Rates of microfilarial production by Onchocerca volvulus are not cumulatively reduced by multiple ivermectin treatments
Rates of microfilarial production by Onchocerca volvulus are not cumulatively reduced by multiple ivermectin treatments
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DOI：
10.1017/s0031182008000425
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发表时间：
2008-11-01
期刊：
影响因子：
2.4
通讯作者：
Basanez, Maria-Gloria
中科院分区：
文献类型：
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作者：
Bottomley, Christian;Isham, Valerie;Basanez, Maria-Gloria
伊维菌素的定期分发通过杀死人体内的寄生虫的微丝蚴阶段（杀微丝蚴作用）来减少盘尾丝虫病的传播和发病率。此外，伊维菌素发挥所谓的胚胎抑制作用，在给药后数周内，成年雌虫的微丝蚴产生受到抑制。为了评估伊维菌素对盘尾丝虫病传播的总体影响，并评价局部消除感染的可能性，重要的是要估计治疗方案过程中抗生育作用的大小。通过开发一个模型，该模型与从危地马拉三个高流行社区收集的数据相拟合，获得了重复药物治疗对成年盘尾丝虫微丝蚴生产的影响估计值，在危地马拉三个高流行社区中，符合条件的居民每年接受两次伊维菌素，为期两年半。这些数据包括皮肤中的微丝蚴负荷测量值，这些测量值是在该方案期间每六个月一次的治疗前收集的。该模型描述了在30个月的研究期间，个别主机的预期微丝蚴负荷的动态。我们采用贝叶斯方法，并使用马尔可夫链蒙特卡罗（McMC）技术来拟合模型的数据。结合三个村庄的估计，治疗后前六个月的平均微丝蚴产量减少了约64%，与治疗前水平相似，无论在合理范围内选择伊维菌素前生育率的值如何。处理后成虫死亡率增加（模拟在程序期间通过结节切除术去除巨丝虫）导致胚胎抑制效应的估计幅度较小（微丝蚴产生率降低，与伊维菌素前值的58%相似）。在随后的治疗后，微丝蚴的产生率似乎也同样降低了。因此，数据和分析不支持多次伊维菌素治疗对雌蠕虫产生微丝蚴的累积效应的假设。
Regular distribution of ivermectin reduces onchocerciasis transmission and morbidity by killing, within humans, the microfilarial stage of the parasite (microfilaricidal effect). In addition, ivermectin exerts a so-called embryostatic effect by which microfilarial production by the adult female worm becomes suppressed during a number of weeks after treatment. To assess the overall effect of ivermectin on onchocerciasis transmission and evaluate the likelihood of local elimination of the infection it is important to estimate the magnitude of the anti-fertility effect over the course of a treatment programme. Estimates of the effect of repeated drug treatments on the production of microfilariae by adult Onchocerca volvulus were obtained by developing a model that was fitted to data collected from three hyperendemic communities in Guatemala, where eligible residents received ivermectin twice per year for two and a half years. The data consist of microfilarial load measurements in the skin, collected just before each six-monthly treatment during the programme. The model that is developed describes the dynamics of an individual host's expected microfilarial load over the 30-month study period. We adopt a Bayesian approach and use Markov chain Monte Carlo (McMC) techniques to fit the model to the data. Combining estimates from the three villages, average microfilarial production in the first six months post-treatment was reduced by similar to 64% of its pre-treatment level, regardless of values chosen for the pre-ivermectin fertility rate within plausible ranges. Increased adult worm death rate after treatment (to mimic removal of macrofilariae via nodulectomy during the programme) resulted in a smaller estimated magnitude of the embryostatic effect (rate of microfilarial production was reduced by similar to 58% of pre-ivermectin value). After subsequent treatments, the rate of microfilarial production appeared to be similarly decreased. The data and analyses therefore do not support the hypothesis of a cumulative effect of multiple ivermectin treatments on microfilarial production by female worms.