Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo

Adekunle, Adeshina I., Pinkevych, Mykola, McGready, Rose, Luxemburger, Christine, White, Lisa J., Nosten, Francois, Cromer, Deborah, and Davenport, Miles P. (2015) Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo. PLoS Neglected Tropical Diseases, 9. e0003595.

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Abstract

The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine). In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation. We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90–96% of blood stage infections arise from hypnozoite reactivation. Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG.

Item ID: 51082
Item Type: Article (Research - C1)
ISSN: 1935-2735
Additional Information:

© 2015 Adekunle 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 of Australia (NHMRC), Wellcome Trust
Projects and Grants: ARC DP120100064, NHMRC APP630542
Date Deposited: 09 Oct 2017 03:24
FoR Codes: 01 MATHEMATICAL SCIENCES > 0102 Applied Mathematics > 010202 Biological Mathematics @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920404 Disease Distribution and Transmission (incl. Surveillance and Response) @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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