Getting ready for malaria elimination: a check list of critical issues to consider

In recent years, a renewed interest in malaria elimination and eradication has emerged and seems to be rooting in the minds of the scientific community, public health specialists, funding bodies, policy makers and politicians. Malaria eradication will certainly benefit from improved and innovative tools; notwithstanding novel knowledge in fields ranging from basic science to mathematical modelling and health systems research. However, the elimination of malaria also encompasses a broad range of essential aspects that countries and other actors need to consider when thinking of embarking on such an adventure, including the implementation of innovative strategies, the ability to incorporate the most up-to-date evidence into policy, the integration of malaria into the broader health agenda, the strengthening of surveillance and health systems, capacity building, funding, advocacy and, very importantly, research. While in some cases this enthusiasm is clearly justified, some countries are still a long way from realistically advancing towards elimination. This paper attempts to provide guidance on all the necessary issues that should be considered when initiating a malaria elimination program.     

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.     

Some lessons for the future from the Global Malaria Eradication Programme (1955-1969)

Encouraged by the early success of using dichloro-diphenyl-trichloroethane (DDT) against malaria, the World Health Organization (WHO) embarked on the Global Malaria Eradication Program (GMEP) in 1955. Fourteen years later, the campaign was discontinued when it was recognised that eradication was not achievable with the available means in many areas, although the long-term goal remained unchanged. During the GMEP, malaria was permanently eliminated from many regions. In other areas, however, substantial gains were lost in resurgences, sometimes of epidemic proportions. During the 1970s and 1980s, because of economic and financial crises, international support for malaria control declined rapidly, but in the past decade, following increasing demands from endemic countries and promising results from scaling up of control activities, interest in malaria elimination and the long-term goal of eradication has received international political and financial support. In 2007, there was a renewed call for malaria eradication and a consultative process to define a research and development agenda for malaria eradication (malERA) was established. Lessons learned from the GMEP (1955-1969) highlight the fact that no single strategy can be applicable everywhere and that a long-term commitment with a flexible strategy that includes community involvement, integration with health systems, and the development of agile surveillance systems is needed.     

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: vaccines

Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of "vaccines that interrupt malaria transmission" (VIMT), which includes not only "classical" transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.     

A research agenda for malaria eradication: drugs

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission.     

生态系统服务建模技术研究进展

在生态系统服务评估模型的数量、类型及应用大量增加的背景下,为将生态系统服务评估有效整合到决策中,系统比较、甄别不同建模工具并筛选出适合决策需求的生态系统服务评估和模拟方法尤为必要。因此,归纳并总结了国内外现有的生态系统服务评估模型的建模技术,包括:相关关系法、生物-物理过程法以及专家知识法;分别对其原理、差异、优缺点以及适用性进行了详尽阐释。大多数相关模型侧重于统计关系,相对容易创建和扩展,适用于生态系统服务的初始评估;生物-物理过程模型难以构建且不易获取,但提供了探索人-地系统相互作用和长期变化的有效机制;专家知识法有效结合了多种类型的知识体系,关注人类社会与自然系统之间反馈和交互动态的系统整合,但当评估地点发生变化时难以验证。在此基础上,介绍了基于上述3种建模技术的典型生态系统服务综合评估模型的发展和应用现状。各类建模技术面临着实用性和科学准确性之间的权衡。通过对不同建模技术的梳理与整合分析旨在提升当前生态系统服务研究的决策支撑能力,并为国内相关研究提供参考和借鉴。     

Commentary: Barriers and Opportunities to Changing the Research Agenda to Support Precaution and Primary Prevention

Conceptual research to define the Precautionary Principle and its rôle in science, science policy, and public health is making substantial progress. In September 2001, participants at the International Summit on Science and the Precautionary Principle developed a vision for science to address the complexity of contemporary health risks in a way that could lead to more precautionary, preventive decisions under uncertainty. Its components include: (1) a more effective linkage between research on hazards and research on primary prevention; (2) increased use of interdisciplinary approaches including better integration of qualitative and quantitative data; (3) innovative methods for analyzing cumulative and interactive effects, populations and systems and vulnerable sub-populations; (4) systems for continuous monitoring to avoid unintended consequences of actions and to identify early warnings of risks; (5) more comprehensive techniques for analyzing and communicating hazards and uncertainties; and (6) a more dynamic interface between science and policy. This article addresses barriers and opportunities to the practical application of this vision for science. Scientists in many fields have recognized the need for innovative approaches and tools to address increasingly complex, uncertain risks of a global scale. While opportunities to apply precautionary concepts in the research agenda exist, public health scientists must be cognizant of current and emerging barriers in the research agenda that balance the research focus on characterizing proximate causal mechanisms of disease, to the detriment of research and policy to support primary prevention.     

