{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T01:43:31Z","timestamp":1772502211219,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.15700.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T00:00:00Z","timestamp":1598313600000}}],"reference-count":75,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T00:00:00Z","timestamp":1598313600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002992","name":"Department for International Development, UK Government","doi-asserted-by":"publisher","award":["204139"],"award-info":[{"award-number":["204139"]}],"id":[{"id":"10.13039\/501100002992","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust","award":["A150007, 096527, 200344"],"award-info":[{"award-number":["A150007, 096527, 200344"]}]},{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","award":["OPP1107113"],"award-info":[{"award-number":["OPP1107113"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>Safe access to the most effective treatment options for\u00a0<ns4:italic>Plasmodium vivax<\/ns4:italic>\u00a0malaria are limited by the absence of accurate point-of-care testing\u00a0to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against\u00a0<ns4:italic>P. vivax\u00a0<\/ns4:italic>hypnozoites. Until recently, only qualitative tests were available in most settings. These can identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female).\u00a0This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females\u2014who, unlike males, can have a heterozygous genotype for G6PD.\u00a0Increasing recognition of the need for radical cure of\u00a0\u00a0<ns4:italic>P. vivax<\/ns4:italic>, first for patients\u2019 health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of user-friendly, affordable, and accurate quantitative point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members.<\/ns4:p>","DOI":"10.12688\/wellcomeopenres.15700.2","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T07:55:05Z","timestamp":1598342105000},"page":"21","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Optimizing G6PD testing for Plasmodium vivax case management and beyond: why sex, counseling, and community engagement matter"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-8214","authenticated-orcid":false,"given":"Cindy S","family":"Chu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-0431","authenticated-orcid":false,"given":"Germana","family":"Bancone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Kelley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Advani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1004-4395","authenticated-orcid":false,"given":"Gonzalo J","family":"Domingo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva M","family":"Cutiongo-de la Paz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"van der Merwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3719-3892","authenticated-orcid":false,"given":"Emily","family":"Gerth-Guyette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"133-201","DOI":"10.1016\/B978-0-12-407826-0.00004-7","article-title":"G6PD deficiency: global distribution, genetic variants and primaquine therapy.","volume":"81","author":"R Howes","year":"2013","journal-title":"Adv Parasitol."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"373-93","DOI":"10.1016\/j.hoc.2015.11.006","article-title":"Glucose-6-Phosphate Dehydrogenase Deficiency.","volume":"30","author":"L Luzzatto","year":"2016","journal-title":"Hematol Oncol Clin North Am."},{"key":"ref-3","article-title":"World Malaria Report 2018","year":"2018"},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"e1001339","DOI":"10.1371\/journal.pmed.1001339","article-title":"G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map.","volume":"9","author":"R Howes","year":"2012","journal-title":"PLoS Med."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"15-34","DOI":"10.4269\/ajtmh.16-0141","article-title":"Global Epidemiology of Plasmodium vivax.","volume":"95","author":"R Howes","year":"2016","journal-title":"Am J Trop Med Hyg."},{"key":"ref-6","article-title":"Control and elimination of Plasmodium vivax malaria\u2014a technical brief","year":"2015"},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"e1001891","DOI":"10.1371\/journal.pmed.1001891","article-title":"Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model.","volume":"12","author":"L Robinson","year":"2015","journal-title":"PLoS Med."},{"key":"ref-8","article-title":"Guidelines for the treatment of malaria","year":"2015"},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"e1002224","DOI":"10.1371\/journal.pmed.1002224","article-title":"Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens.","volume":"14","author":"C Chu","year":"2017","journal-title":"PLoS Med."},{"key":"ref-10","doi-asserted-by":"publisher","DOI":"10.1093\/jtm\/taz023","article-title":"Tafenoquine and G6PD: a primer for clinicians.","volume":"26","author":"C Chu","year":"2019","journal-title":"J Travel Med."