Zika Virus. ZIKA VIRUS & PREGNANCY Stephen Champlin, M.D. FLAVIVIRIDAE VIRUS SPECTRUM. Virus family Flaviviridae

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1 ZIKA VIRUS & PREGNANCY Stephen Champlin, M.D. Zika Virus Virus family Flaviviridae Positive sense, single-stranded RNA virus FLAVIVIRIDAE VIRUS SPECTRUM Arbovirus - spread by arthropods to mammals

2 Flaviviridae Arboviruses Mosquito-borne viruses Yellow Fever virus Dengue virus Chikungunya St. Louis Encephalitis virus Zika virus Yellow Fever Fever Myalgia Chills Symptoms Jaundice Nausea 50% mortality rate Yellow Fever -150,000 to 250,000 yearly infections -40,000 to 60,000 yearly deaths Dengue Fever Symptoms Fever Fatigue Myalgia(severe) Rash Headache

3 Chikungunya Virus DENGUE FEVER break-bone fever 5-10% mortality rate symptoms -fever -arthralgias (severe) -headache -rash CHIKUNGUNYA VIRUS Mortality 0.1% Zika virus ZIKA VIRUS FIRST ISOLATED IN ZIKA FOREST IN UGANDA IN 1947 FROM MONKEYS 1947 isolated in Rhesus monkeys 1948 isolated in Tiger mosquitos

4 Zika Forest, Uganda Zika Forest is 62 acres in size 40 species of mosquitos Zika Fever 80% asymptomatic Zika Fever signs Maculopapular rash conjunctivitis Incubation period 2 14 days Symptoms last 3 7 days Guillain-Barre syndrome risk of development is 1 in every 4000 cases of infection

5 Zika Virus Treatment Zika Virus Transmission no drug or vaccine currently available Simeprevir shows some promise Primarily spread by Aedes Aegypti & Aedes Albopictus mosquito Infected human can pass virus to mosquitos for 2 weeks post symptoms Mosquitos can carry virus for all of their day lifetime NSAIDs, Tylenol, hydration, and rest Mosquito Transmission Blood Transmission 2 cases of transmission in Brazil Blood Transfusion Aedes aegypti has inhabited North America for over 200 years. Aedes albopictus was introduced to the United States in USFDA screens all U.S. blood donations and no transmission has occurred French Polynesia 8% of blood donors tested Zika positive

6 Sexual Transmission Sexual Transmission Vaginal sex Zika virus RNA found in semen 188 days post symptom Sharing of sex toys Sexual Transmission Anal sex Whole zika virus found in semen 69 days post symptom Oral sex Live virus detected in semen, vaginal secretions, saliva, urine, and breast milk Pregnancy Transmission Whole blood Plasma Platelets Chyle Can spread vertically during pregnancy and delivery MATERNAL SOURCE OF INFECTION DOES NOT INFLUENCE THE DEGREE OF INFECTION TO FETUS Vaginal secretions

7 Pregnancy Transmission of the Zika Virus Transplacental transfer from early first trimester (week 6) to delivery is documented Fetal Chorionic Villi Zika virus breaks up the cells making up the chorionic villus, which allows the influx of virus. Zika and Spontaneous Abortions 2016 Rio de Janeiro study of 125 women with 1 st trimester exposure showed 40% spontaneous abortion rate

8 Zika virus spreads across the Globe YAP ISLAND 2007 population: 11,000-7,500 people acquire Zika fever infection no deleterious fetal consequences or GBS French Polynesia FRENCH POLYNESIA, -100 grouped islands Population: 285, ,000 people acquire Zika infection *Neonatal neurological anomalies appear 1 st cases of cerebral anomalies & Guillain- Barre *Guillain-Barre cases appear FRENCH POLYNESIA, IN 2014, THE CASES OF FETAL CEREBRAL ANOMALIES INCREASED 700% FROM PREVIOUS YEAR Fetal cerebral anomalies: - microcephaly - ventricular dilation - thin/absent corpus callosum,vermis

9 BRAZIL, August 2014 Over 28 months millions infected with Zika virus Perfect storm for Zika epidemic Dense population subtropical climate Endemic mosquitos Tourist influx 2015 Costa Rica These are high RISK areas for These pregnant areasttt women or those planning pregancy 2015 Zika Virus arrives Central America Mexico Caribbean Islands Purple designation by the CDC MIAMI, August mosquitoborne infection 847 travel related infections 108 pregnant women infected *No local Zika infections in more than 210 days

