title: Association between response to albendazole treatment and β-tubulin genotype frequencies in soil-transmitted helminths.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Quebéc, Canada.
authors.forename: Aïssatou
authors.initials: A
authors.lastname: Diawara
authors.forename: Carli M
authors.initials: CM
authors.lastname: Halpenny
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Churcher
authors.forename: Charles
authors.initials: C
authors.lastname: Mwandawiro
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kihara
authors.forename: Ray M
authors.initials: RM
authors.lastname: Kaplan
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Streit
authors.forename: Youssef
authors.initials: Y
authors.lastname: Idaghdour
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Scott
authors.forename: Maria-Gloria
authors.initials: MG
authors.lastname: Basáñez
authors.forename: Roger K
authors.initials: RK
authors.lastname: Prichard
mesh_terms: D000293:Adolescent; D015766:Albendazole / Q000627:therapeutic use*; D000723:Ancylostomatoidea / Q000235:genetics* / Q000302:isolation & purification; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D017164:Ascaris lumbricoides / Q000235:genetics* / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005838:Genotype; D006205:Haiti; D006801:Humans; D007223:Infant; D007630:Kenya; D008297:Male; D009349:Nematode Infections / Q000188:drug therapy* / Q000469:parasitology; D010176:Panama; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014258:Trichuris / Q000235:genetics* / Q000302:isolation & purification; D014404:Tubulin / Q000235:genetics*
chemical_list: D000871:Anthelmintics; D014404:Tubulin; D015766:Albendazole