Schistosomiasis and other helminth infections

Schistosomiasis (Box 13.5), together with the gut parasites hookworm, strongyloidiasis, and trichuriasis, are examples of other important diseases caused by helminths infecting man. As with Ascaris infection, only a small proportion of people harbouring these parasites are heavily infected so that about 10% of an affected population typically have 70% of the total parasite burden (Anderson and May 1985). Such effects are felt to relate to differences in exposure and to individual susceptibility. Familial aggregation of these different helminth infections is well documented, together with evidence of individual predisposition and ethnic variability in susceptibility - all suggestive evidence of a role of host genetic variation playing a role in modulating disease (Quinnell 2003). It was noted as early as 1925 in the southern United States that a higher prevalence and intensity of hookworm infection was seen in those of European compared to African ancestry (Smillie and Augustine 1925). Overall, up to 44%

Figure 13.11 Jirel pedigree. The remarkable Jirel population pedigree available for analysis of Ascaris infestation in Nepal is shown. Reproduced with permission from Williams-Blangero et al. (2002) .

of the variability has been attributed to genetic effects (Quinnell 2003). However the many attempts to localize the specific gene regions or genetic variants within them have proved largely frustrating.

Progress has been made in terms of understanding genetic factors influencing infection with S. mansoni in Brazil. Segregation analysis using 20 family pedigrees within an area of Brazil hyperendemic for schistosom-iasis indicated a single codominant major gene effect (Abel et al. 1991). To try to define the responsible gene, a genome-wide linkage study was performed among 142 individuals from 11 informative Brazilian families (Marquet et al. 1996). This showed evidence of linkage to chromosome 5q31-q33, a genomic locus containing many different immune genes including IL4, IL5, and ILT3 members of the interleukin family (Marquet et al. 1996). Further supporting evidence was found from an independent study in an epidemic focus of infection with a shorter history of population exposure in northern

Senegal (Muller-Myhsok et al. 1997). Linkage was found with the same genomic region but without dominant inheritance (Muller-Myhsok et al. 1997).

The 5q31-q33 region has also been associated with levels of IgE production (Marsh et al. 1994), and with susceptibility to several other diseases including asthma and inflammatory bowel disease (Yokouchi et al. 2000; Rioux et al. 2001). Levels of IgE have been shown previously to be an important component of immune resistance to helminth infection (Hagan et al. 1991). The specific genetic variants within the 5q31-q33 region responsible for the genetic effects remain to be localized. However, family-based studies in Mali of infection with S. haematobium, the cause of urinary schistosomiasis, have provided some intriguing possibilities (Kouriba et al. 2005). Here, alleles bearing specific promoter polymorphisms of the ILT3 gene were preferentially inherited by children with the highest 10% levels of infection.

cM 0 — 50 — 100 — 150 — 200 — 250 — 300 —

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