TORCH InfectionsTORCH Infections

Ashley M. Maranich, MDAshley M. Maranich, MD

CPT/USA/MCCPT/USA/MC

Pediatric Infectious Disease FellowPediatric Infectious Disease Fellow

TORCH InfectionsTORCH Infections

• T=toxoplasmosisT=toxoplasmosis• O=other (syphilis)O=other (syphilis)• R=rubellaR=rubella• C=cytomegalovirus (CMV)C=cytomegalovirus (CMV)• H=herpes simplex (HSV)H=herpes simplex (HSV)

• You are taking care of a term newborn You are taking care of a term newborn male with birth weight/length <10male with birth weight/length <10thth %ile. %ile. Physical exam is normal except for a Physical exam is normal except for a slightly enlarged liver span. A CBC is slightly enlarged liver span. A CBC is significant for low platelets. significant for low platelets.

• What, if anything, do you worry about?What, if anything, do you worry about?• How do you proceed with a work-up?How do you proceed with a work-up?

Index of SuspicionIndex of Suspicion

• When do you think of TORCH When do you think of TORCH infections?infections?• IUGR infantsIUGR infants• HSMHSM• ThrombocytopeniaThrombocytopenia• Unusual rashUnusual rash• Concerning maternal historyConcerning maternal history• ““Classic” findings of any specific infectionClassic” findings of any specific infection

Diagnosing TORCH InfectionDiagnosing TORCH Infection

!!!!!!DO NOT USE TORCH TITERS!!!!!!!!!!!!DO NOT USE TORCH TITERS!!!!!!

Diagnosing TORCH InfectionDiagnosing TORCH Infection

• Good maternal/prenatal historyGood maternal/prenatal history• Remember most infections of concern are Remember most infections of concern are

mild illnesses often unrecognizedmild illnesses often unrecognized

• Thorough exam of infantThorough exam of infant• Directed labs/studies based on most Directed labs/studies based on most

likely diagnosis…likely diagnosis…• Again, DO NOT USE TORCH TITERS!Again, DO NOT USE TORCH TITERS!

Screening TORCH InfectionsScreening TORCH Infections

• Retrospective study of 75/182 infants with IUGR who Retrospective study of 75/182 infants with IUGR who were screened for TORCH infectionswere screened for TORCH infections

• 1/75 with clinical findings, 11/75 with abnl lab findings1/75 with clinical findings, 11/75 with abnl lab findings• All patients screened:All patients screened:

• TORCH titers, urine CMV culture, head USTORCH titers, urine CMV culture, head US• Only 3 diagnosed with infectionOnly 3 diagnosed with infection

• NONE by TORCH titer!!NONE by TORCH titer!!

• Overall cost of all tests = $51,715Overall cost of all tests = $51,715

• ““Shotgun” screening approach NOT cost effective nor Shotgun” screening approach NOT cost effective nor particularly usefulparticularly useful

• Diagnostic work-up should be logical and directed by Diagnostic work-up should be logical and directed by history/exam findingshistory/exam findings

Khan, NA, Kazzi, SN. Yield and costs of screening growth-retarded infants for torch infections. Am J Perinatol 2000; 17:131.

ToxoplasmosisToxoplasmosis

• Caused by protozoan – Toxoplasma gondiiCaused by protozoan – Toxoplasma gondii• Domestic cat is the definitive host with infections via:Domestic cat is the definitive host with infections via:

• Ingestion of cysts (meats, garden products)Ingestion of cysts (meats, garden products)• Contact with oocysts in fecesContact with oocysts in feces

• Much higher prevalence of infection in European Much higher prevalence of infection in European countries (ie France, Greece)countries (ie France, Greece)

• Acute infection usually asymptomaticAcute infection usually asymptomatic• 1/3 risk of fetal infection with primary maternal 1/3 risk of fetal infection with primary maternal

infection in pregnancyinfection in pregnancy• Infection rate higher with infxn in 3Infection rate higher with infxn in 3 rdrd trimester trimester• Fetal death higher with infxn in 1Fetal death higher with infxn in 1stst trimester trimester

