A large case-control study of malaria in West African children shows that a human leucocyte class I antigen (HLA-Bw53) and an HLA class II haplotype (DRB1*1302-DQB1*0501), common in West Africans but rare in other racial groups, are independently associated with protection from severe malaria. In this population they account for as great a reduction in disease incidence as the sickle-cell haemoglobin variant. These data support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens.

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Serial clinical and metabolic changes were monitored in 115 Gambian children (1.5-12 years old) with severe malaria. Fifty-three children (46%) had cerebral malaria (coma score < or = 2) and 21 (18%) died. Admission geometric mean venous blood lactate concentrations were almost twice as high in fatal cases as in survivors (7.1 mmol/L vs. 3.6 mmol/L; P < 0.001) and were correlated with levels of tumour necrosis factor (r = 0.42, n = 79; P < 0.0001) and interleukin 1-alpha (r = 0.6, n = 34; P < 0.0001). Admission blood venous glucose concentrations were lower in fatal cases than survivors (3.2 mmol/L, vs. 5.8 mmol/L; P < 0.0001). Treatment with quinine was associated with significantly more episodes of post-admission hypoglycaemia when compared with artemether or chloroquine. After treatment, lactate concentrations fell rapidly in survivors but fell only slightly, or rose, in fatal cases. Plasma cytokine levels fluctuated widely after admission. Sustained hyperlactataemia (raised lactate concentrations, 4 h after admission) proved to be the best overall prognostic indicator of outcome in this series. Lactic acidosis is an important cause of death in severe malaria.