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大规模药物给药莫昔克丁能否加速非洲盘尾丝虫病的消除?

Can mass drug administration of moxidectin accelerate onchocerciasis elimination in Africa?

机构信息

London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK.

MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2023 Oct 9;378(1887):20220277. doi: 10.1098/rstb.2022.0277. Epub 2023 Aug 21.

Abstract

Epidemiological and modelling studies suggest that elimination of transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA. This article is part of the theme issue 'Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

摘要

流行病学和建模研究表明,仅通过每年一次的伊维菌素大规模药物治疗(MDA),在整个非洲消除传播(EoT)可能无法实现,特别是在高度流行和媒介密度高的地区。单次剂量的 II 期和 III 期临床试验表明,莫昔克丁在清除微丝蚴方面优于伊维菌素。我们使用基于个体的随机 EPIONCHO-IBM 模型来比较伊维菌素和莫昔克丁 MDA 在一系列流行程度(基线微丝蚴患病率 30%至 70%)、治疗频率(每年和每两年一次)和治疗覆盖率/依从性值(总人口的 65%和 80%,分别有 5%和 1%的系统性不依从)下达到 EoT 的概率。EPIONCHO-IBM 的预测表明,每两年(每六个月)一次的莫昔克丁 MDA 可以将在中度流行地区达到 EoT 所需的年限减少一半,并且可能是唯一可以在高度流行地区达到 EoT 的策略。需要改进建模预测的数据包括:(i)重复的年度和每两年一次的莫昔克丁治疗的效果;(ii)对莫昔克丁或伊维菌素连续治疗的个体间和个体内反应差异;(iii)莫昔克丁和伊维菌素治疗对 L3 发育为成虫的影响;以及(iv)莫昔克丁和伊维菌素 MDA 依从性模式。本文是主题为“消除被忽视热带病的挑战:伦敦宣言十周年”的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ff3/10440165/486792a9dfa8/rstb20220277f01.jpg

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