Resolving the cause of recurrent Plasmodium vivax malaria probabilistically

Nat Commun. 2019 Dec 6;10(1):5595. doi: 10.1038/s41467-019-13412-x.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / administration & dosage
  • Antimalarials / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Malaria, Vivax / blood
  • Malaria, Vivax / drug therapy*
  • Malaria, Vivax / epidemiology*
  • Malaria, Vivax / parasitology
  • Male
  • Middle Aged
  • Models, Theoretical
  • Myanmar / epidemiology
  • Plasmodium vivax / drug effects
  • Plasmodium vivax / genetics*
  • Plasmodium vivax / pathogenicity
  • Primaquine / administration & dosage
  • Primaquine / therapeutic use*
  • Recurrence
  • Thailand / epidemiology
  • Treatment Outcome
  • Young Adult

Substances

  • Antimalarials
  • Primaquine