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      Development of an agent-based model to assess the impact of substandard and falsified anti-malarials: Uganda case study

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          Abstract

          Background

          Global efforts to address the burden of malaria have stagnated in recent years with malaria cases beginning to rise. Substandard and falsified anti-malarial treatments contribute to this stagnation. Poor quality anti-malarials directly affect health outcomes by increasing malaria morbidity and mortality, as well as threaten the effectiveness of treatment by contributing to artemisinin resistance. Research to assess the scope and impact of poor quality anti-malarials is essential to raise awareness and allocate resources to improve the quality of treatment. A probabilistic agent-based model was developed to provide country-specific estimates of the health and economic impact of poor quality anti-malarials on paediatric malaria. This paper presents the methodology and case study of the Substandard and Falsified Antimalarial Research Impact (SAFARI) model developed and applied to Uganda.

          Results

          The total annual economic impact of malaria in Ugandan children under age five was estimated at US$614 million. Among children who sought medical care, the total economic impact was estimated at $403 million, including $57.7 million in direct costs. Substandard and falsified anti-malarials were a significant contributor to this annual burden, accounting for $31 million (8% of care-seeking children) in total economic impact involving $5.2 million in direct costs. Further, 9% of malaria deaths relating to cases seeking treatment were attributable to poor quality anti-malarials. In the event of widespread artemisinin resistance in Uganda, we simulated a 12% yearly increase in costs associated with paediatric malaria cases that sought care, inflicting $48.5 million in additional economic impact annually.

          Conclusions

          Improving the quality of treatment is essential to combat the burden of malaria and prevent the development of drug resistance. The SAFARI model provides country-specific estimates of the health and economic impact of substandard and falsified anti-malarials to inform governments, policy makers, donors and the malaria community about the threat posed by poor quality medicines. The model findings are useful to illustrate the significance of the issue and inform policy and interventions to improve medicinal quality.

          Electronic supplementary material

          The online version of this article (10.1186/s12936-018-2628-3) contains supplementary material, which is available to authorized users.

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          Most cited references47

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          Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa.

          Poor-quality antimalarial drugs lead to drug resistance and inadequate treatment, which pose an urgent threat to vulnerable populations and jeopardise progress and investments in combating malaria. Emergence of artemisinin resistance or tolerance in Plasmodium falciparum on the Thailand-Cambodia border makes protection of the effectiveness of the drug supply imperative. We reviewed published and unpublished studies reporting chemical analyses and assessments of packaging of antimalarial drugs. Of 1437 samples of drugs in five classes from seven countries in southeast Asia, 497 (35%) failed chemical analysis, 423 (46%) of 919 failed packaging analysis, and 450 (36%) of 1260 were classified as falsified. In 21 surveys of drugs from six classes from 21 countries in sub-Saharan Africa, 796 (35%) of 2297 failed chemical analysis, 28 (36%) of 77 failed packaging analysis, and 79 (20%) of 389 were classified as falsified. Data were insufficient to identify the frequency of substandard (products resulting from poor manufacturing) antimalarial drugs, and packaging analysis data were scarce. Concurrent interventions and a multifaceted approach are needed to define and eliminate criminal production, distribution, and poor manufacturing of antimalarial drugs. Empowering of national medicine regulatory authorities to protect the global drug supply is more important than ever. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            The economic burden of malaria

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              Prevalence and Estimated Economic Burden of Substandard and Falsified Medicines in Low- and Middle-Income Countries

              Key Points Question What are the prevalence and estimated economic burden of substandard and falsified medicines in low- and middle-income countries? Findings In this systematic review of 265 studies comprising 400 647 drug samples and meta-analysis of 96 studies comprising 67 839 drug samples, the prevalence of substandard and falsified medicines in low- and middle-income countries was 13.6% overall (19.1% for antimalarials and 12.4% for antibiotics). Data on the estimated economic impact were limited primarily to market size and ranged widely from $10 billion to $200 billion. Meaning Substandard and falsified medicines are a substantial health and economic problem; a concerted global effort is needed to secure the global supply chain, increase quality control capacity, and improve surveillance to better assess the problem and identify solutions.
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                Author and article information

                Contributors
                919-966-2626 , ozawa@unc.edu
                daniel.r.evans@duke.edu
                collhigg@unc.edu
                sklaing@unc.edu
                pawor@musph.ac.ug
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                9 January 2019
                9 January 2019
                2019
                : 18
                : 5
                Affiliations
                [1 ]ISNI 0000 0001 1034 1720, GRID grid.410711.2, Division of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, , University of North Carolina, ; CB#7574, Beard Hall 115H, Chapel Hill, NC 27599 USA
                [2 ]ISNI 0000 0001 1034 1720, GRID grid.410711.2, Department of Maternal and Child Health, UNC Gillings School of Global Public Health, , University of North Carolina, ; Chapel Hill, NC USA
                [3 ]ISNI 0000 0004 1936 7961, GRID grid.26009.3d, Duke University School of Medicine, ; Durham, NC USA
                [4 ]Department of Community Health and Behavioural Sciences, Makarere University School of Public Health, Kampala, Uganda
                Author information
                http://orcid.org/0000-0001-7608-9038
                Article
                2628
                10.1186/s12936-018-2628-3
                6327614
                30626380
                4040597a-7c34-45d5-afb2-cfd3c0c6a233
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 May 2018
                : 13 December 2018
                Categories
                Methodology
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                antimalarial,quality,substandard,falsified,agent-based model,uganda
                Infectious disease & Microbiology
                antimalarial, quality, substandard, falsified, agent-based model, uganda

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