Seroprevalence of Dengue, Chikungunya and Zika at the epicenter of the congenital microcephaly epidemic in Northeast Brazil: A population-based survey

Background: The four Dengue viruses (DENV) serotypes were re-introduced in Brazil’s Northeast region in a couple of decades, between 1980’s and 2010’s, where the DENV1 was the first detected serotype and DENV4 the latest. Zika (ZIKV) and Chikungunya (CHIKV) viruses were introduced in Recife around 2014 and led to large outbreaks in 2015 and 2016, respectively. However, the true extent of the ZIKV and CHIKV outbreaks, as well as the risk factors associated with exposure to these viruses remain vague. Methods: We conducted a stratified multistage household serosurvey among residents aged between 5 and 65 years in the city of Recife, Northeast Brazil, from August 2018 to February 2019. The city neighborhoods were stratified and divided into high, intermediate, and low socioeconomic strata (SES). Previous ZIKV, DENV and CHIKV infections were detected by IgG-based enzyme linked immunosorbent assays (ELISA). Recent ZIKV and CHIKV infections were assessed through IgG3 and IgM ELISA, respectively. Design-adjusted seroprevalence were estimated by age group, sex, and SES. The ZIKV seroprevalence was adjusted to account for the cross-reactivity with dengue. Individual and household-related risk factors were analyzed through regression models to calculate the force of infection. Odds Ratio (OR) were estimated as measure of effect. Principal findings: A total of 2,070 residents’ samples were collected and analyzed. The force of viral infection for high SES were lower as compared to low and intermediate SES. DENV seroprevalence was 88.7% (CI95%:87.0–90.4), and ranged from 81.2% (CI95%:76.9–85.6) in the high SES to 90.7% (CI95%:88.3–93.2) in the low SES. The overall adjusted ZIKV seroprevalence was 34.6% (CI95%:20.0–50.9), and ranged from 47.4% (CI95%:31.8–61.5) in the low SES to 23.4% (CI95%:12.2–33.8) in the high SES. The overall CHIKV seroprevalence was 35.7% (CI95%:32.6–38.9), and ranged from 38.6% (CI95%:33.6–43.6) in the low SES to 22.3% (CI95%:15.8–28.8) in the high SES. Surprisingly, ZIKV seroprevalence rapidly increased with age in the low and intermediate SES, while exhibited only a small increase with age in high SES. CHIKV seroprevalence according to age was stable in all SES. The prevalence of serological markers of ZIKV and CHIKV recent infections were 1.5% (CI95%:0.1–3.7) and 3.5% (CI95%:2.7–4.2), respectively. Conclusions: Our results confirmed continued DENV transmission and intense ZIKV and CHIKV transmission during the 2015/2016 epidemics followed by ongoing low-level transmission. The study also highlights that a significant proportion of the population is still susceptible to be infected by ZIKV and CHIKV. The reasons underlying a ceasing of the ZIKV epidemic in 2017/18 and the impact of antibody decay in susceptibility to future DENV and ZIKV infections may be related to the interplay between disease transmission mechanism and actual exposure in the different SES. Author summary: The extent and population burden of the Zika and Chikungunya epidemics in Northeast Brazil remains speculative since seroprevalence studies have often been restricted to specific populations and limited by ZIKV and DENV antibody cross-reactivity. Here we conducted a seroepidemiological study in the city of Recife, a metropolitan area in Northeast Brazil using a design stratified by socioeconomic status (SES). We determined the sensitivity and specificity of the assays using a panel of well-characterized samples from the study area and determined optimum cut-offs, which were later validated by selecting a subset of samples that were used to conduct viral neutralizations assays. The results indicated that 89% of the population (older than 5 years of age) had previous dengue infection, which is compatible with our previous serosurvey. Correcting for the sensitivity and specificity of the ZIKV assays, the overall ZIKV IgG seroprevalence was 34.6%, which indicates high transmission during the first outbreak (2015/2016). Interestingly, the age and the SES distribution profiles of ZIKV and CHIKV seroprevalence were remarkably different. This difference cannot be explained by differences in mosquito exposure alone. Future research will need to be conducted to better explain the differences found in the age distributions.