Time Lags between Exanthematous Illness Attributed to Zika Virus, Guillain-Barré Syndrome, and Microcephaly, Salvador, Brazil

Abstract

Zika virus infection emerged as a public health emergency after increasing evidence for its association with neurologic disorders and congenital malformations. In Salvador, Brazil, outbreaks of acute exanthematous illness (AEI) attributed to Zika virus, Guillain-Barré syndrome (GBS), and microcephaly occurred in 2015. We investigated temporal correlations and time lags between these outbreaks to identify a common link between them by using epidemic curves and time series cross-correlations. Number of GBS cases peaked after a lag of 5-9 weeks from the AEI peak. Number of suspected cases of microcephaly peaked after a lag of 30-33 weeks from the AEI peak, which corresponded to time of potential infections of pregnant mothers during the first trimester. These findings support the association of GBS and microcephaly with Zika virus infection and provide evidence for a temporal relationship between timing of arboviral infection of pregnant women during the first trimester and birth outcome.

Keywords: Brazil; Guillain-Barré syndrome; Salvador; Zika virus; epidemiology; exanthematous illness; microcephaly; outbreaks; pregnant women; time lags; viruses.

Figure 1

Epidemiologic curves of weekly cases and moving averages of 3 weeks and 5 weeks for A) acute exanthematous illness (AEI), B) Guillain-Barré syndrome, and C) suspected microcephaly, Salvador, Brazil, 2015–2016. The specific starting date during week 7 was February 15, 2105.

Figure 2

Cross-correlation of acute exanthematous illness with A) Guillain-Barré syndrome and B) suspected microcephaly, Salvador, Brazil, 2015–2016, for a 5-week moving average. Dotted horizontal lines indicate 95% tolerance intervals for a null model of no association. Negative correlations observed at early lag periods are a function of large numbers of acute exanthematous illness cases that occurred early in the study period when there were no suspected cases of microcephaly.