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In the South West Pacific region, the striking geographical correlation between the frequency of alpha+-thalassemia and the endemicity of Plasmodium falciparum suggests that this hemoglobinopathy provides a selective advantage against malaria. In Vanuatu, paradoxically, alpha+-thalassemia increases the incidence of contracting mild malaria in the first 2 years of life, but severe disease was too uncommon to assess adequately. Therefore, we undertook a prospective case-control study of children with severe malaria on the north coast of Papua New Guinea, where malaria transmission is intense and alpha+-thalassemia affects more than 90% of the population. Compared with normal children, the risk of having severe malaria was 0.40 (95% confidence interval 0.22-0.74) in alpha+-thalassemia homozygotes and 0.66 (0.37-1.20) in heterozygotes. Unexpectedly, the risk of hospital admission with infections other than malaria also was reduced to a similar degree in homozygous (0. 36; 95% confidence interval 0.22-0.60) and heterozygous (0.63; 0. 38-1.07) children. This clinical study demonstrates that a malaria resistance gene protects against disease caused by infections other than malaria. The mechanism of the remarkable protective effect of alpha+-thalassemia against severe childhood disease remains unclear but must encompass the clear interaction between this hemoglobinopathy and both malarial and nonmalarial infections.

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

23/12/1997

Volume

94

Pages

14736 - 14741

Keywords

Biology, Case Control Studies, Child Health, Child Survival, Demographic Factors, Developing Countries, Diseases, Health, Hematological Effects, Hemic System, Infections, Length Of Life, Malaria, Melanesia, Mortality, Oceania, Papua New Guinea, Parasitic Diseases, Physiology, Population, Population Dynamics, Research Methodology, Research Report, Studies, Survivorship, Child, Child, Preschool, Communicable Disease Control, Communicable Diseases, Female, Humans, Infant, Malaria, Male, Papua New Guinea, Risk, alpha-Thalassemia