Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
University Teaching Hospital of Butare, University of Rwanda, Butare, Rwanda.
Int J Parasitol Drugs Drug Resist. 2017 Dec;7(3):262-271. doi: 10.1016/j.ijpddr.2017.06.001. Epub 2017 Jun 23.
Control of human soil-transmitted helminths (STHs) relies on preventive chemotherapy of schoolchildren applying the benzimidazoles (BZ) albendazole or mebendazole. Anthelmintic resistance (AR) is a common problem in nematodes of veterinary importance but for human STHs, information on drug efficacy is limited and routine monitoring is rarely implemented. Herein, the efficacy of single dose albendazole (400 mg) was evaluated in 12 schools in the Huye district of Rwanda where Ascaris is the predominant STH. Ascaris eggs were detected by wet mount microscopy and the Mini-FLOTAC method to assess cure rate (CR) and faecal egg count reduction (FECR). Blood and faecal samples were analysed for co-infections with Plasmodium sp. and Giardia duodenalis, respectively. Ascaris positive samples collected before and after treatment were analysed for putatively BZ-resistance associated β-tubulin gene single nucleotide polymorphisms. The overall CR was 69.9% by Mini-FLOTAC and 88.6% by wet mount microscopy. The FECR was 75.4% and the 95% calculated confidence intervals were 50.4-87.8% using sample variance, 55.4-88.8% by bootstrapping, and 75.0-75.7% applying a Markov Chain Monte Carlo Bayesian approach. FECR varied widely between 0 and 96.8% for individual schools. No putative BZ-resistance associated polymorphisms were found in the four Ascaris β-tubulin isotype genes examined. Since FECRs <95% indicate reduced efficacy, these findings raise the suspicion of BZ resistance. In the absence of respective molecular evidence, heritable AR in the local Ascaris populations cannot be formally proven. However, since FECRs <95% indicate reduced efficacy, BZ resistance may be suspected which would be alarming and calls for further analyses and routine monitoring in preventive chemotherapy programs.
控制人体土壤传播性蠕虫(STH)依赖于对在校儿童进行苯并咪唑(BZ)阿苯达唑或甲苯达唑的预防性化疗。驱虫剂耐药性(AR)是兽医重要线虫的常见问题,但对于人体 STH,关于药物疗效的信息有限,常规监测很少实施。在此,在卢旺达胡耶区的 12 所学校评估了单剂量阿苯达唑(400mg)的疗效,在这些学校中,蛔虫是主要的 STH。通过湿载显微镜和 Mini-FLOTAC 方法检测蛔虫卵,以评估治愈率(CR)和粪便卵计数减少率(FECR)。分别分析血液和粪便样本以检测是否存在疟疾原虫和十二指肠贾第鞭毛虫的合并感染。在治疗前后收集的蛔虫阳性样本被分析了潜在的 BZ 耐药相关β-微管蛋白基因单核苷酸多态性。通过 Mini-FLOTAC 和湿载显微镜观察,总体 CR 分别为 69.9%和 88.6%。FECR 为 75.4%,使用样本方差计算的 95%置信区间为 50.4-87.8%,通过自举法计算的置信区间为 55.4-88.8%,通过马尔可夫链蒙特卡罗贝叶斯方法计算的置信区间为 75.0-75.7%。个别学校的 FECR 差异很大,为 0 至 96.8%。在所检查的四个蛔虫β-微管蛋白同工型基因中未发现与潜在 BZ 耐药相关的多态性。由于 FECR<95%表明疗效降低,这些发现引起了对 BZ 耐药性的怀疑。在缺乏相应分子证据的情况下,不能正式证明当地蛔虫种群中存在遗传性 AR。然而,由于 FECR<95%表明疗效降低,可能怀疑存在 BZ 耐药性,这令人担忧,并呼吁在预防性化疗计划中进行进一步分析和常规监测。