Clinical ManifestationsClinical Manifestations

• Most (70-90%) are asymptomatic at birthMost (70-90%) are asymptomatic at birth• Classic triad of symptoms:Classic triad of symptoms:

• ChorioretinitisChorioretinitis• HydrocephalusHydrocephalus• Intracranial calcificationsIntracranial calcifications

• Other symptoms include fever, rash, HSM, Other symptoms include fever, rash, HSM, microcephaly, seizures, jaundice, microcephaly, seizures, jaundice, thrombocytopenia, lymphadenopathythrombocytopenia, lymphadenopathy

• Initially asymptomatic infants are still at high risk of Initially asymptomatic infants are still at high risk of developing abnormalities, especially chorioretinitisdeveloping abnormalities, especially chorioretinitis

Chorioretinitis of congenital toxoChorioretinitis of congenital toxo

DiagnosisDiagnosis

• Maternal IgG testing indicates past Maternal IgG testing indicates past infection (but when…?)infection (but when…?)

• Can be isolated in culture from Can be isolated in culture from placenta, umbilical cord, infant serumplacenta, umbilical cord, infant serum

• PCR testing on WBC, CSF, placentaPCR testing on WBC, CSF, placenta• Not standardizedNot standardized

• Newborn serologies with IgM/IgA Newborn serologies with IgM/IgA

Toxo ScreeningToxo Screening

• Prenatal testing with varied sensitivity Prenatal testing with varied sensitivity not useful for screeningnot useful for screening

• Neonatal screening with IgM testing Neonatal screening with IgM testing implemented in some areasimplemented in some areas• Identifies infected asymptomatic infants Identifies infected asymptomatic infants

who may benefit from therapywho may benefit from therapy

Prevention and TreatmentPrevention and Treatment• Treatment for pregnant mothers diagnosed with acute toxoTreatment for pregnant mothers diagnosed with acute toxo

• Spiramycin dailySpiramycin daily• Macrolide antibioticMacrolide antibiotic

• Small studies have shown this reduces likelihood of congenital Small studies have shown this reduces likelihood of congenital transmission (up to 50%)transmission (up to 50%)

• If infant diagnosed prenatally, treat momIf infant diagnosed prenatally, treat mom• Spiramycin, pyrimethamine (anti-malarial, dihydrofolate reductase Spiramycin, pyrimethamine (anti-malarial, dihydrofolate reductase

inhib), and sulfadiazine (sulfa antibiotic)inhib), and sulfadiazine (sulfa antibiotic)• Leucovorin rescue with pyrimethamineLeucovorin rescue with pyrimethamine

• Symptomatic infantsSymptomatic infants• Pyrimethamine (with leucovorin rescue) and sulfadiazinePyrimethamine (with leucovorin rescue) and sulfadiazine• Treatment for 12 months totalTreatment for 12 months total

• Asymptomatic infantsAsymptomatic infants• Course of same medicationsCourse of same medications• Improved neurologic and developmental outcomes demonstrated Improved neurologic and developmental outcomes demonstrated

(compared to untreated pts or those treated for only one month)(compared to untreated pts or those treated for only one month)

SyphilisSyphilis

• Treponema pallidum (spirochete)Treponema pallidum (spirochete)• Transmitted via sexual contactTransmitted via sexual contact• Placental transmission as early as 6wks Placental transmission as early as 6wks

gestationgestation• Typically occurs during second halfTypically occurs during second half• Mom with primary or secondary syphilis more Mom with primary or secondary syphilis more

likely to transmit than latent diseaselikely to transmit than latent disease• Large decrease in congenital syphilis since Large decrease in congenital syphilis since

late 1990slate 1990s• In 2002, only 11.2 cases/100,000 live births In 2002, only 11.2 cases/100,000 live births

reportedreported

From MMWR – From MMWR – Aug 2004Aug 2004

From MMWR – From MMWR – Aug 2004Aug 2004

Congenital SyphilisCongenital Syphilis

• 2/3 of affected live-born infants are 2/3 of affected live-born infants are asymptomatic at birthasymptomatic at birth

