Association between response to albendazole treatment and β-tubulin genotype frequencies in soil-transmitted helminths.
Association between response to albendazole treatment and β-tubulin genotype frequencies in soil-transmitted helminths.
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DOI：
10.1371/journal.pntd.0002247
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发表时间：
2013
影响因子：
3.8
通讯作者：
Prichard RK
中科院分区：
文献类型：
--
作者：
Diawara A;Halpenny CM;Churcher TS;Mwandawiro C;Kihara J;Kaplan RM;Streit TG;Idaghdour Y;Scott ME;Basáñez MG;Prichard RK
阿苯达唑（ABZ）是一种苯并咪唑（BZ）驱虫剂（AH），常用于治疗土源性蠕虫（STH）。它的定期使用增加了BZ抗性可能发展的可能性，在兽医线虫中，这是由β-微管蛋白基因中位置200、167或198处的单核苷酸多态性（SNP）引起的。这些SNP的相对重要性在迄今为止研究的动物的不同寄生线虫中有所不同，目前尚不清楚这些SNP是否影响BZ对人类STH的疗效。我们评估了ABZ治疗蛔虫、鞭虫和钩虫感染前后的疗效和SNP频率。研究在海地、肯尼亚和巴拿马进行。在ABZ处理前和处理后两周（海地）、一周（肯尼亚）和三周（巴拿马）检查粪便样品，以确定减卵率（ERR）。对鸡蛋进行基因分型，并评估每个SNP的频率。于T.在200位密码子处检测到多态性。治疗后，海地的纯合耐药型从3.1%显著增加到55.3%，肯尼亚的纯合耐药型从51.3%增加到67.8%（错误率分别为49.7%和10.1%）。以.在治疗前和治疗后，均以高频率鉴定了位置167处的SNP，但ABZ疗效仍然很高。在来自肯尼亚的钩虫中，我们在治疗前后以低频率在位置200处鉴定了抗性相关SNP，而ERR值指示良好的药物功效。阿苯达唑对A.蛔虫和钩虫。然而，ABZ对T中200位的β-微管蛋白基因施加选择压力。trichiura，可能解释只有中等ABZ对这种寄生虫的疗效。以.在蛔虫中，密码子167的多态性似乎不影响药物效力，而在钩虫中密码子200的多态性频率很低，因此不能得出结论。土壤传播蠕虫（STH）蛔虫、鞭虫和钩虫钩虫和美洲钩虫是许多热带国家的地方病。常规应用阿苯达唑或甲苯达唑是控制STH的主要手段。然而，用相同类别的苯并咪唑驱肠虫剂重复治疗已引起兽用寄生虫的耐药性，其特征在于β-微管蛋白基因中密码子200、167或198处的突变。人们担心在人类STH中可能会产生耐药性。在T. trichiura、毛尾拟步行虫A.蚯蚓和钩虫收集在海地，肯尼亚和巴拿马之前和之后阿苯达唑治疗。于T.从海地和肯尼亚的trichiura，密码子200处的突变频率显着增加，治疗后确定和药物疗效是平庸的。对A.在蛔虫中，阿苯达唑疗效良好，即使密码子167处的突变频率相对较高，这表明在该线虫中，密码子167多态性不影响疗效。在钩虫中，发现了200号密码子的突变，但频率较低，对阿苯达唑的反应良好。我们的结论是，监测控制方案中可能存在的耐药性。
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. 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.
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影响因子：
3.8
作者：
Halpenny CM;Paller C;Koski KG;Valdés VE;Scott ME
通讯作者：
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