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      Low and heterogeneous prevalence of glucose-6-phosphate dehydrogenase deficiency in different settings in Ethiopia using phenotyping and genotyping approaches

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          Abstract

          Background

          8-Aminoquinolines such as primaquine clear mature Plasmodium falciparum gametocytes that are responsible for transmission from human to mosquitoes and bring radical cure in Plasmodium vivax by clearing dormant liver stages. Deployment of primaquine is thus of relevance for malaria elimination efforts but challenged by the widespread prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd) in endemic countries since primaquine in G6PDd individuals may lead to acute haemolysis. In this study, the prevalence of G6PDd was investigated in different settings in Ethiopia using phenotyping and genotyping approaches.

          Methods

          Community and school based cross-sectional surveys were conducted from October to December 2016 in four administrative regions (Gambela, Benishangul Gumuz, Oromia, and Amhara) in Ethiopia. Finger prick blood samples were collected for G6PD enzyme activity using the CareStart™ G6PD screening test and genotyping of 36 selected single nucleotide polymorphisms (SNPs) located in the G6PD gene and its flanking regions.

          Results

          Overall, the prevalence of phenotypic G6PDd was 1.4% (22/1609). For the first time in the Ethiopian population, the African variant (A−) was detected in 3.5% (7/199) of the limited set of genotyped samples, which were all phenotypically normal. Interestingly, all of these individuals had a variation at the rs2515904 locus. Strong geographical variation was observed for both phenotypic and genotypic G6PDd; three-quarters of the phenotypically G6PDd individuals were detected in Gambela.

          Conclusion

          A very low prevalence of G6PDd was detected in the present study populations. The presence of the A− variant alongside other G6PD mutants and the patchy distribution of G6PDd indicate that larger studies specifically designed to unravel the distribution of G6PDd at small geographical scale may be needed to tailor malaria elimination efforts in Ethiopia to the local context.

          Electronic supplementary material

          The online version of this article (10.1186/s12936-018-2437-8) contains supplementary material, which is available to authorized users.

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          Most cited references47

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          Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination.

          Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.
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            The Relative Contribution of Symptomatic and Asymptomatic Plasmodium vivax and Plasmodium falciparum Infections to the Infectious Reservoir in a Low-Endemic Setting in Ethiopia

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              G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

              Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide. Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug. In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure.
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                Author and article information

                Contributors
                +251912627540 , fitsum.tadesse@radboudumc.nl , fitsum.girma@aau.edu.et
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                2 August 2018
                2 August 2018
                2018
                : 17
                : 281
                Affiliations
                [1 ]ISNI 0000 0004 0439 5951, GRID grid.442845.b, Department of Biomedical Sciences, School of Medical Sciences, , Bahir Dar University, ; Bahir Dar, Ethiopia
                [2 ]ISNI 0000 0000 4319 4715, GRID grid.418720.8, Armauer Hansen Research Institute (AHRI), ; Addis Ababa, Ethiopia
                [3 ]ISNI 0000 0004 0425 469X, GRID grid.8991.9, Department of Immunology and Infection, , London School of Hygiene and Tropical Medicine, ; London, UK
                [4 ]ISNI 0000 0004 4914 796X, GRID grid.472465.6, Department of Biomedical Sciences, School of Medical Sciences, , Wolkite University, ; Wolkite, Ethiopia
                [5 ]ISNI 0000 0004 4684 7098, GRID grid.459905.4, Department of Biomedical Sciences, , Semera University, ; Semera, Ethiopia
                [6 ]Genomics Division, LGC Group ltd, Hertfordshire, UK
                [7 ]ISNI 0000 0001 1250 5688, GRID grid.7123.7, Department of Microbial, Cellular and Molecular Biology, College of Natural Sciences, , Addis Ababa University, ; Addis Ababa, Ethiopia
                [8 ]ISNI 0000 0001 1250 5688, GRID grid.7123.7, Department of Biochemistry, School of Medical Sciences, , Addis Ababa University, ; Addis Ababa, Ethiopia
                [9 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Radboud Institute for Health Sciences, , Radboud University Medical Centre, ; Nijmegen, The Netherlands
                [10 ]ISNI 0000 0001 1250 5688, GRID grid.7123.7, Institute of Biotechnology, , Addis Ababa University, ; PO Box 109, Addis Ababa, Ethiopia
                Article
                2437
                10.1186/s12936-018-2437-8
                6071387
                30071859
                8f319192-959e-46aa-b5ba-68b5c9a80ab5
                © The Author(s) 2018

                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
                : 22 June 2018
                : 30 July 2018
                Funding
                Funded by: Netherlands Organization for Scientific Research
                Award ID: 016.158.306
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: ERC-2014-StG 639776
                Award Recipient :
                Funded by: Bill & Melinda Gates foundation
                Award ID: OP P1173572
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001718, Netherlands Organization for International Cooperation in Higher Education;
                Award ID: NFP-PhD.14/150
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Infectious disease & Microbiology
                radical cure,p. vivax,g6pd,8-aminoquinoline,haemolysis
                Infectious disease & Microbiology
                radical cure, p. vivax, g6pd, 8-aminoquinoline, haemolysis

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