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Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study.
The Lancet Infectious Diseases ( IF 36.4 ) Pub Date : 2020-01-13 , DOI: 10.1016/s1473-3099(19)30633-4
Hannah C Slater 1 , Brian D Foy 2 , Kevin Kobylinski 3 , Carlos Chaccour 4 , Oliver J Watson 1 , Joel Hellewell 1 , Ghaith Aljayyoussi 5 , Teun Bousema 6 , Jeremy Burrows 7 , Umberto D'Alessandro 8 , Haoues Alout 9 , Feiko O Ter Kuile 5 , Patrick G T Walker 1 , Azra C Ghani 1 , Menno R Smit 5
Affiliation  

BACKGROUND Ivermectin is a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious. We aimed to estimate the effect of ivermectin on malaria transmission in various scenarios of use. METHODS We validated an existing population-level mathematical model of the effect of ivermectin mass drug administration (MDA) on the mosquito population and malaria transmission against two datasets: clinical data from a cluster- randomised trial done in Burkina Faso in 2015 wherein ivermectin was given to individuals taller than 90 cm and entomological data from a study of mosquito outcomes after ivermectin MDA for onchocerciasis or lymphatic filariasis in Burkina Faso, Senegal, and Liberia between 2008 and 2013. We extended the existing model to include a range of complementary malaria interventions (seasonal malaria chemoprevention and MDA with dihydroartemisinin-piperaquine) and to incorporate new data on higher doses of ivermectin with a longer mosquitocidal effect. We consider two ivermectin regimens: a single dose of 400 μg/kg (1 × 400 μg/kg) and three consecutive daily doses of 300 μg/kg per day (3 × 300 μg/kg). We simulated the effect of these two doses in a range of usage scenarios in different transmission settings (highly seasonal, seasonal, and perennial). We report percentage reductions in clinical incidence and slide prevalence. FINDINGS We estimate that MDA with ivermectin will reduce prevalence and incidence and is most effective in areas with highly seasonal transmission. In a highly seasonal moderate transmission setting, three rounds of ivermectin only MDA at 3 × 300 μg/kg (rounds spaced 1 month apart) and 70% coverage is predicted to reduce clinical incidence by 71% and prevalence by 34%. We predict that adding ivermectin MDA to seasonal malaria chemoprevention in this setting would reduce clinical incidence by an additional 77% in children younger than 5 years compared with seasonal malaria chemoprevention alone; adding ivermectin MDA to MDA with dihydroartemisinin-piperaquine in this setting would reduce incidence by an additional 75% and prevalence by an additional 64% (all ages) compared with MDA with dihydroartemisinin-piperaquine alone. INTERPRETATION Our modelling predictions suggest that ivermectin could be a valuable addition to the malaria control toolbox, both in areas with persistently high transmission where existing interventions are insufficient and in areas approaching elimination to prevent resurgence. FUNDING Imperial College Junior Research Fellowship.

中文翻译:

伊维菌素作为降低发病率和流行率的新型补充疟疾控制工具:一项建模研究。

背景 伊维菌素是一种潜在的新型病媒控制工具,可减少疟疾传播。以含有伊维菌素的血粉为食的蚊子寿命缩短,这意味着它们不太可能活得足够长以完成孢子繁殖并具有传染性。我们旨在评估伊维菌素在各种使用情况下对疟疾传播的影响。方法 我们针对两个数据集验证了伊维菌素大规模给药 (MDA) 对蚊子种群和疟疾传播影响的现有人群水平数学模型:2015 年在布基纳法索进行的整群随机试验的临床数据,其中给予伊维菌素来自塞内加尔布基纳法索的伊维菌素 MDA 治疗盘尾丝虫病或淋巴丝虫病后蚊子结果研究的高于 90 厘米的个体和昆虫学数据,2008 年至 2013 年期间,我们对现有模型进行了扩展,以包括一系列补充性疟疾干预措施(季节性疟疾化学预防和 MDA 与双氢青蒿素-哌喹),并纳入有关更高剂量伊维菌素具有更长杀蚊效果的新数据。我们考虑两种伊维菌素方案:单剂量 400 μg/kg (1 × 400 μg/kg) 和连续 3 次每日剂量 300 μg/kg (3 × 300 μg/kg)。我们模拟了这两种剂量在不同传播环境(高度季节性、季节性和常年性)的一系列使用场景中的影响。我们报告了临床发病率和滑动患病率的百分比降低。结果 我们估计,含有伊维菌素的 MDA 将降低流行率和发病率,并且在季节性传播强的地区最为有效。在高度季节性的中等传播环境中,三轮伊维菌素仅 MDA 剂量为 3 × 300 μg/kg(轮次间隔 1 个月)和 70% 的覆盖率预计可将临床发病率降低 71%,流行率降低 34%。我们预测,在这种情况下,将伊维菌素 MDA 添加到季节性疟疾化学预防中,与单独进行季节性疟疾化学预防相比,5 岁以下儿童的临床发病率将额外降低 77%;在这种情况下,将伊维菌素 MDA 添加到 MDA 与双氢青蒿素 - 哌喹相比,与单独使用双氢青蒿素 - 哌喹的 MDA 相比,发病率会额外降低 75%,流行率会额外降低 64%(所有年龄段)。解释我们的建模预测表明伊维菌素可能是疟疾控制工具箱的一个有价值的补充,无论是在现有干预措施不足的持续高传播地区,还是在接近消除以防止死灰复燃的地区。资助帝国理工学院初级研究奖学金。
更新日期:2020-01-13
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