Abstract
BACKGROUND: A significant increase in microcephaly incidence was reported in Northeast Brazil at the end of 2015, which has since been attributed to an epidemic of Zika virus (ZIKV) infections earlier that year. Further incidence of congenital Zika syndrome (CZS) was expected following waves of ZIKV infection throughout Latin America; however, only modest increases in microcephaly and CZS incidence have since been observed. The quantitative relationship between ZIKV infection, gestational age and congenital outcome remains poorly understood. METHODOLOGY/PRINCIPLE FINDINGS: We characterised the gestational-age-varying risk of microcephaly given ZIKV infection using publicly available incidence data from multiple locations in Brazil and Colombia. We found that the relative timings and shapes of ZIKV infection and microcephaly incidence curves suggested different gestational risk profiles for different locations, varying in both the duration and magnitude of gestational risk. Data from Northeast Brazil suggested a narrow window of risk during the first trimester, whereas data from Colombia suggested persistent risk throughout pregnancy. We then used the model to estimate which combination of behavioural and reporting changes would have been sufficient to explain the absence of a second microcephaly incidence wave in Bahia, Brazil; a population for which we had two years of data. We found that a 18.9-fold increase in ZIKV infection reporting rate was consistent with observed patterns. CONCLUSIONS: Our study illustrates how surveillance data may be used in principle to answer key questions in the absence of directed epidemiological studies. However, in this case, we suggest that currently available surveillance data are insufficient to accurately estimate the gestational-age-varying risk of microcephaly from ZIKV infection. The methods used here may be of use in future outbreaks and may help to inform improved surveillance and interpretation in countries yet to experience an outbreak of ZIKV infection.