PLoS Medicine (Jan 2012)

Reduced risk of Plasmodium vivax malaria in Papua New Guinean children with Southeast Asian ovalocytosis in two cohorts and a case-control study.

  • Anna Rosanas-Urgell,
  • Enmoore Lin,
  • Laurens Manning,
  • Patricia Rarau,
  • Moses Laman,
  • Nicolas Senn,
  • Brian T Grimberg,
  • Livingstone Tavul,
  • Danielle I Stanisic,
  • Leanne J Robinson,
  • John J Aponte,
  • Elijah Dabod,
  • John C Reeder,
  • Peter Siba,
  • Peter A Zimmerman,
  • Timothy M E Davis,
  • Christopher L King,
  • Pascal Michon,
  • Ivo Mueller

DOI
https://doi.org/10.1371/journal.pmed.1001305
Journal volume & issue
Vol. 9, no. 9
p. e1001305

Abstract

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BackgroundThe erythrocyte polymorphism, Southeast Asian ovalocytosis (SAO) (which results from a 27-base pair deletion in the erythrocyte band 3 gene, SLC4A1Δ27) protects against cerebral malaria caused by Plasmodium falciparum; however, it is unknown whether this polymorphism also protects against P. vivax infection and disease.Methods and findingsThe association between SAO and P. vivax infection was examined through genotyping of 1,975 children enrolled in three independent epidemiological studies conducted in the Madang area of Papua New Guinea. SAO was associated with a statistically significant 46% reduction in the incidence of clinical P. vivax episodes (adjusted incidence rate ratio [IRR] = 0.54, 95% CI 0.40-0.72, p90% binding inhibition) P. vivax Duffy binding protein-specific binding inhibitory antibodies were observed significantly more often in sera from SAO than non-SAO children (SAO, 22.2%; non-SAO, 6.7%; p = 0.008).ConclusionsIn three independent studies, we observed strong associations between SAO and protection against P. vivax malaria by a mechanism that is independent of the Duffy antigen. P. vivax malaria may have contributed to shaping the unique host genetic adaptations to malaria in Asian and Oceanic populations. Please see later in the article for the Editors' Summary.