Seroprevalence of Dengue, Chikungunya and Zika at the epicenter of the congenital microcephaly epidemic in Northeast Brazil: a population-based survey
Authors: Braga Cynthia , Martelli Celina M.T. , Souza Wayner V. , Luna Carlos F. , Albuquerque Maria de Fatima P.M. , Mariz Carolline A. , Brito Carlos A.A. , Melo Carlos Frederico C.A. , Lins Roberto D. , Drexler Jan Felix , Jaenisch Thomas , Marques Ernesto T.A. , Isabelle F.T. Viana 
Published: March 2023

Background

The Dengue viruses (DENV) serotypes 1, 2, 3 and 4 were re-introduced in the Northeast Brazil from the 1980’s until 2010’s. Zika (ZIKV) and Chikungunya (CHIKV) viruses were introduced around 2014 and caused large outbreaks in 2015 and 2016. However, the true extent of the ZIKV and CHIKV outbreaks and the risk factors associated with exposure remain vague.

Methods

We conducted a stratified multistage household serosurvey among residents aged between 5 and 65 years in the city of Recife, Northeastern Brazil, from August 2018 to February 2019. The city neighborhoods were stratified according to 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 were investigated. The forces of infection for high SES were lower for all three viruses as compared to low SES. Overall, DENV seroprevalence was 88.7% (CI95%:87.0-90.4), (81.2% (CI95%:76.9-85.6) in the high SES and 90.7% (CI95%:88.3-93.2) in the low). The overall adjusted ZIKV seroprevalence was 34.6% (CI95%:20.0-50.9), (47.4% (CI95%:31.8-61.5) in the low SES and 23.4% (CI95%:12.2-33.8) in the high). CHIKV seroprevalence was 35.7% (CI95%:32.6-38.9), (38.6% (CI95%:33.6-43.6) in the low SES and 22.3% (CI95%:15.8-28.8) in the high). ZIKV seroprevalence increased with age while CHIKV seroprevalence was almost constant through age. The serological markers of recent infections for ZIKV and CHIKV 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 likely still susceptible to be infected by ZIKV and CHIKV, raising questions on herd immunity and antibody detection thresholds and the reasons underlying cease of the ZIKV epidemic in 2017/18.

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 seroepidemiologicla study in the city of Recife, a metropolitan area in Northeastern Brazil using a design stratified by socio-economic status (SES). We also determined the sensitivity and specificity of the assays used and selected optimum cut-offs, which were and later confirmed by selecting a subset of samples to on which more specific virus neutralizations tests were performed. The result indicated that 89% of the population (older than 5 years of age) had previous dengue infection, compatible with our previous serosurvey. The assay sensitivity and specificity seroprevalences for ZIKV was 34.6% and CHIKV 35.7%, indicating high transmission during the outbreaks (2015/2016). Interestingly, the age distribution profiles of ZIKV and CHIKV seroprevalence were remarkably different. These differences cannot be explained by differences in mosquito exposure alone. Future research will need to be conducted to better explain the differences we found for the age distributions.