Zika Virus - Wild Apricot · 2017. 6. 14. · Zika Virus. US Zika Pregnancy Registry Tracking and Birth Defects Surveillance. Nina Ahmad, MD. Medical Director, Division of Epidemiology

Zika VirusUS Zika Pregnancy Registry Tracking and Birth Defects Surveillance

Nina Ahmad, MDMedical Director, Division of EpidemiologyNew York State Department of HealthJune 7, 2017

Deborah Fox, MPHDirector, Congenital Malformations RegistryNew York State Department of Health

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Zika Virus Timeline

1947Zika first

discovered in Uganda

1970-198014 documented cases

of Zika globally Nigeria, Asia, Indonesia

2007Outbreak in Yap, Pacific

Island 49 confirmed cases

2013Outbreak in French

Polynesia 333 confirmed cases

Guillian-Barre Association

2015 Outbreak in Brazil

400 confirmed cases

2016-2017Zika identified in many, many countries, with some newly identified manifestations

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Incidence of Microcephaly in Brazil

Baseline notification of microcephaly for Brazil: 2010 (n=153), 2011 (n=139), 2012 (n=175), 2013 (n=167) and 2014 (n=147).

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• Asymptomatic (80%) or mild illness• Symptoms

– Rash• Diffuse maculopapular erythematous rash • Pruritic

– Fever • Subjective, low grade

– Joint pain/arthralgia– Myalgia– Conjunctivitis

• Non-suppurative/non-exudative

Zika: Clinical Features

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Zika Virus Disease Natural History• 4-10 day incubation period

• Early viremic phase: typically 3-7 days after symptom onset

• Clinical illness usually mild, lasting for several days to a week

• Severe illness requiring hospitalization uncommon• Fatalities rare • Neurologic complications, specifically Guillain-Barré syndrome• Congenital infection

• Treatment supportive

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Zika Virus- The Basics• Arthropod-borne virus (arbovirus)

• Single stranded RNA Virus of the Genus Flavivirus

• Closely related to dengue, yellow fever, Japanese encephalitis and West Nile viruses

• Primarily transmitted by the Aedes species mosquitoes• Aedes aegypti (Yellow fever mosquito): efficient vectors for Zika• Aedes albopictus (Asian tiger mosquito): possible vector for Zika

• Approximately 80% of cases are asymptomatic

• Zika virus can cause a congenital syndrome characterized by microcephaly and other abnormalities

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Note: Rates based on serosurvey on Yap Island, 2007 (population 7,391)

Duffy M. N Engl J Med 2009

Clinical Presentation – Zika Virus Disease

• Infection rate: 73%

• Symptomatic attack rate among infected: 18%

• All age groups affected

• Adults more likely to present for medical care

• No severe disease, hospitalizations, or deaths

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Modes of Transmission

• Mosquito bite• From infected to uninfected humans and

primates by bite of a mosquito• Maternal-fetal

• Intrauterine• Perinatal

• Other• Sexual transmission • Blood transfusion

• Theoretical • Organ or tissue transplantation• Breast milk

http://www.cdc.gov/zika/pregnancy/index.html

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Mosquitoes: Take-Home Messages• Aedes aegypti is best vector for Zika

• Not present in NY

• Aedes albopictus may be able to transmit Zika• Unclear if involved in transmission • Present in certain parts of NY• Temperature-limited• Different behavioral characteristics make it less likely to produce outbreaks

• Approximately 75 different mosquito species in NY • Only Ae. albopictus potentially implicated in Zika transmission

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CDC Zika Pregnancy Registry• Goals

• To collect information about pregnancy and infant outcomes following Zika virus infection during pregnancy

• To update recommendations for clinical care, plan for services for pregnant women and families, and improve prevention of Zika virus infection during pregnancy

