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在塞内加尔北部,常规吡喹酮治疗不会影响曼氏血吸虫的基因构成。

Regular treatments of praziquantel do not impact on the genetic make-up of Schistosoma mansoni in Northern Senegal.

机构信息

Institute of Tropical Medicine, Department of Biomedical Sciences, Nationalestraat 155, B-2000 Antwerpen, Belgium.

出版信息

Infect Genet Evol. 2013 Aug;18:100-5. doi: 10.1016/j.meegid.2013.05.007. Epub 2013 May 15.

DOI:10.1016/j.meegid.2013.05.007
PMID:23684792
Abstract

The Senegal River Basin (SRB) experienced a major epidemic of intestinal schistosomiasis in the early nineties, after the construction of a dam for irrigation purposes. Exceptionally low cure rates following praziquantel (PZQ) treatment at the onset of the epidemic raised concerns about PZQ resistant strains of Schistosoma mansoni, although they could also be attributed to the intense transmission at that time. A field study in the same region more than 15 years later found cure rates for S. mansoni still to be low, whereas Schistosomahaematobium responded well to treatment. We collected S. mansoni miracidia from children at base-line prior to treatment, six months after two PZQ treatments and two years after the start of the study when they had received a total of five PZQ treatments. In total, 434 miracidia from 12 children were successfully genotyped with at least six out of nine DNA microsatellite loci. We found no significant differences in the genetic diversity of, and genetic differentiation between parasite populations before and after repeated treatment, suggesting that PZQ treatment does not have an impact on the neutral evolution of the parasite. This is in stark contrast with a similar study in Tanzania where a significant decrease in genetic diversity was observed in S. mansoni miracidia after a single round of PZQ treatment. We argue that PZQ resistance might play a role in our study area, although rapid re-infection cannot be excluded. It is important to monitor this situation carefully and conduct larger field studies with short-term follow-up after treatment. Since PZQ is the only general schistosomicide available, the possibility of PZQ resistance is of great concern both for disease control and for curative use in clinical practice.

摘要

塞内加尔河流域(SRB)在 90 年代初因灌溉目的修建水坝后,爆发了大规模的肠道血吸虫病疫情。在疫情爆发之初,采用吡喹酮(PZQ)治疗时,治愈率异常低,这让人担忧是否出现了对吡喹酮具有抗性的曼氏血吸虫(Schistosoma mansoni)菌株,但也可能归因于当时强烈的传播。15 年多后在同一地区进行的一项实地研究发现,曼氏血吸虫的治愈率仍然较低,而埃及血吸虫(Schistosomahaematobium)对治疗反应良好。我们在基线治疗前从儿童身上收集了曼氏血吸虫的尾蚴,在接受了两次吡喹酮治疗和两次研究开始后的两年后,即总共接受了五次吡喹酮治疗后,又收集了这些尾蚴。总共有 12 名儿童的 434 条尾蚴成功地用至少 9 个 DNA 微卫星基因座中的 6 个进行了基因分型。我们发现,在反复治疗前后,寄生虫群体的遗传多样性和遗传分化没有显著差异,这表明吡喹酮治疗对寄生虫的中性进化没有影响。这与坦桑尼亚的一项类似研究形成鲜明对比,在该研究中,单次吡喹酮治疗后,曼氏血吸虫尾蚴的遗传多样性显著下降。我们认为,在我们的研究区域,吡喹酮耐药可能起作用,尽管不能排除快速再感染的可能性。重要的是要仔细监测这种情况,并在治疗后进行短期随访的更大规模实地研究。由于吡喹酮是唯一可用的一般性杀血吸虫药物,吡喹酮耐药的可能性不仅对疾病控制,而且对临床实践中的治疗用途都非常令人担忧。

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