High-Risk Pregnancy Zika Virus This information is taken from High-Risk Pregnancy: Management Options â€“ a new, updatable online product being launched by Cambridge University Press later this year â€“ and is provided free-of-charge as a public service in the current Zika virus emergency. This content his been provided by Professor Bernard Gonik, Fann S. Srere Chair of Perinatal Medicine, Wayne State University School of Medicine. High-Risk Pregnancy is edited by Professor David James, Emeritus Professor of Fetomaternal Medicine, University of Nottingham; Professor Philip Steer, Emeritus Professor of Obstetrics and Gynaecology, Imperial College, London; Professor Carl Weiner, KE Krantz Professor and Chair, Obstetrics and Gynecology, University of Kansas; Professor Bernard Gonik, Fann S. Srere Chair of Perinatal Medicine, Wayne State University School of Medicine; and Professor Stephen Robson, Professor of Fetal Medicine, Newcastle University. To find out more about this and similar products, sign up for our alerts service at www.cambridge.org/alerts
Zika Virus Zika virus is a mosquito-borne flavivirus transmitted by Aedes aegypti mosquitoes. These mosquitoes also transmit dengue and chikungunya virus. They are found throughout much of the Americas and in Africa. An estimated 80% of persons infected with Zika virus are asymptomatic. Symptomatic disease is generally mild and characterized by fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis. Symptoms usually last from several days to one week. Severe disease requiring hospitalization is uncommon, and fatalities are rare. Guillain-BarrĂŠ syndrome has been reported in patients following Zika virus infection. (185, 186)
Maternal and Fetal Risks The natural history of Zika virus infection has not been clearly elucidated, particularly in pregnant women. It appears that pregnant women can be infected with the Zika virus in any trimester. (185) The incidence in pregnancy is not currently known and likely varies substantially based on geographic location. It is not believed that pregnant women are more susceptible to Zika virus infection or experience more severe disease. Maternal-fetal transmission of Zika virus has been documented in pregnancy. (187, 188) Although Zika virus RNA has been detected in the tissue of fetal losses, it is not known if this infection was the etiology for the fetal demise.(189) Zika virus infection has been confirmed in infants identified to have congenital microcephaly.(189) In a recent Zika virus outbreak in Brazil, a marked increase in the number of infants born with microcephaly has been reported, suggesting an association.(190) The full spectrum of outcomes that might be due to Zika virus infections during pregnancy is undetermined and is actively being investigated.
Treatment There is neither a vaccine nor prophylactic pharmacotherapy available to prevent Zika virus infection. The Center for Disease Control and Prevention (CDC) recommends that all pregnant women avoid travel to areas where Zika virus transmission is active. (191) If a pregnant woman must travel to an endemic area for Zika virus infection, she is advised to follow steps to avoid mosquito bite exposures.(192) These include wearing long-sleeved garments and long pants, using U.S. Environmental Protection Agency (EPA)-registered insect repellents, using permethrin-treated clothing, and staying in
Zika Virus screened-in or air-conditioned facilities. When used properly, insect repellents containing DEET, picaridin, and IR3535 are considered safe for pregnant women.(193) The approach to Zika virus identification in maternal serum involves reverse transcription-polymerase chain reaction (RT-PCR) testing for symptomatic patients with onset of symptoms within a one week period-of-time. Immunoglobulin M (IgM) and neutralizing antibody testing should also be performed on specimens collected > 4 days after onset of symptoms. Antibody cross-reactivity with related flaviviruses (e.g., dengue or yellow fever) is common, and may result in diagnostic uncertainty. Given the similar geographic distributions and clinical presentations, selective consideration should be given to a concomitant evaluation for dengue and chikungunya infections. Testing of asymptomatic pregnant women is not recommended in the absence of ultrasoundidentified fetal microcephaly or other related intracranial abnormalities.(194) Preliminary data suggests Zika virus RT-PCR testing can be performed on amniotic fluid samples. However, the sensitivity and specificity for establishing a congenital infection diagnosis has not yet been determined. Similarly, it is at present undetermined if a positive result is predictive of a subsequent fetal abnormality, or what proportion of neonates born after infection will have symptomatic disease.