• Clinical symptoms split into early or late Clinical symptoms split into early or late (2 years is cutoff)(2 years is cutoff)

• 3 major classifications:3 major classifications:• Fetal effectsFetal effects• Early effectsEarly effects• Late effectsLate effects

Clinical ManifestationsClinical Manifestations

• Fetal:Fetal:• StillbirthStillbirth• Neonatal deathNeonatal death• Hydrops fetalisHydrops fetalis

• Intrauterine death in 25%Intrauterine death in 25%• Perinatal mortality in 25-30% if Perinatal mortality in 25-30% if

untreateduntreated

Clinical ManifestationsClinical Manifestations

• Early congenital (typically 1Early congenital (typically 1stst 5 weeks): 5 weeks):• Cutaneous lesions (palms/soles)Cutaneous lesions (palms/soles)• HSMHSM• JaundiceJaundice• AnemiaAnemia• SnufflesSnuffles• PeriostitisPeriostitis and metaphysial dystrophy and metaphysial dystrophy• Funisitis (umbilical cord vasculitis)Funisitis (umbilical cord vasculitis)

Periostitis of long bones Periostitis of long bones seen in neonatal syphilisseen in neonatal syphilis

Clinical ManifestationsClinical Manifestations

• Late congenital:Late congenital:• Frontal bossingFrontal bossing• Short maxillaShort maxilla• High palatal archHigh palatal arch• Hutchinson teethHutchinson teeth• 88thth nerve deafness nerve deafness• Saddle nose Saddle nose • Perioral fissuresPerioral fissures

• Can be prevented with appropriate treatmentCan be prevented with appropriate treatment

Hutchinson teeth – late result of Hutchinson teeth – late result of congenital syphiliscongenital syphilis

Diagnosing SyphilisDiagnosing Syphilis(Not in Newborns)(Not in Newborns)

• Available serologic testingAvailable serologic testing• RPR/VDRL: nontreponemal testRPR/VDRL: nontreponemal test

• Sensitive but NOT specificSensitive but NOT specific• Quantitative, so can follow to determine disease activity Quantitative, so can follow to determine disease activity

and treatment responseand treatment response• MHA-TP/FTA-ABS: specific treponemal testMHA-TP/FTA-ABS: specific treponemal test

• Used for confirmatory testingUsed for confirmatory testing• Qualitative, once positive always positiveQualitative, once positive always positive

• RPR/VDRL screen in ALL pregnant women RPR/VDRL screen in ALL pregnant women early in pregnancy and at time of birthearly in pregnancy and at time of birth• This is easily treated!!This is easily treated!!

CDC Definition of Congenital CDC Definition of Congenital SyphilisSyphilis

• Confirmed if T. pallidum identified in skin Confirmed if T. pallidum identified in skin lesions, placenta, umbilical cord, or at lesions, placenta, umbilical cord, or at autopsyautopsy

• Presumptive diagnosis if any of:Presumptive diagnosis if any of:• Physical exam findingsPhysical exam findings• CSF findings (positive VDRL)CSF findings (positive VDRL)• Osteitis on long bone x-raysOsteitis on long bone x-rays• Funisitis (“barber shop pole” umbilical cord)Funisitis (“barber shop pole” umbilical cord)• RPR/VDRL >4 times maternal testRPR/VDRL >4 times maternal test• Positive IgM antibodyPositive IgM antibody

Diagnosing Congenital SyphilisDiagnosing Congenital Syphilis

• IgG can represent maternal antibody, IgG can represent maternal antibody, not infant infectionnot infant infection

• This is VERY intricate and often This is VERY intricate and often confusingconfusing• Consult your RedBook (or peds ID folks) Consult your RedBook (or peds ID folks)

when faced with this situationwhen faced with this situation

TreatmentTreatment

• Penicillin G is THE drug of choice for ALL Penicillin G is THE drug of choice for ALL syphilis infectionssyphilis infections

• Maternal treatment during pregnancy very Maternal treatment during pregnancy very effective (overall 98% success)effective (overall 98% success)

• Treat newborn if:Treat newborn if:• They meet CDC diagnostic criteriaThey meet CDC diagnostic criteria• Mom was treated <4wks before deliveryMom was treated <4wks before delivery• Mom treated with non-PCN medMom treated with non-PCN med• Maternal titers do not show adequate response Maternal titers do not show adequate response

(less than 4-fold decline)(less than 4-fold decline)

RubellaRubella

• Single-stranded RNA virusSingle-stranded RNA virus• Vaccine-preventable diseaseVaccine-preventable disease

• No longer considered endemic in the U.S.No longer considered endemic in the U.S.

