Sero-catalytic and spatial modeling of dengue virus force of infection in Timor-Leste

Dengue virus (DENV) infection causes significant morbidity and mortality across tropical and sub-tropical regions, including in Timor-Leste. In this study we present the results of a national, population-representative serological survey, used to determine the drivers of observed variations in DENV force-of-infection (FOI, i.e. the average annual per-capita risk of infection for a susceptible person) at high spatial resolution. Households were randomly selected from census data and occupants aged above one year were tested using the Panbio Indirect dengue IgG enzyme-linked immunosorbent assay between October 2021 and February 2023. Sero-catalytic models accounting for household effect were applied to estimate the DENV FOI in enumeration areas (EAs, roughly equivalent to neighbourhoods/villages). Spatial models were applied to the local FOI estimates to assess their associations with climate and environmental factors, and to predict the FOI across the rest of Timor-Leste. A total of 4780 individuals from 1755 households across 102 EAs participated. DENV seroprevalence and FOI estimates were highly spatially heterogeneous across Timor-Leste, ranging from 0.010 (95% Credible Interval (CrI): 0.005, 0.018) in EA 10104032 in Fatubossa, municipality Aileu, to 0.519 (0.295, 0.816) in EA 40403012 in Goulolo, municipality Bobonaro. Relative humidity was negatively associated with DENV FOI. The spatial models predicted highest DENV FOI along the Northern and Eastern coasts, with hotspots of transmission in Dili and Baucau cities. Findings will strengthen surveillance and guide the implementation of additional DENV control strategies such as Wolbachia-carrying mosquitoes (currently being deployed in some parts of Timor-Leste), or vaccination.