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"215-228","DOI":"10.1056\/NEJMoa1710775","article-title":"Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.","volume":"380","author":"M Lacerda","year":"2019","journal-title":"N Engl J Med."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"229-241","DOI":"10.1056\/NEJMoa1802537","article-title":"Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria.","volume":"380","author":"A Llanos-Cuentas","year":"2019","journal-title":"N Engl J Med."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"702-711","DOI":"10.4269\/ajtmh.16-0779","article-title":"Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers.","volume":"97","author":"R Rueangweerayut","year":"2017","journal-title":"Am J Trop Med Hyg."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"e400-1","DOI":"10.1016\/S2352-3026(15)00191-X","article-title":"G6PD deficiency: a polymorphism balanced by heterozygote advantage against malaria.","volume":"2","author":"L Luzzatto","year":"2015","journal-title":"Lancet Haematol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"7-14","DOI":"10.1093\/inthealth\/ihy060","article-title":"Addressing the gender-knowledge gap in glucose-6-phosphate dehydrogenase deficiency: challenges and opportunities.","volume":"11","author":"G Domingo","year":"2019","journal-title":"Int Health."},{"key":"ref-16","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-391","article-title":"G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests.","volume":"12","author":"G Domingo","year":"2013","journal-title":"Malar J."},{"key":"ref-17","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-112","article-title":"Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report.","volume":"12","author":"L von Seidlein","year":"2013","journal-title":"Malar J."},{"key":"ref-18","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-018-2248-y","article-title":"Primaquine-induced haemolysis in females heterozygous for G6PD deficiency.","volume":"17","author":"C Chu","year":"2018","journal-title":"Malar J."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"929-938","DOI":"10.1016\/S0140-6736(19)31285-1","article-title":"Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial.","volume":"394","author":"W Taylor","year":"2019","journal-title":"Lancet."},{"key":"ref-20","doi-asserted-by":"publisher","DOI":"10.5694\/mja2.50426","article-title":"Sex and gender in health research: updating policy to reflect evidence.","year":"2019","journal-title":"Med J Aust."},{"key":"ref-21","doi-asserted-by":"crossref","first-page":"821-5","DOI":"10.1093\/genetics\/152.3.821","article-title":"Hardy, Weinberg and language impediments.","volume":"152","author":"J Crow","year":"1999","journal-title":"Genetics."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"72","DOI":"10.12688\/wellcomeopenres.12338.2","article-title":"Prevalences of inherited red blood cell disorders in pregnant women of different ethnicities living along the Thailand-Myanmar border [version 2; peer review: 2 approved].","volume":"2","author":"G Bancone","year":"2017","journal-title":"Wellcome Open Res."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"1135-1137","DOI":"10.1002\/ccr3.714","article-title":"Glucose-6-phosphate dehydrogenase deficiency: not exclusively in males.","volume":"4","author":"L van den Broek","year":"2016","journal-title":"Clin Case Rep."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3390\/ijns4040034","article-title":"Point-of-Care Testing for G6PD Deficiency: Opportunities for Screening.","volume":"4","author":"A Anderle","year":"2018","journal-title":"Int J Neonatal Screen."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"68-74","DOI":"10.1542\/peds.104.1.68","article-title":"Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes.","volume":"104","author":"M Kaplan","year":"1999","journal-title":"Pediatrics."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"137-40","DOI":"10.1067\/mpd.2001.115312","article-title":"Acute hemolysis and severe neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes.","volume":"139","author":"M Kaplan","year":"2001","journal-title":"J Pediatr."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"191-6.e1","DOI":"10.1016\/j.jpeds.2012.02.018","article-title":"Glucose-6-phosphate dehydrogenase deficiency and borderline deficiency: association with neonatal hyperbilirubinemia.","volume":"161","author":"A Riskin","year":"2012","journal-title":"J Pediatr."},{"key":"ref-28","first-page":"62-7","article-title":"Comparison of detection of glucose-6-phosphate dehydrogenase deficiency using fluorescent spot test, enzyme assay and molecular method for prediction of severe neonatal hyperbilirubinaemia.","volume":"50","author":"F Wang","year":"2009","journal-title":"Singapore Med J."