Cross H F, Bronsvoort B M, Wahl G, Renz A, Achu-Kwi D, Trees A J
Liverpool School of Tropical Medicine, U.K.
Ann Trop Med Parasitol. 1997 Jun;91(4):393-401. doi: 10.1080/00034989761012.
No currently available drug, which is safe for mass treatment, effectively kills adults of Onchocerca volvulus, the causal agent of onchocerciasis in humans, or of O. ochengi, a cattle parasite used as a model of O. volvulus. Since adults of both of these filarial nematodes are found in well developed nodules, the lack of efficacy of these drugs may be a result of their poor penetration into the nodules. To check if this was the problem, the distributions of the microfilaricide, ivermectin, and the partial macrofilaricide, suramin, in plasma, skin, nodule capsules and nodule contents were determined in cattle naturally infected with O. ochengi in Cameroon. The cattle were treated with either a single, subcutaneous injection of 500 micrograms ivermectin/kg, or with intravenous injections of [14C]-labelled suramin, each of 10 mg/kg, given one a day for 6 days. Concentrations of ivermectin and suramin in various tissues were then assayed by high-pressure liquid chromatography and scintillation counting, respectively. On day 7 post-treatment (pt), suramin concentrations were consistently highest in the nodule, contents and capsule wall (11.0 and 8.9 nCi/g, respectively) and significantly less in skin and plasma (1.2 and 1.4 nCi/g, respectively; P < 0.05). The distribution of ivermectin on day 7 pt was similar, with the highest concentrations in the capsule wall, nodule contents and plasma (58.4 ng/g, 43 ng/g and 48.6 ng/ml, respectively; P > 0.05) and the concentration in the skin (6.4 ng/g) significantly lower than those in the capsule or plasma (P < 0.05). High intra-nodular concentrations of both drugs were maintained for 5-7 days at least and those of ivermectin would be expected to kill nematodes other than filariae. It is apparent that failure of ivermectin and suramin to kill adult Onchocerca spp. is not because the drugs penetrate nodules inadequately.
目前尚无对大规模治疗安全的药物能有效杀死盘尾丝虫病的病原体——人体盘尾丝虫的成虫，或作为盘尾丝虫模型的牛寄生虫——奥氏盘尾丝虫的成虫。由于这两种丝虫的成虫都存在于发育良好的结节中，这些药物缺乏疗效可能是由于它们难以渗透到结节中。为了验证是否存在这一问题，在喀麦隆对自然感染奥氏盘尾丝虫的牛进行了研究，测定了微丝蚴杀虫剂伊维菌素和部分成虫杀虫剂苏拉明在血浆、皮肤、结节包膜和结节内容物中的分布情况。这些牛要么皮下注射一次500微克伊维菌素/千克，要么静脉注射[14C]标记的苏拉明，每次10毫克/千克，每天一次，共6天。然后分别通过高压液相色谱法和闪烁计数法测定各种组织中伊维菌素和苏拉明的浓度。治疗后第7天（pt），苏拉明浓度在结节、内容物和包膜壁中始终最高（分别为11.0和8.9纳居里/克），在皮肤和血浆中显著较低（分别为1.2和1.4纳居里/克；P < 0.05）。治疗后第7天伊维菌素的分布情况类似，包膜壁、结节内容物和血浆中的浓度最高（分别为每克58.4纳克、每克43纳克和每毫升48.6纳克；P > 0.05），皮肤中的浓度（每克6.4纳克）显著低于包膜或血浆中的浓度（P < 0.05）。两种药物在结节内的高浓度至少维持了5至7天，伊维菌素的浓度有望杀死丝虫以外的线虫。显然，伊维菌素和苏拉明无法杀死盘尾丝虫成虫并非因为药物对结节的渗透不足。
