Maternally-derived antibody titer dynamics and risk of hospitalised infant dengue disease

Abstract

Dengue virus (DENV) immunity is complex. Maternally-derived DENV antibodies initially provide protection against infection, however, as antibodies decay they can enhance disease severity upon infection. Quantifying antibody titers that are associated with disease risk is complicated by their dynamic nature and imperfect measurement processes. It also remains unknown whether long-term trends in birth rates, population-level infection risks, and maternal ages have altered immune profiles in child-bearing women, leading to shifts in age-specific infant disease risks. Here, we analyse DENV antibody data from two infant cohorts (N=165 infants with 665 blood draws) and 40 years of infant dengue hospitalisation data from Thailand. We use mathematical models to reconstruct maternally-derived antibody dynamics and estimate hospitalisation risk by titer. We find the relative risk of dengue hospitalisation ranges from 0.13 (0.00-0.89) in 1 month olds to 3.52 (3.25-3.79) in 8 month olds, compared to the risk in 12 month olds. We estimate the highest risk of infant dengue hospitalisation occurs at PRNT50 titers of 6.0 (5.7-6.6). Our inferred titer-related risk estimates are consistent with previously identified titer-based correlates of severe disease among older individuals experiencing secondary DENV infections, suggesting a common mechanism of risk enhancement from pre-existing antibodies. Finally, we describe how the shifting epidemiology of dengue in Thailand, combined with declining birth rates, have decreased the absolute risk of infant dengue disease by 64% over a 40 year period while having minimal impact on the mean age of infant hospital-attended dengue disease.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was funded by the National Institutes of Health (Grant Number P01AI034533) and the European Research Council (Grant Number 804744).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

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

The cohort study in Kamphaeng Phet was approved by 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 #2119). The Bangkok cohort study protocol was approved by the Ethics Committee of the Ministry of Public Health of Thailand. Our analysis is based on de-identified antibody titer data as well as de-identified hospital case data only.

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Data Availability

All code and anonymized data to reproduce the analysis will be made available.

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