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"e6682","DOI":"10.1371\/journal.pone.0006682","article-title":"Chlorproguanil-dapsone-artesunate versus artemether-lumefantrine: a randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria.","volume":"4","author":"Z Premji","year":"2009","journal-title":"PLoS One."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"969-78","DOI":"10.4269\/ajtmh.2009.09-0351","article-title":"Chlorproguanil-dapsone-artesunate versus chlorproguanil-dapsone: a randomized, double-blind, phase III trial in African children, adolescents, and adults with uncomplicated Plasmodium falciparum malaria.","volume":"81","author":"A Tiono","year":"2009","journal-title":"Am J Trop Med Hyg."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"4123-33","DOI":"10.1182\/blood-2012-03-416032","article-title":"Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone.","volume":"120","author":"A Pamba","year":"2012","journal-title":"Blood."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"217-8","DOI":"10.1111\/j.1365-2230.1994.tb01168.x","article-title":"Screening for glucose-6-phosphate dehydrogenase deficiency prior to dapsone therapy.","volume":"19","author":"P Todd","year":"1994","journal-title":"Clin Exp Dermatol."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"169-74","DOI":"10.1038\/clpt.2014.97","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype.","volume":"96","author":"M Relling","year":"2014","journal-title":"Clin Pharmacol Ther."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"305-314","DOI":"10.1038\/s41397-018-0043-3","article-title":"Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and phenotype and rasburicase use in patients with hematologic malignancies.","volume":"19","author":"K Robinson","year":"2019","journal-title":"Pharmacogenomics J."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"9822","DOI":"10.1038\/s41598-017-10045-2","article-title":"The G6PD flow-cytometric assay is a reliable tool for diagnosis of G6PD deficiency in women and anaemic subjects.","volume":"7","author":"G Bancone","year":"2017","journal-title":"Sci Rep."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"294-303","DOI":"10.1111\/ejh.13013","article-title":"Cytochemical flow analysis of intracellular G6PD and aggregate analysis of mosaic G6PD expression.","volume":"100","author":"M Kalnoky","year":"2018","journal-title":"Eur J Haematol."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"1003-11","DOI":"10.1369\/jhc.2009.953828","article-title":"Glucose-6-phosphate dehydrogenase deficiency and malaria: cytochemical detection of heterozygous G6PD deficiency in women.","volume":"57","author":"A Peters","year":"2009","journal-title":"J Histochem Cytochem."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"e0006230","DOI":"10.1371\/journal.pntd.0006230","article-title":"Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: Divergent policies and practices in malaria endemic countries.","volume":"12","author":"J Recht","year":"2018","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"1440-1442","DOI":"10.1093\/cid\/ciz122","article-title":"Clinical Spectrum of Primaquine-induced Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficiency: A 9-Year Hospitalization-based Study From the Brazilian Amazon.","volume":"69","author":"J Brito-Sousa","year":"2019","journal-title":"Clin Infect Dis."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"1311-1319","DOI":"10.1093\/cid\/ciy735","article-title":"Chloroquine Versus Dihydroartemisinin-Piperaquine With Standard High-dose Primaquine Given Either for 7 Days or 14 Days in Plasmodium vivax Malaria.","volume":"68","author":"C Chu","year":"2019","journal-title":"Clin Infect Dis."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s12916-019-1386-6","article-title":"The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.","volume":"17","author":"R Commons","year":"2019","journal-title":"BMC Med."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"367-73","DOI":"10.18926\/AMO\/41322","article-title":"Incidence and mutation analysis of glucose-6-phosphate dehydrogenase deficiency in eastern Indonesian populations.","volume":"64","author":"I Tantular","year":"2010","journal-title":"Acta Med Okayama."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"e0206331","DOI":"10.1371\/journal.pone.0206331","article-title":"Field evaluation of quantitative point of care diagnostics to measure glucose-6-phosphate dehydrogenase activity.","volume":"13","author":"M Alam","year":"2018","journal-title":"PLoS One."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"213-221","DOI":"10.4269\/ajtmh.18-0612","article-title":"Evaluation of a Novel Quantitative Test for Glucose-6-Phosphate Dehydrogenase Deficiency: Bringing Quantitative Testing for Glucose-6-Phosphate Dehydrogenase Deficiency Closer to the Patient.","volume":"100","author":"S Pal","year":"2019","journal-title":"Am J Trop Med Hyg."