Zika Clinical Champions Philadelphia Department of Public Health Division of Disease Control, Acute Communicable Disease Program Division of Maternal, Child and Family Health

Objectives Champions will be able to: Identify infants born with congenital defects potentially related to Zika virus infection Provide unique data needed for retrospective and prospective surveillance Identify best means to collaborate in biweekly reporting and active surveillance of congenital birth defects Describe case management, referral services, and follow-up of infants with special needs

Zika Clinical Champion Activities Screening At-Risk Infants: Born with a specific set of congenital birth defects possibly related to congenital Zika infection Known Zika exposure in utero with confirmed, suspected, or probable maternal serology At-risk based on history or clinical presentation, but where there was no maternal testing, inadequate testing, or inconclusive results Collaboration for Active Surveillance of Zika-Related Birth Defects Clinical Champion will provide biweekly reports of infants born with Zika-related birth defects Assist in retrospective identification of infants with Zika-related birth defects PDPH will collaborate with the Zika Clinical Champion when a potential case is identified during the prenatal period Link families to PDPH home visiting nurse who can assist families with infant follow-up and developmental monitoring

Congenital Zika Syndrome Congenital anomalies associated with Zika virus infection during pregnancy include: Severe microcephaly resulting in a partially collapsed skull Thin cerebral cortices with subcortical calcifications Eye anomalies, including macular scarring and focal pigmentary retinal mottling Congenital contractures or limited range of joint motion Marked early hypertonia and symptoms of extrapyramidal involvement Infants can present with normal head circumference at birth and develop signs of congenital Zika syndrome later Please see ICD Codes Related to Congenital Zika Syndrome, attached. Zika is a single-stranded RNA virus, a Flavivirus, related to dengue, West Nile, yellow fever viruses Primarily spread by bite of infected Aedes mosquito, but can be spread sexually, and with vertical transmission to offspring Zika infections in pregnant women can lead to congenital infections, birth defects or fetal loss Zika Clinical Course of Disease Zika in the adult can show symptoms within 2 weeks of infection, but only 20% of those infected have symptoms. Antibodies are developed w/i 7 days. Timeframe for IgM persistence is unknown, but persistence is related to other flavoviruses – WNV – 3 – 12 mos; Neutralizing antibodies to Zika virus develop shortly after IgM antibodies, primarily of IgG antibodies. Neutralizing antibodies are expected to persist for many years after flavivirus infections and are believed to confer prolonged, possibly lifelong, immunity. Common symptoms are fever, rash, joint pain, and conjunctivitis Symptoms last several days to a week, with rare severity of symptoms requiring hospitalization or fatalities Severe symptoms include Guillain-Barré syndrome and other neurologic complications

Potential Risk of Birth Defects Related to Zika Virus Infection Report from CDC found ~ 5% of women with possible recent Zika virus infection had infants born with birth defects potentially related to Zika virus Percentage of pregnancies with birth defects was similar (5-6%) among pregnant women who experienced symptoms and those who were asymptomatic Among women with maternal symptoms OR laboratory evidence of possible Zika virus infection in the first trimester of pregnancy, birth defects were reported in 15% of completed pregnancies Reynolds MR, Jones AM, Petersen EE, et al. (2017). Vital Signs: Update on Zika Virus–Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure — U.S. Zika Pregnancy Registry, 2016. MMWR Morb Mortal Wkly Rep 2017;66:366-373. DOI: http://dx.doi.org/10.15585/mmwr.mm6613e1 Source: Vital Signs: Update on Zika Virus–Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure — U.S. Zika Pregnancy Registry, 2016. https://www.cdc.gov/mmwr/volumes/66/wr/mm6613e1.htm

Testing Testing continues for: Pregnant women - asymptomatic and symptomatic Newborns with: Possible congenital Zika syndrome Mother having evidence of Zika virus infection during pregnancy Mother who resided in a Zika-affected area during pregnancy Asymptomatic women are just as likely to expose offspring to Zika virus Philadelphia and Pennsylvania will continue to test women who: Traveled to an affected area Had unprotected sexual contact with a traveler to an affected area during period of potential viral shedding: Maximum potential shedding duration in semen and vaginal fluids differ. Male travelers: up to 6 months following travel Female travelers: up to 8 weeks following travel Which Patients with Zika Exposure Need Testing? • Pregnant women - asymptomatic and symptomatic • Newborns • Symptomatic non-pregnant persons • Mild fever, rash, arthralgia, or conjunctivitis • During or within two weeks of Zika exposure • Exposed persons with severe Zika manifestations • Guillain-Barré syndrome • Neurologic complications (encephalitis, meningitis, myelitis, etc.)

