The changing endemicity and disease burden of Plasmodium falciparum in Africa since 2000

Lead Research Organisation: University of Oxford
Department Name: Medical Sciences Division

Abstract

Malaria, a parasitic disease spread by mosquitoes, kills around a million people each year and causes illness in hundreds of millions of others. After decades of neglect, the war against malaria has entered an unprecedented era. The disease is high on the policy agenda and a huge surge in international funding is beginning to translate into large increases in the number of people protected by insecticide-treated bed-nets, effective drugs, and other control measures.

Sustaining this flow of funding during times of global economic austerity is a central challenge for the malaria control community. Of fundamental importance is the capacity to reliably measure the risk posed by the disease in different places and how this may be changing in response to control efforts. Without this, it is not possible to provide decision-makers with the evidence they need that investment is having an impact, nor where the priorities are for future funding. Examining how and where malaria risk is changing can also highlight where control measures are not working as might be expected.

Despite this importance, estimation of malaria burden is a neglected topic. In Africa, where malaria is most intense, records of cases from clinics and hospitals are known to be an unreliable way of tracking the disease and other approaches based on maps of risk have been developed as an alternative. These map-based approaches vary in complexity and in the type, quality, and volume of input data and there is therefore no consensus on the number of people currently suffering from malaria each year in Africa. Importantly, there have also been no systematic attempts to assess how malaria risk may be changing. As such, the approximately US$ 2 billion now committed annually on malaria control is spent in the absence of a reliable mechanism for assessing impact or targeting new investment.

To address this paucity of information, I propose in this fellowship to address the following questions:
i) How has the transmission of malaria changed in Africa since 2000, and what are the geographical patterns of this change?
ii) What have been the implications of this change on malaria disease burden over the same period?
iii) How do the patterns of change relate to control efforts in different places, and to other potentially important factors such as changing climate or living standards?

These questions will be answered by developing new state-of-the-art approaches to space-time modelling of malaria risk that will map the evolving landscape of infection through time and predict corresponding changes in the number of people falling ill in each country since the year 2000. The largest challenge is in modelling the uncertainty in these estimates, so that real change can be differentiated from spurious trends resulting from poor data coverage. Existing modelling approaches take enormous computing power and are not well-suited to measuring change through time, and exciting new developments in geospatial modelling and computation will be explored to address these challenges. The Malaria Atlas Project (MAP) already holds the world's largest database of malaria surveys going back to 1985. In the next few years, an unprecedented number of African countries will undertake nationwide malaria surveys and these will be added to the database to provide a rich assembly of input data on changing malaria risk.

The outcomes of this research are anticipated to enhance the evidence base needed for international advocacy and planning of donor investment, give practical information to national malaria programmes for local disease control decision-making and, by evaluating changing disease burden, enable African countries to gauge their success in meeting the malaria targets of Millennium Development Goal 6. MAP's existing network of links to African Ministries of Health and to key international partner agencies will be leveraged to ensure maximum dissemination and impact.

Technical Summary

At a time when increases in funding for malaria control in Africa have led to widespread intervention scale-up, our understanding of how malaria transmission, disease, and death may be changing remains inadequate to support evidence-based decision making and advocacy for sustained finance. The aim of this fellowship is to use the world's largest database of P. falciparum parasite rate surveys and develop novel space-time modelling approaches to assess how malaria endemicity has changed in Africa since 2000, the implications of these changes for malaria disease burdens, and their spatiotemporal association with malaria intervention coverage and efficacy.

A spatiotemporal model-based geostatistical (MBG) modelling framework will be constructed that allows generation of a space-time 'cube' of predicted P. falciparum infection prevalence through time at 5x5 km resolution with appropriate uncertainty metrics, and an ensemble of biological and empirical models will be used to convert this to estimates of clinical incidence. High-resolution multi-temporal population data will then ultimately allow estimation of malaria disease burden by country by year from 2000-2015. Elaborate handling of covariates in time and space will allow assessment of the potentially complex associations between disease control efforts and evolving patterns of malaria endemicity, adjusting for contemporaneous changes in background factors such as climate and socio-demographics. Comparison of the outcome time-series of changing malaria disease burden with equivalent existing estimates of malaria mortality will provide opportunities for epidemiological triangulation and cross-refinement of both approaches. This work will utilise the world's largest database of point-located P. falciparum parasite rate surveys since 1985 augmented with more recent national malaria survey data from around twenty African countries.

