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 'population 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.
Original language | English |
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Article number | e0010990 |
Journal | PLoS Neglected Tropical Diseases |
Volume | 16 |
Issue number | 12 |
DOIs | |
Publication status | Published - 1 Dec 2022 |
Bibliographical note
Funding Information:This work was funded by the Australian Research Council (ARC; https://www.arc.gov.au) (grants DP120100064 & DP180103875 (to DSK, MPD, DC) and DP200100747 (to JAF)) and the National Health and Medical Research Council (NHMRC; https://www.nhmrc.gov.au) of Australia (grants 1082022 (to MPD, DC), 1173528 (to DC), 1141921 (to DSK), 1080001 and 1173027 (to MPD) and Senior Principal Research Fellowship 1135820 (to NMA)). LJR is supported by NHMRC (https://www.nhmrc.gov.au) Career Development Fellowship (GNT1161627). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022 Stadler et al.