Testing Guidance Zika assays available through public health and commercial labs Direct detection: Nucleic Acid Testing (NAT) Immune response: IgM ELISA IgM positive, equivocal, and inconclusive specimens are forwarded to CDC for Plaque Reduction Neutralization Testing (PRNT) Specimen type and testing based on time from symptom onset or last exposure: Before day 14: Collect serum and urine Day 14 to week 12: Collect serum only Collection Serum Collect 3 mL in a red or tiger top tube Zika NAT and IgM testing Urine Collect 3 mL in a sterile container Zika NAT Keep specimens refrigerated until transport Zika Testing For Pregnant Women by Timing of Specimen Collection WITHIN TWO WEEKS OF EXPOSURE Day 1 to 13: serum and urine Zika NAT (PCR) testing For pregnant women, PABOL will perform Zika IgM as well. PABOL tests serum with trioplex PCR (Zika, dengue & chikungunya) Negative results during this time do not exclude Zika infection Collect serum ≥ day 14 for IgM testing. 2+ WEEKS FROM EXPOSURE Day 14 to Week 12: serum Zika IgM testing For pregnant women, PABOL also performs NAT testing. IgM positive, equivocal, and inconclusive specimens forwarded to CDC for Plaque Reduction Neutralization Testing (PRNT). Tested for Zika and Dengue neutralizing antibodies; Turnaround for results: 4 weeks Exceptions for testing >12 weeks after onset/exposure Women who lived in affected areas during pregnancy and were not screened Women with a fetus/newborn with possible congenital Zika infection who were not screened or screened negative  Testing currently not recommended for: 1) Couples planning to get pregnant with exposure and no symptoms; 2) Asymptomatic, exposed males with a pregnant partner Please note: symptomatic patients should also be tested for dengue and chikungunya. IgM and IgG testing for dengue and chikungunya are currently not available at BOL. Separate orders for these arboviruses need to be placed for commercial labs.

Zika Result Interpretation Zika NAT results Zika IgM result PRNT result Interpretation Positive (Serum or Urine) -- Confirmed infection Positive, Negative or Not Performed Positive Zika >10, Dengue <10 Negative or Not Performed Zika >10, Dengue >10 Probable infection (Unspecified flavivirus infection) Equivocal Suspect infection Negative Evidence of past infection (2–12 wks after exp or onset) No evidence of infection RNA NAT (nucleic acid testing); aka PCR

Zika Pregnancy Registry: Maternal Health Monitoring Confirmed, probable, and suspect Zika infections in pregnant women PDPH contact once a trimester to document care: Routine prenatal assessments Serial ultrasounds every 3–4 weeks with fetal MRI if abnormalities noted Monitoring for adverse outcomes Collection of tissues for Zika pathology testing Live births Newborn Zika testing Neonate assessment for abnormalities including head circumference and cranial ultrasounds

Pregnancy Registry: Live Births Newborn specimens: Collect within 2 days of birth Serum (1ml): NAT and IgM testing Urine (0.5–1ml): NAT testing Coordination between newborn nursery (or NICU) and hospital microbiology/virology laboratory Details needed on newborn for Neonate Assessment Anthropometrics at birth and before discharge Head circumference Weight Length Physical exam and description of any abnormalities Hearing assessment outcome Cranial ultrasound or other scan results Retinal exam results

Zika Tissue Testing at Birth Tissue testing informs maternal Zika status Collect tissue for: Symptomatic mothers who are not confirmed Possible adverse outcomes/live births with congenital defects Philly/PA will continue requests for asymptomatic, non-confirmed pregnancy registry cases Coordination between labor and delivery (specimen collection) and pathology laboratory (specimen preparation) Pre-approval from CDC required: PDPH will obtain approval using information from the maternal health form and neonate form CDC will only receive specimens forwarded from state health departments Testing Recommendation Changes Updated recommendations published July 28, 2017 https://www.cdc.gov/mmwr/volumes/66/wr/mm6629e1.htm?s_cid=mm6629e1_w Major changes Removed recommendation for screening exposed, asymptomatic women, but left option to patient, provider, or jurisdiction Philly/PA will continue to test pregnant women regardless of symptoms Scaled back pathology testing to symptomatic mothers (who are not confirmed) and possible adverse outcomes/live births with congenital defects We will continue requests for asymptomatic, non-confirmed pregnancy registry cases HAN, HIP updates, and after-hours protocol revisions forthcoming

