Ascaris Lumbricoides Infection, Susceptibility To

Description

More than a quarter of the human population is affected by soil-transmitted helminthes, which impair nutrition and the immune response to widespread pandemics, such as acquired immunodeficiency syndrome (see 609423) and tuberculosis (see 607948). The roundworm Ascaris lumbricoides, the most common human parasite of the gastrointestinal tract, causes ascariasis, which has a worldwide distribution with highest prevalence in tropical and subtropical regions and in areas with inadequate sanitation. Ascariasis is triggered by ingestion of parasite eggs. During its life cycle, Ascaris threatens human health with nonspecific abdominal symptoms, intestinal obstruction and perforation, biliary colic, gallstone formation, liver abscesses, pancreatitis, and pulmonary eosinophilia (Sanglas et al., 2009).

Pathogenesis

Sanglas et al. (2009) noted that Ascaris roundworms secrete a battery of selective inhibitors to protect themselves from host enzymes and the immune system. Sanglas et al. (2009) cloned the gene encoding an Ascaris metallocarboxypeptidase (MCP) inhibitor, ACI. The crystal structure of ACI complexed to one of its potential host targets, CPA1 (114850), showed that the worm protein entered the funnel-like active-site cavity of the enzyme. Sanglas et al. (2009) proposed that ACI interaction with host MCPs in the intestine and intestinal mucosa mast cells may explain prolonged Ascaris survival in a hostile environment.

Inheritance

Williams-Blangero et al. (1999) stated that a familial patterning to A. lumbricoides infection had been noted in several reports (e.g., Williams et al., 1974 and Forrester et al., 1988), and that the heritability of resistance/susceptibility to gastrointestinal nematodes had been demonstrated in sheep and cattle. Williams-Blangero et al. (1999) presented a genetic epidemiologic analysis of A. lumbricoides infection in the Jirel population of eastern Nepal. A total of 1,261 individuals belonging to a single pedigree were assessed for intensity of Ascaris infection at 2 points in time. Following an initial assessment in which all individuals were treated with albendazole, a follow-up examination was performed 1 year later to evaluate reinfection patterns. They used 3 measures of worm burden, including eggs per gram of feces, direct worm counts, and worm biomass (weight). For all 3 traits, variance component analysis of the familial data provided unequivocal evidence for a strong genetic component accounting for 30 to 50% of the variation in worm burden. Shared environmental (i.e., common household) effects accounted for 3 to 13% of the total phenotypic variants.

Molecular Genetics

Holland et al. (1992) found that A. lumbricoides worm loads in Nigerian children appeared to be related to the major histocompatibility complex.