},{"key":"ref-45","first-page":"601-11","article-title":"Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group.","volume":"67","year":"1989","journal-title":"Bull World Health Organ."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"63-7","DOI":"10.1159\/000113463","article-title":"Management of jaundice and prevention of severe neonatal hyperbilirubinemia in infants >or=35 weeks gestation.","volume":"94","author":"V Bhutani","year":"2008","journal-title":"Neonatology."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"341-54","DOI":"10.1016\/j.clp.2016.01.010","article-title":"Glucose-6-Phosphate Dehydrogenase Deficiency and the Need for a Novel Treatment to Prevent Kernicterus.","volume":"43","author":"A Cunningham","year":"2016","journal-title":"Clin Perinatol."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"148-56","DOI":"10.1016\/j.siny.2009.10.007","article-title":"Glucose-6-phosphate dehydrogenase deficiency and severe neonatal hyperbilirubinemia: a complexity of interactions between genes and environment.","volume":"15","author":"M Kaplan","year":"2010","journal-title":"Semin Fetal Neonatal Med."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"1102-9","DOI":"10.1111\/apa.12735","article-title":"Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose-6-phosphate dehydrogenase deficiency.","volume":"103","author":"B Olusanya","year":"2014","journal-title":"Acta Paediatr."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12887-015-0358-z","article-title":"Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.","volume":"15","author":"B Olusanya","year":"2015","journal-title":"BMC Pediatr."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"29-31","DOI":"10.1159\/000204709","article-title":"Marked decline of favism after neonatal glucose-6-phosphate dehydrogenase screening and health education: the northern Sardinian experience.","volume":"87","author":"T Meloni","year":"1992","journal-title":"Acta Haematol."},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/s41598-017-17667-6","article-title":"Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates.","volume":"8","author":"C Fu","year":"2018","journal-title":"Sci Rep."},{"key":"ref-53","doi-asserted-by":"publisher","first-page":"183-197","DOI":"10.1038\/s41431-018-0252-x","article-title":"The Global State of the Genetic Counseling Profession.","volume":"27","author":"M Abacan","year":"2019","journal-title":"Eur J Hum Genet."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1472-6939-14-41","article-title":"Consulting communities on feedback of genetic findings in international health research: sharing sickle cell disease and carrier information in coastal Kenya.","volume":"14","author":"V Marsh","year":"2013","journal-title":"BMC Med Ethics."},{"key":"ref-55","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0090-9","article-title":"Ethical, social, and cultural issues related to clinical genetic testing and counseling in low- and middle-income countries: a systematic review.","author":"A Zhong","year":"2018","journal-title":"Genet Med."},{"key":"ref-56","doi-asserted-by":"publisher","first-page":"195-202","DOI":"10.1007\/s12687-016-0267-3","article-title":"Community engagement to inform the development of a sickle cell counselor training and certification program in Ghana.","volume":"7","author":"K Anie","year":"2016","journal-title":"J Community Genet."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"23-34","DOI":"10.1007\/s12687-016-0284-2","article-title":"Leaves imitate trees: Minnesota Hmong concepts of heredity and applications to genomics research.","volume":"8","author":"K Culhane-Pera","year":"2017","journal-title":"J Community Genet."},{"key":"ref-58","doi-asserted-by":"publisher","first-page":"117-125","DOI":"10.1007\/s12687-017-0292-x","article-title":"Engaging Hmong adults in genomic and pharmacogenomic research: Toward reducing health disparities in genomic knowledge using a community-based participatory research approach.","volume":"8","author":"K Culhane-Pera","year":"2017","journal-title":"J Community Genet."},{"key":"ref-59","doi-asserted-by":"publisher","first-page":"2333794x16637767","DOI":"10.1177\/2333794X16637767","article-title":"Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening.","volume":"3","author":"N Green","year":"2016","journal-title":"Glob Pediatr Health."},{"key":"ref-60","doi-asserted-by":"publisher","first-page":"221-7","DOI":"10.1159\/000363645","article-title":"Developing clinical cancer genetics services in resource-limited countries: the case of retinoblastoma in Kenya.","volume":"17","author":"L He","year":"2014","journal-title":"Public Health Genomics."},{"key":"ref-61","article-title":"Feasibility of a Community-Based Sickle Cell Trait Testing and Counseling Program.","volume":"9","author":"A Housten","year":"2016","journal-title":"J Health Dispar Res Pract."