Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.
Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.
复制标题
DOI：
10.1371/journal.pntd.0000660
复制
发表时间：
2010-04-13
影响因子：
3.8
通讯作者：
Taylor MJ
中科院分区：
文献类型：
--
作者：
Turner JD;Tendongfor N;Esum M;Johnston KL;Langley RS;Ford L;Faragher B;Specht S;Mand S;Hoerauf A;Enyong P;Wanji S;Taylor MJ
伊维菌素治疗盘尾丝虫病后，在与血吸虫病共同流行的地区发生严重不良事件的风险，目前损害了控制方案的制定和联合感染者的治疗。因此，我们评估了在不使用伊维菌素的情况下，是否可以使用多西环素来有效地治疗螺旋体丝虫病和成人生存能力。此外，我们评估了在服用伊维菌素之前使用多西环素治疗的安全性，这些患者合并感染了低到中等强度的LOA-LOA微丝虫病。采用随机双盲现场试验，对150例螺旋体感染患者进行了6周的单用多西环素(200 mg/d)、多西环素联合伊维菌素(150µg/kg)+4个月或安慰剂配伍多西环素+伊维菌素+4个月的治疗。另外22例感染旋毛虫和低至中强度LOA感染的患者接受了6周的疗程，多西环素联合伊维菌素治疗+4个月。在多西环素治疗开始后的4个月、12个月和21个月测定治疗效果，以及不良事件的频率和严重程度。104名参与者(60.5%)在21个月的试验期内完成了所有治疗分配和随访评估。在12个月时，与伊维菌素或单用多西环素组相比，多西环素/伊维菌素治疗组的微丝状皮炎水平较低，而无微丝状皮炎的发生率较高。在21个月时，多西环素/伊维菌素组和单用多西环素组的微丝虫病与单用伊维菌素组相比显著减少。89%的多西环素/伊维菌素组和67%的多西环素组有微丝状皮炎，而单用伊维菌素组的这一比例为21%。多西环素组的旋毛虫在子宫内的沃尔巴克氏菌和所有胚胎阶段都被耗尽。值得注意的是，在多西环素处理组中，雌性成虫的生存能力显著降低，而添加伊维菌素对其大丝虫杀灭和杀菌活性没有影响。多西环素治疗耐受性良好，多西环素或伊维菌素的不良事件发生率在治疗组之间没有显著差异。一个为期六周的多西环素疗程提供了杀灭大丝虫和消毒的活性，这不依赖于联合使用伊维菌素。中度微丝虫病合并感染的患者对多西环素耐受性良好。因此，有必要进行进一步的试验，以评估基于多西环素的干预措施对标准治疗有严重不良反应风险的个人的安全性和有效性，这些患者由于高强度的钩端螺旋体寄生虫病的共存而存在严重不良反应。在与伊维菌素有严重不良反应风险的地区，开发一种与丙二醛控制方案相适应的抗沃尔巴克氏菌治疗方案，可为控制盘尾丝虫病提供另一种选择。受控试验网站ISRCTN48118452非洲盘尾丝虫病的控制依赖于伊维菌素的持续给药。在某些地区，在人口覆盖率较高的情况下提供年度治疗至少15-17年可以阻断传播。在其他流行环境中，单靠这一战略被认为不足以根除这种疾病。主要限制之一出现在与另一种由Loa Loa引起的丝虫病共同流行的地区，因为与大量寄生的L.Loa微丝虫迅速死亡相关的罕见严重不良事件的风险。最近有证据表明伊维菌素的药效降低，并可能产生抗药性，这也令人担忧。另一种方法是用抗生素多西环素来靶向钉螺的沃尔巴克氏菌细菌内共生体。在喀麦隆盘尾丝虫病和血吸虫病共同流行的一个地区，我们进行了一项试验，比较多西环素加或不加伊维菌素治疗和单用伊维菌素治疗。一个为期六周的多西环素疗程提供了杀灭大丝虫和消毒的活性，这不依赖于联合使用伊维菌素。中度微丝虫病合并感染的患者对多西环素耐受性良好。试验表明，在盘尾丝虫病和血吸虫病共同流行的社区，抗沃尔巴克氏菌治疗是伊维菌素的可行替代品。
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. A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 µg/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. 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. 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. Controlled-Trials.com ISRCTN48118452 The control of onchocerciasis in Africa relies on the sustained delivery of ivermectin. In certain areas, annual treatments delivered with high population coverage for at least 15–17 years can break transmission. In other endemic settings this strategy alone is thought to be insufficient to eradicate the disease. One of the major limitations occurs in areas that are co-endemic with another filarial infection caused by Loa loa, due to the risk of a rare severe adverse event associated with the rapid killing of L. loa microfilariae in heavily parasitized individuals. There are also concerns over recent evidence of reduced efficacy of ivermectin and the possible development of resistance. An alternative approach is to target the Wolbachia bacterial endosymbionts of Onchocerca volvulus with the antibiotic, doxycycline. In an area of Cameroon co-endemic for onchocerciasis and loiasis we conducted a trial comparing doxycycline with or without ivermectin treatment to ivermectin treatment alone. 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. The trial indicates that anti-wolbachial therapy is a feasible alternative to ivermectin in communities co-endemic for onchocerciasis and loiasis.
登录
查看更多内容
DOI：
10.1186/1475-2883-2-10
发表时间：
2003-05-09
期刊：
Filaria journal
影响因子：
--
作者：
Büttner DW;Wanji S;Bazzocchi C;Bain O;Fischer P
通讯作者：
Fischer P
DOI：
10.1186/1475-2883-2-2
发表时间：
2003-02-07
期刊：
Filaria journal
影响因子：
--
作者：
Dadzie Y;Neira M;Hopkins D
通讯作者：
Hopkins D
通过超声检查经常检测到Onchocercal结节中的蠕虫运动。
DOI：
10.1186/1475-2883-4-1
发表时间：
2005-03-23
期刊：
Filaria journal
影响因子：
--
作者：
Mand S;Marfo-Debrekyei Y;Debrah A;Buettner M;Batsa L;Pfarr K;Adjei O;Hoerauf A
通讯作者：
Hoerauf A
DOI：
10.1080/00034983.1980.11687330
发表时间：
1980-01-01
影响因子：
--
作者：
AWADZI, K
通讯作者：
AWADZI, K
DOI：
10.1016/j.trstmh.2007.03.018
发表时间：
2007-08-01
影响因子：
2.2
作者：
Kamgno, Joseph;Pion, Sebastien D. S.;Boussinesq, Michel
通讯作者：
Boussinesq, Michel