at the onset of labor orat the onset of labor orprodromal symptoms# vaginal delivery is acceptableprodromal symptoms# vaginal delivery is acceptable

• Deli#er by cesarean section +C)section,Deli#er by cesarean section +C)section, in womenin womenwho have clinically apparent &;V infection (definitelywho have clinically apparent &;V infection (definitely

for primary infection and most e"perts also recommendfor primary infection and most e"perts also recommendin secondary infection as well), ?ebate e"ists ifin secondary infection as well), ?ebate e"ists ifmembranes have already been ruptured for h, 9ostmembranes have already been ruptured for h, 9oste"perts still recommend C+section,e"perts still recommend C+section,



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• 'nfants with 8nown infection or e"posure to &;V'nfants with 8nown infection or e"posure to &;V

be placed in contact isolationbe placed in contact isolation• !nfants born to mothers .ith a genital lesion5!nfants born to mothers .ith a genital lesion5 'f'f

it is a 8nown recurrent lesion and the infant isit is a 8nown recurrent lesion and the infant is

asymptomatic# the infection rate is .+/, Conasymptomatic# the infection rate is .+/, Con

sider surface screen cultures of the infant at 5+sider surface screen cultures of the infant at 5+

3 h of age, !reat if symptoms develop or if the3 h of age, !reat if symptoms develop or if the

culture is positiveculture is positive

• 'f maternal infection is primary# the ris8 to the'f maternal infection is primary# the ris8 to theinfant is +14/* therefore# most cliniciansinfant is +14/* therefore# most clinicians

recommend empiric acyclovir at birth afterrecommend empiric acyclovir at birth after

cultures have been obtainedcultures have been obtained


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)I% infection)I% infection

&'V is an enveloped %- virus that is a&'V is an enveloped %- virus that is a

member of themember of the "enti#irus su$family "enti#irus su$family ofof

retrovirusesretroviruses, 'nfection is most, 'nfection is most

commonly secondary to &'V+.commonly secondary to &'V+.

'stimated &umer of People'stimated &umer of People


73/85

'stimated &umer of People'stimated &umer of People

(iving +ith )I%(iving +ith )I%

!otal #1 (#. – #.) million!otal #1 (#. – #.) million

8estern 9Central %urope

0,74 million0,74 million[0,58 – 0,97 million][0,58 – 0,97 million]

'orth (frica 9 Middle %ast0,46 million0,46 million

[0,27 – 0,76 million][0,27 – 0,76 million]

$ub)$aharan (frica

24.7 million24.7 million[21.8 – 27.7 million][21.8 – 27.7 million]

%astern %urope9 Central (sia

1.7 million [1.2 – 2.6 million]

$outh 9 $outh)%ast (sia


:ceania


'orth (merica

1.4 million1.4 million[0,88 – 2.2 million][0,88 – 2.2 million]

Caribbean


&atin (merica


%ast (sia

0,75 million0,75 million[0,46 – 1.2 million][0,46 – 1.2 million]

,&AID*-)/0 1223,&AID*-)/0 1223


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Ris4 of infant5s infectiRis4 of infant5s infectionon

36 infants +ill36 infants +ill

not enot e

infectedinfected

67 infants +ill67 infants +ill

e infected +ithe infected +ith

)I%)I%7

89

89

36

&umer )I% negative&umer )I% negative

&umer infected during t+o years of reast feeding&umer infected during t+o years of reast feeding

&umer infected during laour&umer infected during laour

&umer infected during pregnancy&umer infected during pregnancy

P"TCT Intervention andP"TCT Intervention and


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ART ART %% breastfeeding replacement breastfeeding replacement

No ART No ART breastfeeding replacement breastfeeding replacement

ART ART ! years breastfeeding ! years breastfeeding

NoNo ART ART ! years breastfeeding ! years breastfeeding

;


76/85

Features of the infectionFeatures of the infection

• Vertically infected children e"perienceVertically infected children e"periencemore rapid disease progressionmore rapid disease progressionthan those infected at an older age orthan those infected at an older age or

adultsadults• 9ore than 34/ of vertically infected9ore than 34/ of vertically infected

children manifest &'V+.+related symptomschildren manifest &'V+.+related symptomsor C? !+cell depletion by 5 years of ageor C? !+cell depletion by 5 years of age

• -n -'?;+defining condition developed in -n -'?;+defining condition developed in+5/ by . year and in +4/ by years of+5/ by . year and in +4/ by years ofage in vertically infected infantsage in vertically infected infants



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• !he newborn may be asymptomatic or may have!he newborn may be asymptomatic or may have

low birth weight# weight loss# or failure to thrivelow birth weight# weight loss# or failure to thrive• %ecurrent upper respiratory tract infections# otitis%ecurrent upper respiratory tract infections# otitis

media# sinusitis# and invasive bacterial infections aremedia# sinusitis# and invasive bacterial infections arecommoncommon

• %ecurrent oral thrush is common# and Candida%ecurrent oral thrush is common# and Candidaesophagitis may become particularly troublesomeesophagitis may become particularly troublesome

• $ther infections that increase in frequency and$ther infections that increase in frequency and

difficulty to control include acute and recurrent VVdifficulty to control include acute and recurrent VVinfections# measles# C9V# and gastrointestinalinfections# measles# C9V# and gastrointestinalinfections (eg#infections (eg# Salmonella, &iaria, Campylo$acter,Salmonella, &iaria, Campylo$acter,rotavirus# androtavirus# and Cryptosporiium'Cryptosporiium'



