Zika Virus A Public Health Emergency of Olympic Proportions

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1 Zika Virus A Public Health Emergency of Olympic Proportions Carrie L. Byington M.D.** HA and Edna Benning Presidential Professor Division of Pediatric Infectious Diseases ** With Thanks to Andrew Pavia, MD

2 Disclosure Carrie Byington Has IP and receives royalties from BioFire Diagnostics

3 Map What is Zika? Where did it come from? Epidemiology and transmission? Why worry? Why is it emerging now and where is it going? What do we know and not know about congenital Zika syndrome? What is the Olympic study and how will it help us answer the unknowns?

4 Zika virus basics Discovered by Rockefeller Foundation arbovirus researchers Macaque 1947, Mosquito 1948, Human 1954 Genus Flavivirus (Family Flaviviridae) 26 vector borne human pathogenstick & mosquito vectors neuroinvasive or hemorrhagic Hepatitis C WNV JEV SLV DNV YFV

5 What a long strange trip it s been Virus isolated by Haddow and Dick in 1947 from ill monkey, transmitted to brains of mice detected in mosquitoes 1952 published findings human cases 1956 William Bearcroft injected himself with suspension of Zika infected mouse brains and developed fever and headache

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8 Rates of Microcephaly by State in Brazil vs

9 AP Photos/Felipe Dana

10 The more we learn, the worse things seem to get Anthony Fauci March 10, 2016 They misunderestimated me George W Bush Nov 6, 2000

11 October 5, 2016

12 Zika Virus Transmission

13 Approximate Ranges of A. aegypti and A. albopictus in the United States (as of March 2016) Petersen LR et al. N Engl J Med 2016;374:

14 Clinical Spectrum of Zika Virus Infection Asymptomatic infection (80%) Zika virus syndrome Congenital Zika Syndrome Guillain Barre Syndrome Uveitis Encephalitis Myelitis ITP Viral sepsis syndrome

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16 Evidence supporting maternal fetal transmission and fetal toxicity Epidemiologic consistency across countries Strength of association Zika virus detected prenatally in amniotic fluid in abnormal pregnancy Zika virus infection confirmed in infants with Zika virus RNA identified in specimens of fetal losses Case Control Study OR 55 (Lancet ID Sept 16, 2016) Evidence of viral tropism and killing of neural progenitors Mouse models Rasmussen, et al., N Engl J Med May 19.

17 Mlakar J, et al., N Engl J Med Feb 10.

18 Figure 1 The Lancet , DOI: ( /S (16) )

19 Cases of Zika Virus (ZIKV) Disease and the Guillain Barré Syndrome (GBS). dos Santos T et al. N Engl J Med DOI: /NEJMc

20 Cases of Zika Virus (ZIKV) Disease and the Guillain Barré Syndrome (GBS). dos Santos T et al. N Engl J Med DOI: /NEJMc

21 Sex in the age of Zika Male to female, male to male and female to male documented Vaginal, anal, oral sex and sharing of sex toys Strongest link with M to F during symptomatic infection Transmission in absence of symptoms documented Duration of infectivity unknown. RNA in semen at 6 months in 2 men

22 Prevention Pregnant women should avoid travel to areas of transmission Mosquito bite avoidance Prevent sexual transmission to pregnant women Men with pregnant partner Use condoms or abstain for duration of pregnancy If not contemplating pregnancy Men should use condoms/abstain for 6 months Women should abstain/use condoms for 8 weeks

23 Testing PCR detects infection in blood 3 7 days; urine for at least 14 days Trioplex rrt PCR detects ZKV, DNV, Chikungunya Zika IgM Antibody capture ELISA (MAC ELISA) positive 2 12 weeks after infection Extensive cross reaction with DNV, Chik, YFV Must be confirmed by PRNT Test pregnant women (PCR) up to 2 wks after symptoms Test pregnant women (IgM) 2 12 weeks after last exposure To discuss testing, contact your local health department or UDOH,

24 Updated (Aug 2016) pregnancy guidance

25 Why now? Why is transmission so explosive? Why more severe disease? Why more congenital disease?

26 Why so explosive Transmission has changed to urban suburban cycle Naïve population Adaptation to different Aedes sp.? Longer viremia? More efficient sexual transmission?

27 Why so severe Antibody dependent enhancement? Viral adaptation for trophoblast and neural progenitor cell infection? Improved recognition during an enormous outbreak?

28 Calvet Lancet 2016 epub Feb 18 Has Zika Virus changed?

29 Structural changes in Asian/American lineage Wang L. Cell Host & Microbe (2016),

30 Prospects for control Exhaustion of susceptibles Screening of blood and organ donors Vector control Risk of unintended consequences Vaccine Who to target? Antivirals (J Infect Dis Sep 1;214(5):707 11) For pregnant women?, infants? Grinding to a halt for lack of appropriations

31 Source: Duane Gubler

32 Congenital Zika Virus Syndrome

33 Definition Pattern of anomalies (Franca, G Lancet 2016) Microcephaly (1 13% of pregnancies) Intracranial Calcifications Eye Anomalies Our understanding of the syndrome is evolving Infants with ZIKV syndrome may be born to women with or without symptoms of Zika virus infection Some infants are born with normal head circumference Anomalies may not be detected at birth

34 Brain Vasco Aragano BMJ April 2016 Microcephaly Epidemic Research Group EID June 2016 Seizures and Cognitive Impairment

35 Vision DeMiranda HA Ophthalmology online May 2016 Hemorrhagic retinopathy Abnormal vasculature Torpedo and/or pigmentary maculopathy

36 Hearing Leal, MC, MMWR Sept 2, 2016 Two studies of Brazilian infants with ZIKV 5/69 (7%) with sensorineural hearing loss Other causes excluded Bilateral 3/5 Unilateral 2/5 Newborn Hearing Screen ABR

37 Orthopedic Abnormalities Van der Linden, V BMJ Aug 2016 Arthrogryposis Neurogenic Motor Neurons Central Peripheral Fixed position in utero Dislocated hips

38 Endocrine Abnormalities Infants with abnormal brain development are at risk for hypothalamic dysfunction which may lead to pituitary insufficiency Newborn screening may not detect endocrine abnormalities Thyroid screening recommended at 2 weeks and repeat at 3 months

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42 CDC and UDOH Resources ZIKV Pregnancy Registry Eligibility Pregnant women in US with lab evidence of ZIKV and their periconceptionally, prenatally or perinatally exposed Infants with lab evidence of congenital ZIKV Contact CDC or UDOH CDC: OR UDOH: Pregnancy Risk Line OR Bureau of Epidemiology

43 Training Opportunities Announcement in October 2016

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46 University of Utah Team Zika

47 NIH Supported Specific Aims

48 Results To Date 963 USOC travelers to Rio for Olympics enrolled 49% Women and 51% Men Approximately 13% of participants intend to conceive after the Games 19 participants were pregnant or had a pregnant partner at the time of the Games

49 Anticipated Results Zika Potentially 30 participants with evidence of Zika virus infection We will closely follow each one 7 dedicated specialists These individuals will submit body fluids each month for PCR testing for Zika virus to be performed at BioFire Validation of new Fever ID Panel

50 Anticipated Results Zika We will learn how long the virus persists in body fluids Symptomatic vs. asymptomatic Opportunity to look for transmission to partners We will capture reproductive outcomes Fertility after infection Pregnancy outcomes Outcomes of infants at birth and one year

51 Thank You