Malaria modeling: In vitro stem cells vs in vivo models

The recent development of stem cell research and the possibility of generating cells that can be stably and permanently modified in their genome open a broad horizon in the world of in vitro modeling. The malaria field is gaining new opportunities from this importantbreakthrough and novel tools were adapted and opened new frontiers for malaria research. In addition to the new in vitro systems, in recent years there were also significant advances in the development of new animal models that allows studying the entire cell cycle of human malaria. In this paper, we review the different protocols available to study human Plasmodium species either by using stem cell or alternative animal models.     

Modeling the role of environmental variables on the population dynamics of the malaria vector Anopheles gambiae sensu stricto

ABSTRACT: BACKGROUND: The impact of weather and climate on malaria transmission has attracted considerable attention in recent years, yet uncertainties around future disease trends under climate change remain. Mathematical models provide powerful tools for addressing such questions and understanding the implications for interventions and eradication strategies, but these require realistic modeling of the vector population dynamics and its response to environmental variables. METHODS: Published and unpublished field and experimental data are used to develop new formulations for modeling the relationships between key aspects of vector ecology and environmental variables. These relationships are integrated within a validated deterministic model of Anopheles gambiae s.s. population dynamics to provide a valuable tool for understanding vector response to biotic and abiotic variables. RESULTS: A novel, parsimonious framework for assessing the effects of rainfall, cloudiness, wind speed, desiccation, temperature, relative humidity and density-dependence on vector abundance is developed, allowing ease of construction, analysis, and integration into malaria transmission models. Model validation shows good agreement with longitudinal vector abundance data from Tanzania, suggesting that recent malaria reductions in certain areas of Africa could be due to changing environmental conditions affecting vector populations. CONCLUSIONS: Mathematical models provide a powerful, explanatory means of understanding the role of environmental variables on mosquito populations and hence for predicting future malaria transmission under global change. The framework developed provides a valuable advance in this respect, but also highlights key research gaps that need to be resolved if we are to better understand future malaria risk in vulnerable communities.     

Systems immunology of human malaria

Plasmodium falciparum malaria remains a global public health threat. Optimism that a highly effective malaria vaccine can be developed stems in part from the observation that humans can acquire immunity to malaria through experimental and natural P. falciparum infection. Recent advances in systems immunology could accelerate efforts to unravel the mechanisms of acquired immunity to malaria. Here, we review the tools of systems immunology, their current limitations in the context of human malaria research, and the human 'models' of malaria immunity to which these tools can be applied.     

Risk management to prioritise the eradication of new and emerging invasive non-native species

Robust tools are needed to prioritise the management of invasive non-native species (INNS). Risk assessment is commonly used to prioritise INNS, but fails to take into account the feasibility of management. Risk management provides a structured evaluation of management options, but has received little attention to date. We present a risk management scheme to assess the feasibility of eradicating INNS that can be used, in conjunction with existing risk assessment schemes, to support prioritisation. The Non-Native Risk Management scheme (NNRM) can be applied to any predefined area and any taxa. It uses semi-quantitative response and confidence scores to assess seven key criteria: Effectiveness, Practicality, Cost, Impact, Acceptability, Window of opportunity and Likelihood of re-invasion. Scores are elicited using expert judgement, supported by available evidence, and consensus-building methods. We applied the NNRM to forty-one INNS that threaten Great Britain (GB). Thirty-three experts provided scores, with overall feasibility of eradication assessed as ‘very high’ (8 species), ‘high’ (6), ‘medium’ (8), ‘low’ (10) and ‘very low’ (9). The feasibility of eradicating terrestrial species was higher than aquatic species. Lotic freshwater and marine species scored particularly low. Combining risk management and existing risk assessment scores identified six established species as priorities for eradication. A further six species that are not yet established were identified as priorities for eradication on arrival as part of contingency planning. The NNRM is one of the first INNS risk management schemes that can be used with existing risk assessments to prioritise INNS eradication in any area.     

Health Security and Risk Aversion

Health security has become a popular way of justifying efforts to control catastrophic threats to public health. Unfortunately, there has been little analysis of the concept of health security, nor the relationship between health security and other potential aims of public health policy. In this paper I develop an account of health security as an aversion to risky policy options. I explore three reasons for thinking risk avoidance is a distinctly worthwhile aim of public health policy: (i) that security is intrinsically valuable, (ii) that it is necessary for social planning and (iii) that it is an appropriate response to decision‐making in contexts of very limited information. Striking the right balance between securing and maximizing population health thus requires a substantive, and hitherto unrecognized, value judgment. Finally, I critically evaluate the current health security agenda in light of this new account of the concept and its relationship to the other aims of public health policy.     

Patient Knowledge on Malaria Symptoms Is a Key to Promoting Universal Access of Patients to Effective Malaria Treatment in Palawan,the Philippines

Introduction

Palawan, where health care facilities are still limited, is one of the most malaria endemic provinces in the Philippines. Since 1999, microscopists (community health workers) have been trained in malaria diagnosis and feasibility of early diagnosis and treatments have been enhanced throughout the province. To accelerate the universal access of malaria patients to diagnostic testing in Palawan, positive health seeking behavior should be encouraged when malaria infection is suspected.

