Malaria Eradication Research Agenda Research Articles

MalERA: An updated research agenda for basic science and enabling technologies in malaria elimination and eradication.

Basic science holds enormous power for revealing the biological mechanisms of disease and, in turn, paving the way toward new, effective interventions. Recognizing this power, the 2011 Research Agenda for Malaria Eradication included key priorities in fundamental research that, if attained, could help accelerate progress toward disease elimination and eradication. The Malaria Eradication Research Agenda (malERA) Consultative Panel on Basic Science and Enabling Technologies reviewed the progress, continuing challenges, and major opportunities for future research. The recommendations come from a literature of published and unpublished materials and the deliberations of the malERA Refresh Consultative Panel. These areas span multiple aspects of the Plasmodium life cycle in both the human host and the Anopheles vector and include critical, unanswered questions about parasite transmission, human infection in the liver, asexual-stage biology, and malaria persistence. We believe an integrated approach encompassing human immunology, parasitology, and entomology, and harnessing new and emerging biomedical technologies offers the best path toward addressing these questions and, ultimately, lowering the worldwide burden of malaria.

MalERA: An updated research agenda for malaria elimination and eradication.

Achieving a malaria-free world presents exciting scientific challenges as well as overwhelming health, equity, and economic benefits. WHO and countries are setting ambitious goals for reducing the burden and eliminating malaria through the “Global Technical Strategy” and 21 countries are aiming to eliminate malaria by 2020. The commitment to achieve these targets should be celebrated. However, the need for innovation to achieve these goals, sustain elimination, and free the world of malaria is greater than ever. Over 180 experts across multiple disciplines are engaged in the Malaria Eradication Research Agenda (malERA) Refresh process to address problems that need to be solved. The result is a research and development agenda to accelerate malaria elimination and, in the longer term, transform the malaria community’s ability to eradicate it globally.

MalERA: An updated research agenda for characterising the reservoir and measuring transmission in malaria elimination and eradication.

This paper summarises key advances in defining the infectious reservoir for malaria and the measurement of transmission for research and programmatic use since the Malaria Eradication Research Agenda (malERA) publication in 2011. Rapid and effective progress towards elimination requires an improved understanding of the sources of transmission as well as those at risk of infection. Characterising the transmission reservoir in different settings will enable the most appropriate choice, delivery, and evaluation of interventions. Since 2011, progress has been made in a number of areas. The extent of submicroscopic and asymptomatic infections is better understood, as are the biological parameters governing transmission of sexual stage parasites. Limitations of existing transmission measures have been documented, and proof-of-concept has been established for new innovative serological and molecular methods to better characterise transmission. Finally, there now exists a concerted effort towards the use of ensemble datasets across the spectrum of metrics, from passive and active sources, to develop more accurate risk maps of transmission. These can be used to better target interventions and effectively monitor progress toward elimination. The success of interventions depends not only on the level of endemicity but also on how rapidly or recently an area has undergone changes in transmission. Improved understanding of the biology of mosquito–human and human–mosquito transmission is needed particularly in low-endemic settings, where heterogeneity of infection is pronounced and local vector ecology is variable. New and improved measures of transmission need to be operationally feasible for the malaria programmes. Outputs from these research priorities should allow the development of a set of approaches (applicable to both research and control programmes) that address the unique challenges of measuring and monitoring transmission in near-elimination settings and defining the absence of transmission.

MalERA: An updated research agenda for insecticide and drug resistance in malaria elimination and eradication.

Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts. Suboptimal responses to drugs and insecticides are both spreading geographically and emerging independently and are being seen at increasing intensities. Whilst resistance is unavoidable, its effects can be mitigated through resistance management practices, such as exposing the parasite or vector to more than one selective agent. Resistance contributed to the failure of the 20th century Global Malaria Eradication Programme, and yet the global response to this issue continues to be slow and poorly coordinated—too often, too little, too late. The Malaria Eradication Research Agenda (malERA) Refresh process convened a panel on resistance of both insecticides and antimalarial drugs. This paper outlines developments in the field over the past 5 years, highlights gaps in knowledge, and proposes a research agenda focused on managing resistance. A deeper understanding of the complex biological processes involved and how resistance is selected is needed, together with evidence of its public health impact. Resistance management will require improved use of entomological and parasitological data in decision making, and optimisation of the useful life of new and existing products through careful implementation, combination, and evaluation. A proactive, collaborative approach is needed from basic science and the development of new tools to programme and policy interventions that will ensure that the armamentarium of drugs and insecticides is sufficient to deal with the challenges of malaria control and its elimination.

