Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Quebéc, Canada.
PLoS Negl Trop Dis. 2013 May 30;7(5):e2247. doi: 10.1371/journal.pntd.0002247. Print 2013.
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.
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.
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.
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.
阿苯达唑（ABZ）是一种苯并咪唑（BZ）驱虫药（AH），常用于治疗土壤传播的蠕虫（STHs）。它的常规使用增加了产生 BZ 耐药性的可能性，而在兽医线虫中，这种耐药性是由β-微管蛋白基因中位置 200、167 或 198 的单个核苷酸多态性（SNP）引起的。迄今为止，在研究过的不同动物寄生线虫中，这些 SNP 的相对重要性各不相同，目前尚不清楚这些 SNP 是否会影响 ABZ 对人类 STH 的疗效。我们评估了阿苯达唑治疗前后蛔虫、鞭虫和钩虫感染的疗效和 SNP 频率。
研究在海地、肯尼亚和巴拿马进行。在 ABZ 治疗前和治疗后两周（海地）、一周（肯尼亚）和三周（巴拿马），进行粪便样本检查，以确定卵减少率（ERR）。对卵进行基因分型，并评估每个 SNP 的频率。
在鞭虫中，检测到密码子 200 的多态性。治疗后，在海地，纯合耐药型的比例从 3.1%显著增加到 55.3%，在肯尼亚从 51.3%增加到 67.8%（ERR 分别为 49.7%和 10.1%）。在蛔虫中，167 位的 SNP 在前、后治疗时均被鉴定为高频，但 ABZ 的疗效仍然很高。在肯尼亚的钩虫中，我们在治疗前后均检测到低频率的与耐药相关的 200 位 SNP，而 ERR 值表明药物疗效良好。
阿苯达唑对蛔虫和钩虫有效。然而，ABZ 对鞭虫β-微管蛋白基因的 200 位施加了选择压力，这可能解释了 ABZ 对这种寄生虫的疗效仅为中等水平。在蛔虫中，167 位密码子的多态性似乎不会影响药物疗效，而钩虫中 200 位密码子的多态性频率如此之低，无法得出结论。
