Association between Response to Albendazole Treatment and β-Tubulin Genotype Frequencies in Soil-transmitted Helminths
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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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It was suggested that the gene mutation at codon 200 might be related with the drug resistance in T. trichiura.
“It was suggested that the gene mutation at codon 200 might be related with the drug resistance [340,341].”
From Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update (2021) · cites this paper as [341]
Diawara et al. identified a single nucleotide polymorphism at position 167 of A. lumbricoides β-tubulin.
“Reversely, Diawara et al. [341] identified a single nucleotide polymorphism at position 167 of A. lumbricoides β-tubulin.”
From Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update (2021) · cites this paper as [341]
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- Authors
- Diawara, A., Halpenny, C. M., Churcher, T. S., Mwandawiro, C., Kihara, J., Kaplan, R. M., Streit, T. G., Idaghdour, Y., Scott, M. E., Basáñez, M.-G., & Prichard, R. K.
- Affiliations
- McGill University (CA)
- Imperial College London (GB)
- Kenya Medical Research Institute (KE)
- University of Georgia (US)
- University of Notre Dame (US)
- Université de Montréal (CA)
- Corresponding author
- Prichard, Roger K.
- ORCID
- Venue
- PLoS Neglected Tropical Diseases
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-05-30
- Volume
- 7
- Issue
- 5
- Pages
- e2247
- ISSN
- 1935-2727 (ISSN-L)
- 1935-2735
- PMC
- PMC3667785
- OpenAlex
- W2043375010
- Cited by
- 180
- References
- 43
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 23 · 2023: 7 · 2022: 22 · 2021: 16 · 2020: 17 · 2019: 11 · 2018: 15 · 2017: 11 · 2016: 9 · 2015: 7 · 2014: 12 · 2013: 3 · 2012: 1
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS neglected tropical diseases (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- McGill University
- Imperial College London
- Fonds Québécois de la Recherche sur la Nature et les Technologies
- Medical Research Council (MR/K010174/1)
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Health Sciences › Veterinary › Small Animals › Helminth infection and control
- Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
- Keywords
- albendazole, beta-tubulin gene, single nucleotide polymorphisms, soil-transmitted helminths, Ascaris lumbricoides, Trichuris trichiura, hookworm, egg reduction rate, drug efficacy, selection pressure
- MeSH terms
- Adolescent, Ancylostomatoidea, Animals, Anthelmintics, Child, Child, Preschool, Cross-Sectional Studies, Drug Resistance, Genotype, Haiti, Humans, Infant, Kenya, Male, Nematode Infections, Panama, Trichuris, Tubulin, Albendazole, Treatment Outcome, Ascaris lumbricoides, Polymorphism, Single Nucleotide
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