PEDIATRICS Vol. 95 No. 6 June 1995, pp. 844
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A PROSPECTIVE STUDY OF THE INFLUENCE OF agr-THALASSAEMIA ON MORBIDITY FROM MARLARIA AND IMMUNE RESPONSES TO DEFINED PLASMODIUM FALCIPARUM ANTIGENS IN GAMBIAN CHILDREN

S. J. Allen , P. Rowe , and C. E. M. Allsop

agr-Thalassaemia is the most common haemoglobinopathy in Africa and is due to a defect in agr-globin chain synthesis. Earlier studies have indicated that agr-Thalassaemia may provide a selective advantage against Plasmodium falciparum malaria and account for the increased prevalence of agr-Thalassaemia in malarial endemic areas. The mechanism by which agr-Thalassaemia is protective against malaria is not clear. One hypothesis is that there is a greater binding of immunoglobulin molecules to the surface of thalassaemic red cells resulting in better clearance of parasitized erythrocytes. The present authors conducted a study on children living in two groups of villages in Gambia to test this hypothesis. These studies were conducted once at the beginning of May and once at the end of October, which is the end of the rainy season and a period of intense malaria transmission. In addition to definition of active and asymptomatic malarial infection, the authors conducted a number of studies including genotyping for haemoglobinopathies (specifically agr-Thalassaemia and sickle cell), measurement of antibody to a variety of antigens related to malarial parasite, and in vitro cellular immune response to specific malarial antigens. They included a control group of 30 Swedish children who had never been exposed to malaria. They also used PHA, candida, and PPD as control antigens for in vitro stimulation of lymphocytes. They looked at the lymphocyte stimulation index and IFNggr production in vitro in response to various mitogens.

The authors did not find an increased parasite rate in children with agr-Thalassaemia. A similar proportion of normal and heterozygotes thalassaemia children acquired malaria. This was different from earlier studies conducted in Papua, New Guinea. They also noted a higher rate of infection among children with hemoglobin AS and heterozygote for \g=a\-Thalassaemia than in those with normal hemoglobin and heterozygote for \g=a\-Thalassaemia. There was no difference between children with \g=a\-Thalassaemia and those with normal genes in the prevalence of antibodies to any of the malarial antigens. However, in the in vitro assay they noted greater lymphoproliferative responses to some of the soluble antigens and lower IFN\g=g\ production response to two of the recombinant antigens for merozoite protein in \g=a\-Thalassaemic children compared with normal children. However, considering the number of antigens that were tested, these abnormalities may have been by chance.

Although there was no difference in the frequency of malaria among children with \g=a\-Thalassaemia and those with normal haemoglobin genotype, there were few children who had both \g=a\-Thalassaemia and sickle cell trait with fewer clinical episodes of malaria than children with sickle cell trait alone. This is an unexpected finding. This finding may be more important to follow than the original question with which the authors started the study.