MalERA: An updated research agenda for health systems and policy research in malaria elimination and eradication.

Health systems underpin disease elimination and eradication programmes. In an elimination and eradication context, innovative research approaches are needed across health systems to assess readiness for programme reorientation, mitigate any decreases in effectiveness of interventions (‘effectiveness decay’), and respond to dynamic and changing needs. The malaria eradication research agenda (malERA) Refresh consultative process for the Panel on Health Systems and Policy Research identifies opportunities to build health systems evidence and the tools needed to eliminate malaria from different zones, countries, and regions and to eradicate it globally. The research questions are organised as a portfolio that global health practitioners, researchers, and funders can identify with and support. This supports the promotion of an actionable and more cohesive approach to building the evidence base for scaled-up implementation of findings. Gaps and opportunities discussed in the paper include delivery strategies to meet the changing dynamics of needs of individuals, environments, and malaria programme successes; mechanisms and approaches to best support accelerated policy and financial responsiveness at national and global level to ensure timely response to evidence and needs, including in crisis situations; and systems’ readiness tools and decision-support systems.

The need for operational research and capacity-building in support of the Global Technical Strategy for Malaria 2016-2030.

The need for operational research and capacity-building in support of the Global Technical Strategy for Malaria 2016-2030.

Alan Magill, ASTMH Immediate Past President, 1953-2015.

Alan Magill, ASTMH Immediate Past President, 1953-2015.

Malaria vaccines for eradication

In achieving the goal of malaria eradication, vaccines could play a crucial role. Current attempts to develop malaria vaccines are primarily focused on Plamosdium falciparum and are directed towards reducing morbidity and mortality. This is the case of the RTS,S vaccine candidate, the most developed at the moment and currently undergoing the final analysis of a multicentric, international Phase III clinical trial. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for malaria eradication, they will need to have an impact on malaria transmission, contributing to lower the reproductive rate to less than one. The consultative group on vaccines of the Malaria Eradication Research Agenda (malERA) initiative identified key features of vaccines especially suited for malaria eradication. The group introduced the concept of “Vaccines that Interrupt Malaria Transmission” (VIMTs), broadening the classical definition of Transmission Blocking Vaccines (TBVs) -that target sexual and mosquito stages of the parasite-, in order to also include any other parasite life stages that may interrupt transmission of malaria. This would include pre-erythrocytic and asexual stage vaccines to reduce prevalence and densities of sexual forms of the parasite, as well as vaccines against mosquito gut antigens impeding parasite development in the vector. Moreover, malaria eradication would necessarily need to target not only P. falciparum but also P. vivax, for which therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple parasite stages could have enormous impact. Development of VIMTs require the advancement of basic understanding of interactions of the malaria parasite with humans and vectors, as well as the development of tools to measuring infectivity at the individual level and assessing transmission within a given population. VIMTs may have primarily an effect at the population level and could be crucial not only for eradication, but also in areas where malaria control is still the main issue to be addressed. In order to accelerate the actual implementation of such vaccines, it is also important to address regulatory issues and to develop appropriate delivery platforms.

Correction: A Research Agenda for Malaria Eradication: Basic Science and Enabling Technologies

Correction: A Research Agenda for Malaria Eradication: Basic Science and Enabling Technologies

A research agenda for malaria eradication: basic science and enabling technologies.

Today's malaria control efforts are limited by our incomplete understanding of the biology of Plasmodium and of the complex relationships between human populations and the multiple species of mosquito and parasite. Research priorities include the development of in vitro culture systems for the complete life cycle of P. falciparum and P. vivax and the development of an appropriate liver culture system to study hepatic stages. In addition, genetic technologies for the manipulation of Plasmodium need to be improved, the entire parasite metabolome needs to be characterized to identify new druggable targets, and improved information systems for monitoring the changes in epidemiology, pathology, and host-parasite-vector interactions as a result of intensified control need to be established to bridge the gap between bench, preclinical, clinical, and population-based sciences.

A research agenda for malaria eradication: modeling.

