alpha+-Thalassemia protects children against disease caused by other infections as well as malaria.
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.
Allen
S J
SJ
Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom. sallen@hammer.imm.ox.ac.uk
O'Donnell
A
A
Alexander
N D
ND
Alpers
M P
MP
Peto
T E
TE
Clegg
J B
JB
Weatherall
D J
DJ
D002648:Child; D002675:Child, Preschool; D003140:Communicable Disease Control; D003141:Communicable Diseases / Q000150:complications / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D008288:Malaria / Q000150:complications* / Q000453:epidemiology* / Q000517:prevention & control; D008297:Male; D010219:Papua New Guinea / Q000453:epidemiology; D012306:Risk; D017085:alpha-Thalassemia / Q000150:complications* / Q000453:epidemiology*