Zika virus and microcephalyKrisztian Magori, Ph.D.

Assistant Professor of BiostatisticsDepartment of Biology

Eastern Washington University

Zika virus in the news

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?

What is Zika virus disease?

Zika Fever: mostly asymptomaticresolves in <1 week

Guillain-Barre Syndrome:paralysis

Congenital microcephaly

How do we define microcephaly?

HC<2 SD less than mean

HC<3 SD less than mean

Calcifications, ventriculomegaly

What is Zika virus?

• +-sense double-stranded RNA virus• Flaviviridae family• Discovered in the Ziika Forest in Uganda in 1947

How is Zika virus transmitted?

The spread of Zika virus around the globe

Evidence for Zika virus causing microcephaly

Case studies

Mlakar et al., NEMJ 201625 yr old European women who got pregnant in Natal, Brazil in February 2015symptoms of Zika infection in 13th week of gestation

Zika virus infects human neural progenitor cells

Tang et al., Cell Stem Cell 2016

Zika virus infection causes placental damage and fetal demise in mice

Miner et al., Cell 2016

Zika virus infects neural progenitors in the adult brain of mice

Li et al., Cell Stem Cell 2016

Zika virus causes fetal brain damage following infection of pregnant macaque

Waldorf et al., Nature Medicine 2016

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

What percentage of infected mothers’ children have brain abnormalities?

French Polynesia (1%) Brazil (20%)

Brasil et al., NEJM 2016Cauchemez et al., Lancet 2016

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

Dengue antibodies enhance Zika infection

Dejnirattisai et al., Nature Immunology 2016

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

What is the prognosis?

Da Silva et al., Emerg. Inf. Dis. 2016

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

Similarities to other neuroteratogenicdiseases

In Humans:TORCH: Toxoplasma, Other, Rubella, Cytomegalovirus, Herpes SimplexOther: VEEV, JEV

In Animals:JEV, Schmallenberg, Akabane, Cache Valley, Aino, Bluetongue, Bovine viral diarrhea, Border disease, Classical Swine Fever

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?

Areas with active Zika virus transmission

Local transmission in Miami-Dade county, FL180 local cases reported

potentially 10 times as many

endemic

potential recursion in the Spring

Imported cases in the US4016 cases in US States

899 pregnancies

27,402 cases inUS territories

1,927 pregnancies in US territories

28 microcephaly

What is the situation in WA state?

• 48 reported cases

• All imported

• No local transmission

• WA does not have the right mosquito species

Aedes aegypti (yellow fever mosquito)

Aedes albopictus (Asian tiger mosquito)

Mosquitoes in WA

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

Avoid travel to areas w active transmission

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

If have to travel, practice extreme personal protection

If already visited, get tested for ZIKV All pregnant patients should be assessed for possible Zikavirus 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

Resources if you have a patient with confirmed Zika virus infection

1. US Zika Pregnancy Registryhttp://www.cdc.gov/zika/hc-providers/registry.html

2. Jackson Memorial Hospital, University of Miami Zikaresponse unithttp://pediatrics.med.miami.edu/zika-response-team

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