• Mild, self-limiting illnessMild, self-limiting illness• Infection earlier in pregnancy has a Infection earlier in pregnancy has a

higher probability of affected infanthigher probability of affected infant

Copyright ©2006 American Academy of PediatricsMeissner, H. C. et al. Pediatrics 2006;117:933-935

Reported rubella and CRS: United States, 1966-2004

Clinical ManifestationsClinical Manifestations

• Sensorineural hearing loss (50-75%)Sensorineural hearing loss (50-75%)• Cataracts and glaucoma (20-50%)Cataracts and glaucoma (20-50%)• Cardiac malformations (20-50%)Cardiac malformations (20-50%)• Neurologic (10-20%)Neurologic (10-20%)• Others to include growth retardation, Others to include growth retardation,

bone disease, HSM, thrombocytopenia, bone disease, HSM, thrombocytopenia, “blueberry muffin” lesions“blueberry muffin” lesions

““Blueberry muffin” spots representingBlueberry muffin” spots representing

extramedullary hematopoesisextramedullary hematopoesis

DiagnosisDiagnosis

• Maternal IgG may represent immunization or Maternal IgG may represent immunization or past infection - Useless!past infection - Useless!

• Can isolate virus from nasal secretionsCan isolate virus from nasal secretions• Less frequently from throat, blood, urine, CSFLess frequently from throat, blood, urine, CSF

• Serologic testingSerologic testing• IgM = recent postnatal or congenital infectionIgM = recent postnatal or congenital infection• Rising monthly IgG titers suggest congenital Rising monthly IgG titers suggest congenital

infectioninfection

• Diagnosis after 1 year of age difficult to Diagnosis after 1 year of age difficult to establishestablish

TreatmentTreatment

• Prevention…immunize, immunize, Prevention…immunize, immunize, immunize!immunize!

• Supportive care only with parent Supportive care only with parent educationeducation

Cytomegalovirus (CMV)Cytomegalovirus (CMV)

• Most common congenital viral infectionMost common congenital viral infection• ~40,000 infants per year in the U.S.~40,000 infants per year in the U.S.

• Mild, self limiting illnessMild, self limiting illness• Transmission can occur with primary infection Transmission can occur with primary infection

or reactivation of virusor reactivation of virus• 40% risk of transmission in primary infxn40% risk of transmission in primary infxn

• Studies suggest increased risk of Studies suggest increased risk of transmission later in pregnancytransmission later in pregnancy• However, more severe sequalae associated with However, more severe sequalae associated with

earlier acquisitionearlier acquisition

Clinical ManifestationsClinical Manifestations

• 90% are asymptomatic at birth!90% are asymptomatic at birth!• Up to 15% develop symptoms later, Up to 15% develop symptoms later,

notably sensorineural hearing lossnotably sensorineural hearing loss• Symptomatic infectionSymptomatic infection

• SGA, HSM, petechiae, jaundice, SGA, HSM, petechiae, jaundice, chorioretinitis, chorioretinitis, periventricular calcificationsperiventricular calcifications, , neurological deficitsneurological deficits

• >80% develop long term complications>80% develop long term complications• Hearing loss, vision impairment, developmental Hearing loss, vision impairment, developmental

delaydelay

Ventriculomegaly and Ventriculomegaly and calcifications of calcifications of congenital CMVcongenital CMV

DiagnosisDiagnosis• Maternal IgG shows only past infectionMaternal IgG shows only past infection