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• onspecific features of infection can includeonspecific features of infection can include

hepatosplenomegaly# lymphadenopathy# andhepatosplenomegaly# lymphadenopathy# andfever fever

• eurologic disease may be either static (delayedeurologic disease may be either static (delayedattainment of milestones) or progressive# withattainment of milestones) or progressive# with

impaired brain growth# failure to reach milestones#impaired brain growth# failure to reach milestones#and progressive motor deficitsand progressive motor deficits

• Common C! scan findings include basal gangliaCommon C! scan findings include basal gangliacalcification and cortical atrophy, Cardiaccalcification and cortical atrophy, Cardiacabnormalities# pericardial disease# myocardialabnormalities# pericardial disease# myocardialdysfunction# dysrhythmias# and cardiomyopathiesdysfunction# dysrhythmias# and cardiomyopathiesare common# particularly in advanced diseaseare common# particularly in advanced disease

DiagnosisDiagnosis


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DiagnosisDiagnosis• ?iagnosis is based on?iagnosis is based on

(.)(.) suspicion of infection because ofsuspicion of infection because of

epidemiologic ris8 or clinical presentationepidemiologic ris8 or clinical presentation

andand

(5)(5) confirmation by different virologic assaysconfirmation by different virologic assaysin infants .3 months old or serologic testsin infants .3 months old or serologic tests

if the infant is .3 months oldif the infant is .3 months old

• $urrogate mar?ers for disease5$urrogate mar?ers for disease5 'mmunologic'mmunologic

abnormalities# including hypergammaglobulin+abnormalities# including hypergammaglobulin+

emia# a low C?: !+lymphocyte count# or aemia# a low C?: !+lymphocyte count# or a

decreased C?: percentagedecreased C?: percentage $% mar8er$% mar8er

diseasesdiseases

'lective Caesarean *ection'lective Caesarean *ectionC ld d C


80/85

Could Reduce "TCT yCould Reduce "TCT y

92:92:

• =lective caesarean section should be=lective caesarean section should berecommended to &'V+positive women andrecommended to &'V+positive women and

performed atperformed at

– 3 wee8s of pregnancy3 wee8s of pregnancy

– Prior contractionsPrior contractions

– 'f the rupture of membranes is less than 'f the rupture of membranes is less than

hourshours

*afe %aginal Delivery*afe %aginal Delivery


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g yPracticesPractices

• 0se partogram to monitor labour 0se partogram to monitor labour • -void unnecessary frequent cervical -void unnecessary frequent cervical

e"aminationse"aminations

• Prevent long rupture of membranes (Prevent long rupture of membranes (hours increases 9!C! by 14/)hours increases 9!C! by 14/)

• -void invasive obstetric interventions and -void invasive obstetric interventions andprocedures during labour procedures during labour – Promote free position for women duringPromote free position for women during

deliverydelivery

• -void prolonged labour -void prolonged labour

)/0 CDC0 122;)/0 CDC0 122;

AR% prevention in laourAR% prevention in laour


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AR% prevention in laourAR% prevention in laour

• oman treated from 5+53 wee8s by ?Voman treated from 5+53 wee8s by ?V – abour idovudine (?V) until delivery : amivoudineabour idovudine (?V) until delivery : amivoudine

(!C) : evirapine (VP) at onset of labour (!C) : evirapine (VP) at onset of labour

– Caesarean section continue ?VCaesarean section continue ?V• oman treated for less than wee8s by ?Voman treated for less than wee8s by ?V

– idovudine (?V) : amivoudine (!C) : evirapineidovudine (?V) : amivoudine (!C) : evirapine(VP)(VP)

– 'ndependently of the mode of delivery'ndependently of the mode of delivery

• oman did not receive -%V during pregnancyoman did not receive -%V during pregnancy – idovudine (?V) : evirapine (VP) : amivoudineidovudine (?V) : evirapine (VP) : amivoudine

(!C)(!C) – 'ndependently of the mode of delivery'ndependently of the mode of delivery

)/ ',R/0 1223)/ ',R/0 1223

Assess ARV drugs taken during pregnancy, thus selectAssess ARV drugs taken during pregnancy, thus select

the ARV regimen based on obstetric scenario and priorthe ARV regimen based on obstetric scenario and priorARV treatmentARV treatment

*pecic Care for Infant*pecic Care for Infanti i< t )I% P iti


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84/85

AR% preventionAR% prevention

8H:@ =//38H:@ =//3

I fI f t


85/85

Infant careInfant care

• 'nfant &'V testing'nfant &'V testing – Polymerase Chain %eaction + PC% ?- &'VPolymerase Chain %eaction + PC% ?- &'V

Could be done after 3 hoursCould be done after 3 hours

–&'V =';- test&'V =';- test

$nly after .5 to .3 months$nly after .5 to .3 months

• Prophylactic of Pneumocistic cariniiProphylactic of Pneumocistic cariniipneumonia starting after wee8spneumonia starting after wee8s

– Cotrimo"azole syrup (54 mgM1ml)Cotrimo"azole syrup (54 mgM1ml)• 4#1 mlM8gM5h4#1 mlM8gM5h

• times a wee8 until confirmation of &'V+negative times a wee8 until confirmation of &'V+negative

Documents

Perinatal Infections Engl