• Inclusion criteria: Any pregnant woman with laboratory evidence of possible Zika virus infection and their infants• Infants of women who meet inclusion criteria will be

followed at regular intervals for the first year of life

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http://www.cdc.gov/zika/geo/pregwomen-uscases.htmlhttp://www.cdc.gov/zika/geo/pregnancy-outcomes.html

Outcomes for Completed Pregnancies in the United States and District of Columbia, 2016-2017(1,579 completed pregnancies with or without birth defects)

http://www.cdc.gov/zika/geo/pregwomen-uscases.html

http://www.cdc.gov/zika/geo/pregnancy-outcomes.html

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Zika Pregnancy Registry Cases in NYS (excluding NYC) as of 6/2/17

• Pregnancies- 98• Completed pregnancies- 78

• Fetal losses- 3

• Fetus’ / infants with an anomaly reported- 5• Preg reg inclusion criteria - 3

• Including one that meets CSTE case definition

• One infant is under investigation

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• Liveborn infant with• Congenital microcephaly• Intracranial calcifications• Structural brain or eye abnormalities• Other congenital central nervous system-related abnormalities not explained

by another etiology

CSTE Definition of Congenital Malformation

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Zika Pregnancy Registry Inclusion CriteriaBrain abnormalities with and without microcephaly•Confirmed or possible congenital microcephaly#

•Intracranial calcifications•Cerebral atrophy•Abnormal cortical formation

(e.g., polymicrogyria, lissencephaly, pachygyria, schizencephaly, gray matter heterotopia) •Corpus callosum abnormalities•Cerebellar abnormalities•Porencephaly•Hydranencephaly•Ventriculomegaly / hydrocephaly

(excluding “mild” ventriculomegaly without other brain abnormalities)•Fetal brain disruption sequence

(collapsed skull, overlapping sutures, prominent occipital bone, scalp rugae)•Other major brain abnormalities, including intraventricular hemorrhage in utero

(excluding post-natal IVH)

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Zika Pregnancy Registry Inclusion Criteria

• Early brain malformations, eye abnormalities, or consequences of central nervous system (CNS) dysfunction• Neural tube defects (NTD)

Anencephaly / AcraniaEncephaloceleSpina bifida Holoprosencephaly / Arhinencephaly

• Structural eye abnormalitiesMicrophthalmia / AnophthalmiaColobomaCataractIntraocular calcificationsChorioretinal anomalies involving the macula (e.g., chorioretinal atrophy and scarring, macular pallor, gross pigmentary mottling and retinal hemorrhage); excluding retinopathy of prematurity Optic nerve atrophy, pallor, and other optic nerve abnormalities

• Congenital contractures (e.g., arthrogryposis, club foot, congenital hip dysplasia) with associated brain abnormalities• Congenital deafness documented by postnatal testing

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Microcephaly Diagnosis• Prenatally:

• Can be difficult to diagnose• May be detected by routine ultrasound at

18-20 weeks • However, best identified on ultrasound later

in pregnancy (late second trimester, early third trimester)

• Infant: • CDC defines as head circumference < 3rd

percentile • CDC recommends INTERGROWTH-21st

standards http://intergrowth21.ndog.ox.ac.uk/

• Standard growth charts by gestation, sex, and age

http://intergrowth21.ndog.ox.ac.uk/

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Useful teaching video on how to measuring head circumferencehttps://www.youtube.com/watch?v=LW38bgQ9vVY

Measuring Head Circumference (HC)• Use tape measure that cannot be stretched• Securely wrap tape around widest possible

circumference of head– 1-2 finger-widths above eyebrow on forehead– At the most prominent part of back of head

• Take measurement 3 times and select the largest measurement to nearest 0.1 cm

• Optimal measurement at 24-36 hours after birth when molding of head has subsided

– Head shape can affect the accuracy of HC estimate of brain volume

https://www.youtube.com/watch?v=LW38bgQ9vVY

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Infectious Causes of Congenital Microcephaly

