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      Healthcare professionals’ perspective can guide post-marketing surveillance of artemisinin-based combination therapy in Uganda

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          Abstract

          Background

          Efficient testing to identify poor quality artemisinin-based combination therapy (ACT) is important to optimize efforts to control and eliminate malaria. Healthcare professionals interact with both ACT and malaria patients they treat and hence could observe, first-hand, suspect poor quality artemisinin-based combinations linked to poor malaria treatment outcomes and the factors associated with inappropriate use or treatment failure.

          Methods

          A cross-sectional study of 685 HCP perspectives about the efficacy of ACT between June and July 2018 at selected health facilities in Uganda. Medicine samples were obtained from the seven regions of Uganda and tested for quality using the Germany Pharma Health Fund™ minilabs.

          Results

          The average age of the 685 respondents was 30 (SD = 7.4) years. There was an almost equal distribution between male and female respondents (51:49), respectively. Seventy percent (n = 480) were diploma holders and the nurses contributed to half (49%, n = 334) of the study population. Sixty-one percent of the HCPs reported having ever encountered ACT failures while treating uncomplicated malaria. Nineteen percent of HCPs thought that dihydroartemisinin/piperaquine gave the most satisfactory patient treatment outcomes, while 80% HCPs thought that artemether/lumefantrine gave the least satisfactory patient treatment outcomes, possibly due to dosing schedule and pill burden. Healthcare professionals from the Central region (OR = 3.0, CI 0.3–1.0; P = 0.0001), Eastern region (OR = 5.4, CI 2.9–9.8; P = 0.0001) and Northern region (OR = 5.3, CI 2.9–9.9; P = 0.0001) had a higher chance of encountering ACT failure in 4 weeks prior to the survey as compared to those from the western region. Healthcare professionals from private health facilities also had higher chances of encountering ACT failures in past 4 weeks as compared to those from public health facilities (OR = 2.7, CI 1.7–3.9; P = 0.0001). All 192 samples passed the quality screening tests. The random sample of 10% of all samples randomly obtained by the laboratory staff also passed the chemical content analysis and dissolution tests.

          Conclusion

          ACT medicines are widely available over-the-counter to the public and it is very difficult to report and monitor a decrease in efficacy or treatment failure. The perspectives of HCPs on treatment failure or lack of efficacy may potentially guide optimization efforts of sampling methodologies for the quality survey of ACT medicines.

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          Most cited references23

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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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            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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              The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread

              Abstract Artemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria, and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability profile is excellent. Unfortunately, Plasmodium falciparum infections with mutations in the ‘K13’ gene, with reduced ring-stage susceptibility to artemisinins, and slow parasite clearance in patients treated with ACTs, are now widespread in Southeast Asia. We review clinical efficacy data from the region (2000–2015) that provides strong evidence that the loss of first-line ACTs in western Cambodia, first artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to K13 mutated parasites. The ring-stage activity of artemisinins is therefore critical for the sustained efficacy of ACTs; once it is lost, rapid selection of partner drug resistance and ACT failure are inevitable consequences. Consensus methods for monitoring artemisinin resistance are now available. Despite increased investment in regional control activities, ACTs are failing across an expanding area of the Greater Mekong subregion. Although multiple K13 mutations have arisen independently, successful multidrug-resistant parasite genotypes are taking over and threaten to spread to India and Africa. Stronger containment efforts and new approaches to sustaining long-term efficacy of antimalarial regimens are needed to prevent a global malaria emergency.
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                Author and article information

                Contributors
                hndagije@nda.or.ug
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                10 February 2020
                10 February 2020
                2020
                : 19
                : 63
                Affiliations
                [1 ]National Pharmacovigilance Centre, National Drug Authority, Kampala, Uganda
                [2 ]GRID grid.11194.3c, ISNI 0000 0004 0620 0548, Department of Pharmacology and Therapeutics, , Makerere University, ; Kampala, Uganda
                [3 ]Pharmacovigilance Consulting, Uppsala, Sweden
                [4 ]GRID grid.7942.8, ISNI 0000 0001 2294 713X, Institute of Health and Society (IRSS), , Université catholique de Louvain, ; Brussels, Belgium
                Author information
                http://orcid.org/0000-0001-5802-4791
                Article
                3148
                10.1186/s12936-020-3148-5
                7011371
                32041619
                507d942f-a0f7-4d1c-aff0-0d2fb579935e
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 30 September 2019
                : 30 January 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Infectious disease & Microbiology
                healthcare professional perspectives,artemisinin-based combination therapy,perceived treatment failure

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