TORCHI nfecti onsNatalie Neu, MD, MPHa,*, Jennifer Duchon, MDCM,
MPHb,Philip Zachariah, MDbINTRODUCTIONCongenital infection is a
well-describedcause of stillbirths, as well as perinatalmorbidity.
TORCHinfectionsclassicallycomprisetoxoplasmosis,
Treponemapal-lidum,rubella,cytomegalovirus(CMV),herpessimplex
virus(HSV),hepatitisviruses,humanimmunodeficiency virus (HIV),
andother infections, suchas
varicellaandparvovirusB19.Theepidemiologyoftheseinfectionsvaries,andinlow-incomeandmiddle-income
countries, where the burden of disease is greatest, TORCH
infectionsaremajor contributorstoprenatal andinfant
morbidityandmortality(Table1).114Transmissionof
thepathogensmayoccur prenatally, perinatally,
andpostnatally,through, respectively, transplacental passage of
organisms, from contact with bloodand vaginal secretions, or from
exposure to breast milk for CMV, HIV, and HSV. Evi-denceof
infectionmaybeseenat birth, ininfancy, or not evenuntil
yearslater,Disclosurestatement:theauthorshavenothingtodisclose.aDivision
of Pediatric InfectiousDisease, Columbia University Medical Center,
622 West 168thStreet, PH-468, NewYork, NY10032, USA;bDivisionof
Pediatric Infectious Disease,
NewYork-PresbyterianMorganStanleyChildrens Hospital, 622West
168thStreet, PH-471,
NewYork,NY10032,USA*Correspondingauthor.E-mailaddress:[email protected]
TORCH Toxoplasmosis Treponemapallidum Rubella Parvovirus HIV
HepatitisB HepatitisCKEYPOINTS The TORCH pneumonic typically
comprises toxoplasmosis, Treponema pallidum,
rubella,cytomegalovirus, herpesvirus, hepatitisBvirus,
hepatitisCvirus, humanimmunodefi-ciency virus and other viruses,
including varicella, parvovirus B19. These infections are
well-described causes of stillbirth and may account for up to half
of allperinatal deaths globally. The burden is especially great in
developing countries. Stigmata of disease may be seen at birth, in
the early neonatal period, or later. Treatment strategies are
available for many of the TORCH infections. Early recognition,
including maternal prenatal screening and treatment when available,
arekey aspects in management of TORCH infections.Clin Perinatol -
(2015)--http://dx.doi.org/10.1016/j.clp.2014.11.001
perinatology.theclinics.com0095-5108/15/$ see front matter 2015
Elsevier Inc. All rights reserved.becausethefetal origins of adult
disease arenowincreasingly recognized. Theinfectednewborninfant
mayshowabnormal growth, developmental anomalies, ormultiple
clinical and laboratory abnormalities. Many of the clinical
syndromes for thoseviruses that present in the immediate neonatal
period overlap, as shown in Table 2.15Somehaveclassicphysical
stigmata, asshowninFigs.
1and2.16,17Formanyofthesepathogens,treatmentorpreventionstrategiesareavailable;earlyrecognition,includingprenatal
screening,iskey,andrecognizednational andinternational stan-dards
and protocolsare availableto theprovider.This
articlecoverstoxoplasmosis,parvovirusB19, syphilis, rubella,
hepatitisBvirus(HBV), hepatitisCvirus(HCV),HIV; other sections are
dedicated to HSV, CMV, and varicella zoster
virus.TOXOPLASMOSISDiseaseDescriptionThe protozoa Toxoplasma gondii
is an obligate intracellular parasite, which is ubiquitousin the
environment, and whose only definitive hosts are members of the
feline family. Theforms of the parasite are oocysts, which contain
sporozoites; these sporozoites divideand become tachyzoites;
tachyzoites localize in neural and muscle tissue and developunder
thepressureof thehost immunesystemintobradyzoites,
whichcongregateintotissuecysts. Thesecysts remaininskeletal
andheart muscle, brainandretinal tissue,and lymph nodes. Cats
acquire the infection either by consuming tissue cysts
fromtheirpreyor ingestingoocystsinsoil.
