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

Abstract

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.

Family analysis of malaria infection in Dienga, Gabon.

“…A recent study conducted in Sri Lanka, in an endemic area for P. falciparum and P. vivax, seems to show that real differences exist in the genetic mechanisms that control the two species. 20 In accordance with several studies, the authors have observed a marked deficit in mixed-species infections. [21][22][23][24] In contrast to P. falciparum and P. vivax co-infections, mixed-species infections with P. falciparum and P. malariae exhibited a marked excess of prevalence than expected in the case of non-related infections.…”

Human Genetic Contribution to the Outcome of Infection with Malaria Parasites

“…Moreover, the heritability of the number of clinical episodes is quite conserved irrespective of the phenotypic definitions used, the geographical region and even the Plasmodium species implicated. Similar values were observed in a study in Kenya (20%; Mackinnon et al, 2005) and a study in Sri Lanka (15%; Mackinnon et al, 2000) and for P. vivax (19% in Thailand (Phimpraphi et al, 2008b) and 15% in Sri Lanka).…”

La Región “Urabá Antioqueño-Cuencas altas de los ríos Sinú y San Jorge-Bajo Cauca Antioqueño”: “guarida” del paludismo colombiano

“…En La Región hay al menos cuatro niveles de intensidad pluviométrica: 1) en la parte sur del golfo de Urabá se presentan 2.500-3000 mm 3 51 .…”

“…La heterogeneidad de la transmisión malárica está comprobada a escala global, regional y en escala fina en, por ejemplo, Mali, Ghana, Etiopía, Kenia y Tanzania [1][2][3][4][5][6][7][8][9] . No conocemos estudios de puntos calientes/guaridas en Colombia pero sí sabemos de datos que indican, con claridad, que esto sucede también en el país.…”