Seroprevalence of Dengue, Zika, and Chikungunya Viruses in Humans and Colocated Macaques in Thailand and Cambodia

Abstract

Background: Arboviruses-short for "arthropod-borne viruses"-are transmitted to humans and animals by infected arthropods. Aedes mosquito-borne arboviruses such as dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) impose major public health burdens in Southeast Asia. The potential role of sylvatic reservoirs, such as macaques, in maintaining arboviral transmission remains unclear.

Methods: We assessed the role of sylvatic reservoirs in arboviral circulation by examining serological evidence of exposure to DENV, ZIKV, and CHIKV among humans and macaques living in close proximity in endemic regions. Cross-sectional serosurveys were carried out during 2019-2022, involving 649 humans and 398 macaques colocated across 4 sites in Thailand (Hua Hin, Laem Chabang, and Muang Lop Buri) and Cambodia (Chbar Mon). Seropositivity was evaluated using plaque reduction neutralization tests (PRNT50).

Results: We found overall higher seropositivity rates across arboviruses among human populations compared to macaques (38.5%-74.4% vs 0%-8.0%, respectively, using PRNT50 cutoff). Virus seroprevalence differed between Thai and Cambodian cohorts and age was the only significant predictor of human seropositivity in multivariate analyses.

Conclusions: The low seropositivity among macaques suggests a limited role of macaques in sustaining and amplifying urban arboviral cycles; rather, low-level macaque seropositivity may signal virus spillback from human populations.

Keywords: Chikungunya; Zika; dengue; seroprevalence.

Figure 1.

Study locations in Thailand and Cambodia. Map of the Greater Mekong Subregion showing land mass and country borders denoted by solid black lines. Diamonds denote study sites in Thailand (Hua Hin [Western Thailand], Laem Chabang [Eastern Thailand], and Muang Lop Buri [Central Thailand]), and Cambodia (Chbar Mon).

Figure 2.

Heatmaps of PRNT₅₀ neutralizing antibody titers in humans (left) and colocated macaques (right). Rows denote individuals, stratified by study site (shown in colored boxes to the right of each panel). Shading of each cell corresponds to log PRNT₅₀ titers, as indicated by the legend (right). Abbreviations: CHIKV, chikungunya virus; DENV, dengue virus; PRNT₅₀, 50% plaque reduction neutralization test; ZIKV, Zika virus.

Figure 3.

Correlation matrices of PRNT₅₀ neutralizing antibody titers to different arboviruses in humans (A) and macaques (B). Numbers within cells and cell coloring denote Spearman correlation coefficients, or strength of coloration between PRNT₅₀ titers for each pair of arboviruses (labeled by row and column). Abbreviations: CHIKV, chikungunya virus; DENV, dengue virus; PRNT₅₀, 50% plaque reduction neutralization test; ZIKV, Zika virus.

Figure 4.

Univariate logistic regression of predictors of human arboviral seropositivity. OR and 95% CI of demographic and serologic predictors of seropositivity to (A) DENV1, (B) DENV2, (C) DENV3, (D) DENV4, (E) ZIKV, and (F) CHIKV. Dotted line indicates an OR of 1. Abbreviations: CHIKV, chikungunya virus; CI, confidence interval; DENV, dengue virus; OR, odds ratio; Ref, reference; ZIKV, Zika virus.

Figure 5.

Multivariate logistic regression of predictors of human arboviral seropositivity. Odds ratios (OR) and 95% confidence intervals (CI) of (A) participant age, (B) participant sex, (C) participant years of residence at sampling location, and (D) country of sampling, as predictors of human seropositivity to DENV1, DENV2, DENV3, DENV4, ZIKV, and CHIKV. Dotted line indicates an OR of 1. Abbreviations: CHIKV, chikungunya virus; CI, confidence interval; DENV, dengue virus; OR, odds ratio; Ref, reference; ZIKV, Zika virus.