Replicationoccursintheintestineof thecat, andoocystsare formed,
excreted, and sporulate to become infectious in as little as 24
hours.1821Transmission/PathogenesisBothanimalsinthewildandanimalsbredfor
humanconsumptionmaybecomeinfected from oocysts in the environment.
Human infection (other than congenital) oc-curs by ingestion of the
tissue cysts from undercooked or raw meat or oocysts fromcontact
with cat feces or contaminated food or soil, or from transfusion of
blood prod-ucts or organ transplantation. Three genotypes (I, II,
III) of T gondii have been isolated.Table 1Worldwide prevalence
estimates of selected TORCH infectionsWorldwidePrevalenceUS
Prevalence ofCongenitallyAcquired Disease inthe United
StatesSeropositivity in Women of ChildbearingAgeaLow Prevalence (%)
High Prevalence (%)Toxoplasmosis 201,000b1033/100,000 livebirths11
(Europe) 77 (South America)Treponemapallidum36.4 million7.8/100,000
livebirths0.67 (North America) 10 (Central Africa)CMV
Unavailable800/1000,000 livebirths3050 (United States) >90
(South America)Hepatitis B 240 million 90%) of these children live
in sub-Saharan Africa. Interventions
institutedinresource-limitedsettingshavereducedtheestimatednumber
of childrennewlyNeu et al 12infectedwithHIVfromgreater
than400,000in2009toapproximately200,000in2013.68HIV-2 is endemic in
some West African countries but rare in the United Statesand is not
discussed further in this article. Table 4, from the Global Update
on HealthSector Response to HIV, describes the impact of efforts to
prevent MTCT of HIV.Transmission/PathogenesisThereareseveral
factorsthatincreasetheriskofperinatal
HIVtransmission.Thesefactorsincludematernal plasmaviral load,
maternal CD4count, moreadvancedWHOclinical diseasestage,
breastfeedingandmastitis, andacutematernal
infec-tion.69,70Arecentmeta-analysis71reportedthatincidentHIVduringpregnancyandpostpartumwasassociatedwithasignificantlyhigherriskofMTCTofHIV.Table5shows
the timing of HIV transmission and some possible mechanisms
fortransmission.72,73DiscussionDiagnosisandtreatmentIn the United
States, recommendations for HIV testing in early pregnancy have
beenpromoted by many prominent medical service groups, including
the Panel onTable 4The global impact of prevention of
MTCTYearEstimated Number ofPregnant Women Livingwith HIV
(Range)EstimatedMother-to-ChildTransmission Rateof HIV (Range)
(%)Estimated Number ofChildren Newly Infectedwith HIV
(Range)EstimatedCumulativeNumber ofInfectionsAverted byPreventionof
MTCT(Range)a2005 1,410,000(1,320,0001,520,000)33 (3136) 470,000
(430,000510,000) 41,0002006 1,390,000(1,290,0001,490,000)32 (3035)
450,000 (420,000490,000) 73,0002007 1,370,000(1,270,0001,470,000)31
(2933) 420,000 (390,000460,000) 130,0002008
1,360,000(1,260,0001,450,000)29 (2731) 400,000 (360,000430,000)
200,0002009b1,340,000(1,250,0001,430,000)26 (2428) 350,000
(310,000380,000) 320,0002010 1,330,000(1,230,0001,420,000)23 (2125)
300,000 (280,000330,000) 480,0002011
1,310,000(1,210,0001,400,000)21 (2023) 280,000 (250,000300,000)
660,0002012 1,290,000(1,190,0001,380,000)17 (1619) 220,000
(200,000250,000) 880,0002013 1,260,000(1,170,0001,360,000)16 (1517)
200,000 (170,000230,000) 1,120,000aCompared with the counterfactual
scenario in which no ARVs are provided for MTCT.bBaseline year for
the Global
Plan.FromWHO.GlobalupdateonthehealthsectorresponsetoHIV,2014.Geneva:WorldHealthOrganization,
2014; with permission.TORCH Infections 13Antiretroviral Therapy and
Medical Management of HIV-Infected Children, the US Pub-lic Health
