The problem with TORCH screening

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2 : Beyond TORCHeS TORCH or STORCH-a helpful mnemonic? Toxoplasma Other Rubella CMV HSV (HIV) Syphilis 3 The problem with TORCH screening TORCH-first proposed by Nahmias et.al. (Pediatr Res 1971) Toxo, Rubella, CMV and HSV Groups together the most common congenital infections TORCH testing: Single serum testing Expansion to TORCHS (or TORCHeS or STORCHeZ?) Add syphilis, Other: Parvovirus, Enterovirus, Hepatitis B, HIV, Zika Virus. More appropriate to consider the individual infant and the presentation Congenital Infection: Typical Presentation SGA/IUGR Rash Hepatosplenomegaly Thrombocytopenia Transaminitis Ophthalmologic findings Chorioretinitis Cataracts Intracranial calcifications Bone lesions: metaphyseal lucencies, periostitis Congenital CMV Most common congenital infection 1% of all live births Women can transmit CMV from both primary and reactivation infection Transmission during any trimester of pregnancy Most infections are asymptomatic 10-15% of asymptomatic infants will have progressive SNHL leading to a significant cause of deafness in the US 90% of symptomatic infants will have neurological impairment and or progressive deafness. 7

3 Symptomatic Newborn 30% 70% Death Survival 80% Severe Neurologic Deficits Primary Maternal CMV Infection 30-40% Fetal Infection 10-15% 85-90% Asymptomatic Newborn 10-15% Developmental Abnormalities (usually by age 2) Sensory hearing loss Microcephaly Motor deficits Mental retardation Chorioretinitis Congenital Toxoplasmosis Treatment Primary maternal disease Most infants are asymptomatic at birth (70-90%) TRIAD: Chorioretinitis, Intracranial calcifications Hydrocephalus Neurological manifestations may appear years later SNHL Visual impairments (due to chorioretinitis) Learning disabilities and developmental delay CMV Asymptomatic- none Symptomatic: GCV Cytomegalic inclusion disease Hepatitis, refractory, thrombocytopenia CNS disease SNHL Toxoplasmosis Pregnant women Spiramycin (first and early second trimesters) pyrimethamine/sulfadiazine (late second and third trimesters) Infants Pyrimethamine + sulfadiazine Leucovorin Congenital Rubella Syndrome (CRS) Primary maternal infection in the 1st trimester 85% first 12 weeks 50% 13 to 16 weeks 25% at the end of the second trimester TRIAD: Cataracts CHD (PDA, PS, VSD, TOF, aortic coarctation) SNHL

4 Congenital Rubella Microphthalmos Cataracts Microcephaly Metaphyseal radio-lucent changes Congenital Rubella Syndrome Significantly reduced by widespread immunization US and Europe: >90% Areas with lower seropositivity have higher rates of CRS Latin America: 62% Africa: 60-70% Asia: 70-80% (Japan ) rubella pandemic 50,000 pregnant women in the US were exposed to rubella Miscarriages, stillbirths 20,000 babies born CRS Rubella Vaccine Licensed in 1970 s Zika Virus Mosquito borne Flavivirus (ssrna) First identified in 1947 in Uganda from a monkey Sporadic human disease reported Outbreaks in Southeast Asia in the last decade Yap Island (Duffy M, et. al. NEJM 2007) Came to the Americas in May 2015 (Brazil) Over a million cases reported by the WHO Spread to multiple countries in South and Central America, the Caribbean, and the Pacific Islands Zika Virus Transmission: Aedes aegypti /Aedes albopictus Day biting, polka-dot mosquito Sexual Blood transfusion?organ transplantation Transplacental**