Planned Impact

The underlying motivation for my research to-date, and the rationale for the work proposed in this application, is to generate research outcomes that can underpin optimal control, audit global progress in disease reduction, and support international advocacy for investment against malaria. The ultimate beneficiaries, then, are the more than two billion people worldwide living at risk of the disease, for whom the sustainability and appropriate disbursement of funding for malaria control is an issue of the most profound importance. Tangible impact towards this objective will be achieved at three levels.

First, detailed descriptions of sub-national change in the landscape of malaria transmission will form an important aspect of the evidence base for formulating appropriate control strategies within national malaria control programmes. Identifying areas where endemicity and disease burden have declined, remained steady, or increased in relation to the deployment of interventions provides a fundamentally important monitoring and evaluation vehicle for iterative improvements in control strategies. Whilst most programmes will undertake their own evaluations, resources constraints mean these are often rudimentary and sub-optimal for decision making, despite large amounts invested in data collection. I will ensure this impact is realised by exploiting existing networks of contacts and mechanisms for national-level engagement and dissemination within the Malaria Atlas Project (see Pathways to Impact).

Second, improved understanding of what, where and, potentially, why different types and levels of malaria control have led to different transmission and disease burden responses can improve the evidence-base for appropriate and equitable disbursement of international funds, and can act as a powerful resource for international organisations seeking to advocate for sustained financing. As the flow of international development aid is placed under increasing strain, donors are acutely aware of the need to demonstrate that disease control dollars are being spent strategically and that cost-effective impact is being achieved. The absence of robust and transparent mechanisms for tracking recent change in malaria transmission and disease burden can no longer be justified and the research outputs of this fellowship can contribute to overcoming this shortfall. Appropriate engagement with the international community will be achieved primarily via dissemination at policy fora, high-impact publications and effective interactions with the media, all of which build on my existing experience (see Pathways to Impact).

Third, robust modelled evaluations of changing transmission intensity will represent a valuable open-access resource to a diverse constituency of technical users in academia and operational research investigating policy-relevant questions in malaria control. Numerous large research programmes are using transmission models to assess and optimise control options, and models describing observed changes provide ideal baseline data for testing and calibration. This feeds directly into contemporary questions in malaria control concerning the effect of vector control, drugs and vaccines and timelines to elimination.

Publications

10 25 50
 
Description JTEG/QUIVER
Geographic Reach Africa 
Policy Influence Type Participation in advisory committee
Impact I participated in the JTEG/QUIVER Technical Expert Group on Malaria Vaccines tasked to formulate WHO guidelines for uptake of the candidate RTS-S malaria vaccine currently in Phase III trials. This is a pivotal policy decision that will have a major bearing on investments addressing malaria morbidity in Africa
 
Description MBE-ERG
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact I participated in the WHO Expert Review Group on Malaria Burden Estimation. This is a key avenue for impact of this award, and entails the contribution of refined estimates of malaria morbidity to the WHO and the wider public health community. These annual estimates form a key piece of international monitoring and evaluation informing malaria financing and control.
 
Description Provision of official UN estimates on malaria incidence and intervention coverage
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in other policy documents
Impact The central research output from this CDA fellowship is an improved understanding of the nature, causes, and implications of changing malaria transmission in Africa. In order to translate these research outputs into maximum impact on policy, I have been collaborating closely with the World Health Organization Global Malaria Programme (WHO-GMP), and my estimates of changing P.falciparum infection prevalence and clinical incidence now form the official WHO and United Nations figures on malaria morbidity for sub-Saharan Africa. They have also adopted my new methodology for estimating national population coverage of the primary malaria control intervention - insecticide treated bednets (ITNs). These estimates appear in the annual WHO World Malaria Report, which forms the formal channel for UN malaria tracking. These estimates are then widely used by other international organizations (UNICEF, Global Fund, DFiD, Bill and Melinda Gates Foundation etc) as well as by regional and national-level malaria control programmes.
 
