Resolving the cause of recurrent Plasmodium vivax malaria probabilistically

Aimee R. Taylor (), James A. Watson (), Cindy S. Chu, Kanokpich Puaprasert, Jureeporn Duanguppama, Nicholas P. J. Day, Francois Nosten, Daniel E. Neafsey, Caroline O. Buckee, Mallika Imwong and Nicholas J. White ()
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Aimee R. Taylor: Harvard T. H. Chan School of Public Health
James A. Watson: Mahidol University
Cindy S. Chu: University of Oxford
Kanokpich Puaprasert: Mahidol University
Jureeporn Duanguppama: Mahidol University
Nicholas P. J. Day: Mahidol University
Francois Nosten: University of Oxford
Daniel E. Neafsey: Broad Institute of MIT and Harvard
Caroline O. Buckee: Harvard T. H. Chan School of Public Health
Mallika Imwong: Mahidol University
Nicholas J. White: Mahidol University

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Relapses arising from dormant liver-stage Plasmodium vivax parasites (hypnozoites) are a major cause of vivax malaria. However, in endemic areas, a recurrent blood-stage infection following treatment can be hypnozoite-derived (relapse), a blood-stage treatment failure (recrudescence), or a newly acquired infection (reinfection). Each of these requires a different prevention strategy, but it was not previously possible to distinguish between them reliably. We show that individual vivax malaria recurrences can be characterised probabilistically by combined modelling of time-to-event and genetic data within a framework incorporating identity-by-descent. Analysis of pooled patient data on 1441 recurrent P. vivax infections in 1299 patients on the Thailand–Myanmar border observed over 1000 patient follow-up years shows that, without primaquine radical curative treatment, 3 in 4 patients relapse. In contrast, after supervised high-dose primaquine only 1 in 40 relapse. In this region of frequent relapsing P. vivax, failure rates after supervised high-dose primaquine are significantly lower (∼3%) than estimated previously.

Date: 2019
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DOI: 10.1038/s41467-019-13412-x

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