title: An analysis of genetic diversity and inbreeding in Wuchereria bancrofti: implications for the spread and detection of drug resistance.
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 beta-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.
authors.affiliation: Department of Infectious Disease Epidemiology, St. Mary's Campus, Imperial College London, London, United Kingdom. thomas.churcher@imperial.ac.uk
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Churcher
authors.forename: Anne E
authors.initials: AE
authors.lastname: Schwab
authors.forename: Roger K
authors.initials: RK
authors.lastname: Prichard
authors.forename: María-Gloria
authors.initials: MG
authors.lastname: Basáñez
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005369:Filaricides / Q000494:pharmacology; D014644:Genetic Variation; D005838:Genotype; D007178:Inbreeding; D008297:Male; D008962:Models, Theoretical; D014404:Tubulin / Q000235:genetics; D014958:Wuchereria bancrofti / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles; D005369:Filaricides; D014404:Tubulin; C031000:benzimidazole