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

制定方法来评估疟疾干预措施对传播的影响以及消除疟疾的进展

• 批准号: MR/L012189/1
• 负责人: Patrick Walker
• 金额: $ 38.2万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL012189%2F1
• 关键词: Developing; methods; assess; impact; malaria

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.

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的供资有所增加，目的是减少传播，从而减轻疾病负担。这导致在世界许多地方大规模分发廉价和有效的干预措施，例如提供保护性蚊帐和抗疟疾药物。然而，疟疾是一种复杂的疾病。它通过蚊子在人与人之间传播，人们感染得越多，对这种疾病的免疫力就越强（没有感染的人免疫力就越弱）。这使得很难计算在减少传播方面取得的进展。例如，蚊子叮咬次数减少50%并不一定会使疟疾患者比例减少50%。此外，由于传播是不完全的，并且需要受感染的蚊子存活到感染人类为止，因此没有必要杀死所有蚊子或防止种群的所有成员被叮咬以实现消除。在肯尼亚西部，特别是维多利亚湖沿岸，疟疾传播仍然很严重，即使在大多数人口使用蚊帐已有十多年的地区，尽管对疟疾患者有有效的抗疟疾药物，也是如此。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抗疟疾药物，以试图阻断传播。为了更好地了解实现这一目标的进展情况，以及试验结果对更广泛地消除疟疾的影响，重要的是要了解从传播角度（即感染者通过蚊子将感染传染给他人的机会）来看，试验是从哪里开始和在哪里结束的，因为这是衡量消除疟疾可能可持续程度的唯一可靠指标。在这个项目中，帝国理工学院传染病流行病学系的研究员Patrick Walker博士将使用疟疾传播的数学模型来估计在该试验期间发生的传播变化，以评估在局部消除该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，该技术能够估计先前在同一地区试用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，以及在不同地区设置防护网对传播强度的影响。这一技术随后将被调整并应用于药物试验的不同阶段，同时考虑到试验开始前传播的变化。如果大规模服用抗疟疾药物被证明是帮助肯尼亚西部消灭疟疾的有效工具，这项研究将有助于进一步确定标准，以判断世界上其他地方的干预措施可能有效。或者，如果干预措施没有证明有效，工作将提供实现消除所需的额外控制水平的指示。此外，监测整个试验过程中传播是否发生变化，可以提供抗疟疾药物的有效性在整个试验过程中是否保持不变的指示，鉴于对耐药性的关注，这是一个重要的考虑因素。

项目成果

MOESM1 of Using ante-natal clinic prevalence data to monitor temporal changes in malaria incidence in a humanitarian setting in the Democratic Republic of Congo

MOESM1 使用产前诊所患病率数据监测刚果民主共和国人道主义环境中疟疾发病率的时间变化

• DOI: 10.6084/m9.figshare.7027064
• 发表时间: 2018
• 作者: Hellewell J

Estimated impact on birth weight of scaling up intermittent preventive treatment of malaria in pregnancy given sulphadoxine-pyrimethamine resistance in Africa: A mathematical model.

• DOI: 10.1371/journal.pmed.1002243
• 发表时间: 2017-02
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Walker PG;Floyd J;Ter Kuile F;Cairns M
• 通讯作者: Cairns M

Value of additional chemotherapy for malaria in pregnancy.

妊娠期疟疾额外化疗的价值。

• DOI: 10.1016/s2214-109x(15)70081-1
• 发表时间: 2015
• 期刊: The Lancet. Global health
• 作者: Walker PG

Using ante-natal clinic prevalence data to monitor temporal changes in malaria incidence in a humanitarian setting in the Democratic Republic of Congo.

• DOI: 10.1186/s12936-018-2460-9
• 发表时间: 2018-08-29
• 期刊: Malaria journal
• 影响因子: 3
• 作者: Hellewell J;Walker P;Ghani A;Rao B;Churcher TS
• 通讯作者: Churcher TS

Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting.

• DOI: 10.1038/s41467-018-04577-y
• 发表时间: 2018-06-26
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Routledge I;Chevéz JER;Cucunubá ZM;Rodriguez MG;Guinovart C;Gustafson KB;Schneider K;Walker PGT;Ghani AC;Bhatt S
• 通讯作者: Bhatt S