Human helminth co-infection: No evidence of common genetic control of hookworm and Schistosoma mansoni infection intensity in a Brazilian community

Abstract

Strong statistical associations between soil transmitted helminths and schistosomes are frequently observed in co-endemic human populations, although the underlying explanations remain poorly understood. This study investigates the contribution of host genetics and domestic environment to hookworm and Schistosoma mansoni infection intensity and evaluates the role of genetic and non-genetic factors in covariation of infection intensity. Detailed genealogical information allowed assignment of 1,303 individuals living in the Brazilian community of Americaninhas, Minas Gerais state, to 25 pedigrees (containing between two and 1,159 members) residing in 303 households. The prevalence of co-infection with both hookworms and schistosomes was high (38.5%), with significant correlation between Necator americanus and S. mansoni faecal egg counts (r = 0.242; P < 0.0001). Bivariate variance component analysis demonstrated a modest but significant species-specific heritability for intensity of N. americanus (h2 = 0.196) and S. mansoni infection (h2 = 0.230). However, after accounting for demographic, socio-economic and household risk factors, no evidence for common genetic control of intensity of hookworm and schistosome infection was observed (genetic correlation ρG = 0.15; P = 0.52). There was some evidence for residual clustering within households (household correlation ρC = 0.45; P = 0.06), but the majority (63%) of the covariance between N. americanus and S. mansoni infection intensity remained specific to the individual and could not be explained by shared genes, shared environment or other shared demographic, socio-economic or environmental risk factors. Our results emphasize the importance of exposure to hookworm and schistosome infection in driving the association between levels of infection with these species in hosts resident in areas of high transmission and suggest that much of this common exposure occurs outside the home.

Genetic and Household Determinants of Predisposition to Human Hookworm Infection in a Brazilian Community

“…However, our estimate of 17% is comparable to hookworm studies elsewhere which estimate heritability as 10-25% [18, 20], or 15-37% when not modeling household effects [18, 19]. Estimates for other human helminths vary from 9-44% [11, 12, 31]; one study of Schistosoma japonicum infection did not find significant heritability [32]. Most previous studies have looked at pretreatment intensity only.…”

Causes and consequences of intra‐ and inter‐host heterogeneity in defence against nematodes

“…Pedigree‐based variance components analysis has shown that additive genetic (heritable) effects account for a significant proportion of the variation in human nematode burdens and immune responses . By accounting for risk factors such as common household effects and social status, the relative roles of exposure and genetic variation in resistance may be separated . In agricultural settings, the spiralling costs and reduced effectiveness of anthelmintic drugs have seen increased research into the genetic basis of nematode resistance in the last twenty years.…”

“…Epidemiological studies of co‐infection in humans generally focus on the factors associated with the risk of co‐infection with pairs of species, which can often be ascribed to variation in exposure rather than immune‐mediated resistance, caused by socio‐economic status, shared transmission routes and behaviour . However, by controlling statistically for these exposure‐related variables, it may be shown that the presence and intensity of infection of co‐infecting species are correlated.…”

The potential economic value of a hookworm vaccine

“…[30] This vaccine contains the Na-Asp-2 antigen, targeting the larval form of N. americanus , the most prevalent type of hookworm in this region. [46–47] Its suspected mechanisms of action include reducing larval penetration of human tissue and preventing the developmental progression of larvae into adults. [30] Other candidate antigens currently at the forefront of the pre-clinical development are Na-GST-1 and Na-APR-1, which would likely be combined into a bivalent vaccine, target adult hookworm and may serve an additional therapeutic purpose.…”