5 Zika Virus: Clinical Manifestations Asymptomatic Mild illness Fever (mild), maculopapular rash (pruritic), arthralgias, conjunctivitis Guillain-Barré syndrome (proposed) Clinical features of Zika Virus Infection in Pregnant Women. Fever-mild Maculopapular rash (blanching) Arthralgias Non purulent conjunctivitis Retroauricular lymphadenopathy Increase in cases reported in Zika endemic areas Congenital infection (proposed) Brasil P et al. N Engl J Med ZIKV and Microcephaly Maternal-fetal transmission Virus detected in amniotic fluid 2 infants born with microcephaly and intracranial calcificationsmothers had history of symptoms consistent with Zika infection Amniotic fluid tested positive for Zika by RT-PCR Virus identified in specimens of fetal losses (NEJM) Definitive causal association remains uncertain Potential co-factors required? Timing of infection Risk factors (maternal) for transmission Congenital Infection with ZIKV 32 year old woman Infected in 13 th week of pregnancy in Brazil Returned home to Slovenia in 28 th week Abnormalities on U/S detected Termination at 32 weeks Zika Virus RT-PCR positive fetal brain samples NEJM February 10, 2016 ZIKV Infection and Eye Abnormalities 29 infants with microcephaly examined 80% of mothers reported Zika symptoms 35% had ocular abnormalities Bilateral common Chorioretinal atrophy Optic nerve abnormalities ZIKV and Fetal Outcome Researchers in Brazil enrolled 88 pregnant women with rash 82% tested positive for Zika Virus infection 42 women were followed with serial ultrasounds 12 (29%) had abnormalities detected IUGR Microcephaly CNS lesions Fetal death (2) Brasil P et al. N Engl J Med 2016 JAMA Ophthalmology 2016

6 ZIKV and the 2016 Summer Olympics August 5-21, 2016 Paralympics September 7-18, ,000 visitors expected 200,000 American visitors Spread after returning from Brazil? CDC recommendations for travel: Pregnant women should not go Men attending the Olympics should use condoms if they have a pregnant partner ZIDV Testing (Infants) Tests ZIKV RNA (RT-PCR) IgM (cross reactivity with other flaviviruses) Neutralizing antibodies Clinical specimens: Serum CSF Tissue-placenta and umbilical cord Testing for Dengue Beyond TORCHeS Lymphocytic Choriomeningitis Virus (LCMV) Rodent-borne arenavirus: house mouse, hamsters Epidemic infection in mice (9% in one survey in Baltimore) Approximately 5% humans have serologic evidence of past infection Inhalation of virus (rodent feces) Post natal infection-asymptomatic/aseptic meningitis Congenital infection similar to other TORCH infections: Hydrocephalus, chorioretinitis, intracranial calcifications Diagnosis: Serology, PCR available (CDC) Beyond TORCHeS Parvovirus B19 Typically causes non-immune hydrops Classic TORCH presentation reported Bony lesions (metaphyseal lucencies) also reported Diagnosis: Serology (IgM), PCR Enterovirus Abortion, stillbirth and neonatal sepsis with thrombocytopenia Myocarditis, multi-organ failure (liver, kidney) No recognizable congenital malformations Diagnosis: culture (throat, rectal), PCR Congenital Infection: Evaluation Antenatal history Ultrasounds Maternal infection and serologic screening Maternal history (including immunizations) Prenatal exposures (specific risk factors including travel history) Infant s clinical presentation Characteristics of rash (purpura, vesicles) CNS: micro or hydrocephaly Eye exam: chorioretinitis, cataracts, glaucoma Imaging: location of calcifications, hydrocephalus Congenital Infection: Diagnosis Toxoplasmosis: Serologic testing Palo Alto Medical Foundation: ISAGA IgM testing Rubella: Serologic testing, viral culture CMV: Urine culture or PCR in the first 3 weeks of life HSV: Viral DFA, PCR and culture of lesions, CSF and surface sites Syphilis: Serologic testing RPR, VDRL with confirmatory treponemal testing on positive ZIKV- serology and PCR LCMV- serology and PCR

7 Congenital Infection: Who should be tested? Classic TORCH infection symptoms Meningoencephalitis Hearing impairment 23% of children with profound SNHL will have congenital CMV Also consider congenital rubella infection Ophthalmologic abnormalities (cataracts, CR, glaucoma) SGA infants? Not likely to be helpful unless there are other findings : Take Home Points Order tests for congenital infection based on the infant s signs and symptoms. Don t send: Consider less common causes of congenital infections and obtain pertinent maternal prenatal history including travel.