Research Article: A Research Agenda to Underpin Malaria Eradication

Date Published: January 25, 2011

Publisher: Public Library of Science

Author(s): Pedro L. Alonso, Graham Brown, Myriam Arevalo-Herrera, Fred Binka, Chetan Chitnis, Frank Collins, Ogobara K. Doumbo, Brian Greenwood, B. Fenton Hall, Myron M. Levine, Kamini Mendis, Robert D. Newman, Christopher V. Plowe, Mario Henry Rodríguez, Robert Sinden, Laurence Slutsker, Marcel Tanner

Abstract: Pedro Alonso and colleagues introduce the Malaria Eradication Research Agenda (malERA) initiative and the set of articles published in this PLoS Medicine Supplement that distill the research questions key to malaria eradication.

Partial Text: The unacceptable health burden of malaria, and its economic and social impacts on development, have made it a focal point of the international development agenda, and the world has embraced an ambitious plan for scaling up malaria control that progresses towards country-by-country and regional elimination and the ultimate goal of global eradication [1]. Over the past decade, resources and control efforts have intensified to a level not seen since the early days of the World Health Organization’s Global Malaria Eradication Program (GMEP) in the late 1950s. Nonetheless, in 2009, with 3.28 billion people living in areas that have some risk of malaria transmission and about 1.2 billion people (one-fifth of the world’s population) living in areas with a high risk of transmission (more than one reported case per 1,000 population per year), there were about 225 million cases of clinical malaria and 781,000 malaria-related deaths. Today, there is ongoing malaria transmission in 106 countries. Eighty-one of these countries are focusing on control, while 25 are in pre-elimination, elimination, and prevention of reintroduction phases; Morocco, the United Arab Emirates, and Turkmenistan have recently been certified as malaria free [2]–[4].

A detailed discussion of all the factors involved in the partial success of the past eradication campaign is beyond the scope of this introduction, but three critical elements can be highlighted. First, there was insufficient recognition of the heterogeneity of malaria transmission and disease. Much of the optimism that inspired WHO GMEP in 1955 was based on the successful outcomes of earlier control programs that benefited from a combination of biological, parasitological, social, and environmental factors that favoured success (e.g., the rarity of DDT-resistant Anophelines and of chloroquine-resistant parasites). Second, the first WHO GMEP (1955-1969) was predicated on an assumption that the available knowledge and tools were sufficient to achieve worldwide eradication. A single strategy that would work everywhere—“one size fits all”—proved to be ill-founded because it underestimated the challenges of dealing with the extremely efficient vectors in Africa (An. gambiae) and with transmission by outdoor-feeding mosquitoes that were not susceptible to attack by indoor residual insecticide. It also did not allow for the lack of safe drugs for mass administration to remove all infectious parasites from symptomatic and asymptomatic carriers, particularly from people carrying P. vivax or P. ovale, species that establish latent liver infections that are responsible for relapses months or years following initial infection. Third, insufficient research in biomedical and social sciences and inadequate local application of research findings across a wide variety of settings are widely viewed to have contributed to demoralization and waning effort when tools proved ineffective or could not be adequately implemented. The neglect of malaria research during and after the campaign did long-term damage. These elements resulted in a lack of progress that in turn compromised continued financial support [7].

The past decade has witnessed renewed investment in malaria control and substantial increases in funding for malaria research. The Roll Back Malaria Global Malaria Action Plan (GMAP) and WHO have recently revised and updated the strategy and the steps for scaling up and sustaining malaria control (Figure 1). In addition, the Malaria Elimination Group (MEG), a group of scientists, public health decision makers, control program managers, and funders, has compiled a guide to policy makers for areas that embark or have embarked on elimination strategies [8].

To catalyze this paradigm shift towards malaria elimination and eradication, it was necessary to design a process to bring together the best scientific minds in the malaria community. That process is the Malaria Eradication Research Agenda (malERA) initiative, which was established to complement GMAP and which aims to define the critical knowledge base, strategies, and tools required to reduce the basic reproduction rate (R0 or the number of secondary cases arising from a single case) to less than one.

To reduce the basic reproduction rate to less than 1, and hence to interrupt transmission, interventions are needed to reduce the reservoir of infection, the time that a person or a mosquito is infectious, and the rate at which infections are spread. This goal can be achieved by drugs or vaccines directed against the parasite or by new tools that attack the vector, with the support of improved diagnostics and surveillance.

The previous formal attempt at global eradication of malaria (1955–1969) depended largely on vertical operations that often bypassed health systems and their health services because it was assumed that eradication operations could be run most efficiently in this way. Many of the elimination efforts failed, because the health systems failed, leading to a pessimistic view that malaria can only be eliminated where economic progress, governance, and efficient health systems are in place to support maintenance of conditions necessary to block transmission [32],[33].

The last time the world community tried to eliminate malaria, so the joke goes, the only thing that was eliminated was malariologists. For a renewed malaria eradication campaign to have a chance to succeed, it will be essential to train the malariologists and scientists in the multiple disciplines needed for an eradication campaign that might last 50 years, especially in endemic countries. This need cannot be overemphasized. The malaria research community remains small and often dominated by the views and strategies of scientists who sit far away from the problems. A massive effort to train, empower, and sustain research capacity in the endemic countries will be a critical factor for the success of improved control efforts and for the ultimate elimination and eradication of malaria.

The past 2 years have reinvigorated an old malaria paradigm in which reduction of transmission is the driving strategy for malaria interventions. The malaria community has now used the malERA process to propose a research and development agenda that will be essential for regional elimination and eventual global eradication of malaria. Not every tool or strategy considered by the malERA Consultative Groups (see Box 2) will be essential in every situation (see Figure 4), but the complexity and heterogeneity, and in some places, the sheer intensity of transmission, demand that we start without delay to prepare for the most difficult challenges. This focus on the end goal of eradication must not displace our determination and efforts to continue to scale up ongoing efforts for control and to include a research agenda for reducing morbidity in areas of continuing moderate or high transmission. Rather, it must encourage us to supplement our efforts with a structured agenda that can realize the ultimate goal of eradication envisaged by the Global Malaria Action Plan and the Roll Back Malaria Partnership. An important lesson we can learn from other disease elimination efforts is that complacency is dangerous. The parasite and the vector are always evolving, and the human environment is always changing. Thus, new research questions will continually arise during the course of elimination [42], and active malaria research, particularly on the development of new tools, must continue up to the point when eradication is finally achieved. We anticipate that the results of research efforts proposed by our Consultative Groups for each stage of progression, from scaling up for improved control to the elimination phases, will have great synergy in design and application.



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