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As governments and the global malaria community seek to achieve these goals, their efforts should be informed by the substantial past experiences of other disease elimination and eradication programmes, including that of the only successful eradication programme of a human pathogen to date: smallpox.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A review of smallpox literature was conducted to evaluate how the smallpox programme addressed seven challenges that will likely confront malaria eradication efforts, including fostering international support for the eradication undertaking, coordinating programmes and facilitating research across the world\u2019s endemic countries, securing sufficient funding, building domestic support for malaria programmes nationally, ensuring strong community support, identifying the most effective programmatic strategies, and managing national elimination programmes efficiently.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Review of 118 publications describing how smallpox programmes overcame these challenges suggests eradication may succeed as a collection of individual country programmes each deriving local solutions to local problems, yet with an important role for the World Health Organization and other international entities to facilitate and coordinate these efforts and encourage new innovations. Publications describing the smallpox experience suggest the importance of avoiding burdensome bureaucracy while employing flexible, problem-solving staff with both technical and operational backgrounds to overcome numerous unforeseen challenges. Smallpox\u2019s hybrid strategy of leveraging basic health services while maintaining certain separate functions to ensure visibility, clear targets, and strong management, aligns with current malaria approaches. Smallpox eradication succeeded by employing data-driven strategies that targeted resources to the places where they were most needed rather than attempting to achieve mass coverage everywhere, a potentially useful lesson for malaria programmes seeking universal coverage with available tools. Finally, lessons from smallpox programmes suggest strong engagement with the private sector and affected communities can help increase the sustainability and reach of today\u2019s malaria programmes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>It remains unclear whether malaria eradication is feasible, but neither was it clear whether smallpox eradication was feasible until it was achieved. To increase chances of success, malaria programmes should seek to strengthen programme management, measurement, and operations, while building flexible means of sharing experiences, tools, and financing internationally.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12936-019-2956-y","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T12:02:46Z","timestamp":1569240166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["\u201cRemarkable solutions to impossible problems\u201d: lessons for malaria from the eradication of smallpox"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4481-6784","authenticated-orcid":false,"given":"Justin M.","family":"Cohen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,23]]},"reference":[{"key":"2956_CR1","unstructured":"WHO. 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