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

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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding: European Commission (ZIKA Alliance H2020 734548) German Centre for Infection Research (DZIF), Heidelberg Site, Germany Pan American Health Organization, World Health Organization/Brazilian Ministry of Health (SCON2018-00276) National Council for Scientific and Technological Development, Brazil (CNPq scholarship – CB (303953/2018-7), WVS (308000/2021-8), MFPMA (CNPq 302696/2021-0) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research project was reviewed and approved by the Research Ethics Committee of the Aggeu Magalhães Institute (Fiocruz, Pernambuco) (CAEE: 79605717.9.0000.5190, report number 2.734.481). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable All relevant data are within the manuscript and its Supporting Information files. Additional information will be provided upon request