Quantifying genetic and nongenetic contributions to malarial infection in a Sri Lankan population.

Explaining the causes of variation in the severity of malarial disease remains a major challenge in the treatment and control of malaria. Many factors are known to contribute to this variation, including parasite genetics, host genetics, acquired immunity, and exposure levels. However, the relative importance of each of these to the overall burden of malarial disease in human populations has not been assessed. Here, we have partitioned variation in the incidence of malarial infection and the clinical intensity of malarial disease in a rural population in Sri Lanka into its component causes by pedigree analysis of longitudinal data. We found that human genetics, housing, and predisposing systematic effects (e. g., sex, age, occupation, history of infections, village) each explained approximately 15% of the variation in the frequency of malarial infection. For clinical intensity of illness, 20% of the variation was explained by repeatable differences between patients, about half of which was attributable to host genetics. The other half was attributable to semipermanent differences among patients, most of which could be explained by known predisposing factors. Three percent of variation in clinical intensity was explained by housing, and an additional 7% was explained by current influences relating to infection status (e.g., parasitemia, parasite species). Genetic control of Plasmodium falciparum infections appeared to modulate the frequency and intensity of infections, whereas genetic control of Plasmodium vivax infections appeared to confer absolute susceptibility or refractoriness but not intensity of disease. Overall, the data show consistent, repeatable differences among hosts in their susceptibility to clinical disease, about half of which are attributable to host genes.

Malaria risk factors in an endemic region of Sri Lanka, and the impact and cost implications of risk factor-based interventions.

In an 18-month study of malaria in a population of 1,875 residents in 423 houses in an endemic area in southern Sri Lanka, the risk of malaria was found to be 2.5-fold higher in residents of poorly constructed houses than in those living in houses of good construction type. In residents of poorly constructed houses but not in others, the risk was even greater when the house was located near a source of water that could act as a potential breeding place for malaria vector mosquitoes (P = 0.0001). Based on previous findings that confirmed that house construction type was itself a risk determinant, and not merely a marker of other behavioral factors, we have estimated the potential impact of two feasible interventions to reduce the risk of malaria: 1) the imposition of a buffer zone of 200 meters around bodies of water from which houses of poor construction were excluded, which was estimated to lead to a 21% reduction of the malaria incidence in the overall population and a 43% reduction in the relocated community; and 2) the conversion of houses of poor construction type located in the buffer zone to those of a good construction type, which was estimated to lead to a 36% reduction in the incidence rates in the whole population and a 76% reduction in the residents of houses whose construction type was improved. Taking into consideration the cost to the Government of malaria prevention, we estimated the worth of a Government's investment in improving house construction type. The investment in housing was estimated to be offset in 7.2 years by savings to the Government on malaria costs alone, and beyond this period, to bring a return on the Government's investment by way of savings to the malaria control program.