1. Association between Response to Albendazole Treatment and β-Tubulin Genotype Frequencies in Soil-transmitted Helminths.
- Author
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Diawara, Aïssatou, Halpenny, Carli M., Churcher, Thomas S., Mwandawiro, Charles, Kihara, Jimmy, Kaplan, Ray M., Streit, Thomas G., Idaghdour, Youssef, Scott, Marilyn E., Basáñez, Maria-Gloria, and Prichard, Roger K.
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HOOKWORM disease ,ALBENDAZOLE ,SINGLE nucleotide polymorphisms ,ASCARIS lumbricoides ,HELMINTHS ,DRUG efficacy - Abstract
Background: Albendazole (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. Methods: Studies 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. Findings: In 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. Conclusion: Albendazole 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. Author Summary: The soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and the hookworms Ancylostoma duodenale and Necator americanus are endemic in many tropical countries. Regular treatment with albendazole or mebendazole is the major means for controlling STHs. However, repeated treatment with the same class of benzimidazole anthelmintics has caused resistance in veterinary parasites, characterized by mutations at either codon 200, 167 or 198 in the β-tubulin gene. There is a concern that resistance may develop in human STH. Drug efficacy and mutation frequencies were assessed in T. trichiura, A. lumbricoides and hookworms collected in Haiti, Kenya and Panama prior to and after albendazole treatment. In T. trichiura from Haiti and Kenya, a significant increase of the frequency of the mutation at codon 200 was identified after treatment and drug efficacy was mediocre. Against A. lumbricoides, albendazole efficacy was good, even though the frequency of a mutation at codon 167 was relatively high, suggesting that, in this nematode, the codon 167 polymorphism does not impact efficacy. In hookworms, the mutation at codon 200 was identified, but at low frequencies and the response to albendazole was good. We conclude that monitoring for possible resistance in control programmes should be undertaken. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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