{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T01:44:19Z","timestamp":1782870259142,"version":"3.54.5"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["JC 41 (J C Bose Fellowship)"],"award-info":[{"award-number":["JC 41 (J C Bose Fellowship)"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The emergence of resistance against antimalarials and insecticides poses a significant threat to malaria elimination strategies. It is crucial to explore potential risk factors for malaria to identify new targets and alternative therapies. Malnutrition is a well-established risk factor for malaria. Deficiencies of micronutrients such as vitamin A, zinc, iron, folic acid, and phenotypic measures of malnutrition, such as stunting and wasting, have been studied extensively in the context of malaria. Vitamin B2, also known as riboflavin, is a micronutrient involved in maintaining cellular homeostasis. Riboflavin deficiency has been shown to have an inverse correlation with malarial parasitaemia. This article reviews the role of riboflavin in maintaining redox homeostasis and probes how riboflavin deficiency could alter malaria pathogenesis by disrupting the balance between oxidants and antioxidants. Though riboflavin analogues have been explored as antimalarials, new <jats:italic>in vivo<\/jats:italic> and patient-based research is required to target riboflavin-associated pathways for antimalarial therapy.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011991","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T18:25:03Z","timestamp":1709317503000},"page":"e1011991","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Role of riboflavin deficiency in malaria pathophysiology"],"prefix":"10.1371","volume":"20","author":[{"given":"Shweta","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arathy","family":"Ramachandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-0034","authenticated-orcid":true,"given":"Amit","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"ppat.1011991.ref001","unstructured":"Dissecting the mechanisms of pathogenesis in cerebral malaria. 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Available from: https:\/\/gh.bmj.com\/content\/8\/1\/e010781.","DOI":"10.1136\/bmjgh-2022-010781"},{"issue":"8467","key":"ppat.1011991.ref007","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/S0140-6736(85)91598-3","article-title":"Antimalarial effects of riboflavin deficiency","volume":"2","author":"DI Thurnham","year":"1985","journal-title":"Lancet Lond Engl"},{"issue":"12","key":"ppat.1011991.ref008","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1016\/j.bbamem.2011.08.004","article-title":"Differential expression of human riboflavin transporters -1, -2, & -3 in polarized epithelia: a key role for hRFT-2 in intestinal riboflavin uptake","volume":"1808","author":"VS Subramanian","year":"2011","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"ppat.1011991.ref009","doi-asserted-by":"crossref","first-page":"G100","DOI":"10.1152\/ajpgi.00120.2011","article-title":"Role of cysteine residues in cell surface expression of the human riboflavin transporter-2 (hRFT2) in intestinal epithelial cells.","volume":"301","author":"VS Subramanian","year":"2011","journal-title":"Am J Physiol-Gastrointest Liver Physiol."},{"key":"ppat.1011991.ref010","unstructured":"Riboflavin (vitamin B2) and oxidative stress: a review. Br J Nutr | Cambridge Core [Internet]. [cited 2023 Sep 12]. Available from: https:\/\/www.cambridge.org\/core\/journals\/british-journal-of-nutrition\/article\/riboflavin-vitamin-b2-and-oxidative-stress-a-review\/808987B9D15917EC23885EDFF5E17534."},{"key":"ppat.1011991.ref011","volume-title":"StatPearls","author":"N Mahabadi","year":"2023"},{"issue":"3","key":"ppat.1011991.ref012","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0035-9203(57)90023-8","article-title":"The effect of paraminobenzoic acid, parahydroxybenzoic acid and riboflavin on Plasmodium gallinaceum in chicks","volume":"51","author":"AE Taylor","year":"1957","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"3","key":"ppat.1011991.ref013","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0035-9203(83)90180-3","article-title":"Riboflavin status and malaria in infants in Papua New Guinea","volume":"77","author":"DI Thurnham","year":"1983","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"4","key":"ppat.1011991.ref014","first-page":"277","article-title":"Riboflavin deficiency and severity of malaria.","volume":"42","author":"BS Das","year":"1988","journal-title":"Eur J Clin Nutr."