Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial.
Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial.
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强力霉素会导致在重复的伊维尔梅克蛋白治疗后持续的微毛皮里岛的区域中，在持续的微丝菌中杀死女性OnChocerca volvulus蠕虫的无菌性和增强，这是一项随机，安慰剂对照，双盲试验。
DOI：
10.1093/cid/civ363
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发表时间：
2015-08-15
期刊：
影响因子：
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通讯作者：
Hoerauf A
中科院分区：
文献类型：
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作者：
Debrah AY;Specht S;Klarmann-Schulz U;Batsa L;Mand S;Marfo-Debrekyei Y;Fimmers R;Dubben B;Kwarteng A;Osei-Atweneboana M;Boakye D;Ricchiuto A;Büttner M;Adjei O;Mackenzie CD;Hoerauf A
对伊维菌素（IVM）的次优反应已经出现。使用强力霉素靶向盘尾丝虫沃尔巴克氏体内共生体可有效清除患有持续性微丝蚴病的盘尾丝虫病患者的微丝蚴，并在重复标准 IVM 治疗后增强对成虫的杀灭作用。背景。 伊维菌素（IVM）已成为治疗盘尾丝虫病的首选药物。然而，有报道称，来自加纳流行区的个体在多轮 IVM 后出现持续性微丝蚴病，引发了对反应不佳甚至出现耐药性的担忧。由于继续仅依靠 IVM 来对抗这种现象被认为是有风险的，因此我们评估了用多西环素针对盘尾丝虫沃尔巴克氏体内共生体对这些反应欠佳的个体的效果。方法。 在 IVM 反应欠佳的地区招募了 167 名患者，其中大多数接受了多轮 IVM，并接受 100 毫克/天的多西环素治疗 6 周。多西环素治疗后 3 个月和 12 个月，患者参加标准 IVM 治疗。结果。 治疗后 20 个月时，安慰剂组中 80% 的活雌性蠕虫呈沃尔巴克氏体阳性，而强力霉素治疗组中只有 5.1% 含有细菌。与胚胎发生中断一致，从强力霉素治疗的患者中取出的结节中没有一个含有微丝蚴，并且这些患者中 97% 没有微丝蚴病，而安慰剂患者则保持在治疗前水平 (P < .001)。此外，使用强力霉素后观察到死亡蠕虫数量显着增加。结论。 针对盘尾丝虫中的沃尔巴克氏体，可有效清除患有持续性微丝蚴病的盘尾丝虫病患者皮肤中的微丝蚴，并可在重复标准 IVM 治疗后增强对成虫的杀灭作用。现在可以制定策略，包括使用强力霉素来控制盘尾丝虫病，尽管这些地区经常使用 IVM，但感染仍然存在。临床试验注册。 ISRCTN 66649839。
Sub-optimal responses to ivermectin (IVM) have emerged. Targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline is effective in clearing microfilariae in onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839.