},{"key":"ref-62","doi-asserted-by":"publisher","first-page":"17-20","DOI":"10.1038\/s41588-019-0542-4","article-title":"Returning incidental findings in African genomics research.","volume":"52","author":"A Wonkam","year":"2020","journal-title":"Nat Genet."},{"key":"ref-63","doi-asserted-by":"publisher","first-page":"343-59","DOI":"10.1080\/13557858.2010.541903","article-title":"'All her children are born that way': gendered experiences of stigma in families affected by sickle cell disorder in rural Kenya.","volume":"16","author":"V Marsh","year":"2011","journal-title":"Ethn Health."},{"key":"ref-64","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1186\/s12936-015-0896-8","article-title":"The challenges of introducing routine G6PD testing into radical cure: a workshop report.","volume":"14","author":"B Ley","year":"2015","journal-title":"Malar J."},{"key":"ref-65","doi-asserted-by":"publisher","first-page":"121-8","DOI":"10.1159\/000113873","article-title":"Thalassaemia and glucose-6-phosphate dehydrogenase screening in 13- to 14-year-old students of the Sardinian population: preliminary findings.","volume":"11","author":"A Cao","year":"2008","journal-title":"Community Genet."},{"key":"ref-66","doi-asserted-by":"publisher","first-page":"S87-98","DOI":"10.1016\/j.amepre.2016.01.016","article-title":"Community Health Workers as Support for Sickle Cell Care.","volume":"51","author":"L Hsu","year":"2016","journal-title":"Am J Prev Med."},{"key":"ref-67","doi-asserted-by":"publisher","first-page":"e569-e570","DOI":"10.1016\/S2214-109X(17)30171-7","article-title":"Recognising the role of community-directed treatment and of women in the fight against NTDs.","volume":"5","author":"U Amazigo","year":"2017","journal-title":"Lancet Glob Health."},{"key":"ref-68","doi-asserted-by":"publisher","first-page":"340-347","DOI":"10.1016\/j.trstmh.2012.02.009","article-title":"Changes in stigma and discrimination of onchocerciasis in Africa.","volume":"106","author":"Y Tchounkeu","year":"2012","journal-title":"Trans R Soc Trop Med Hyg."},{"key":"ref-69","doi-asserted-by":"publisher","first-page":"e0005884","DOI":"10.1371\/journal.pntd.0005884","article-title":"Feasibility of utilizing the SD BIOLINE Onchocerciasis IgG4 rapid test in onchocerciasis surveillance in Senegal.","volume":"11","author":"Y Dieye","year":"2017","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-70","doi-asserted-by":"publisher","first-page":"25","DOI":"10.12688\/wellcomeopenres.15100.2","article-title":"The impact of using primaquine without prior G6PD testing: a case series describing the obstacles to the medical management of haemolysis.","volume":"4","author":"C Chu","year":"2019","journal-title":"Wellcome Open Res."},{"key":"ref-71","first-page":"149-55","article-title":"Neonatal jaundice. A second 4-year experience in Toa Payoh Hospital (1986-1989).","volume":"33","author":"N Ho","year":"1991","journal-title":"J Singapore Paediatr Soc."},{"key":"ref-72","doi-asserted-by":"crossref","first-page":"1003-9","DOI":"10.47102\/annals-acadmedsg.V36N12p1003","article-title":"Identifying risk of neonatal hyperbilirubinaemia and early discharge for glucose-6-phosphate dehydrogenase deficient newborns in Singapore.","volume":"36","author":"V Shah","year":"2007","journal-title":"Ann Acad Med Singapore."},{"key":"ref-73","doi-asserted-by":"publisher","first-page":"e0005602","DOI":"10.1371\/journal.pntd.0005602","article-title":"Using G6PD tests to enable the safe treatment of Plasmodium vivax infections with primaquine on the Thailand-Myanmar border: A cost-effectiveness analysis.","volume":"11","author":"A Devine","year":"2017","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-74","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12936-016-1140-x","article-title":"Cost-effectiveness analysis of rapid diagnostic tests for G6PD deficiency in patients with Plasmodium vivax malaria in the Brazilian Amazon.","volume":"15","author":"H Peixoto","year":"2016","journal-title":"Malar J."},{"key":"ref-75","doi-asserted-by":"publisher","first-page":"722-9","DOI":"10.4269\/ajtmh.14-0295","article-title":"G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic.","volume":"93","author":"J Xu","year":"2015","journal-title":"Am J Trop Med Hyg."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:43:10Z","timestamp":1696578190000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,25]]},"references-count":75,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.15700.2","relation":{},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,25]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17206.r39288, Chansuda Wongsrichanalai, Independent Consultant, Bangkok, Thailand, 15 Jul 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v1#referee-response-39288","order":0,"name":"referee-response-39288","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Cindy Chu<\/b>; <i>Posted: 06 Aug 2020<\/i>; We would like to thank Reviewer 1 for their constructive comments on this manuscript. <b>Reply:<\/b>&nbsp;In the abstract, we have changed the word \u201csimple\u201d to \u201c <i>user-friendly<\/i>\u201d. The issue of test simplicity is addressed in the 3 <sup>rd<\/sup>&nbsp;paragraph of the Cost effectiveness section. We have amended the last sentence to read \u201c <i>Introduction<\/i>&nbsp;in selected primary-level facilities&nbsp; <i>would depend on the ease of use by health care providers who deliver care at this level and is a considerable limitation to the implementation of quantitative G6PD testing in field settings<\/i>.