Chavasse D C, Post R J, Lemoh P A, Whitworth J A
Medical Research Council Laboratory, Bo, Sierra Leone.
Trop Med Parasitol. 1992 Dec;43(4):256-62.
The effects of single and multiple doses of ivermectin on mortality and morphology were assessed in over 700 female Onchocerca volvulus worms and the effects on embryogenesis were assessed in 490. Nodules were surgically removed from Sierra Leoneans recruited from a double-blind placebo controlled study of ivermectin given at six-monthly intervals. Nodules were digested in collagenase to isolate whole adult worms. After four or five doses of ivermectin there were significant increases in the numbers of discoloured and calcified worms and possibly a trend towards increased mortality, but this was not seen consistently. There was no evidence of a prophylactic effect of the drug. Worms were then homogenised and embryograms constructed. A single dose of ivermectin produced large numbers of degenerating intrauterine microfilariae, but embryonic development occurred normally. After multiple doses we observed almost complete cessation of embryogenesis, with a highly significant decrease in the numbers of viable multicellular embryonic stages, while oocytes appeared to be produced normally. Development is probably impeded at the single cell stage, possibly because of reduced fertilization. In planning the future role of ivermectin as a control measure for onchocerciasis it is crucial to determine if these effects on embryogenesis are reversible.
在700多条雌性盘尾丝虫上评估了单剂量和多剂量伊维菌素对死亡率和形态的影响，并在490条虫上评估了其对胚胎发生的影响。结节取自参加伊维菌素双盲安慰剂对照研究的塞拉利昂人，该研究每六个月给药一次，通过手术切除结节。将结节用胶原酶消化以分离出完整的成虫。给予四或五剂伊维菌素后，变色和钙化的虫体数量显著增加，死亡率可能有上升趋势，但并不一致。没有证据表明该药物有预防作用。然后将虫体匀浆并构建胚胎图。单剂量伊维菌素可使大量子宫内微丝蚴发生退化，但胚胎发育正常。多剂量给药后，我们观察到胚胎发生几乎完全停止，存活的多细胞胚胎阶段数量显著减少，而卵母细胞似乎正常产生。发育可能在单细胞阶段受到阻碍，可能是由于受精减少。在规划伊维菌素作为盘尾丝虫病控制措施的未来作用时，确定这些对胚胎发生的影响是否可逆至关重要。