Zika Testing and Newborn Imaging at Delivery: Previously Screened Mothers Mom tested during pregnancy Mom resided in affected area while pregnant Newborn with defects due to Zika Collect Serum from Mom at Time of Birth Collect Serum and Urine from Newborn Collect Placenta and Umbilical Cord Newborn Cranial U/S or Imaging Yes - Confirmed Yes or No No Yes Yes – Probable, Suspect , or IgM positive and PRNT pending Yes, continue Yes – Neg IgM Repeat if not done prior

Zika Testing and Newborn Imaging at Delivery: Mothers Not Tested Mom tested during pregnancy Mom resided in affected area while pregnant Newborn with defects due to Zika Collect Serum from Mom at Time of Birth Collect Serum and Urine from Newborn Collect Placenta and Umbilical Cord Newborn Cranial U/S or Imaging No Yes

Pregnancy Registry: Infant Monitoring and Assessments For confirmed, probable, or suspect congenital Zika infections: Neurology referral for any abnormalities Newborn ophthalmology exam normal - repeat at age 3 mos. Newborn hearing screen normal - perform ABR at age 4–6 mos. Thyroid testing at age 2 weeks and repeat at age 3 mos. If abnormal, evaluate pituitary function further. Referral to developmental specialist and early intervention services Healthy infants born to Pregnancy Registry moms Routine care, neurology referral for any concerns identified, and referral to appropriate specialist Get from cdc

Pregnancy Registry: Infant Follow-Up Assessments PDPH will contact pediatrician at: 2 months 6 months 12 months Possibly longer... Details collected at each time point: Measures (HC, Weight, Length) Physical exam and description of any abnormalities Developmental milestones reached & description of delays Cranial ultrasound or other scan results Hearing re-screen or other audiological evaluation Retinal exam results

Case Management Services for Families of Infants with Zika-Related Birth Defects Philadelphia Infant Referral Service (PIRS) Team: Zika Nurse Coordinator: Sharon Starr, RN, MSN Zika Surveillance Coordinator: Rachel Blumenfeld, MPH Zika Social Worker: Silvina Godoy, MSW PIRS Case Management Services: Identify and address medical needs including active insurance, access to primary and specialty care, education regarding infant’s exposure, education regarding recommended clinical assessment and care, and pregnancy planning for recently exposed parents Provide direct clinical follow up and data gathering of all recommended medical and behavioral assessments Identify and address social needs including immigration issues, safe housing, transportation, health literacy, food insecurity, and family/community support

U.S. Zika Pregnancy Registry Active Birth Defects Surveillance Zika Birth Defects Surveillance & the U.S. Zika Pregnancy Registry U.S. Zika Pregnancy Registry (USZPR) Pregnant women with laboratory evidence of possible Zika virus infection and their infants Active Birth Defects Surveillance All infants with birth defects of interest, with and without congenital Zika exposure General goal of the surveillance systems: Monitor pregnancy and infant outcomes Learn more about the timing, absolute risk, and spectrum of outcomes associated with Zika virus infection during pregnancy Help inform clinical guidance and direct public health action Infant & Child Follow-up for Prenatal Zika Exposure Referral to Services – Infants with Birth Defects

Birth Defects Surveillance Surveillance of birth defects of interest related to Zika virus infection at each delivery hospital Monitor pregnancy and infant outcomes, prospectively and retrospectively Inform clinical and public health entities about timing, absolute risk, and spectrum of outcomes associated with Zika virus infection How can we best collaborate with your agency for retrospective surveillance of birth defects related to Zika? From 2016 to mid/late 2017 Flag medical records for ICD codes of interest Health IT support for listed birth defects Birth defects records within hospital How can we best collaborate with your agency for prospective surveillance of birth defects? From 2017 onward (TBD) Biweekly reporting with follow-up on birth defects identified Other collaborative means?

Maternal, Child and Family Health Sharon Starr, RN, MSN Sharon.Starr@phila.gov Office: 215-685-5255 Mobile: 267-342-5962 Rachel Blumenfeld, MPH Rachel.Blumenfeld@phila.gov Mobile: (267) 886-0532 Secure Fax: (215) 238-6947 Division of Disease Control Dana Perella, MPH Office (215) 685-6742