– In utero infections• Toxoplasmosis• Rubella• Cytomegalovirus (CMV)• Herpes• Human Immunodeficiency Virus (HIV)• Syphilis• Zika virus

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Study: Characterizing the Pattern of Anomalies in Congenital Zika Virus Syndrome for Pediatric Clinicians

Features differentiating Congenital Zika Virus Syndrome from other congenital infections:

• Severe microcephaly with partially collapsed skull• Thin cerebral cortices with subcortical calcifications• Macular scarring and focal pigmentary retinal mottling• Congenital contractures• Marked early hypertonia with symptoms of

extrapyramidal involvement

Moore CA et al.JAMAPediatr.2016Nov.doi:10.1001/jamapediatrics.2016.3982

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Congenital Zika Virus Syndrome (CZVS)

Courtesy of CDC: https://www.youtube.com/watch?v=6P6008JbfIE

https://www.youtube.com/watch?v=6P6008JbfIE

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Etiology of Zika-related adverse fetal effects•Detected in brain tissue of a microcephalic fetus•Zika virus has been detected in chorionic villi in the placenta• Zika virus appears to primarily target neural progenitor cells resulting in:

• cell death • disruption of neuronal proliferation, migration and differentiation,

which slows brain growth and affects neural cell viability

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Cranial MorphologyProminent occiputSkin rugae

Biparietal depression

Courtesy of CDC: https://www.youtube.com/watch?v=6P6008JbfIE

Partial collapse of the skull with overlapping sutures

Consistent with fetal brain disruption sequence (FBDS)

Not all severe microcephaly will look like this

https://www.youtube.com/watch?v=6P6008JbfIE

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The Phenotypic Spectrum of CZVS

American Journal of Medical Genetics Part AVolume 173, Issue 4, pages 841-857, 22 MAR 2017 DOI: 10.1002/ajmg.a.38170http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.38170/full#ajmga38170-fig-0001

http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.v173.4/issuetoc

http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.38170/full#ajmga38170-fig-0001

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Craniofacial Disproportion




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Narrow and Laterally Depressed Frontal Bone




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Occipital Prominence




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Less Severe Microcephaly




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No Occipital Prominence




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Periorbital Fullness




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Epicanthial fold


Typically associated with syndromes



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Retrognathia


Pulmonary dysfunction Sleep apnea



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Redundant Skin



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Contractures and Deep Elbow Dimpling



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Hypertonia and Spasticity



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Eye Anomalies

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Coloboma

Congenital Cataract

Intraocular calcificationsMicropthalmia

Chorioretinal atropy Optic Nerve Atrophy

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Based on nearly 1,000 pregnant women with evidence of Zika who completed their pregnancies in 2016– 5% with possible Zika had birth defects – 10% with confirmed Zika had birth defects – 15% with confirmed Zika in the first

trimester had birth defects

New Vital Signs ReportZika Virus: Protecting Pregnant Women and Babies

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CZVS Long Term Effects- van der Linden Study•13 Zika positive infants with normal head circumference at birth in Brazil•All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome,

• Including decreased brain volume• Ventriculomegaly• Subcortical calcifications• Cortical malformations.

•All infants, head growth was documented to have decelerated • As early as 5 months of age• 11 infants had microcephaly

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CZVS Long Term Effects

•Functional effects include:• Intellectual impairment• Seizures• Feeding difficulties• Visual and hearing impairment• Movement disorder

•Range may include milder effects (neurodevelopmental delays) not seen in newborns

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Clinical Care: Evaluation of Pregnant Women

• Obtain recent travel history from all pregnant women about their travel and their sexual partner’s travel

• NYSDOH recommends providers offer testing for all pregnant women who may have been exposed to Zika virus – Whether pregnant woman is symptomatic OR

asymptomatic– Any time after travel* (NYS specific)– Ideally as soon as possible after symptoms– Whether or not the partner had symptoms

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Sexual Transmission - Recommendations

