Authors
BP Jones3; AH van Vliet3; EJ Lacourse1; S Roose2; P Geldhof2; M Betson3; 1 Liverpool School of Tropical Medicine / UoL, UK; 2 Ghent University, Belgium; 3 University of Surrey, UK Discussion
Ascaris lumbricoides and Ascaris suum are intestinal roundworms that infect humans and pigs respectively, and cause the disease known as ascariasis. Ascariasis affects half a billion people, with chronic infections leading to reduced growth and cognitive ability. Ascariasis affects pigs worldwide and can reduce production yields via decreased growth and condemnation of livers.
The predominant drugs used to treat ascariasis are the benzimidazoles (BZ). Despite the farming industry using these drugs for decades, and BZ resistance occurring in numerous livestock helminths, there has been little work on the development of BZ resistance in pig ascariasis. Benzimidazoles work by interacting with β-tubulin, and the mutations causing resistance are known in ruminant nematodes. In most nematodes there are multiple β-tubulin isotypes. Only a few of these are expressed at high levels, with others being restricted to specialised cells or specific developmental stages. Recent work in other ascarids has shown that the canonical benzimidazole-resistance associated mutations, originally identified in ruminant nematodes, are not found in the β-tubulins of Ascaridia or Parascaris, even in phenotypically resistant populations.
We have conducted widespread screening of two Ascaris β-tubulin isotypes highly expressed in adult worms from Ascaris samples from pigs and humans across the world using deep amplicon sequencing techniques. We then used these data to study the population dynamics of Ascaris and highlighted the differences in diversity between the two isotypes, and the differences between genotypes found in each species. Screening of both human- and pig-derived Ascaris isolates found no evidence of any canonical BZ resistance mutations. Overall, there was a clear difference seen in the genetic diversity of each isotype with differences seen in the distribution of β-tubulin genotypes between human- and pig-derived isolates.
This work suggests that resistance via the canonical β-tubulins mutations is not a problem in Ascaris and BZ are likely to be an effective means of control for the near future. However, alternative modes of resistance may emerge therefore continued monitoring of drug efficacy will be required. 
