Development of the egg hatch assay for detection of anthelminthic resistance in human hookworms
Development of the egg hatch assay for detection of anthelminthic resistance in human hookworms
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DOI：
10.1016/j.ijpara.2005.02.016
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发表时间：
2005-06-01
影响因子：
4
通讯作者：
Bickle, Q
中科院分区：
文献类型：
--
作者：
Albonico, M;Wright, V;Bickle, Q
兽医线虫中驱虫药耐药性的发展和快速传播的证据引起了人们的关注，即在基于化疗的计划中越来越频繁地使用控制人类土源性蠕虫的治疗方法可能会选择耐药蠕虫。本研究的目的是调整、完善和评估已用于兽医线虫的卵孵化试验 (EHA) 测试，用于现场测试人类钩虫的苯并咪唑 (BZ) 敏感性/抗性。第二个目标是利用该 EHA 来评估奔巴岛经常接受治疗的儿童亚群中是否已经形成了对甲苯咪唑 (MBZ) 具有抗药性的蠕虫种群。对第一班（标准 1）和第五班（标准 5）注册的 470 名学童的粪便进行了基线检查和 500 mg MBZ 或安慰剂片剂治疗后 21 天的检查。标准I儿童从未接受过任何MBZ治疗，而标准5儿童总共接受了13轮治疗。 EHA 涉及对药物浓度不断增加的纯化卵进行培养，结果显示，对于噻苯达唑 (TBZ)，所有儿童基线时的平均 ED(50)s（阻止 50% 活卵孵化所需的浓度）在 48 小时时为 0.079 μg/ml，在 72 小时时为 0.120 μg/ml（P < 0.001）。对于 MBZ，所有儿童基线时的平均 ED(50) 分别为 48 小时时 0.895 μg/ml 和 72 小时时 1.50 μg/ml（P < 0.001）。对于 TBZ 和 MBZ，标准 I 的 ED50 与标准 5 儿童在 48 小时和 72 小时的 ED50 相似。在 TBZ 和 MBZ 的随访中，接受 MBZ 的儿童和接受安慰剂治疗的儿童的 ED50 之间没有显着差异。在彭巴岛，未暴露儿童（标准 1）和暴露儿童（标准 5）接受 MBZ 治疗的 TBZ ED50 值，以及接受 MBZ 和安慰剂治疗的儿童的数据表明，治疗个体中尚未形成耐药蠕虫种群，并且定期治疗尚未选择广泛的 BZ 耐药性，至少达到本研究中 EHA 可检测到的阈值。然而，从从未接触过 BZ 处理的马菲亚岛分离出的菌株的 ED50 值低于彭巴岛，表明从彭巴岛儿童中回收的钩虫卵对 BZ 的敏感性较低。 (c) 2005 年澳大利亚寄生虫学协会。由 Elsevier Ltd 出版。保留所有权利。
Evidence of development and rapid spread of anthelminthic resistance in veterinary nematodes raises concern that the increasingly frequent treatments used in chemotherapy-based programmes to control human soil-transmitted helminths may select resistant worms. The aim of this study was to adapt, refine, and evaluate the Egg Hatch Assay (EHA) test, which has been used for veterinary nematodes, for field testing of benzimidazole (BZ) susceptibility/resistance in human hookworms. A second objective was to use this EHA to assess whether a population of worms resistant to mebendazole (MBZ) has built up in a sub-population of frequently treated children in Pemba Island. Stools from 470 school children enrolled in the first (Standard 1) and in the fifth (Standard 5) class were examined at baseline and at 21 days after treatment with 500 mg MBZ or placebo tablets. Standard I children had never received any MBZ treatment whilst Standard 5 children had received a total of 13 rounds of treatment. The EHA, involving culture of purified eggs with increasing drug concentrations showed that, for thiabendazole (TBZ), the mean ED(50)s (concentrations required to prevent 50% of the viable eggs from hatching) for all children at baseline were 0.079 mu g/ml at 48 h and 0.120 mu g/ml at 72 h (P < 0.001). For MBZ, the mean ED(50)s for all children at baseline were 0.895 mu g/ml at 48 h and 1.50 mu g/ml at 72 h (P < 0.001). For TBZ and for MBZ the ED50 from Standard I were similar to those from Standard 5 children both at 48 and at 72 h. At the follow-up for TBZ and for MBZ, there was no significant difference between the ED50 from children who had received MBZ and children treated with placebo. In Pemba, TBZ ED50 values of children non-exposed (Standard 1) and of children exposed (Standard 5) to MBZ treatment, and data from children treated with MBZ and placebo indicate that a drug-resistant worm population has not built up within treated individuals, and that periodic treatment has not yet selected for widespread BZ resistance, at least at the threshold detectable by the EHA in this study. However, ED50 values for strains isolated from Mafia island, an area never exposed to BZ treatment were lower than for Pemba, suggesting lowered sensitivity of hookworm eggs recovered from Pembian children towards BZ. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.