Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
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DOI：
10.1371/journal.pcbi.1003434
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发表时间：
2014-01
影响因子：
4.3
通讯作者：
Fidock DA
中科院分区：
文献类型：
--
作者：
Johnston GL;Gething PW;Hay SI;Smith DL;Fidock DA
实现消除疟疾的理论基础将需要详细了解患者寻求治疗的行为，治疗覆盖率和治疗性疗法的效果之间的定量关系，这些治疗性疗法也可以阻止疟原虫寄生虫传播给蚊子媒介。在这里，我们报告了一个机制，在主机内的数学模型，使用药代动力学（PK）和药效学（PD）的数据来模拟青蒿素为基础的联合疗法（ACT）对恶性疟原虫传播的影响。为了将该模型置于背景中，我们创建了一组全球地图，这些地图显示了将疟疾RC（即其基本繁殖数）降低到1以下并因此中断传播所需的倍数降低。该模型适用于低传输设置，定义为基于2010年数据的R 0 <10。我们的模型预测，在发烧后5天内用ACT治疗93-98%的有症状感染将中断东南亚91%的高危人群和全球74%的高危人群的疟疾传播，并导致这些人群消除疟疾。这一治疗覆盖率相当于这些环境中所有感染者的估计81-85%。在青蒿素综合疗法的这一覆盖水平上，添加杀配子细胞剂伯氨喹在减少传播方面没有取得重大进展。事实上，我们估计，需要将10180人从青蒿素综合疗法转换为青蒿素综合疗法加伯氨喹，才能达到与将一个人从未经治疗转换为青蒿素综合疗法治疗相同的传播减少。因此，我们的模型预测，在治疗方案中加入杀配子药物提供了非常小的人群范围内的好处，在东南亚的控制工作的重点应该是增加及时ACT覆盖率。目前，由于感染率高，治疗频率低，速度慢，撒哈拉以南非洲大部分地区消除疟疾的前景似乎不太乐观。我们利用疟疾传播的宿主内数学模型来预测抗疟治疗在地球仪上的效果。根据对2010年治疗和传播水平的评估，我们预测，如果至少93-98%的有症状的个体及时接受有效的青蒿素类联合疗法（ACT）治疗，东南亚91%的高危人群所在地区可以实现消除。达到这一覆盖水平的好处远远超过在现有的青蒿素综合疗法中增加额外的配子细胞特异性传播阻断药物。我们在东南亚倡导消除计划，重点是最大限度地扩大ACT覆盖面。
Achieving a theoretical foundation for malaria elimination will require a detailed understanding of the quantitative relationships between patient treatment-seeking behavior, treatment coverage, and the effects of curative therapies that also block Plasmodium parasite transmission to mosquito vectors. Here, we report a mechanistic, within-host mathematical model that uses pharmacokinetic (PK) and pharmacodynamic (PD) data to simulate the effects of artemisinin-based combination therapies (ACTs) on Plasmodium falciparum transmission. To contextualize this model, we created a set of global maps of the fold reductions that would be necessary to reduce the malaria RC (i.e. its basic reproductive number under control) to below 1 and thus interrupt transmission. This modeling was applied to low-transmission settings, defined as having a R0<10 based on 2010 data. Our modeling predicts that treating 93–98% of symptomatic infections with an ACT within five days of fever onset would interrupt malaria transmission for ∼91% of the at-risk population of Southeast Asia and ∼74% of the global at-risk population, and lead these populations towards malaria elimination. This level of treatment coverage corresponds to an estimated 81–85% of all infected individuals in these settings. At this coverage level with ACTs, the addition of the gametocytocidal agent primaquine affords no major gains in transmission reduction. Indeed, we estimate that it would require switching ∼180 people from ACTs to ACTs plus primaquine to achieve the same transmission reduction as switching a single individual from untreated to treated with ACTs. Our model thus predicts that the addition of gametocytocidal drugs to treatment regimens provides very small population-wide benefits and that the focus of control efforts in Southeast Asia should be on increasing prompt ACT coverage. Prospects for elimination in much of Sub-Saharan Africa appear far less favorable currently, due to high rates of infection and less frequent and less rapid treatment. We utilize a within-host mathematical model of malaria transmission to predict the effects of antimalarial treatment across the globe. We predict that areas containing 91% of the at-risk population of Southeast Asia can achieve elimination if at least 93–98% of symptomatic individuals are promptly treated with effective artemisinin-based combination therapies (ACTs), based on assessments of treatment and transmission levels as of 2010. The benefit of attaining this level of coverage far outperforms that of adding additional gametocyte-specific transmission-blocking drugs to current ACTs. We advocate for elimination programs in Southeast Asia to focus on maximizing ACT coverage.
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影响因子：
15.8
作者：
Delves M;Plouffe D;Scheurer C;Meister S;Wittlin S;Winzeler EA;Sinden RE;Leroy D
通讯作者：
Leroy D
影响因子：
3.7
作者：
Gurarie, David;Karl, Stephan;Davis, Timothy M. E.
通讯作者：
Davis, Timothy M. E.
影响因子：
15.8
作者：
Griffin, Jamie T.;Hollingsworth, T. Deirdre;Ghani, Azra C.
通讯作者：
Ghani, Azra C.
影响因子：
3
作者：
Gething PW;Patil AP;Smith DL;Guerra CA;Elyazar IR;Johnston GL;Tatem AJ;Hay SI
通讯作者：
Hay SI
影响因子：
168.9
作者：
Feachem, Richard G. A.;Phillips, Allison A.;Targett, Geoffrey A.;Snow, Robert W.
通讯作者：
Snow, Robert W.