This presentation summarizes what we know as of 10/27/16 about the connection between Zika virus and microcephaly, and what advice physicians could provide for their patients who are currently pregnant, or planning a pregnancy

1. Zika virus and microcephaly
Krisztian Magori, Ph.D.
Assistant Professor of Biostatistics
Department of Biology
Eastern Washington University

2. Zika virus in the news

3. 1. What is Zika virus disease? How is it connected to microcephaly?
2. How much risk there is in WA state?
3. What can you tell to your concerned patients?

4. What is Zika virus disease?
Zika Fever:
mostly asymptomatic
resolves in <1 week
Guillain-Barre Syndrome:
paralysis
Congenital microcephaly

5. How do we define microcephaly?
HC<2 SD
less than
mean
HC<3 SD
less than
mean
Calcifications,
ventriculomegaly

6. What is Zika virus?
• +-sense double-stranded RNA virus
• Flaviviridae family
• Discovered in the Ziika Forest in Uganda in 1947

7. How is Zika virus transmitted?

8. The spread of Zika virus around the globe

9. Evidence for Zika virus causing microcephaly

10. Case studies
Mlakar et al., NEMJ 2016
25 yr old European women who got pregnant in Natal,
Brazil in February 2015
symptoms of Zika infection in 13th week of gestation

11. Zika virus infects human neural progenitor
cells
Tang et al., Cell Stem Cell 2016

12. Zika virus infection causes placental damage
and fetal demise in mice
Miner et al., Cell 2016

13. Zika virus infects neural progenitors in the
adult brain of mice
Li et al., Cell Stem Cell 2016

14. Zika virus causes fetal brain damage following
infection of pregnant macaque
Waldorf et al., Nature Medicine 2016

15. Association between Zika virus infection and
brain abnormalities in case-control study
• 8 public hospitals in Recife, Brazil
• Cases are newborns with microcephaly
• 2 controls for each case
De Araujo, Lancet Inf Dis 2016

16. What percentage of infected mothers’
children have brain abnormalities?
French Polynesia (1%) Brazil (20%)
Brasil et al., NEJM 2016Cauchemez et al., Lancet 2016

17. Potential role of prior dengue virus infection
Anti-body dependent enhancement (dengue viruses)
Lots of dengue transmission in Brazil but not in
French Polynesia
Zika virus and dengue viruses closely related
Hypothesis: prior dengue infection of the mother
leads to more severe Zika infection through antibody-
dependent enhancement

18. Dengue antibodies enhance Zika infection
Dejnirattisai et al., Nature Immunology 2016

19. What is the prognosis for babies born with
Zika virus disease?
48 infants born in Brazil with probable congenital Zika virus
syndrome
Da Silva et al., Emerg. Inf. Dis. 2016

20. What is the prognosis?
Da Silva et al., Emerg. Inf. Dis. 2016

21. What is the prognosis?
6 infants born without
microcephaly developed
microcephaly subsequently
Cost of raising child w microcephaly
could be up to $4 M
Da Silva et al., Emerg. Inf. Dis. 2016

22. Similarities to other neuroteratogenic
diseases
In Humans:
TORCH: Toxoplasma, Other, Rubella,
Cytomegalovirus, Herpes Simplex
Other: VEEV, JEV
In Animals:
JEV, Schmallenberg, Akabane, Cache
Valley, Aino, Bluetongue, Bovine viral
diarrhea, Border disease, Classical
Swine Fever

23. 1. What is Zika virus disease? How is it connected to microcephaly?
2. How much risk there is in WA state?
3. What can you tell to your concerned patients?

24. Areas with active Zika virus transmission

25. Local transmission in Miami-Dade county, FL
180 local cases
reported
potentially 10
times as many
endemic
potential
recursion in the
Spring

26. Imported cases in the US
4016 cases in US
States
899 pregnancies
27,402 cases in
US territories
1,927
pregnancies in
US territories
28 microcephaly

27. What is the situation in WA state?
• 48 reported cases
• All imported
• No local transmission
• WA does not have the right
mosquito species

28. Aedes aegypti (yellow fever mosquito)

29. Aedes albopictus (Asian tiger mosquito)

30. Mosquitoes in WA

31. What can you tell to your patients concerned
about Zika virus disease?
1. Avoid travel to areas with active ZIKV transmission
2. Practice safe sex with partner who visited areas with
active ZIKV transmission in the last 6 month
3. If cannot avoid travel, practice extreme personal
protection
4. If already visited or had unprotected sex with partner
who visited, get tested

32. Avoid travel to areas w active transmission

33. Practice safe sex
Both men and women should
practice safe sex or abstinence
for 6 month following travel to
areas with active transmission or
6 month after onset of symptoms

34. If have to travel, practice extreme personal
protection

35. If already visited, get tested for ZIKV
All pregnant patients
should be assessed
for possible Zika
virus exposure at
each prenatal visit
Those who meet the
criteria should be
tested
RT-PCR, IgM, cross-
reactivity, PRNT
http://www.doh.wa.gov/YouandYourFamily/IllnessandDisease/ZikaVirus/healthcareprovidersClinicallabs

36. Resources if you have a patient with
confirmed Zika virus infection
1. US Zika Pregnancy Registry
http://www.cdc.gov/zika/hc-providers/registry.html
2. Jackson Memorial Hospital, University of Miami Zika
response unit
http://pediatrics.med.miami.edu/zika-response-team

37. Take-home messages
1. Zika virus causes a terrible disease, including
microcephaly and other adverse outcomes
2. Zika virus is actively transmitted by mosquitoes in
many parts of the world, but not WA
3. Pregnant women should not visit areas with active
transmission, and should practice safe sex with
partners who did travel to those areas
4. While the risk is real, it is very low, unless you visit
areas with active transmission