Uncovering rates at which susceptible individuals become infected with a pathogen, i.e. the force of infection (FOI), is essential for assessing transmission risk and reconstructing distribution of immunity in a population. For dengue, reconstructing exposure and susceptibility statuses from the measured FOI is of particular significance as prior exposure is a strong risk factor for severe disease. FOI can be measured via many study designs. Longitudinal serology are considered gold standard measurements, as they directly track the transition of seronegative individuals to seropositive due to incident infections (seroincidence). Cross-sectional serology can provide estimates of FOI by contrasting seroprevalence across ages. Age of reported cases can also be used to infer FOI. Agreement of these measurements, however, have not been assessed. Using 26 years of data from cohort studies and hospital-attended cases from Kamphaeng Phet province, Thailand, we found FOI estimates from the three sources to be highly inconsistent. Annual FOI estimates from seroincidence was 2.46 to 4.33-times higher than case-derived FOI. Correlation between seroprevalence-derived and case-derived FOI was moderate (correlation coefficient=0.46) and no systematic bias. Through extensive simulations and theoretical analysis, we show that incongruences between methods can result from failing to account for dengue antibody kinetics, assay noise, and heterogeneity in FOI across ages. Extending standard inference models to include these processes reconciled the FOI and susceptibility estimates. Our results highlight the importance of comparing inferences across multiple data types to uncover additional insights not attainable through a single data type/analysis.

The authors have declared no competing interest.

This study was funded by the Military Infectious Disease Research Program and the US National Institutes of Health (program project award P01 AI034533 and 1R01AI175941-01). ATH was supported by the Herchel Smith Fellowship.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Use of data from the Kamphaeng Phet Hospital were reviewed and approved by Walter Reed Army Institute of Research Institutional Review Board (protocol number 1313 and 1957). The study protocol for KPS1 was approved by the Office of the Army Surgeon General, University of the Massachusetts Medical School, and the Ministry of Public Health, Thailand. The protocol for KPS2 was additionally approved by the University of California Davis and San Diego State University (protocol number 654 and 1042). The KPS 3 and KFCS cohort study was approved by the Thailand Ministry of Public Health Ethical Research Committee; Siriraj Ethics Committee on Research Involving Human Subjects; Institutional Review Board for the Protection of Human Subjects, State University of New York Upstate Medical University; and Walter Reed Army Institute of Research Institutional Review Board (protocol number 1552 and 2119).

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