},{"issue":"2","key":"ppat.1011991.ref015","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1079\/BJN19810031","article-title":"Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages","volume":"46","author":"HJ Powers","year":"1981","journal-title":"Br J Nutr"},{"issue":"18","key":"ppat.1011991.ref016","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1016\/S0021-9258(18)99775-9","article-title":"Effects of Sulfhydryl Inhibition on Red Blood Cells","volume":"241","author":"HS Jacob","year":"1966","journal-title":"J Biol Chem"},{"key":"ppat.1011991.ref017","volume-title":"StatPearls","author":"AS Ogun","year":"2023"},{"key":"ppat.1011991.ref018","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev.nutr.20.1.153","article-title":"Biosynthesis of vitamin b2 (riboflavin).","volume":"20","author":"A Bacher","year":"2000","journal-title":"Annu Rev Nutr"},{"key":"ppat.1011991.ref019","author":"K. Easton","year":"2012","journal-title":"Riboflavin utilisation by the malaria parasite, Plasmodium falciparum, as a target for novel antimalarials"},{"issue":"2","key":"ppat.1011991.ref020","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1590\/S0036-46651988000200010","article-title":"Glutathione reductase activity and its relation with riboflavin levels measured by methemoglobin reduction by cystamine in patients with malaria (preliminary report).","volume":"30","author":"B Barraviera","year":"1988","journal-title":"Rev Inst Med Trop Sao Paulo"},{"issue":"5719","key":"ppat.1011991.ref021","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/280245a0","article-title":"Oxidant damage mediates variant red cell resistance to malaria","volume":"280","author":"MJ Friedman","year":"1979","journal-title":"Nature"},{"issue":"4","key":"ppat.1011991.ref022","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1600-0609.1989.tb01225.x","article-title":"Genetic and other influences on red-cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with beta-thalassaemia","volume":"42","author":"BB Anderson","year":"1989","journal-title":"Eur J Haematol"},{"issue":"Pt 9","key":"ppat.1011991.ref023","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/brain\/aws161","article-title":"Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease","volume":"135","author":"JO Johnson","year":"2012","journal-title":"Brain J Neurol"},{"issue":"1","key":"ppat.1011991.ref024","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1600-0609.1987.tb01417.x","article-title":"Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency","volume":"38","author":"BB Anderson","year":"1987","journal-title":"Eur J Haematol"},{"issue":"7","key":"ppat.1011991.ref025","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1093\/jn\/nxaa119","article-title":"The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age","volume":"150","author":"BA Williams","year":"2020","journal-title":"J Nutr"},{"issue":"10","key":"ppat.1011991.ref026","doi-asserted-by":"crossref","first-page":"e7303","DOI":"10.1371\/journal.pone.0007303","article-title":"Inherited Glutathione Reductase Deficiency and Plasmodium falciparum Malaria\u2014A Case Study.","volume":"4","author":"V Gallo","year":"2009","journal-title":"PLoS ONE."},{"issue":"3","key":"ppat.1011991.ref027","doi-asserted-by":"crossref","first-page":"495","DOI":"10.4269\/ajtmh.1987.37.495","article-title":"Antimalarial activity of a riboflavin analog against Plasmodium vinckei in vivo and Plasmodium falciparum in vitro","volume":"37","author":"WB Cowden","year":"1987","journal-title":"Am J Trop Med Hyg"},{"issue":"10","key":"ppat.1011991.ref028","doi-asserted-by":"crossref","first-page":"e0054022","DOI":"10.1128\/aac.00540-22","article-title":"Roseoflavin, a Natural Riboflavin Analogue, Possesses In Vitro and In Vivo Antiplasmodial Activity","volume":"66","author":"AL Hemasa","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"issue":"1\u20134","key":"ppat.1011991.ref029","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1159\/000149804","article-title":"Influence of Chlorpromazine on Eryptosis, Parasitemia and Survival of Plasmodium berghei Infected Mice","volume":"22","author":"S Koka","year":"2008","journal-title":"Cell Physiol Biochem"},{"issue":"1","key":"ppat.1011991.ref030","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12936-019-2724-z","article-title":"The past, present and future of anti-malarial medicines.","volume":"18","author":"EG Tse","year":"2019","journal-title":"Malar J."},{"issue":"2","key":"ppat.1011991.ref031","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/0035-9203(87)90244-6","article-title":"Effect of supplementary vitamins and iron on malaria indices in rural Gambian children","volume":"81","author":"CJ Bates","year":"1987","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ppat.1011991.ref032","unstructured":"Nmoris OPG, Ukwandu NCD, Isaac C, Egwunyenga AO, Alawode PO, Anyanwu LC. Riboflavin and thiamin status of Nigerian children with Plasmodium falciparum malaria."},{"issue":"1","key":"ppat.1011991.ref033","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.parint.2013.09.001","article-title":"In vivo imaging in NHP models of malaria: Challenges, progress and outlooks","volume":"63","author":"AS Beignon","year":"2014","journal-title":"Parasitol Int"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T18:25:17Z","timestamp":1709317517000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011991"}},"subtitle":[],"editor":[{"given":"Laura J.","family":"Knoll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,1]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011991","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,1]]}}}