\u201d &nbsp;We agree with the reviewer that getting the radical cure only to primary health care facilities may significantly curtail the percentage of patients who benefit.&nbsp;&nbsp;To reflect this, we have inserted into the \u2018Cost effectiveness of G6PD testing\u2019 section the sentence below. There are reasons beyond that of the complexity of G6PD testing (for example complexity of treatment algorithm) that may impose the need to consider alternative service delivery models. \u201c <i>Depending on country settings and health seeking behaviors, a significant proportion of malaria patients would still not have access to safe radical cure unless radical cure can be administered safely by village health workers. Alternative service delivery models would need to be investigated to extend the reach of 8-aminoquinolines will ensuring safety<\/i>\u201d.We agree with the reviewer that getting the radical cure only to primary health care facilities may significantly curtail the percentage of patients who benefit.&nbsp;&nbsp;To reflect this, we have inserted into the \u2018Cost effectiveness of G6PD testing\u2019 section the sentence below. There are reasons beyond that of the complexity of G6PD testing (for example complexity of treatment algorithm) that may impose the need to consider alternative service delivery models. \u201c <i>Depending on country settings and health seeking behaviors, a significant proportion of malaria patients would still not have access to safe radical cure unless radical cure can be administered safely by village health workers. Alternative service delivery models would need to be investigated to extend the reach of 8-aminoquinolines will ensuring safety<\/i>\u201d. <b>Reply:&nbsp;<\/b>This is a good point. We have introduced the following statement:&nbsp; <i>\u201cBecause efficacy of radical cure is highly related to completion of primaquine regimens, ensuring dose adherence will greatly enhance the cost effectiveness; this is less of a challenge with the single day regimen Kozenis. \u201c<\/i> <b>Reply:<\/b>&nbsp;It is true that the messaging that accompanies a new test should be clear and consistent to avoid misunderstanding by the user. From the authors\u2019 perspective a G6PD quantitative test could be used in any situation where a diagnosis of deficient, intermediate or normal G6PD deficiency would improve clinical management. For newborns the thresholds for defining these categories may be different (likely higher). While there is one near-patient instrument: Finder from Baebies,&nbsp;&nbsp;(https:\/\/baebies.com\/products\/finder\/) that seems to be indicated for this purpose, it is unlikely to be suitable for low resource settings. In agreement with the reviewers comment we have introduced the following statement: \u201c <i>Most point-of-care tests for G6PD deficiency are not currently indicated for use with neonates. Clinical studies to support this indication should be performed.\u201d<\/i> <b>Reply:<\/b>&nbsp;We have amended the sentence to include the Brazil and Thailand as countries that have registered tafenoquine. \u201cA new, single-dose radical cure for&nbsp; <i>Plasmodium vivax<\/i>, tafenoquine has received registration in Australia (Kozenis&reg;), the United States (Krintafel&reg;),&nbsp; <i>and more recently in Brazil and Thailand.<\/i>\u201d &nbsp;","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v2#referee-comment-4308","order":1,"name":"referee-comment-4308","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17206.r38264, Manoj Menon, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 28 Jul 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v1#referee-response-38264","order":2,"name":"referee-response-38264","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Cindy Chu<\/b>; <i>Posted: 06 Aug 2020<\/i>; We would like to thank Reviewer 2 for their helpful comments on this manuscript. <b>Reply:<\/b>&nbsp;To improve the rationale of this paper earlier in the introduction, we have modified the 2 <sup>nd<\/sup>&nbsp;sentence of the introduction to read \u201cThis combined with the drive to eliminate malaria, is encouraging malaria-endemic countries to increase access to testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency.