Developing methods to assess the impact of malaria interventions upon transmission and the progress towards elimination

疟疾是一种由蚊子传播的传染病，估计每年造成约100万人死亡，其中大多数死亡发生在撒哈拉以南非洲，主要是幼儿。在过去十年中，高收入国家和全球机构增加了资金，目的是减少传播，从而减轻疾病负担。这导致在世界许多地区大规模分发廉价和有效的干预措施，例如提供防护蚊帐和抗疟疾药物。它通过蚊子在人类之间传播，人们感染得越多，对这种疾病的免疫力就越强（当他们没有感染时，免疫力就越差）。这使得很难计算出在减少传播方面取得的进展。例如，蚊子叮咬次数减少50%不一定会导致疟疾患者比例减少50%。此外，由于传播是不完全的，需要受感染的蚊子存活到对人类具有传染性，因此没有必要杀死所有蚊子或防止所有人口被叮咬以实现消除。在肯尼亚西部，特别是在维多利亚湖沿岸，疟疾传播仍然很严重，即使在大多数人使用蚊帐已有十多年的地区，尽管疟疾患者可以获得有效的抗疟疾药物。因此，目前正在考虑采取进一步的干预措施，包括即将进行的一项试验，研究对一个村庄内的所有居民进行感染检测的效果，并向所有感染检测呈阳性的人提供高效的抗疟疾药物，以阻断传播。为了更好地了解实现这一目标的进展情况，以及试验结果对更普遍地消除疟疾的影响，重要的是要了解试验在传播方面的开始和结束（即感染者通过蚊子将感染传播给他人的机会），因为这是消除疟疾可能持续程度的唯一可靠衡量标准。在这个项目中，帝国理工学院传染病流行病学系的研究员帕特里克步行者博士将使用疟疾传播的数学模型来估计在这个试验期间发生的传播变化，以评估在当地消除这种疾病方面正在取得的进展。这将首先涉及开发一种统计技术，能够估计在同一地区以前试验防护网期间传播强度的变化。这项工作还将使他能够调查疾病从一个村庄传播到另一个村庄的程度，以及不同地区内防护网的存在对疾病传播的影响。这项技术将被调整并应用于药物试验的不同分支，考虑到试验开始前传播的变化，如果抗疟疾药物的大规模管理被证明是帮助肯尼亚西部消除疟疾的有效工具，这项研究将有助于进一步确定判断世界其他地方干预措施有效的标准。或者，如果干预措施证明无效，则工作将表明实现消除所需的额外控制水平。此外，监测整个试验期间的传播变化是否可以提供抗疟疾药物的有效性是否在整个试验期间保持不变的指示，这是考虑到对耐药性的担忧的一个重要考虑因素。

Malaria, an infectious disease transmitted by mosquitoes, is estimated to cause around 1 million deaths per year, with the majority of these deaths occurring in sub-Saharan Africa, primarily amongst young children. Over the last decade there has been an increase in funding from high-income countries and global agencies with the aim of reducing transmission and hence decreasing the burden of disease. This has resulted in the large-scale distribution of interventions of cheap and effective interventions such as the provision of protective bed nets and antimalarial medication in many parts of the world.Malaria is, however, a complicated disease. It is spread between humans by mosquitoes and people become more immune to the disease the more they are infected (and less immune when they are not). This makes it difficult to work out the progress that has been made in reducing transmission. For example, a 50% reduction in the number of mosquito bites would not necessarily produce a 50% reduction in the proportion of people with malaria. Moreover, as transmission is imperfect and requires an infected mosquito to survive until it becomes infectious to humans, it is not necessary to kill all mosquitoes or prevent all members of the population from being bitten to achieve elimination. In Western Kenya, particularly around the shores of Lake Victoria, malaria transmission remains intense, even in areas where bed nets have been used by the majority of the population for over a decade and despite the availability of effective anti-malarial medication for those with the disease. As a result, further intervention measures are currently being considered, including a forthcoming trial looking at the effects of testing all residents within a village for infection and giving highly effective anti-malarial medication to all those who test positive to infection in an attempt to break transmission. In order to better understand the progress towards this goal, and the implication the trial outcome has for malaria elimination more generally, it is important to understand where the trial started and where the trial ended in terms of transmission (i.e. the chances of an infected person passing infection to others via a mosquito), as this is the only reliable measure of the extent to which elimination is likely to be sustainable. In this project, Dr Patrick Walker, a researcher at the Department of Infectious Disease Epidemiology, Imperial College, will use mathematical models of the spread of malaria to estimate the changes in transmission that occur during this trial to assess the progress being made towards local elimination of the disease. This will first involve developing a statistical technique which is able to estimate changes in transmission intensity during a previous trial of protective nets in the same area This work will also allow him to investigate the extent to which the disease spreads from one village to another and how this is affected by the presence of nets within different areas. This technique will then be adapted and applied to the different arms of the drug trial, taking into account changes in transmission up to the beginning of the trial.In the event that the mass administration of anti-malarials proves effective as a tool for helping Western Kenya to eliminate malaria, this research will help to further define the criteria by which to judge where else in the world the intervention could be effective. Alternatively, if the intervention does not prove effective the work will provide an indication of the additional level of control required to achieve elimination. Moreover, monitoring whether transmission changes throughout the trial could provide an indication as to whether the effectiveness of anti-malarial drugs remains the same throughout the trial, which is an important consideration in light of concerns about drug resistance.