• If partner is pregnant – Abstain or condom use throughout the duration of the pregnancy– Consider same for non-pregnant partners

• If not pregnant and not trying to get pregnant use contraception

• Suggested timeframe to wait before trying to conceive – Women should wait at least 8 weeks after possible exposure– Men should wait at least 6 months after possible exposure

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1. PCR assay: 1. To detect viral RNA in serum and urine

2. Antibody testing: 1.Screening antibody tests (Zika IgM ELISA and Flavivirus Total Antibody (WNV MIA))

• If negative (and correct timing) done2.If either screen is positive a more specific antibody test - PRNT

• Plaque reduction neutralization test (PRNT) to determine if neutralizing antibodies to Zika or Dengue

Diagnostic Testing for Zika Virus

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• More specific diagnostic assay • It is a biological assay based on the interaction of virus and

antibody resulting in inactivation of virus so it is no longer able to infect and replicate in cell culture

• This assay measures the titer of the antibodies in the serum of the infected individual – Total antibody test (mostly IgG)– Cross reacting antibodies

Arbovirus Plaque Reduction Neutralization Test (PRNT)

http://www.cdc.gov/dengue/clinicalLab/laboratory.html

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Reporting Suspect Zika Virus Cases

• Healthcare providers are required to report all suspected cases to the local health

department where the patient resides

• Timely reporting allows NYSDOH and local health departments to assess and reduce the

risk of local transmission or mitigate further spread

Contact the NYSDOH Zika Information Line at:1-888-364-4723

9AM-5PM weekdays

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New York City Contact Information

Provider Access Line (PAL): 1-866-692-3641Monday to Friday, 9 a.m. to 5 p.m., weekdays

Additional information is available at: www.nyc.gov/zika/provider

http://www.nyc.gov/zika/provider

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Why is it important to monitor birth defects?• Relatively common: 3-5% of live births

• Leading contributor to infant and childhood deaths

• While the majority of children will survive, they and their families may face health, financial and/or other challenges

• Effective/timely referral to health/social services can drastically improve long term outcomes and quality of life

• Cause of 80% of birth defects is unknown

• Studying birth defects will eventually help us understand what causes them and lead towards prevention Zika virus

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Congenital Malformations Registry (CMR) CMR established under Environmental Disease Surveillance Program in

1982, as a result of “Love Canal” (Niagara Falls, NY) Includes children diagnosed up to 2 years of age, born/residing in NY,

with a major birth defect, chromosomal anomaly or persistent metabolic defect. Requires reporting by hospitals & physicians within 10 days of diagnosis.

Improve quality and completeness through: match with Hospital Discharge database (SPARCS), discharge index review, audits

In NYS, there are about 240,000 births every year. Over 12,000 of these infants will have a major birth defect (about 5% of all births).

May 2016: • Nurse practitioners, physician assistants, midwives must report• Reporting of prenatally diagnosed defects required• Up to age 10 for fetal alcohol syndrome, heart defects, muscular

dystrophies and genetic conditions

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6/13/2017

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Q04 Other congenital malformations of the brain

Q04.8

Other specified congenital malformations of the brainArnold-Chiari syndrome, type IVAgenesis of part brainAgyriaAplasia of part of brainHydranencephalyHypoplasia of part of brainLissencephalyMicrogyriaPachygyria

Detail important for Zika BD Surveillance

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Non-Infectious Causes of Congenital Microcephaly

– Genetic causes• Single gene disorders (syndromes)• Chromosomal abnormalities, microdeletions, microduplications• Mitochondrial mutations

– In utero ischemia/hypoxia (e.g., placental insufficiency or abruption)– Teratogens (e.g., maternal alcohol, hydantoin)– Radiation– Mercury (e.g., fish and seafood)– Maternal conditions (e.g., poorly controlled diabetes, hyperphenylalaninemia)

