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首页> 外文OA文献 >Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.
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Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.

机译：仅在强力霉素共流行病地区使用强力霉素对小肠盘尾丝虫的强杀线虫作用：一项随机对照试验。

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BACKGROUND: The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. \ud\udMETHODS: A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 microg/kg) at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events. \ud\udRESULTS: One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia and all embryonic stages in utero. Notably, the viability of female adult worms was significantly reduced in doxycycline treated groups and the macrofilaricidal and sterilising activity was unaffected by the addition of ivermectin. Treatment with doxycycline was well tolerated and the incidence of adverse event to doxycycline or ivermectin did not significantly deviate between treatment groups. \ud\udCONCLUSIONS: A six-week course of doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. Therefore, further trials are warranted to assess the safety and efficacy of doxycycline-based interventions to treat onchocerciasis in individuals at risk of serious adverse reactions to standard treatments due to the co-occurrence of high intensities of L. loa parasitaemias. The development of an anti-wolbachial treatment regime compatible with MDA control programmes could offer an alternative to the control of onchocerciasis in areas of co-endemicity with loiasis and at risk of severe adverse reactions to ivermectin.
机译：背景：在伊维菌素与地方性流行病共存的地区，用伊维菌素治疗盘尾丝虫病后出现严重不良事件的风险目前损害了控制程序和共同感染者的治疗。因此，我们评估了是否可以在不随后给予伊维菌素的情况下使用强力霉素治疗，以有效地对肠粘膜小肠粘膜微丝ari虫症和成人生存能力产生持续影响。此外，我们评估了在伊维菌素给药之前，在低至中等强度的Loa loa微丝丝虫血症共感染的盘尾丝虫病个体中强力霉素治疗的安全性。 \ ud \ ud方法：进行了一项双盲，随机，现场试验，研究了单独使用强力霉素（200 mg /天），强力霉素与依维菌素（150 microg / kg）联合使用的情况，在4个月时或与强力霉素+伊维菌素相匹配的安慰剂，共6周。在+4个月内感染了Onchocerca volvulus的150个人中。在+4个月时，对另外22名感染肠弯曲杆菌和中低强度Loa loa感染的个体进行了6周的强力霉素和伊维菌素的疗程。在开始强力霉素治疗后的第4、12和21个月确定治疗效果以及不良事件的发生频率和严重程度。结果：在21个月的试验期内，一百零四名（60.5％）参与者完成了所有治疗分配并进行了随访评估。与仅使用伊维菌素或强力霉素的组相比，用强力霉素/伊维菌素治疗的患者在12个月时具有较低的微丝虫病水平和较高的微丝菌病发生率。与仅伊维菌素组相比，强力霉素/伊维菌素和仅多西环素组在21个月时的微丝虫病明显减少。强力霉素/伊维菌素组为89％，仅强力霉素组为67％，而仅伊维菌素组为21％。多西环素组的肠螺旋体中的沃尔巴氏菌和子宫内所有胚胎期都被消耗掉。值得注意的是，在多西环素治疗组中，成年雌性蠕虫的活力显着降低，并且加入伊维菌素不会影响大杀线和杀菌活性。多西环素的治疗耐受性良好，治疗组之间对多西环素或伊维菌素的不良事件发生率没有显着差异。结论：强力霉素的六周疗程可提供大杀线和杀菌活性，而这并不依赖于伊维菌素的共同给药。在中等强度的lo。loa微丝aria病合并感染的患者中，强力霉素具有良好的耐受性。因此，有必要进行进一步的试验来评估基于强力霉素的高剂量寄生虫血症同时发生而对标准治疗有严重不良反应风险的个体中以强力霉素为基础的干预措施治疗盘尾丝虫病的安全性和有效性。与MDA控制程序兼容的抗狼疮治疗方案的开发，可以在与肥胖症共存的流行区和对伊维菌素有严重不良反应风险的地方提供控制盘尾丝虫病的替代方法。

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