The Efficacy of Doxycycline Treatment on Mansonella perstans Infection: An Open-Label, Randomized Trial in Ghana
The Efficacy of Doxycycline Treatment on Mansonella perstans Infection: An Open-Label, Randomized Trial in Ghana
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DOI：
10.4269/ajtmh.18-0491
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Hoerauf, Achim
中科院分区：
文献类型：
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作者：
Debrah, Linda Batsa;Phillips, Richard O.;Hoerauf, Achim
治疗持久性曼森氏菌的挑战是注册的抗蠕虫药疗效低。沃尔巴克氏体内细菌提供了一种替代治疗靶点，因为消耗导致班氏吴策线虫和盘尾丝虫感染的丝虫感染中的无微丝蚴血症。这项开放标签、随机化研究试图证实i）Wolbachia存在于M。ii）多西环素治疗将耗尽沃尔巴克氏体并导致微丝蚴（MF）的缓慢、持续下降。202名加纳人和M。将感染持久性有机污染物的受试者随机分为早期（立即）和延迟（延迟6个月）治疗组，给予多西环素200 mg/天，持续6周，并在基线、研究开始后4、12和24个月（=早期组的随机化时间和治疗开始时间）监测MF和Wolbachia水平。符合方案分析显示，早期组的中位MF/mL从基线时的138降至第4个月时的64，并进一步降至第12个月时的0。在延迟组中，MF负荷没有从基线中位数97变化到第4个月的102，但在第12个月（即接受治疗后6个月）下降到42，如预期的那样落后于早期组。到第24个月，两个治疗组的中位MF水平均达到0。治疗后，与基线水平相比，Wolbachia从MF中消耗>= 1-log下降。我们的结论是M.加纳的持久性有机污染物携带沃尔巴克氏体，这些沃尔巴克氏体被多西环素有效耗尽，随后MF负荷减少，最有可能是因为成虫生育力的中断。
Treating Mansonella perstans is challenged by the low efficacy of registered antihelminthics. Wolbachia endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with Wuchereria bancrofti and Onchocerca volvulus infections. This open-label, randomized study sought to confirm that i) Wolbachia are present in M. perstans in Ghana and ii) doxycycline treatment will deplete Wolbachia and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with M. perstans infection were randomized into early (immediate) and delayed (6 months deferred) treatment groups, given doxycycline 200 mg/day for 6 weeks, and monitored for MF and Wolbachia levels at baseline, 4, 12, and 24 months after the study onset (= time of randomization and start of treatment for the early group). Per protocol analysis revealed that the median MF/mL in the early group declined from 138 at baseline to 64 at month 4 and further to 0 at month 12. In the delayed group, MF load did not change from a baseline median of 97 to 102 at month 4 but declined to 42 at month 12, that is, 6 months after receiving treatment, trailing the early group as expected. By month 24, both treatment groups had reached a median MF level of 0. After treatment, Wolbachia were depleted from MF by >= 1-log drop compared with baseline levels. We conclude that M. perstans in Ghana harbor Wolbachia that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.