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多西环素治疗班氏吴策线虫后的杀成虫活性:一项双盲、随机、安慰剂对照试验

Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial.

作者信息

Taylor Mark J, Makunde Williams H, McGarry Helen F, Turner Joseph D, Mand Sabine, Hoerauf Achim

机构信息

Filariasis Research Group, Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK.

出版信息

Lancet. 2005;365(9477):2116-21. doi: 10.1016/S0140-6736(05)66591-9.

DOI:10.1016/S0140-6736(05)66591-9
PMID:15964448
Abstract

BACKGROUND

Wolbachia endosymbionts of filarial nematodes are vital for larval development and adult-worm fertility and viability. This essential dependency on the bacterium for survival of the parasites has provided a new approach to treat filariasis with antibiotics. We used this strategy to investigate the effects of doxycycline treatment on the major cause of lymphatic filariasis, Wuchereria bancrofti.

METHODS

We undertook a double-blind, randomised, placebo-controlled field trial of doxycycline (200 mg per day) for 8 weeks in 72 individuals infected with W bancrofti from Kimang'a village, Pangani, Tanzania. Participants were randomly assigned by block randomisation to receive capsules of doxycycline (n=34) or placebo (n=38). We assessed treatment efficacy by monitoring microfilaraemia, antigenaemia, and ultrasound detection of adult worms. Follow-up assessments were done at 5, 8, 11, and 14 months after the start of treatment. Analysis was per protocol.

FINDINGS

One person from the doxycycline group died from HIV infection. Five (doxycycline) and 11 (placebo) individuals were absent at the time of ultrasound analysis. Doxycycline treatment almost completely eliminated microfilaraemia at 8-14 months' follow-up (for all timepoints p<0.001). Ultrasonography detected adult worms in only six (22%) of 27 individuals treated with doxycycline compared with 24 (88%) of 27 with placebo at 14 months after the start of treatment (p<0.0001). At the same timepoint, filarial antigenaemia in the doxycycline group fell to about half of that before treatment (p=0.015). Adverse events were few and mild.

INTERPRETATION

An 8-week course of doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia.

摘要

背景

丝虫线虫的沃尔巴克氏体共生菌对幼虫发育以及成虫的生育能力和生存能力至关重要。寄生虫对这种细菌的这种基本依赖为用抗生素治疗丝虫病提供了一种新方法。我们采用此策略来研究强力霉素治疗对淋巴丝虫病的主要病原体——班氏吴策线虫的影响。

方法

我们在坦桑尼亚潘加尼基曼加村的72名感染班氏吴策线虫的个体中进行了一项双盲、随机、安慰剂对照的现场试验,给予强力霉素(每日200毫克),为期8周。参与者通过区组随机化被随机分配接受强力霉素胶囊(n = 34)或安慰剂(n = 38)。我们通过监测微丝蚴血症、抗原血症以及超声检测成虫来评估治疗效果。在治疗开始后的5、8、11和14个月进行随访评估。分析按照方案进行。

结果

强力霉素组有1人死于HIV感染。在超声分析时,强力霉素组有5人、安慰剂组有11人未到场。在8 - 14个月的随访中,强力霉素治疗几乎完全消除了微丝蚴血症(所有时间点p < 0.001)。在治疗开始14个月后,超声检查仅在接受强力霉素治疗的27名个体中的6人(2 / 7)检测到成虫,而接受安慰剂治疗的27名个体中有24人(88%)检测到成虫(p < 0.0001)。在同一时间点,强力霉素组的丝虫抗原血症降至治疗前的约一半(p = 0.015)。不良事件少且轻微。

解读

为期8周的强力霉素疗程是一种安全且耐受性良好的治疗淋巴丝虫病的方法,对成虫和微丝蚴血症具有显著活性。

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