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

The 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 i...

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Published in:	PLoS medicine 2012-09, Vol.9 (9), p.e1001305-e1001305
Main Authors:	Rosanas-Urgell, Anna, Lin, Enmoore, Manning, Laurens, Rarau, Patricia, Laman, Moses, Senn, Nicolas, Grimberg, Brian T, Tavul, Livingstone, Stanisic, Danielle I, Robinson, Leanne J, Aponte, John J, Dabod, Elijah, Reeder, John C, Siba, Peter, Zimmerman, Peter A, Davis, Timothy M E, King, Christopher L, Michon, Pascal, Mueller, Ivo
Format:	Article
Language:	eng
Subjects:	Biology Case-Control Studies Cohort Studies Development and progression Elliptocytosis, Hereditary - epidemiology Erythrocytes Health aspects Hemolytic anemia Malaria Malaria, Vivax - epidemiology Medical research Medicine Microscopy Papua New Guinea - epidemiology Physiological aspects Plasmodium Plasmodium vivax Polymerase Chain Reaction Proteins Risk factors Studies
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Summary:	The 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. The 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). In 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.
ISSN:	1549-1676 1549-1277 1549-1676