Methods

In this cross-sectional study, structured interviews were carried out with residents (N = 218) of 20 remote malaria-endemic villages throughout Palawan with a history of suspected malaria from January to February in 2012. Structural equation modeling (SEM) was conducted to determine factors associated with appropriate treatment, which included: (1) socio-demographic characteristics; (2) proximity to a health facility; (3) health seeking behavior; (4) knowledge on malaria; (5) participation in community awareness-raising activities.

Results

Three factors independently associated with appropriate treatment were identified by SEM (CMIN = 10.5, df = 11, CFI = 1.000, RMSEA = .000): “living near microscopist” (p < 0.001), “not living near private pharmacy” (p < 0.01), and “having severe symptoms” (p < 0.01). “Severe symptoms” were positively correlated with more “knowledge on malaria symptoms” (p < 0.001). This knowledge was significantly increased by attending “community awareness-raising activities by microscopists” (p < 0.001).

Conclusions

In the resource-limited settings, microscopists played a significant role in providing appropriate treatment to all participants with severe malaria symptoms. However, it was considered that knowledge on malaria symptoms made participants more aware of their symptoms, and further progressed self-triage. Strengthening this recognition sensitivity and making residents aware of nearby microscopists may be the keys to accelerating universal access to effective malaria treatment in Palawan.     

Study of protein complexes via homology modeling,applied to cysteine proteases and their protein inhibitors

This paper develops and evaluates large-scale calculation of 3D structures of protein complexes by homology modeling as a promising new approach for protein docking. The complexes investigated were papain-like cysteine proteases and their protein inhibitors, which play numerous roles in human and parasitic metabolisms. The structural modeling was performed in two parts. For the first part (evaluation set), nine crystal structure complexes were selected, 1325 homology models of known complexes were rebuilt by various templates including hybrids, allowing an analysis of the factors influencing the accuracy of the models. The important considerations for modeling the interface were protease coverage and inhibitor sequence identity. In the second part (study set), the findings of the evaluation set were used to select appropriate templates to model novel cysteine protease-inhibitor complexes from human and malaria parasites Plasmodium falciparum and Plasmodium vivax. The energy scores, considering the evaluation set, indicate that the models are of high accuracy.     

Complexity in Urban Development and Management

Systems dynamics, cellular automata, agent-based modeling, and network analyses have been used in population, land use, and transport planning models. An overview of complex systems science as applied to urban development is presented, and examples are given of where the problems of housing people and anticipating their movements have been addressed with complex approaches, sometimes in concert with deterministic, large-scale urban models. Planning for cities today has additional environmental and social priorities in common with many topics that concern industrial ecology. The research agenda suggested here is that this, too, can be enriched with complex systems thinking and models to complement the often static assessment of environmental performance and better inform decision processes.     

Malaria eradication: the Taiwan experience

In November 1965, the World Health Organization (WHO) certified Taiwan as an area where malaria had been eradicated. Malaria eradication in Taiwan resulted from government initiatives and involvement, careful planning and organization, the development of basic health structure and community support, as well as the cooperation and assistance of international agencies. The Japanese colonial government of Taiwan had contributed to the antimalarial efforts through the establishment of a rudimentary health infrastructure and introduction of measures to combat malaria and other diseases during their occupation of the island from 1895 to 1945. The Chinese government regained control of the island after Japan's surrender in 1945, and with the support of the Rockefeller Foundation, established a research institute to investigate the malaria problem. Political instability in 1949, however, caused the Foundation to end its support. After the Nationalist government moved to Taiwan, it continued antimalarial efforts which received the support of WHO and other international agencies. While Taiwan followed closely WHO's guidelines and plan of attack, the development of the program illustrates the importance of local factors in shaping its actual implementation and eventual success. Malaria eradication in Taiwan went through the following phases: preparatory (1946-1951); attack (1952-1957); consolidation (1958-1964); and maintenance (after 1965).     

The United States Army and malaria control in World War II

The United States Army faced difficult malaria control problems both at home and abroad during World War II. This challenge forced the Army to develop new tools and strategies for use in malarious areas where fighting was occurring. Due to the severe malaria problems being faced in some combat areas and the need to solve these problems quickly, intensive malaria research and operational programs were developed and implemented. With these concerted efforts and the simultaneous development of new control technologies, malaria was successfully controlled in most locations. In order to accomplish this high level of control both in the US and overseas, the Army developed a very organized approach to the malaria problem and implemented it in an effective manner. The creation of new technical solutions was also strongly emphasized and out of this effort came the development of effective antimalaria drugs to replace quinine, of new insecticides and of more effective systems for delivering these insecticides. Some of the major new tools which came out of this research were DDT and drugs such as Atabrine and chloroquine. The availability of Atabrine and DDT revolutionized malaria control throughout the world. The knowledge and experience gained through the use of these new tools by the US Army and other agencies in World War II provided the basis for a new optimism regarding malaria control which then led to the development of the global malaria eradication strategy in the post-war years.