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

2. 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

3. 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

4. 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

5. 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, MMWR Morb Mortal Wkly Rep 2017;66: DOI:
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,

6. 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.)

7. 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.

8. 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

9. 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

10. 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

11. 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,
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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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?

19. Maternal, Child and Family Health
Sharon Starr, RN, MSN
Office:
Mobile:
Rachel Blumenfeld, MPH
Mobile: (267)
Secure Fax: (215)
Division of Disease Control
Dana Perella, MPH
Office (215)