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      Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?

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          Abstract

          Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication.

          Abstract

          Malaria elimination in many settings will not be possible without new vaccines, drugs, and vector control products. Although a healthy pipeline of new products in each of these areas has been developed over the past decade, significant work is required to bring these products to market and deploy optimal strategies for their use.

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          Most cited references25

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          Rapid diagnostic tests for malaria parasites.

          Malaria presents a diagnostic challenge to laboratories in most countries. Endemic malaria, population movements, and travelers all contribute to presenting the laboratory with diagnostic problems for which it may have little expertise available. Drug resistance and genetic variation has altered many accepted morphological appearances of malaria species, and new technology has given an opportunity to review available procedures. Concurrently the World Health Organization has opened a dialogue with scientists, clinicians, and manufacturers on the realistic possibilities for developing accurate, sensitive, and cost-effective rapid diagnostic tests for malaria, capable of detecting 100 parasites/microl from all species and with a semiquantitative measurement for monitoring successful drug treatment. New technology has to be compared with an accepted "gold standard" that makes comparisons of sensitivity and specificity between different methods. The majority of malaria is found in countries where cost-effectiveness is an important factor and ease of performance and training is a major consideration. Most new technology for malaria diagnosis incorporates immunochromatographic capture procedures, with conjugated monoclonal antibodies providing the indicator of infection. Preferred targeted antigens are those which are abundant in all asexual and sexual stages of the parasite and are currently centered on detection of HRP-2 from Plasmodium falciparum and parasite-specific lactate dehydrogenase or Plasmodium aldolase from the parasite glycolytic pathway found in all species. Clinical studies allow effective comparisons between different formats, and the reality of nonmicroscopic diagnoses of malaria is considered.
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            Characterizing, controlling and eliminating residual malaria transmission

            Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) interventions can reduce malaria transmission by targeting mosquitoes when they feed upon sleeping humans and/or rest inside houses, livestock shelters or other man-made structures. However, many malaria vector species can maintain robust transmission, despite high coverage of LLINs/IRS containing insecticides to which they are physiologically fully susceptible, because they exhibit one or more behaviours that define the biological limits of achievable impact with these interventions: (1) Natural or insecticide-induced avoidance of contact with treated surfaces within houses and early exit from them, thus minimizing exposure hazard of vectors which feed indoors upon humans; (2) Feeding upon humans when they are active and unprotected outdoors, thereby attenuating personal protection and any consequent community-wide suppression of transmission; (3) Feeding upon animals, thus minimizing contact with insecticides targeted at humans or houses; (4) Resting outdoors, away from insecticide-treated surfaces of nets, walls and roofs. Residual malaria transmission is, therefore, defined as all forms of transmission that can persist after achieving full universal coverage with effective LLINs and/or IRS containing active ingredients to which local vector populations are fully susceptible. Residual transmission is sufficiently intense across most of the tropics to render malaria elimination infeasible without new or improved vector control methods. Many novel or improved vector control strategies to address residual transmission are emerging that either: (1) Enhance control of adult vectors that enter houses to feed and/or rest by killing, repelling or excluding them; (2) Kill or repel adult mosquitoes when they attack people outdoors; (3) Kill adult mosquitoes when they attack livestock; (4) Kill adult mosquitoes when they feed upon sugar or; (5) Kill immature mosquitoes in aquatic habitats. To date, none of these options has sufficient supporting evidence to justify full-scale programmatic implementation. Concerted investment in their rigorous selection, development and evaluation is required over the coming decade to enable control and, ultimately, elimination of residual malaria transmission. In the meantime, national programmes may assess options for addressing residual transmission under programmatic conditions through pilot studies with strong monitoring, evaluation and operational research components, similar to the Onchocerciasis Control Programme.
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              Malaria resurgence: a systematic review and assessment of its causes

              Background Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past. Methods A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance. Results The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance. Conclusions Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today’s successful malaria control programmes.
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                Author and article information

                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                2 March 2016
                March 2016
                2 March 2016
                : 14
                : 3
                : e1002380
                Affiliations
                [1 ]Liverpool School of Tropical Medicine, Liverpool, United Kingdom
                [2 ]Malaria Elimination Initiative, Global Health Group, University of California, San Francisco, San Francisco, California, United States of America
                [3 ]Medicines for Malaria Venture, Geneva, Switzerland
                [4 ]Global Good Fund and Intellectual Ventures Laboratory, Bellevue, Washington, United States of America
                [5 ]Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Center, University of Bamako, Bamako, Mali
                [6 ]Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, United States of America
                [7 ]Jiangsu Institute of Parasitic Diseases, Meiyuan, Wuxi, Jiangsu, People’s Republic of China
                Author notes

                The authors have declared that no competing interests exist.

                Article
                PBIOLOGY-D-15-01924
                10.1371/journal.pbio.1002380
                4774904
                26934361
                d9137a87-ee74-4c3d-90a4-725194f566ba
                © 2016 Hemingway et al

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

                History
                Page count
                Figures: 1, Tables: 3, Pages: 14
                Funding
                The Article Processing Charges for this paper were funded by The Bill & Melinda Gates Foundation, who also provided funding for a commissioning fee of $2,000. The Bill & Melinda Gates Foundation had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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