(194) The CDC recommends that for a live birth with evidence of maternal or fetal Zika virus infection, the following tests be undertaken: 路 histopathologic examination of the placenta and umbilical cord; 路 testing of frozen placental tissue or cord tissue for Zika virus RNA; 路 testing of cord blood for Zika and dengue virus IgM and neutralizing antibodies. Since most commercial laboratories do not routinely run these studies, coordinated efforts should be undertaken with governmental health agencies. If a pregnancy results in a fetal loss in a symptomatic women with a travel history to an endemic area during or within 2 weeks of travel, or there is a finding of fetal microcephaly, Zika virus RTPCR and immunohistochemical staining should be performed on fetal tissues, umbilical cord and placenta.(194) No specific antiviral therapy is available for Zika virus infection. Treatment is generally supportive and can include rest, fluids, and use of analgesics and antipyretics. In a pregnant woman with laboratory evidence of Zika virus in serum or amniotic fluid, serial ultrasound scans should be considered to monitor fetal anatomy and growth through the remainder of the pregnancy.(194) Weblink: wwwnc.cdc.gov/travel/notices
Summary of Management Options Zika virus Management Options
Diagnosis (serological testing requires liaison with approved laboratory): · In symptomatic pregnant women: maternal serum testing one week after symptoms with
– reverse transcription-polymerase chain reaction (RT-PCR) testing – Immunoglobulin M (IgM) and neutralizing antibody testing NOTE: Antibody cross-reactivity with related flaviviruses (e.g., dengue or yellow fever) is common so test for concomitant infection with these · Significance of positive testing for fetus and newborn is unknown · In asymptomatic pregnant women testing is not recommended in the absence of ultrasound-identified fetal microcephaly or other intracranial abnormalities · For livebirth with evidence of maternal and/or fetal Zika infection – histopathologic examination of the placenta and umbilical cord – test frozen placental tissue or cord tissue for Zika virus RNA; – test cord blood for Zika and dengue virus IgM and neutralizing antibodies. Treatment: · Pregnant women should avoid travel to areas where there is active Zika transmission
191 192, 193
· Normal measures to avoid mosquito bites: – long-sleeved garments and long pants – use Environmental Protection Agency (EPA)-registered insect repellents – use permethrin-treated clothing – stay in screened-in or air-conditioned facilities NOTE Insect repellents containing DEET, picaridin, & IR3535 are considered safe in pregnancy · With symptomatic women with positive serological testing: – Supportive treatment (rest, fluids, analgesics, antipyretics) – Serial ultrasound scans to monitor fetal anatomy and growth (especially head)
Zika Virus 185. CDC. Zika virus. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. 186. Oehler E, Watrin L, Larre P, et al. Zika virus infection complicated by Guillain-Barre syndrome – case report, French Polynesia, December 2013. Euro Surveill 2014;19:4-6. 187. Besnard M, Lastere S, Teissier A, Cao-Lormeau V, Musso D. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill 2014;19:13. 188. Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 2016;47:6-7. 189. CDC. CDC health advisory: recognizing, managing, and reporting Zika virus infections in travelers returning from Central America, South America, the Caribbean and Mexico. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. 190. European Centre for Disease Prevention and Control. Rapid risk assessment. Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. Stockholm, Sweden: European Centre for Disease Prevention and Control; 2015. 191. CDC. Travelers’ health. CDC issues interim travel guidance related to Zika virus for 14 countries and territories in Central and South America and the Caribbean. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. 192. CDC. Zika virus: prevention. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. 193. CDC. West Nile virus: insect repellent use & safety. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. 194. Petersen EE, Staples JE, Meaney-Delma D, et al. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak – United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65:3033. CDC; 2015.
Free online Zika Virus chapter from the forthcoming Cambridge University Press product 'High Risk Pregnancy'