Genetic epidemiology of human schistosomiasis in Brazil

Human schistosomiasis presents the classic, complex disease phenotype, with marked variation in the intensity of infection, the immune response to infection, and the development of schistosome-related pathology. Determining the role of host genetics in schistosomiasis is complicated by the numerous parasite and environmental factors involved in transmission. However, as a result of the increased availability of sequence data, novel statistical methods, and new methods of study design, the last decade has seen significant advances in identifying the role of host genetics in schistosome infection around the world. Many of these advances have taken place in Brazil. Epidemiological studies in Brazil have shown that the intensity of infection (worm burden) is a heritable phenotype (41%). Human genome scans have identified a locus responsible for controlling Schistosoma mansoni infection intensity on chromosome 5q31–q33. There is also evidence for genetic control of pathology due to S. mansoni, with linkage reported to a region containing the gene for the interferon-gamma receptor 1 subunit. Numerous association studies have also provided evidence for major histocompatibility complex control of pathology in schistosomiasis. Recent candidate gene studies suggest a role of other immune response genes in controlling helminth infection and pathology. We chronicle the many advances made in understanding the role of host genetics in S. mansoni infection that have taken place in Brazil by phenotype studied: infection intensity, immune response, and disease development. Results from Brazilian studies are compared with studies of S. mansoni and other schistosome species elsewhere in the world.