Description RBM-MERG
Geographic Reach Africa 
Policy Influence Type Participation in advisory committee
Impact I am a core member of the Roll Back Malaria Monitoring and Evaluation Reference Group (RBM-MERG) that acts as an interface between scientists, funders, international agencies, and national malaria control programmes to advise on improving the efficiency and accuracy of monitoring and evaluation practices to better inform control planning and implementation.
 
Description WHO-GMP SME-TEG
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact I am an elected inaugural member of the newly formed Surveillance, Monitoring and Evaluation Technical Expert Group (SME-TEG), convened by the World Health Organization Global Malaria Programme (WHO-GMP). In this role I influence WHO policy on the measurement of global malaria morbidity and mortality, the evaluation of malaria control efforts. SME is recognized as a fundamental pillar of the effort to reduce malaria illness and death, and this committee is the formal interface for academic and other experts to influence the way this is carried out.
 
Description Andrew B, Imperial 
Organisation Imperial College London
Department Department of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We contributed modelled predictions of required effect sizes needed to reduce transmission to an R0 of less than one, thereby ultimately bringing about elimination. This triangulated with estimates made by the Imperial team regarding possible effect sizes of transmission blocking antimalarial drugs.
Collaborator Contribution PKPD modelling and laboratory experiments on mice investigating transmission blocking drugs.
Impact Peer-reviewed journal article: 10.1038/ncomms2840
Start Year 2012
 
Description Bobby R, UC Davis 
Organisation University of California, Davis
Department Department of Entomology and Nematology
Country United States 
Sector Academic/University 
PI Contribution We participate in a large review of mathematical models of vector-borne pathogens, and contributed meta-analyses for the resulting data extractions
Collaborator Contribution The UC Davis team led this work - overseeing the review process and compiling the meta-analyses.
Impact Peer-reviewed journal article: 10.1098/rsif.2012.0921
Start Year 2012
 
Description JHSPH 
Organisation Johns Hopkins University
Department John Hopkins Malaria Research Institute
Country United States 
Sector Academic/University 
PI Contribution We contributed conceptual ideas and modelling methodology to this collaboration investigating the dynamics of malaria transmission as control brings it close to zero, and the implications for prospects for elimination
Collaborator Contribution The Johns Hopkins team led this analysis and undertook the main analysis
Impact Peer-reviewed journal articles: 10.1098/rstb.2012.0145 10.1126/science.1229509
Start Year 2012
 
Description Urbanization 
Organisation University of Southampton
Department Faculty of Natural and Environmental Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Development of statistical modelling approaches to evaluating role of urbanization in long-term patterns of changing malaria prevalence globally
Collaborator Contribution The Southampton team led this research - they assembled the data and undertook the main analyses
Impact Journal article: 10.1186/1475-2875-12-133
Start Year 2012
 
Description WHO-GMP 
Organisation World Health Organization (WHO)
Department Global Malaria Programme
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution We contribute data (parasite rate, intervention coverage, clinical incidence), statistical expertise (space-time geostatistical modelling, Bayesian inference and computation), and are generating the modelled outputs (geospatial models of p. falciparum infection prevalence and clinical incidence, and evaluations of trends through time).
Collaborator Contribution WHO-GMP are providing some additional data (routine case reporting for malaria, some programmatic data on intervention coverage), along with their expertise in interpreting this type of information, and more broadly in framing appropriate questions and assisting with communication and dissemination to policy and decision makers.
Impact No Published outputs in this first year of the collaboration. Nearly all of the key peer-reviewed articles that are in preparation for this project will have some form of input from WHO-GMP - either in an advisory role or co-authors. Additionally, our evaluations of changing prevalence and incidence will be published in forthcoming World Malaria Reports - the annual WHO audit of the global status of malaria and efforts to control it.
Start Year 2012