&nbsp; <i>G6PD deficiency is&nbsp;<\/i>the most common sex-linked genetic abnormality in humans, affecting more than 400 million people worldwide,&nbsp; <i>and it is associated with increased haemolytic risk during treatment with oxidative drugs, including radical curative treatments against Plasmodium vivax malaria<\/i>.\u201d <b>Reply:<\/b>&nbsp;&nbsp;We have specified the sentence as follows \u201cFor most countries&nbsp; <i>outside sub-Saharan Africa<\/i>&nbsp;approaching malaria elimination,&nbsp; <i>P. vivax<\/i>&nbsp;is now the main contributor to malaria disease burden\u2026.\u201d, and a reference to the WHO malaria report, 2019 has been added. <b>Reply:<\/b>&nbsp;Qualitative tests are not built to identify intermediate levels of G6PD activity, therefore when using qualitative tests, 100% of females with intermediate activity are classified as normal. The fluorescent spot test is sometimes considered as a semi-quantitative test but in the authors\u2019 experience the capacity to identify intermediate activities with this test is very limited. <b>Reply:<\/b>&nbsp;&nbsp;We agree with the reviewer and we have now modified the title in order to capture the different components of the manuscript. In relation to the newborn screening, we think that using G6PD testing more broadly (both within malaria endemic countries and outside for neonatal screening) can enhance the cost-effectiveness of the test and possibly even lower its price at the benefit of low-resource and malaria-endemic settings. <b>Reply:<\/b>&nbsp;This section was written to provide additional clinical scenarios (with data on G6PD heterozygous females with intermediate G6PD deficiency) where quantitative G6PD testing could be used to benefit females with an intermediate G6PD status; linking to the section on \u2018Cost effectiveness\u2019, later in the paper. As the reviewer states, there are other more commonly used drugs where quantitative G6PD testing would be helpful however, data on heterozygous intermediate G6PD females are available only in the clinical situations as stated in the paper (rasburicase, dapsone, neonatal hyperbilirubinaemia). To clarify we have amended the sentence in the second paragraph of the section \u2018G6PD deficiency in females\u2019 to \u201cOther than the malaria radical curative indication, quantitative screening for G6PD deficiency&nbsp; <i>can be expanded to&nbsp;<\/i>clinical&nbsp; <i>scenarios to improve patient care in females with intermediate G6PD status (where evidence is available) with an additional benefit of cost sharing. \u201d&nbsp;&nbsp;<\/i>We have also added a sentence at the end of the section: \u201c <i>Quantitative G6PD testing could be used prior to prescription of other haemolytic agents (such as co-trimoxazole or nitrofurantoin) as more data are collected on their effects in heterozygous females with intermediate G6PD activity<\/i>.\u201d <b>Reply:<\/b>&nbsp;We have corrected this to \u2018X-linked\u2019. Thank you for noticing this error. <b>Reply:<\/b>&nbsp;This would certainly reduce the cost per test from 2-3 USD for a G6PD Biosensor test compared to 1-2 USD for the Carestart G6PD RDT. It may not improve the cost effectiveness of the quantitative G6PD testing device, which becomes more cost effective if it is used frequently. There are also added importation fees in some countries that would affect the cost effectiveness. Ideally, each country, hospital, or region would decide on what is cost effective for their local context.&nbsp;We have inserted the following sentence in the cost effectiveness section:&nbsp; <i>\u201c<\/i> <i>A combination of screening males with the more affordable qualitative test and females with the quantitative test may reduce commodity costs, but operational feasibility and costs of maintaining two products and training on their appropriate would need to be investigated.\u201d<\/i> <b>Reply:<\/b>&nbsp;&nbsp;We appreciate the reviewer\u2019s comments, but given already the extensive length of the article, we would like to keep the description of the Figure 1 in the figure legend and research agenda\/topics contained in the table. We hope this is acceptable to the reviewer.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-21\/v2#referee-comment-4309","order":3,"name":"referee-comment-4309","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust through a Wellcome Trust Strategic Award [096527] and a Research Enrichment - Public Engagement Award to MK [200344]. CSC and GB are part of the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Unit, funded by the Wellcome Trust (United Kingdom) [A150007]. This work was funded by the United Kingdom\u2019s Department for International Development (DFID) [204139], and the Bill & Melinda Gates Foundation [OPP1107113]. The findings and conclusions contained within are those of the authors and do not necessarily reflect the positions of DFID or the Bill & Melinda Gates Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}