Service, the AAP, the American College of Obstetricians and
Gynecologists,andtheUSPreventiveServicesTaskForce.Thesetestingalgorithmshavemadeasignificant
impact onperinatal HIVas aresult of early identificationof
maternalinfection.7480Prenatal:maternaltestingOpportunities for
testing include: Early in pregnancy Third trimester of pregnancy At
the time of labor or delivery Immediately post partumPostnatal
testing of HIV-exposed infants Diagnosisof
HIVinfectionininfantsrequirestheuseof nucleicacidtests(NATs),
includingHIVDNAorHIVRNAassays. Forhigh-riskexposures, such as
maternal HIV, or when maternal HIV status is unknown, testing of
theinfant at birth is recommended.75In general, testing for the
HIV-exposed infant should be: Within 48 hours of birth At 2 weeks
of life At 4 to 6 weeks of life At 4 to 6 months of lifeBoth HIV
DNA PCR and qualitative HIV RNA are sensitive for the diagnosis of
peri-natallyacquiredinfection,
althoughHIVDNAPCRmaybelessaffectedbycART.Therefore,infantswhoreceivecARTatbirthshouldberetestedwithanHIVNATto4
weeks after cessation of cART. HIV RNA testing of infants does have
the advantageof being more sensitive than HIV DNA PCR for
nonsubtype B viruses, which are foundaround the world. An
HIV-exposed infant is generally considered to be HIV-1 negativeif
the HIV NAT is negative at up to 4 months of age. Any infant with a
positive HIV NATshould have the test repeated immediately to
confirm the result.75Treatment
EarlycARTforHIV-infectedinfantsisassociatedwithreducedmortalityandattainment
of normal developmental milestonesandgrossmotor
skillswhencomparedwithinfantswhohavecARTdelayed.81,82Thereportedfunctional
cureinan HIV-infected child in Mississippi led many experts to
consider early cART initiationfor HIV-exposed infants. This child
was treated at 30 hours of life to 18 months of ageand maintained
HIV viral suppression for a period.83However, current data now
showHIV viral rebound in this child off therapy. Therefore,
empirical treatment at birth andinterruption of therapy after early
initiation cannot be recommended.84Table 5Mechanisms and timing of
MTCT of HIVTiming ofTransmission Rate (%) Mechanism PreventionIn
utero Approximately 30 Placental breakdown
andmicrotransfusions;chorioamnionitisEarly maternal
diagnosisMaternal cARTIntrapartum Approximately 50 Contact with
infant mucousmembranes and >4 h ruptureof amniotic
membranescARTCesarean sectionNeonatal ARTBreastfeeding
Approximately 20 Contact with infant mucousmembranesNo
breastfeedingNeu et al 14The latest guideline recommendations for
infant antiretroviral (ARV) prophylaxis areshown in Table 6 and
include85: Six-week zidovudine regimen or 4-week regimen if
maternal cART was given withconsistent viral suppression and no
concerns for lack of maternal adherence Zidovudine regimen started
as close to birth as possible and within 6 to 12 hoursof delivery
Infants born to women who did not receive cART should receive 6
weeks of
zido-vudinecombinedwith3dosesofnevirapineinthefirstweekoflife(firstdosegivenfrombirthto8hours,
seconddosegiven48hoursafter thefirst dose,and third dose given 96
hours after the second dose)Table 6Recommendation for prophylaxis
of newborns exposed to HIVAll HIV-Exposed Infants (Initiated as
Soon After Delivery as Possible)ZDV Dosing DurationZDV 35 wk
gestation at birth: 4 mg/kg/dose PO twicedaily, started as soon
after birth as possible andpreferably within 612 h of delivery (or,
if unableto tolerate oral agents, 3 mg/kg/dose IV,beginning within
612 h of delivery, then every12 h)Birth to 46 wkaZDV 30 to
