Population heterogeneity in Plasmodium vivax relapse risk

Stadler, Eva, Cromer, Deborah, Mehra, Somya, Adekunle, Adeshina I., Flegg, Jennifer A., Anstey, Nicholas M., Watson, James A., Chu, Cindy S., Mueller, Ivo, Robinson, Leanne J., Schlub, Timothy E., Davenport, Miles P., and Khoury, David S. (2022) Population heterogeneity in Plasmodium vivax relapse risk. PLoS Neglected Tropical Diseases, 16 (12). e0010990.

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Abstract

A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to ‘temporal heterogeneity’ in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to ‘popula-tion heterogeneity’ in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934.

Item ID: 77545
Item Type: Article (Research - C1)
ISSN: 1935-2735
Copyright Information: Copyright: © 2022 Stadler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funders: Australian Research Council (ARC), National Health and Medical Research Council (NHMRC)
Projects and Grants: ARC grant DP120100064, ARC grant DP180103875, ARC grant DP200100747, NHMRC grant 1082022, NHMRC grant 1173528, NHMRC grant 1141921, NHMRC grant 1080001, NHMRC grant 1173027, NHMRC Senior Principal Research Fellowship 1135820, NHMRC Career Development Fellowship GNT1161627
Date Deposited: 18 Apr 2023 01:36
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 100%
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