多西环素治疗常现曼森线虫感染的随机试验。
A randomized trial of doxycycline for Mansonella perstans infection.
作者信息
Coulibaly Yaya I, Dembele Benoit, Diallo Abdallah A, Lipner Ettie M, Doumbia Salif S, Coulibaly Siaka Y, Konate Siaka, Diallo Dapa A, Yalcouye Daniel, Kubofcik Joseph, Doumbo Ogobara K, Traore Abdel K, Keita Adama D, Fay Michael P, Traore Sekou F, Nutman Thomas B, Klion Amy D
机构信息
Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako, Mali.
出版信息
N Engl J Med. 2009 Oct 8;361(15):1448-58. doi: 10.1056/NEJMoa0900863.
BACKGROUND
Mansonella perstans infection is common in areas of Africa where Wuchereria bancrofti, a causative agent of lymphatic filariasis, is endemic. M. perstans is refractory to standard antifilarial therapies. The recent discovery of bacterial endosymbionts (e.g., wolbachia) in most filarial species, including M. perstans, provides new therapeutic options for reducing microfilaremia.
METHODS
In an open-label, randomized trial, we recruited subjects with M. perstans microfilaremia, with or without concomitant W. bancrofti infection, from four villages in Mali and randomly assigned them to receive doxycycline, at a dose of 200 mg daily for 6 weeks (106 subjects), or no treatment (110). At 6 months, subjects who were coinfected with W. bancrofti underwent a second random assignment, to treatment with a single dose of albendazole (400 mg) and ivermectin (150 microg per kilogram of body weight) or no treatment. Subjects were monitored daily during the first 6-week study period for adverse events. M. perstans and W. bancrofti microfilarial levels were assessed at 6, 12, and 36 months.
RESULTS
At 12 months, 67 of 69 subjects who had received treatment with doxycycline only (97%) had no detectable M. perstans microfilariae per 60 microl of blood, as compared with 10 of 63 subjects who had received no treatment (16%) (relative risk, 6.18; 95% confidence interval, 3.63 to 11.89; P<0.001). At 36 months, M. perstans microfilaremia remained suppressed in 48 of 64 subjects who had received treatment with doxycycline only (75%), a finding that was consistent with a macrofilaricidal effect of doxycycline. Vomiting was more frequent in the doxycycline-treated group than in the untreated group (17% vs. 4%).
CONCLUSIONS
These results are consistent with previous findings that M. perstans harbors the intracellular endosymbiont, wolbachia, and suggest that doxycycline is an effective therapy for M. perstans infection. (ClinicalTrials.gov number, NCT00340691.)
背景
持久曼森线虫感染在非洲一些地区很常见，而淋巴丝虫病的病原体班氏吴策线虫在这些地区也是地方病。持久曼森线虫对标准抗丝虫疗法具有耐药性。最近在包括持久曼森线虫在内的大多数丝虫物种中发现了细菌内共生体（如沃尔巴克氏体），这为降低微丝蚴血症提供了新的治疗选择。
方法
在一项开放标签的随机试验中，我们从马里的四个村庄招募了患有持久曼森线虫微丝蚴血症的受试者，无论其是否合并班氏吴策线虫感染，并将他们随机分配接受强力霉素治疗，剂量为每日200毫克，持续6周（106名受试者），或不接受治疗（110名）。在6个月时，合并班氏吴策线虫感染的受试者进行第二次随机分组，接受单剂量阿苯达唑（4mg）和伊维菌素（每千克体重150μg）治疗或不接受治疗。在为期6周的研究的第一个阶段，每天对受试者进行不良事件监测。在6个月、12个月和36个月时评估持久曼森线虫和班氏吴策线虫的微丝蚴水平。
结果
在12个月时，仅接受强力霉素治疗的69名受试者中有67名（97%）每60微升血液中未检测到持久曼森线虫微丝蚴，而未接受治疗的63名受试者中有10名（16%）检测到（相对风险，6.18；95%置信区间，3.63至11.89；P<0.001）。在36个月时，仅接受强力霉素治疗的64名受试者中有48名（75%）持久曼森线虫微丝蚴血症仍受到抑制，这一发现与强力霉素的杀成虫作用一致。强力霉素治疗组的呕吐发生率高于未治疗组（17%对4%）。
结论
这些结果与之前关于持久曼森线虫携带细胞内共生体沃尔巴克氏体的研究结果一致，并表明强力霉素是治疗持久曼森线虫感染的有效疗法。（临床试验注册号，NCT00340691。）
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