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Types of microcephaly• Disproportionate – Head is small out of proportion to weight and length, which may be normal

for age and sex

• Proportionate – Head size, weight and length are all small for age and sex but proportional to each other

• “Relative” microcephaly – Head size measures within the normal range for age and sex, but is small out of proportion to the weight and length

• Congenital vs. acquired• Congenital: usually present prenatally or at birth/delivery

• Abnormal development of the brain (often genetic)• Arrest or destruction of normally-forming brain (e.g., infection, vascular disruption)

• Acquired: develops as result of late onset infection/insult (e.g., perinatal stroke), or after birth due to delivery complications, postnatal insult, trauma or infection

• HC is normal at birth. As the baby grows in length, the head becomes comparatively smaller

Surveillance is challenging!

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CMR Response to Zika: Monitor prevalence of Zika-related birth defects over time

• Establish baseline prevalence for microcephaly (births 2013-15)– Apply National Birth Defects Prevention Network definition

• Active surveillance of newborn Zika-related defects through medical record review

• Active surveillance of prenatally diagnosed defects (with maternal medical record review)

• Connecting families of affected newborns to Early Intervention services

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“Newborn” Microcephaly Cases by Birth Year, from SPARCS Inpatient (1990-2014)

150

100

50

0

150 cases

Upstate NY

NYC

CRUDE Microcephaly prevalence: 2-12/10,000 live births (US)(for births in 2009-13) 4.6-6.7/10,000 live births (NY)

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Exclusions:Acquired Microcephaly

(n=6)Possible Microcephaly (n=5)

Other Microcephaly, HC >5%Median: 12%,

Range: 5.1% – 99%

2.1/10,000 live births (n=146; 32%)

Less Severe Microcephaly, 3% ≤ HC ≤ 5%

0.7/10,000 live births(n=49; 11%)

Severe Microcephaly, HC <3%

3.6/10,000 live births(n=259; 57%)

Total Identified by Hospitals

(N=489)

Crude Microcephaly

6.6/10,000 live births(n=465)

No Documented Physician Diagnosis and No Abstractor

Diagnosis

(n=24)

Summary of Newborn Microcephaly Cases — NYS, 2013–2015

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Severe Congenital Microcephaly Cases and Prevalence —New York State, 2013–2015

LocationNo. (Prevalence per 10,000 live births)

2013 2014 2015 Total

New York State 81(3.4) 79(3.3) 99(4.2) 259(3.6)

New York City 52(4.7) 50(4.5) 55(5.0) 157(4.7)

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Health Service Area # of newborns with microcephaly

# of Births Prevalence (per 10,000 live births)

Western NY 33 45,914 7.2

Finger Lakes 23 39,301 5.9

Central NY 16 45,412 3.5

NY-Penn 2 8,547 2.3

Northeastern NY 7 40,676 1.7

Mid-Hudson 22 70,512 3.1

NYC 162 336,047 4.8

Nassau-Suffolk 19 86,668 2.2

ALL AREAS 284 673,077 4.2

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MediumPoverty

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NYCSeve

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Severe Congenital Microcephaly Prevalence Stratified by Census Tract Poverty — NYC, 2013–2015

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Requests for monthly discharge summaries and medical records

CDC provided a list of Birth Defects Potentially Linked to Zika Virus (Case Inclusion Guidance for Medical Record Abstraction)

Current CMR Goals: Determine prevalence of birth outcomes and birth defects related to Zika from Jan. 2016 onward

“Active surveillance”

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Surveillance for Prenatal Zika-related Defects ChallengingO35.xXXx Maternal care for known/suspected fetal abnormality

• O35.0XXx CNS malformation (7%)• O35.1XXx Chromosomal malformation (2%)• O35.3XXx Fetal damage from maternal viral disease (CMV, Rubella)• O35.8XXx Other fetal damage from listeriosis & toxoplasmosis (78%)• O35.9XXx Fetal anomaly, damage unspecified (12%)

