Why Did ZIKV Perinatal Outcomes Differ in Distinct Regions of Brazil? An Exploratory Study of Two Cohorts.

Luana Damasceno,Cassia F Estofolete,Isa Cristina R Piaulino,Andrea A Zin,Trevon Fuller,Nikos Vasilakis,Erna G Kroon,Maria E Moreira,Flor E Martinez Espinosa,Márcia C Castilho,Adriana Andrade,Zilton Vasconcelos,Jose P Pereira,Patricia Brasil,Maurício L Nogueira,Karin Nielsen-Saines,Ana Carolina B Terzian

doi:10.3390/v13050736

Abstract

The Zika virus (ZIKV) epidemic in Brazil occurred in regions where dengue viruses (DENV) are historically endemic. We investigated the differences in adverse pregnancy/infant outcomes in two cohorts comprising 114 pregnant women with PCR-confirmed ZIKV infection in Rio de Janeiro, Southeastern Brazil (n = 50) and Manaus, in the north region of the country (n = 64). Prior exposure to DENV was evaluated through plaque reduction neutralizing antibody assays (PRNT 80) and DENV IgG serologies. Potential associations between pregnancy outcomes and Zika attack rates in the two cities were explored. Overall, 31 women (27%) had adverse pregnancy/infant outcomes, 27 in Rio (54%) and 4 in Manaus (6%), p < 0.001. This included 4 pregnancy losses (13%) and 27 infants with abnormalities at birth (24%). A total of 93 women (82%) had evidence of prior DENV exposure, 45 in Rio (90%) and 48 in Manaus (75%). Zika attack rates differed; the rate in Rio was 10.28 cases/10,000 and in Manaus, 0.6 cases/10,000, p < 0.001. Only Zika attack rates (Odds Ratio: 17.6, 95% Confidence Interval 5.6–55.9, p < 0.001) and infection in the first trimester of pregnancy (OR: 4.26, 95% CI 1.4–12.9, p = 0.011) were associated with adverse pregnancy and infant outcomes. Pre-existing immunity to DENV was not associated with outcomes (normal or abnormal) in patients with ZIKV infection during pregnancy.

Highlights

In recent decades, Brazil has experienced significant flavivirus epidemics, including dengue serotype 1 (DENV-1) in 1998, dengue viruses (DENV)-3 in 2002, DENV-2 in 2008, DENV-4 in 2010, Zika virus (ZIKV) in 2015–2016, and the reemergence of the Yellow Fever (YF) in 2017 [1,2]
Women infected in the first trimester were more likely to deliver infants with abnormalities, adding to the growing evidence that ZIKV infection early in pregnancy has a generalizable association with microcephaly [29]
A theory has been mooted that pre-existing immunity to co-circulating flaviviruses from prior natural infection or from vaccination to YF may influence ZIKV disease severity and pregnancy outcomes [42]

Summary

Introduction

Brazil has experienced significant flavivirus epidemics, including dengue serotype 1 (DENV-1) in 1998, DENV-3 in 2002, DENV-2 in 2008, DENV-4 in 2010, Zika virus (ZIKV) in 2015–2016, and the reemergence of the Yellow Fever (YF) in 2017 [1,2]. Among these flaviviruses, dengue and Zika had the highest prevalence and the greatest degree of geographic overlap and co-circulation in large cities [2,3]. Between 2015 and 2016, Rio de Janeiro reported 578 cases of microcephaly, while Amazonas reported 25 cases [12]

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Conclusion