Association between Response to Albendazole Treatment and β-Tubulin Genotype Frequencies in Soil-transmitted Helminths

Aïssatou Diawara, Carli M. Halpenny, Thomas S. Churcher, Charles Mwandawiro, Jimmy Kihara, Ray M. Kaplan, Thomas G. Streit, Youssef Idaghdhour, Marilyn E. Scott, Maria Gloria Basáñez, Roger K. Prichard

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere2247
JournalPLoS Neglected Tropical Diseases
Volume7
Issue number5
DOIs
StatePublished - Jan 1 2013

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Albendazole
Helminths
Tubulin
Soil
Single Nucleotide Polymorphism
Ascaris lumbricoides
Genotype
Kenya
Haiti
Trichuris
Ancylostomatoidea
Codon
Panama
Gene Order
Ovum
Hookworm Infections
Anthelmintics
Pharmaceutical Preparations
Eggs
Parasites

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Diawara, A., Halpenny, C. M., Churcher, T. S., Mwandawiro, C., Kihara, J., Kaplan, R. M., ... Prichard, R. K. (2013). Association between Response to Albendazole Treatment and β-Tubulin Genotype Frequencies in Soil-transmitted Helminths. PLoS Neglected Tropical Diseases, 7(5), [e2247]. https://doi.org/10.1371/journal.pntd.0002247

Association between Response to Albendazole Treatment and β-Tubulin Genotype Frequencies in Soil-transmitted Helminths. / Diawara, Aïssatou; Halpenny, Carli M.; Churcher, Thomas S.; Mwandawiro, Charles; Kihara, Jimmy; Kaplan, Ray M.; Streit, Thomas G.; Idaghdhour, Youssef; Scott, Marilyn E.; Basáñez, Maria Gloria; Prichard, Roger K.

In: PLoS Neglected Tropical Diseases, Vol. 7, No. 5, e2247, 01.01.2013.

Research output: Contribution to journalArticle

Diawara, A, Halpenny, CM, Churcher, TS, Mwandawiro, C, Kihara, J, Kaplan, RM, Streit, TG, Idaghdhour, Y, Scott, ME, Basáñez, MG & Prichard, RK 2013, 'Association between Response to Albendazole Treatment and β-Tubulin Genotype Frequencies in Soil-transmitted Helminths', PLoS Neglected Tropical Diseases, vol. 7, no. 5, e2247. https://doi.org/10.1371/journal.pntd.0002247
Diawara, Aïssatou ; Halpenny, Carli M. ; Churcher, Thomas S. ; Mwandawiro, Charles ; Kihara, Jimmy ; Kaplan, Ray M. ; Streit, Thomas G. ; Idaghdhour, Youssef ; Scott, Marilyn E. ; Basáñez, Maria Gloria ; Prichard, Roger K. / Association between Response to Albendazole Treatment and β-Tubulin Genotype Frequencies in Soil-transmitted Helminths. In: PLoS Neglected Tropical Diseases. 2013 ; Vol. 7, No. 5.
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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.",
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AU - Mwandawiro, Charles

AU - Kihara, Jimmy

AU - Kaplan, Ray M.

AU - Streit, Thomas G.

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AU - Basáñez, Maria Gloria

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