Malaria modeling can inform policy and guide research for malaria elimination and eradication from local implementation to global policy. A research and development agenda for malaria modeling is proposed, to support operations and to enhance the broader eradication research agenda. Models are envisioned as an integral part of research, planning, and evaluation, and modelers should ideally be integrated into multidisciplinary teams to update the models iteratively, communicate their appropriate use, and serve the needs of other research scientists, public health specialists, and government officials. A competitive and collaborative framework will result in policy recommendations from multiple, independently derived models and model systems that share harmonized databases. As planned, modeling results will be produced in five priority areas: (1) strategic planning to determine where and when resources should be optimally allocated to achieve eradication; (2) management plans to minimize the evolution of drug and pesticide resistance; (3) impact assessments of new and needed tools to interrupt transmission; (4) technical feasibility assessments to determine appropriate combinations of tools, an associated set of target intervention coverage levels, and the expected timelines for achieving a set of goals in different socio-ecological settings and different health systems; and (5) operational feasibility assessments to weigh the economic costs, capital investments, and human resource capacities required.

A Research Agenda for Malaria Eradication: Cross-Cutting Issues for Eradication

Discipline-specific Malaria Eradication Research Agenda (malERA) Consultative Groups have recognized several cross-cutting issues that must be addressed to prevent repetition of some of the mistakes of past malaria elimination campaigns in future programs. Integrated research is required to develop a decision-making framework for the switch from malaria control to elimination. Similarly, a strong economic case is needed for the very long-term financial support that is essential for elimination. Another cross-cutting priority is the development of improved measures of intensity of transmission, especially at low and nonrandom levels. Because sustained malaria elimination is dependent on a functioning health system, a further key cross-cutting research question is to determine how inputs for malaria can strengthen health systems, information systems, and overall health outcomes. Implementation of elimination programs must also be accompanied by capacity building and training to allow the assessment of the impact of new combinations of interventions, new roles for different individuals, and the operational research that is needed to facilitate program expansion. Finally, because community engagement, knowledge management, communication, political, and multisectoral support are critical but poorly understood success factors for malaria elimination, integrated research into these issues is vital.

A Research Agenda for Malaria Eradication: Monitoring, Evaluation, and Surveillance

Monitoring, evaluation, and surveillance measure how well public health programs operate over time and achieve their goals. As countries approach malaria elimination, these activities will need to shift from measuring reductions in morbidity and mortality, to detecting infections (with or without symptoms) and measuring transmission. Thus, the monitoring and evaluation and surveillance research and development agenda needs to develop the tools and strategies that will replace passive surveillance of morbidity with active and prompt detection of infection, including confirmation of interruption of transmission by detecting present and past infections, particularly in mobile populations. The capacity to assess trends and respond without delay will need to be developed, so that surveillance itself becomes an intervention. Research is also needed to develop sensitive field tests that can detect low levels of parasitaemia, together with strategies for their implementation. Other areas to explore include the rigorous evaluation of the utility of more detailed maps of disease and infection incidence and prevalence, the development of new maps to inform programmatic responses and the use of surveillance technologies based on cell phone or real-time internet Web-based reporting. Because any new strategies for monitoring and evaluation and surveillance for eradication have major implications for program implementation, research is also needed to test systems of delivery for acceptability, feasibility, efficiency, cost-effectiveness, and community engagement. Finally, there is a clear need to systematically review the information from past elimination efforts for malaria and other infectious diseases.

A research agenda for malaria eradication: health systems and operational research.

Health systems research and development is needed to support the global malaria eradication agenda. In this paper, we (the malERA Consultative Group on Health Systems and Operational Research) focus on the health systems needs of the elimination phase of malaria eradication and consider groupings of countries at different stages along the pathway to elimination. We examine the difference between the last attempt at eradication of malaria and more recent initiatives, and consider the changing health system challenges as countries make progress towards elimination. We review recent technological and theoretical developments related to health systems and the renewed commitment to strengthening health systems for universal access and greater equity. Finally, we identify a number of needs for research and development, including tools for analyzing and improving effective coverage and strengthening decision making and discuss the relevance of these needs at all levels of the health system from the community to the international level.

A research agenda to underpin malaria eradication.

The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda--primarily directed towards reducing morbidity and mortality--with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda.