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      Efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials

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          Abstract

          Background

          Emergence of Plasmodium falciparum resistance to artemisinin and its derivatives poses a threat to the global effort to control malaria. The emergence of anti-malarial resistance has become a great public health challenge and continues to be a leading threat to ongoing malaria control efforts. The aim of this review was to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria among children in Africa.

          Methods

          A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Central Register of Controlled Trials’ database (CENTRAL) for retrieving randomized control trials comparing efficacy of DHA-PQ and AL for treatment of uncomplicated falciparum malaria in African children. The search was performed from August 2020 to April 2021. Using Rev-Man software (V5.4.1), R-studio and Comprehensive Meta-analysis software version 3, the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI).

          Results

          In this review, 25 studies which involved a total of 13,198 participants were included. PCR-unadjusted treatment failure in children aged between 6 months and 15 years was significantly lower in the DHA-PQ treatment arm on day 28 than that of AL (RR 0.14, 95% CI 0.08–0.26; participants = 1302; studies = 4; I 2 = 0%, high quality of evidence). Consistently, the PCR-adjusted treatment failure was significantly lower with DHA-PQ treatment group on day 28 (RR 0.45, 95% CI 0.29–0.68; participants = 8508; studies = 16; I 2 = 51%, high quality of evidence) and on day 42 (RR 0.60, 95% CI 0.47–0.78; participants = 5959; studies = 17; I 2 = 0%, high quality of evidence). However, the efficacy was ≥ 95% in both treatment groups on day 28.

          Conclusion

          From this review, it can be concluded that DHA-PQ reduces new infection and recrudescence on days 28 and 42 more than AL. This may trigger DHA-PQ to become a first-line treatment option.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12936-021-03873-1.

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          Most cited references57

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            Outlier and influence diagnostics for meta-analysis.

            The presence of outliers and influential cases may affect the validity and robustness of the conclusions from a meta-analysis. While researchers generally agree that it is necessary to examine outlier and influential case diagnostics when conducting a meta-analysis, limited studies have addressed how to obtain such diagnostic measures in the context of a meta-analysis. The present paper extends standard diagnostic procedures developed for linear regression analyses to the meta-analytic fixed- and random/mixed-effects models. Three examples are used to illustrate the usefulness of these procedures in various research settings. Issues related to these diagnostic procedures in meta-analysis are also discussed. Copyright © 2010 John Wiley & Sons, Ltd.
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              GRADE guidelines 6. Rating the quality of evidence--imprecision.

              GRADE suggests that examination of 95% confidence intervals (CIs) provides the optimal primary approach to decisions regarding imprecision. For practice guidelines, rating down the quality of evidence (i.e., confidence in estimates of effect) is required if clinical action would differ if the upper versus the lower boundary of the CI represented the truth. An exception to this rule occurs when an effect is large, and consideration of CIs alone suggests a robust effect, but the total sample size is not large and the number of events is small. Under these circumstances, one should consider rating down for imprecision. To inform this decision, one can calculate the number of patients required for an adequately powered individual trial (termed the "optimal information size" [OIS]). For continuous variables, we suggest a similar process, initially considering the upper and lower limits of the CI, and subsequently calculating an OIS. Systematic reviews require a somewhat different approach. If the 95% CI excludes a relative risk (RR) of 1.0, and the total number of events or patients exceeds the OIS criterion, precision is adequate. If the 95% CI includes appreciable benefit or harm (we suggest an RR of under 0.75 or over 1.25 as a rough guide) rating down for imprecision may be appropriate even if OIS criteria are met. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                dawit.getachew@aau.edu.et
                Journal
                Malar J
                Malar J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                12 August 2021
                12 August 2021
                2021
                : 20
                : 340
                Affiliations
                [1 ]GRID grid.7123.7, ISNI 0000 0001 1250 5688, Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, , Addis Ababa University, ; Addis Ababa, Ethiopia
                [2 ]GRID grid.472268.d, ISNI 0000 0004 1762 2666, Department of Nursing, College of Health Science and Medicine, , Dilla University, ; Dilla, Ethiopia
                [3 ]GRID grid.7123.7, ISNI 0000 0001 1250 5688, Department of Pharmacology and Clinical Pharmacy, College of Health Sciences, , Addis Ababa University, ; Addis Ababa, Ethiopia
                Author information
                http://orcid.org/0000-0002-9951-5762
                Article
                3873
                10.1186/s12936-021-03873-1
                8359548
                34384431
                2cbe09af-3ca2-4ff8-a939-74d823f92867
                © The Author(s) 2021

                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
                : 16 July 2021
                : 3 August 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100007941, addis ababa university;
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Infectious disease & Microbiology
                uncomplicated plasmodium falciparum,children,randomized control trial,artemisinin combination therapy,dihydroartemisinin-piperaquine,artemether-lumefantrine,systematic review and meta-analysis,africa

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