An investigation of the relationship between malaria and red-cell polymorphisms in Madang, Papua New Guinea
In 1949, JBS Haldane proposed that the high frequency of the thalassaemias might reflect a heterozygote survival advantage against malaria. This “malaria hypothesis” formed the basis for this programme of research. Between 1993 and 2006, | conducted a series of comprehensive and detailed studies of the relationships between malaria and the common red-cell variants a-thalassaemia and Southeast Asian ovalocytosis (SAO) in children and pregnant women in the North coastal region of Papua New Guinea. The clinical and laboratory features of malaria in children were described. In multiple regression analysis, raised plasma lactate (>5mmol/l) was the major predictor of death. Acidosis and impaired renal function were also independent predictors of mortality, and muscle-cell injury was identified as a cause of dark urine. A case-control study of 249 children admitted to hospital with severe malaria and 233 children with severe non-malaria illnesses was undertaken to investigate the possible protective effect of a*-thalassaemia and SAO against the severe manifestations of malaria and other severe illnesses. Homozygous a+-thalassaemia reduced the risk of severe malaria by 60% and SAO appeared to provide complete protection against cerebral malaria. Interestingly, a+-thalassaemia also protected against hospital admission in children with nonmalarial illnesses. | investigated the frequencies of a+-thalassaemia and SAO, and their relationship with malaria in pregnancy and pregnancy outcome, in over 900 women who delivered their babies in hospital. My findings suggest that neither a+-thalassaemia nor SAO protected against malaria in pregnancy or improved pregnancy outcome. During these studies, | identified the haematological and red-cell abnormalities most consistent with the band 3 deletion for SAO, which may be used to improve the diagnosis, where molecular methods are not available. The findings of the potent protection afforded by a+-thalassaemia and SAO against severe malaria in children will encourage further investigation of the underlying mechanisms. In turn, this may offer new approaches to the design of targeted interventions for the prevention and treatment of malaria that will improve the health of the millions of children who suffer from this devastating disease every year.
Networked Digital Library of Theses and Dissertations