Genetics of host response to malaria
Introduction
With the realisation that eradication of malaria is not possible, control of the disease has focussed on minimisation of morbidity and mortality[1]. With this shift in emphasis in malarial control must come a shift in the direction of research. Where much effort has been spent on the biology of the parasite, often with small regard to the host, now much work must be directed at the host in an effort to understand those factors that control host response. Over the past few years, notable progress has been made using genetics as a tool towards the discovery of loci encoding host resistance to malaria2, 3. The growing body of evidence suggests that the host response to malaria is influenced by complex genetics. Significant effort is now being directed towards the cloning of these loci, in order to unravel the genetic interactions involved. Current studies are being conducted in both the human population and animal models in order to approach the problem from different angles. The first section of this review will address recent advances in the mapping of murine malarial resistance loci, and the second section will collate the findings of several human studies.
Section snippets
Mapping host resistance genes using murine models
Several animal models of malaria exist that parallel, to varying degrees, the disease progression observed in humans. Four species of malarial parasites can infect laboratory rodents: Plasmodium chabaudi, Plasmodium yoelii, Plasmodium vinckei, and Plasmodium berghei. It has long been known that inbred strains of mice are differentially susceptible to infection with these parasites[4]. In the past, the quest to explain this differential susceptibility has been plagued by studies examining a
Mapping host resistance genes using human populations
Despite the difficulties associated with mapping complex traits in human populations, some progress has been made towards the mapping of malaria resistance genes. Malaria acts as a significant selective pressure on human populations[11]. As a consequence, several mutations that are deleterious when homozygous, have been selected for as a result of the disease. The high frequency of these mutations in areas where malaria is endemic is probably due to their conferring protection against severe
Conclusion
As we come to the end of the millennium, we can still see a long stretch ahead on the road to understanding the host response to malaria. At this point we have gathered an eclectic collection of clues about the genetics of the resistance mechanisms. Human studies have concluded that the MHC plays a definite role in both control of blood parasite levels and resistance to severe forms of disease. These results are supported by the murine studies in which specific regions of the H-2 locus have
Acknowledgements
I thank Simon Foote for contributing to the preparation of this manuscript. This work was supported by the Wellcome Trust, the National Health and Medical Research Council of Australia and an Australian Postgraduate Award.
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