Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3

Southeast Asian ovalocytosis (SAO) occurs at high frequency in malarious re gions of the western Pacific and may afford a survival advantage against ma laria. It is caused by a deletion of the erythrocyte membrane band 3 gene a nd the band 3 protein mediates the cytoadherence of parasitized erythrocyte s irt vitro. The SAO band 3 variant may prevent cerebral malaria but it exa cerbates malaria anemia and may also increase acidosis, a major determinant of mortality in malaria. We undertook a case-control study of children adm itted to hospital in a malarious region of Papua New Guinea. The SAO band 3 , detected by the polymerase chain reaction, was present in 0 of 68 childre n with cerebral malaria compared with six (8.8%) of 68 matched community co ntrols (odds ratio = 0, 95% confidence interval = 0-0.85). Median hemoglobi n levels were 1.2 g/dl lower in malaria cases with SAO than in controls (P = 0.035) but acidosis was not affected. The remarkable protection that SAO band 3 affords against cerebral malaria may offer a valuable approach to a better understanding of the mechanisms of adherence of parasitized erythroc ytes to vascular endothelium, and thus of the pathogenesis of cerebral mala ria.