Johnston Geoffrey L, Gething Peter W, Hay Simon I, Smith David L, Fidock David A
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America ; School of International and Public Affairs, Columbia University, New York, New York, United States of America ; Bloomberg School of Public Health, John Hopkins University, Baltimore, Maryland, United States of America.
Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom.
PLoS Comput Biol. 2014 Jan;10(1):e1003434. doi: 10.1371/journal.pcbi.1003434. Epub 2014 Jan 23.
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 R C (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 R 0<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.
要为疟疾消除建立理论基础，需要详细了解患者寻求治疗行为、治疗覆盖率以及既能治愈疾病又能阻断疟原虫向蚊媒传播的疗法效果之间的定量关系。在此，我们报告了一个宿主内机制数学模型，该模型利用药代动力学（PK）和药效学（PD）数据来模拟基于青蒿素的联合疗法（ACTs）对恶性疟原虫传播的影响。为了将该模型置于实际情境中，我们创建了一组全球地图，展示了将疟疾的R C（即其在控制下的基本繁殖数）降至1以下从而中断传播所需的降低倍数。该模型应用于低传播环境，根据2010年数据，低传播环境定义为R 0<10。我们的模型预测，在发热 onset 五天内用ACT治疗93 - 98%的有症状感染，将使东南亚约91%的高危人群和全球约74%的高危人群中断疟疾传播，并使这些人群朝着消除疟疾的方向发展。这种治疗覆盖率相当于这些环境中所有感染个体的约81 - 85%。在这种ACT治疗覆盖率水平下，添加杀配子剂伯氨喹在减少传播方面没有显著收益。实际上，我们估计大约需要将180人从ACTs改为ACTs加伯氨喹，才能实现与将一个人从未治疗改为用ACTs治疗相同的传播减少效果。因此，我们的模型预测，在治疗方案中添加杀配子药物对整个人口带来的益处非常小，东南亚控制工作的重点应是提高ACT的及时覆盖率。目前，撒哈拉以南非洲大部分地区的消除疟疾前景似乎远不乐观，因为感染率高，治疗频率低且不迅速。