10 BROWNSVILLE, TX November cases of endogenous Zika fever New Orleans It s a small world Rio de Janeiro to Brownsville: 4,960 miles Zika virus traveled there in 20 months -1 case in 2017 Brownsville to New Orleans: 699 miles Brownsville Consequences of Maternal to Fetal Transmission of the Zika Virus targets neuronal progenitor cells and neuronal cells at all stages of maturity disrupts neuronal proliferation, migration, and differentiation slows brain development in utero and in infancy SYMPTOMATIC VS. ASYMPTOMATIC Maternal infection symptoms do not matter with regard to fetal consequences Remember - 80% of infected individuals are asymptomatic

11 Timing of Maternal Infection The earlier in gestation, the worse the prognosis study 433 Brazilian patients 1 st Trimester 2 nd Trimester 55% adverse outcome 52% adverse outcome Pregnancy outcomes in U.S. and U.S. territories ,427 zika affected pregancies 1,784 completed pregnancies 91 infants zika-associated birth defect Overall adverse outcome rate of all congenital Zika infections is ~42% 3 rd Trimester 29% adverse outcome 5.1% affected rate at birth Congenital neurologic manifestations hypoplasia/absent: cerebellum vermis brainstem corpus callosum cerebral lobes optic abnormalities hearing loss Congenital neurologic manifestations Cerebral calcifications Abnormal gyrations

12 Congenital neurologic manifestations microcephaly ventriculomegaly Other congenital manifestations clubfoot arthrogryposis limb hypertonia Use mosquito nets and fix screens in doors and windows Remove standing water from surroundings

13 Prevention of Zika infection: travel Prevention of Zika infection: sex Pregnant women: NO travel to areas where mosquito borne Zika infections are ongoing Women considering pregnancy: wait at least 8 weeks after travel to Zikaexposed areas to conceive Pregnant women: NO unprotected sex with a partner who traveled to Zika-affected areas for the entire pregnancy Women considering pregnancy: NO unprotected sex with a partner who traveled to Zika-affected areas for 6 months after travel Who to screen during pregnancy? Those who traveled to a Zikaaffected area during pregnancy, or within 8 weeks before conception. Those who have had unprotected sex during pregnancy with a person who has traveled to a Zika-affected area within 6 months (men) or 8 week (women). NAT (RT-PCR) within 60 days of exposure or symptom onset Blood, urine, amniotic fluid acceptable Testing for Zika Elisa IgM 2-12 weeks post-exposure or symptom onset blood, urine, or amniotic fluid acceptable Plaque reduction neutralization test distinguishes among Zika Dengue fever & Chikungunya infection with + IgM.

14 RT-PCR 14 days after exposure (+) zika IgM 2-12 weeks after exposure (-) no recent infection (+) perform PRNT Pregnant and exposed to Zika? (+) zika (-) non-zika serial U/S monitor head growth and anatomy UPDATED CDC MATERNAL SCREENING JULY 24, 2017 PREGNANT AND EXPOSED SYMPTOMATIC TEST BLOOD,URINE WITH NAT & ELISA IgM + NAT - NAT/+ IGM - NAT/ - IgM ACUTE ZIKA INFECTION PRNT NO ACUTE ZIKA INFECTION UPDATED CDC MATERNAL SCREENING JULY 24, 2017 PREGNANT AND EXPOSED ONGOING EXPOSURE TEST X 3 BLOOD, URINE NAT ASYMPTOMATIC NON-ONGOING EXPOSURE COUNSEL ABOUT TESTING INFANT TESTING urine & blood NAT, IgM head ultrasound hearing test Placenta and Umbilical cord NAT, virus immunohistochemical staining Zika positive mother at delivery

15 Future pregnancies in Zika-exposed mother future pregnancies are not affected by a current Zika infection virus is cleared from mother in 6 8 weeks Long-term immunity via IgG may happen, partial or complete, for an unknown time amount educate Physician patient dialog educate educate Physician-patient dialog about Zika virus with all women planning pregnancies Similar tombs erected quickly during the 1878 yellow fever epidemic in New Orleans. Lafayette Cemetary No. 1 Those who fail to learn from history are doomed to repeat it. George Santayana

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