During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests. Sera sampled retrospectively during 2013 to 2015 from 277 HIV-infected patients were used to assess the spread of ZIKV over time. Individuals were georeferenced, and sociodemographic indicators were compared between ZIKV-positive and -negative areas and areas with and without microcephaly cases. Epidemiological key parameters were modeled in a Bayesian framework. ZIKV seroprevalence increased rapidly during 2015 to 2016, reaching 63.3% by 2016 (95% confidence interval [CI], 59.4 to 66.8%), comparable to the seroprevalence of DENV (75.7%; CI, 69.4 to 81.1%) and higher than that of CHIKV (7.4%; CI, 5.6 to 9.8%). Of 19 microcephaly pregnancies, 94.7% showed ZIKV IgG antibodies, compared to 69.3% of 257 non-microcephaly pregnancies (P = 0.017). Analyses of sociodemographic data revealed a higher ZIKV burden in low socioeconomic status (SES) areas. High seroprevalence, combined with case data dynamics allowed estimates of the basic reproduction number R0 of 2.1 (CI, 1.8 to 2.5) at the onset of the outbreak and an effective reproductive number Reff of <1 in subsequent years. Our data corroborate ZIKV-associated congenital disease and an association of low SES and ZIKV infection and suggest that population immunity caused cessation of the outbreak. Similar studies from other areas will be required to determine the fate of the American ZIKV outbreak.

The majority of cases of congenital ZIKV syndrome have other ultrasonographic findings in addition to microcephaly. ZIKV-related CNS anomalies present mainly as progressive CNS lesions and slowing rate of growth of the fetal head, and this seems to be evident only in the late second trimester, even when maternal infection occurs in the first trimester. Other ultrasound findings, such as ventriculomegaly, brain calcifications and posterior fossa destruction lesions, are also common in this congenital syndrome. Posterior fossa destruction lesions and arthrogryposis are an uncommon finding in other congenital infections, perhaps suggesting a novel severe congenital syndrome associated with fetal ZIKV. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

ZIKV-specific neutralizing antibody titers were significantly higher in 28 mothers of children with microcephaly than in 122 controls from northeastern Brazil, suggesting an unusually strong immunological stimulus and potential utility of maternal antibody titers to corroborate congenital ZIKV infection.

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