Previously considered to cause limited human infection and mild disease, Zika virus (ZIKV) caused several large outbreaks in Yap Island in 2007, in French Polynesia in 2013-2014 and the 2015-2016 epidemic across the Americas which resulted in large outbreaks in several regions of the world. These outbreaks identified severe neurological complications associated with acute ZIKV infection, including congenital malformations in fetuses and newborns and Guillain-Barré syndrome in adults. Our projects on ZIKV seek to quantify the risk of adverse health outcomes following ZIKV infection and contribute to better understanding the health impact of ZIKV around the world.
During the 2013-2014 epidemic in French Polynesia, the first neurological complications associated with ZIKV infection were described. A case control study of 42 adult patients in French Polynesia during the ZIKV epidemic with Guillain Barré syndrome, found all cases to have detectable neutralizing antibodies against ZIKV, implicating ZIKV as the cause of Guillain Barré syndrome (Cao-Lormeau et al, 2016). In retrospective analysis of data from the epidemic, we were also able to demonstrate an increased risk of microcephaly in fetuses of women who had ZIKV infection during pregnancy (Cauchemez S et al, 2016).
French territories of the Americas
During the 2016 epidemic, we conducted a population-based cohort study of pregnant women in Guadeloupe, Martinique and French Guiana. We were able to estimate a 7% (95%CI:5-10) risk of neurologic and ocular abnormalities in the fetuses or neonates of women with symptomatic, RT-PCR-confirmed ZIKV infection during pregnancy (Hoen B et al, 2018). In further assessment of these neurologic and ocular abnormalities in fetuses born to women without ZIKV infection during pregnancy, we were able to revise the risk of birth defects attributable to ZIKV infection to 1.6% (95% CI:0.4-4.1) (Funk AL et al, 2021). In the follow-up study of toddlers born to women who were pregnant during the 2016 epidemic, we found that among toddlers with and without in utero ZIKV exposure, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age (Grant R et al, 2021).
Enhanced epidemiological surveillance for ZIKV infection following the 2015-2016 epidemic in the Americas identified RT-PCR confirmed infections in pregnant women in Southern Vietnam. In prospective virological and epidemiological analyses, we were able to identify a clade within the ZIKV Asian lineage implicated in the outbreak, to describe adverse pregnancy outcomes, including fetal abnormalities, and demonstrate the persistence of anti-ZIKV antibodies beyond three years post-infection (Grant R et al, 2021).
Cao-Lormeau VM, Blake A, Mons S, Lastère S, Roche C, Vanhomwegen J, Dub T, Baudouin L, Teissier A, Larre P, Vial AL, Decam C, Choumet V, Halstead SK, Willison HJ, Musset L, Manuguerra JC, Despres P, Fournier E, Mallet HP, Musso D, Fontanet A, Neil J, Ghawché F. Guillain-Barré syndrome outbreak caused by Zika virus infection in French Polynesia: a case control study. Lancet 2016; 387:1531–9.
Cauchemez S, Besnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D, Salje H, Van Kerkhove MD, Abadie V, Garel C, Fontanet A, Mallet HP. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet. 2016;387(10033):2125–2132.
Hoen B, Schaub B, Funk AL, Ardillon V, Boullard M, Cabié A, Callier C, Carles G, Cassadou S, Césaire R, Douine M, Herrmann-Storck C, Kadhel P, Laouénan C, Madec Y, Monthieux A, Nacher M, Najioullah F, Rousset D, Ryan C, Schepers K, Stegmann-Planchard S, Tressières B, Voluménie JL, Yassinguezo S, Janky E, Fontanet A. Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas. N Engl J Med. 2018 Mar 15;378(11):985–994.
Funk AL, Hoen B, Vingdassalom I, Ryan C, Kadhel P, Schepers K, Gaete S, Tressières B, Fontanet A. Reassessment of the risk of birth defects due to Zika virus in Guadeloupe, 2016. PLoS Negl Trop Dis. 2021; 15: e0009048.
Grant R, Fléchelles O, Tressières B, Dialo M, Elenga N, Mediamolle N, Mallard A, Hebert JC, Lachaume N, Couchy E, Hoen B, Fontanet A. In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study. BMC Med. 2021;19(1):12.
Grant R, Nguyen TTT, Dao MH, Pham HTT, Piorkowski G, Pham TDT, Cao MT, Huynh LTK, Nguyen QH, Vien LDK, Lemoine F, Zhukova A, Hoang DTN, Nguyen HT, Tran NT, Le LB, Ngo MNQ, Tran TC, Le NNT, Nguyen MN, Pham HT, Hoang TTD, Dang TV, Vu AT, Nguyen QNT, De Lamballerie X, Pham QD, Luong QC, Fontanet A. Maternal and neonatal outcomes related to Zika virus in pregnant women in Southern Vietnam: an epidemiological and virological prospective analysis. The Lancet Regional Health – Western Pacific. 2021 (Accepted for publication)
Shen S, Xiao W, Zhang L, Lu J, Funk A, He J, Tu S, Yu J, Yang L, Fontanet A, Bao W, Cheng KK, Qiu X. Prevalence of congenital microcephaly and its risk factors in an area at risk of Zika outbreaks. BMC Pregnancy Childbirth. 2021;21:214. doi: 10.1186/s12884-021-03705-9.
Pomar L, Lambert V, Madec Y, Vouga M, Pomar C, Matheus S, Fontanet A, Panchaud A, Carles G, Baud D. Placental infection by Zika virus in French Guiana. Ultrasound Obstet Gynecol. 2019. doi: 10.1002/uog.21936
Hoen B, Carpentier M, Gaete S, Tressières B, Herrmann-Storck C, Vingadassalom I, Huc-Anaïs P, Funk AL, Fontanet A, de Lamballerie X. Kinetics of Anti-Zika Virus Antibodies after Acute Infection in Pregnant Women. J Clin Microbiol. 2019;57. pii: e01151-19. doi: 10.1128/JCM.01151-19.
Depoux A, Philibert A, Rabier S, Philippe HJ, Fontanet A, Flahault A. A multi-faceted pandemic: a review of the state of knowledge on the Zika virus. Public Health Rev. 2018 May 15;39:10.
Dub T, Fontanet A. Zika virus and Guillain-Barré syndrome. Rev Neurol (Paris). 2017;173:361-363.
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