Abstract
BackgroundAlbendazole (ABZ), a benzimidazole (BZ) anthelmintic (AH), is commonly used for treatment of soil-transmitted helminths (STHs). Its regular use increases the possibility that BZ resistance may develop, which, in veterinary nematodes is caused by single nucleotide polymorphisms (SNPs) in the β-tubulin gene at positions 200, 167 or 198. The relative importance of these SNPs varies among the different parasitic nematodes of animals studied to date, and it is currently unknown whether any of these are influencing BZ efficacy against STHs in humans. We assessed ABZ efficacy and SNP frequencies before and after treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections.MethodsStudies were performed in Haiti, Kenya, and Panama. Stool samples were examined prior to ABZ treatment and two weeks (Haiti), one week (Kenya) and three weeks (Panama) after treatment to determine egg reduction rate (ERR). Eggs were genotyped and frequencies of each SNP assessed.FindingsIn T. trichiura, polymorphism was detected at codon 200. Following treatment, there was a significant increase, from 3.1% to 55.3%, of homozygous resistance-type in Haiti, and from 51.3% to 67.8% in Kenya (ERRs were 49.7% and 10.1%, respectively). In A. lumbricoides, a SNP at position 167 was identified at high frequency, both before and after treatment, but ABZ efficacy remained high. In hookworms from Kenya we identified the resistance-associated SNP at position 200 at low frequency before and after treatment while ERR values indicated good drug efficacy.ConclusionAlbendazole was effective for A. lumbricoides and hookworms. However, ABZ exerts a selection pressure on the β-tubulin gene at position 200 in T. trichiura, possibly explaining only moderate ABZ efficacy against this parasite. In A. lumbricoides, the codon 167 polymorphism seemed not to affect drug efficacy whilst the polymorphism at codon 200 in hookworms was at such low frequency that conclusions cannot be drawn.
Highlights
Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are the most common species of soil-transmitted helminths infecting humans worldwide
In A. lumbricoides, the codon 167 polymorphism seemed not to affect drug efficacy whilst the polymorphism at codon 200 in hookworms was at such low frequency that conclusions cannot be drawn
Each study included a treatment with ABZ, stool examinations, and genotyping of the b-tubulin gene in eggs collected before and after ABZ treatment to assess the drug efficacy against soil-transmitted helminths (STH) and to examine at each time point the frequency of possible single nucleotide polymorphisms (SNPs) associated with ABZ resistance in nematodes of veterinary importance
Summary
Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and Necator americanus/Ancylostoma duodenale (hookworms) are the most common species of soil-transmitted helminths infecting humans worldwide. More than a billion people are infected with at least one species and 300 million are estimated to have severe infections with more than one of these parasites [1]. Infected children can be malnourished and experience stunting growth and intellectual retardation, with cognitive and educational deficits [1]. Because of all these characteristics and according to estimates by the World Health Organization (WHO) [4], STHs are included in the group of the so-called neglected tropical diseases (NTDs). We assessed ABZ efficacy and SNP frequencies before and after treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections
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