Yale Partnerships for Global Health, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut.
Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
Am J Trop Med Hyg. 2019 Feb;100(2):351-356. doi: 10.4269/ajtmh.18-0727.
Hookworm infection causes anemia, malnutrition, and growth delay, especially in children living in sub-Saharan Africa. The World Health Organization recommends periodic mass drug administration (MDA) of anthelminthics to school-age children (SAC) as a means of reducing morbidity. Recently, questions have been raised about the effectiveness of MDA as a global control strategy for hookworms and other soil-transmitted helminths (STHs). Genomic DNA was extracted from hookworm eggs isolated from SAC enrolled in a cross-sectional study of STH epidemiology and deworming response in Kintampo North Municipality, Ghana. A polymerase chain reaction (PCR) assay was then used to identify single-nucleotide polymorphisms (SNPs) associated with benzimidazole resistance within the β-tubulin gene. Both F167Y and F200Y resistance-associated SNPs were detected in hookworm samples from infected study subjects. Furthermore, the ratios of resistant to wild-type SNP at these two loci were increased in posttreatment samples from subjects who were not cured by albendazole, suggesting that deworming drug exposure may enrich resistance-associated mutations. A previously unreported association between F200Y and a third resistance-associated SNP, E198A, was identified by sequencing of F200Y amplicons. These data confirm that markers of benzimidazole resistance are circulating among hookworms in central Ghana, with unknown potential to impact the effectiveness and sustainability of chemotherapeutic approaches to disease transmission and control.
钩虫感染会导致贫血、营养不良和生长迟缓,尤其是生活在撒哈拉以南非洲的儿童。世界卫生组织建议对学龄儿童(SAC)定期进行驱虫药集体给药(MDA),以作为降低发病率的一种手段。最近,人们对 MDA 作为钩虫和其他土壤传播性蠕虫(STHs)全球控制策略的有效性提出了质疑。从加纳金坦波北市进行的 STH 流行病学和驱虫反应横断面研究中招募的 SAC 中分离出钩虫卵,提取基因组 DNA。然后使用聚合酶链反应(PCR)检测鉴定与 β-微管蛋白基因中苯并咪唑耐药相关的单核苷酸多态性(SNP)。在感染研究对象的钩虫样本中均检测到 F167Y 和 F200Y 耐药相关 SNP。此外,在未被阿苯达唑治愈的治疗后样本中,这两个位点的耐药 SNP 与野生型 SNP 的比值增加,这表明驱虫药物暴露可能会富集耐药相关突变。通过对 F200Y 扩增子的测序,发现了 F200Y 与第三个耐药相关 SNP(E198A)之间的先前未报道的关联。这些数据证实了苯并咪唑耐药标记物在加纳中部的钩虫中传播,这可能对化疗方法在疾病传播和控制方面的有效性和可持续性产生未知的影响。