O36.4XXx Maternal care for intrauterine death, fetal death NOS, fetal death after 20weeks gestation, late fetal death, or missed delivery

Z37.x Stillbirths

2016 SPARCS Inpatient Discharges for O35.xXXx and Z37.x: 1,354

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Report of Zika-related BDs, 2013-14*Characteristic Brain abnormality

or microcephalyNTDs & other

early brain malfs.Eye

abnormalitiesOther CNS

dysfunctionTotal

# infants/fetuses (n=747) 392 (52%) 229 (31%) 81 (11%) 45 (6%) 100%Pregnancy outcome:

Live birthLoss

89%11%

52%48%

100%0%

96%4%

79%21%

Earliest age defect noted (n=410): Prenatally<=28 days of delivery>28 days of delivery

55%27%18%

89%8%4%

7%54%39%

18%70%11%

56%28%17%

Prevalence/1,000 live births 1.50 0.88 0.31 0.17Expected #s in NYS Pre-Zika 360 211 74 41 686*Baseline Prevalence of Birth Defects Associated with Congenital Zika Virus Infection – MA, NC, Atlanta GA, 2013-14, MMWR, March 3, 2017

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CMR Connecting Families to Early Intervention (EI) Services

6/13/2017

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• Match newborns with Zika-related birth defects to EI

• If no referral made, EI Program in Albany will contact EI staff in local health departments to request follow up

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Zika birth defects surveillance team: Laura Brady, Amanda Stolz, Jessica Palacios, Marilyn Browne, Shriharsha Kothuru, Betsy Rees, Kassandra Piatt, Lisa Jackson, Sarah Bower, June Moore, Cris Pantea, Maria Ostoyich,

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Future Info• Several studies being done throughout world, especially in South American• CDC study

– Follow-up of children in Puerto Rico for 3 years - Zika Active Pregnancy Surveillance System (ZAPSS)

– Follow-up of children in US for 1 year US - Zika Pregnancy Registry (USZPR)• Potential for vaccine is moving quickly• Zika Vital Signs

– Look for CDC's new Vital Signs materials at https://www.cdc.gov/vitalsigns. – Zika Care Connect – now only 10 jurisdictions but growing, including link for HCP

to find labs • Identifying providers who can specifically care for Zika exposed women and children

– Available in English and Spanish

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https://www.statnews.com/2017/04/27/zika-microcephaly-brazil/


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"Zika and other diseases spread by (the Aedes aegypti mosquito) are really not controllable with current technologies," CDC Director Thomas Frieden said. "We will see this become endemic in the hemisphere.”

-Dr. Tom FriedenFormer CDC DirectorOctober 25, 2016



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Zika ResourcesCDC Zika Virus Information Page

Q&As for Obstetricians and Pediatricians http://www.cdc.gov/zika/index.html

NYSDOH Zika Virus Information PageAdvisories and webinarsTesting process one page information sheet for the publicStatewide mosquito-borne disease weekly reportSpecimen collection guidance at birth, pediatric guidance, laboratory result interpretation guidancehttp://www.health.ny.gov/diseases/zika_virus/

NYC DOHMH Zika virus Information Pagenyc.gov/zika/provider

http://www.cdc.gov/zika/index.html

http://www.health.ny.gov/diseases/zika_virus/

https://www1.nyc.gov/site/doh/health/health-topics/zika-virus.page

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Thank You!

Deborah Fox, MPH DirectorCongenital Malformations Registry(518) [email protected]

Nina Ahmad, MDMedical DirectorBureau of Epidemiology(518) [email protected]

QUESTIONS??

mailto:[email protected]

mailto:[email protected]

Documents

Zika Virus - Wild Apricot · 2017. 6. 14. · Zika Virus. US Zika Pregnancy Registry Tracking and Birth Defects Surveillance. Nina Ahmad, MD. Medical Director, Division of Epidemiology