Global seroprevalence of Zika virus in asymptomatic individuals: A systematic review

Background: Zika virus (ZIKV) has spread to five of the six World Health Organization (WHO) regions. Given the substantial number of asymptomatic infections and clinical presentations resembling those of other arboviruses, estimating the true burden of ZIKV infections is both challenging and essential. Therefore, we conducted a systematic review and meta-analysis of seroprevalence studies of ZIKV IgG in asymptomatic population to estimate its global impact and distribution. Methodology/Principal findings: We conducted extensive searches and compiled a collection of articles published from Jan/01/2000, to Jul/31/2023, from Embase, Pubmed, SciELO, and Scopus databases. The random effects model was used to pool prevalences, reported with their 95% confidence interval (CI), a tool to assess the risk of study bias in prevalence studies, and the I2 method for heterogeneity (PROSPERO registration No. CRD42023442227). Eighty-four studies from 49 countries/territories, with a diversity of study designs and serological tests were included. The global seroprevalence of ZIKV was 21.0% (95%CI 16.1%-26.4%). Evidence of IgG antibodies was identified in all WHO regions, except for Europe. Seroprevalence correlated with the epidemics in the Americas (39.9%, 95%CI:30.0–49.9), and in some Western Pacific countries (15.6%, 95%CI:8.2–24.9), as well as with recent and past circulation in Southeast Asia (22.8%, 95%CI:16.5–29.7), particularly in Thailand. Additionally, sustained low circulation was observed in Africa (8.4%, 95%CI:4.8–12.9), except for Gabon (43.7%), and Burkina Faso (22.8%). Although no autochthonous transmission was identified in the Eastern Mediterranean, a seroprevalence of 16.0% was recorded. Conclusions/Significance: The study highlights the high heterogeneity and gaps in the distribution of seroprevalence. The implementation of standardized protocols and the development of tests with high specificity are essential for ensuring a valid comparison between studies. Equally crucial are vector surveillance and control methods to reduce the risk of emerging and re-emerging ZIKV outbreaks, whether caused by Ae. aegypti or Ae. albopictus or by the Asian or African ZIKV. Author summary: Zika virus (ZIKV) remains an important public health concern. Estimating the true burden of the disease is a major challenge, often underestimated due to the substantial number of asymptomatic infections. Consequently, seroprevalence studies are valuable for determining the geographic extent of the virus, measuring levels of human immunity, and assessing potential infection-related risks. Thus, we conducted a systematic review and meta-analysis of the literature addressing the seroprevalence of ZIKV in asymptomatic individuals worldwide. The overall seroprevalence of ZIKV IgG antibodies was 21.0%, calculated based on 84 studies published between January 2000 and July 2023. Antibodies have been found in all WHO regions, but none in Europe, with rates ranging from 8.4% in Africa to 39.9% in America. Further standardized surveillance studies are needed to understand immunity per region and over time, evaluate vector dynamics, and assess the risk of future outbreaks.