Abstract
Estimates of genetic diversity in helminth infections of humans often have to rely on genotyping (immature) parasite transmission stages instead of adult worms. Here we analyse the results of one such study investigating a single polymorphic locus (a change at position 200 of the β-tubulin gene) in microfilariae of the lymphatic filarial parasite Wuchereria bancrofti. The presence of this genetic change has been implicated in benzimidazole resistance in parasitic nematodes of farmed ruminants. Microfilariae were obtained from patients of three West African villages, two of which were sampled prior to the introduction of mass drug administration. An individual-based stochastic model was developed showing that a wide range of allele frequencies in the adult worm populations could have generated the observed microfilarial genetic diversity. This suggests that appropriate theoretical null models are required in order to interpret studies that genotype transmission stages. Wright's hierarchical F-statistic was used to investigate the population structure in W. bancrofti microfilariae and showed significant deficiency of heterozygotes compared to the Hardy-Weinberg equilibrium; this may be partially caused by a high degree of parasite genetic differentiation between hosts. Studies seeking to quantify accurately the genetic diversity of helminth populations by analysing transmission stages should increase their sample size to account for the variability in allele frequency between different parasite life-stages. Helminth genetic differentiation between hosts and non-random mating will also increase the number of hosts (and the number of samples per host) that need to be genotyped, and could enhance the rate of spread of anthelmintic resistance.
Highlights
In recent years there has been a substantial increase in the use of mass drug administration (MDA) to reduce the morbidity associated with helminth infections of humans [1], increasing the probability that anthelmintic resistance may become a public health concern in the future
This genetic change has been identified in W. bancrofti [13], though the phenotypic studies relating the substitution to a decreased albendazole efficacy have not been undertaken in this species
The number of studies looking for genetic markers of drug resistance has increased noticeably
Summary
In recent years there has been a substantial increase in the use of mass drug administration (MDA) to reduce the morbidity associated with helminth infections of humans [1], increasing the probability that anthelmintic resistance may become a public health concern in the future. A phenylalanine to tyrosine substitution at position 200 on the b-tubulin isotype 1 molecule has been identified in a number of helminth parasites of farmed ruminants including Haemonchus contortus [14,15], Cooperia oncophora [16], and Teladorsagia circumcincta [17] and is associated with benzimidazole (BZ) resistance in these species This genetic change has been identified in W. bancrofti [13], though the phenotypic studies relating the substitution to a decreased albendazole efficacy have not been undertaken in this species. To aid clarity the two alleles at position 200 on the b-tubulin isotype 1 molecule shall be referred to as allele F (phenylalanine) for susceptibility and allele Y (tyrosine) for putative resistance
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