• Infection common – this is uselessInfection common – this is useless• Viral isolation from urine or saliva in 1Viral isolation from urine or saliva in 1stst

3weeks of life3weeks of life• Afterwards may represent post-natal infectionAfterwards may represent post-natal infection

• Viral load and DNA copies can be assessed Viral load and DNA copies can be assessed by PCRby PCR• Less useful for diagnosis, but helps in following Less useful for diagnosis, but helps in following

viral activity in patientviral activity in patient• Serologies not helpful given high antibody in Serologies not helpful given high antibody in

populationpopulation

TreatmentTreatment

• Ganciclovir x6wks in symptomatic infantsGanciclovir x6wks in symptomatic infants• Studies show improvement or no progression of Studies show improvement or no progression of

hearing loss at 6moshearing loss at 6mos• No other outcomes evaluated (development, etc.)No other outcomes evaluated (development, etc.)• Neutropenia often leads to cessation of therapyNeutropenia often leads to cessation of therapy

• Treatment currently not recommended in Treatment currently not recommended in asymptomatic infants due to side effectsasymptomatic infants due to side effects

• Area of active research to include use of Area of active research to include use of valgancyclovir, treating asx patients, etc.valgancyclovir, treating asx patients, etc.

Herpes Simplex (HSV)Herpes Simplex (HSV)

• HSV1 or HSV2HSV1 or HSV2• Primarily transmitted through infected Primarily transmitted through infected

maternal genital tractmaternal genital tract• Rationale for C-section delivery prior to Rationale for C-section delivery prior to

membrane rupturemembrane rupture

• Primary infection with greater Primary infection with greater transmission risk than reactivationtransmission risk than reactivation

Clinical ManifestationsClinical Manifestations

• Most are asymptomatic at birthMost are asymptomatic at birth• 3 patterns of ~ equal frequency with 3 patterns of ~ equal frequency with

symptoms between birth and 4wks:symptoms between birth and 4wks:• Skin, eyes, mouth (SEM)Skin, eyes, mouth (SEM)• CNS diseaseCNS disease• Disseminated disease (present earliest)Disseminated disease (present earliest)

• Initial manifestations very nonspecific with Initial manifestations very nonspecific with skin lesions NOT necessarily presentskin lesions NOT necessarily present

Presentations of congenital HSVPresentations of congenital HSV

DiagnosisDiagnosis

• Culture of maternal lesions if present at Culture of maternal lesions if present at deliverydelivery

• Cultures in infant:Cultures in infant:• Skin lesions, oro/nasopharynx, eyes, urine, blood, Skin lesions, oro/nasopharynx, eyes, urine, blood,

rectum/stool, CSFrectum/stool, CSF

• CSF PCRCSF PCR• Serologies again not helpful given high Serologies again not helpful given high

prevalence of HSV antibodies in populationprevalence of HSV antibodies in population

TreatmentTreatment

• High dose acyclovir 60mg/kg/day High dose acyclovir 60mg/kg/day divided q8hrsdivided q8hrs• X21days for disseminated, CNS diseaseX21days for disseminated, CNS disease• X14days for SEMX14days for SEM

• Ocular involvement requires topical Ocular involvement requires topical therapy as welltherapy as well

Which TORCH Infection Presents Which TORCH Infection Presents With…With…• Snuffles?Snuffles?

• syphilissyphilis• Chorioretinitis, hydrocephalus, and Chorioretinitis, hydrocephalus, and

intracranial calcifications? intracranial calcifications? • toxotoxo

• Blueberry muffin lesions?Blueberry muffin lesions?• rubellarubella

• Periventricular calcifications?Periventricular calcifications?• CMVCMV

• No symptoms?No symptoms?• All of themAll of them

Which TORCH Infections Can Which TORCH Infections Can Absolutely Be Prevented?Absolutely Be Prevented?• RubellaRubella

• SyphilisSyphilis

When Are TORCH Titers Helpful When Are TORCH Titers Helpful in Diagnosing Congenital in Diagnosing Congenital Infection?Infection?

• NEVER!NEVER!

Questions?Questions?