{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:28:22Z","timestamp":1793413702500,"version":"4.5.0"},"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","award":["MR\/W006731\/1"],"award-info":[{"award-number":["MR\/W006731\/1"]}],"id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-063472"],"award-info":[{"award-number":["INV-063472"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680"],"award-info":[{"award-number":["106680"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223004"],"award-info":[{"award-number":["223004"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dengue is a growing public health threat with increasing case numbers globally. Despite the substantial burden, there are no licensed therapeutics for patients with dengue. To inform the design of large-scale practice-changing clinical trials and to assess the feasibility of an individual patient data platform for meta-analysis, we conducted a systematic mapping review of clinical trials evaluating dengue therapeutics. Our aims were to characterise published and registered dengue therapeutic trials, describe their endpoints, and assess study design quality and internal validity to inform feasibility of meta-analysis and future research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched Ovid MEDLINE, Ovid EMBASE, WHO ICTRP and ClinicalTrials.gov for prospective clinical trials evaluating therapeutics in patients with symptomatic dengue. Two independent reviewers screened records using Covidence. Data were extracted into a REDCap database, and risk of bias was assessed using the ROB-2 and ROBINS-I tools to describe trial design rigour. Descriptive analyses summarised the interventions, trial characteristics, study populations, and primary endpoints. This systematic review was pre-registered with PROSPERO (CRD42023469022).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results &amp; discussion<\/jats:title>\n                    <jats:p>A total of 121 clinical studies were identified, comprising 72 published trials and 49 registered but unpublished studies. Interventions were categorised according to the authors\u2019 proposed mechanism of action: antiviral (n\u2009=\u200910), host-directed (HDT, n\u2009=\u200934), supportive (n\u2009=\u200931), or undefined (n\u2009=\u200946). Aside from the studies of supportive therapies (n\u2009=\u200931) and unpublished studies (n\u2009=\u200937) which were only reviewed for their primary outcomes, 53 publications remained for review of therapeutic efficacy. Methodological concerns were common \u2013 24 of 53 published trials (45%) were classified as having high or critical risk of bias. Corticosteroids were the most frequently evaluated intervention, involving a total of 944 randomised patients. The primary endpoints used in both antiviral and HDT trials were highly heterogeneous, limiting comparability. The combination of methodological concerns and non-standardised endpoints precluded meta-analysis for any intervention. No single treatment had sufficient or consistent evidence to support recommendations for use in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings highlight a remarkably sparse evidence base for dengue therapeutics and a lack of standardised, clinically meaningful endpoints. These factors have hindered progress in evaluating candidate treatments and limited the potential for individual patient data meta-analyses. Large, high-quality trials - powered for harmonised and clinically relevant endpoints - are urgently needed to advance the development of effective therapies for dengue.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014382","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:49:03Z","timestamp":1780681743000},"page":"e0014382","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["A systematic mapping review of therapeutic clinical trials in dengue"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1916-2678","authenticated-orcid":true,"given":"Tran Bang","family":"Huyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"McBride","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tun-Linn","family":"Thein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khoi Minh","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran","family":"Luu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Quang","family":"Huy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Harriss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.W.","family":"Kain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cattrall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Naylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Quang","family":"Chanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Lam","family":"Vuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Munblit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ying","family":"Chia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phung Khanh","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Yacoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"issue":"7446","key":"pntd.0014382.ref001","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"S Bhatt","year":"2013","journal-title":"Nature"},{"issue":"12","key":"pntd.0014382.ref002","article-title":"The impact of climate suitability, urbanisation, and connectivity on the expansion of dengue in 21st century Brazil","volume":"15","author":"SA Lee","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0014382.ref003","article-title":"Assessing the global dengue burden: Incidence, mortality, and disability trends over three decades","volume":"19","author":"W-X Zhang","year":"2025","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014382.ref004","unstructured":"WHO. WHO dengue factsheet. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue. Accessed 2025 November 11."},{"key":"pntd.0014382.ref005","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.ijid.2021.07.062","article-title":"Risk factors for hospitalization and mortality due to dengue fever in a Mexican population: A retrospective cohort study","volume":"110","author":"R Fonseca-Portilla","year":"2021","journal-title":"Int J Infect Dis"},{"issue":"244","key":"pntd.0014382.ref006","first-page":"1272","article-title":"Admitted cases of dengue fever among dengue positive cases in a tertiary care hospital: A descriptive cross-sectional study","volume":"59","author":"S Poudyal","year":"2021","journal-title":"JNMA J Nepal Med Assoc"},{"key":"pntd.0014382.ref007","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1056\/NEJMra1110265","article-title":"Dengue","volume":"366","author":"CP Simmons","year":"2012","journal-title":"N Engl J 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McBride","year":"2022","journal-title":"BMC Infect Dis"},{"issue":"3","key":"pntd.0014382.ref011","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0012071","article-title":"Endothelial and inflammatory pathophysiology in dengue shock: New insights from a prospective cohort study in Vietnam","volume":"18","author":"A McBride","year":"2024","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0014382.ref012","first-page":"1072","article-title":"Serum ferritin as a prognostic indicator in adult dengue patients","volume":"104","author":"SC Suresh","year":"2020","journal-title":"Am J Trop Med Hyg"},{"issue":"8","key":"pntd.0014382.ref013","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1093\/infdis\/jiac093","article-title":"Hyperinflammatory syndrome, natural killer cell function, and genetic polymorphisms in the pathogenesis of severe dengue","volume":"226","author":"NL Vuong","year":"2022","journal-title":"J Infect 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Sterne","year":"2019","journal-title":"BMJ"},{"key":"pntd.0014382.ref018","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions version 6.5 (updated August 2024)","author":"JPT Higgins","year":"2024"},{"issue":"10","key":"pntd.0014382.ref019","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciaa1332","article-title":"Ivermectin accelerates circulating nonstructural protein 1 (NS1) clearance in adult dengue patients: A combined phase 2\/3 randomized double-blinded placebo controlled trial","volume":"72","author":"Y Suputtamongkol","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"8","key":"pntd.0014382.ref020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000785","article-title":"A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adults","volume":"4","author":"V Tricou","year":"2010","journal-title":"PLoS Negl Trop 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Johnson & Johnson to Discontinue Phase 2 Field Study Evaluating Investigational Antiviral for the Prevention of Dengue. https:\/\/www.jnj.com\/media-center\/press-releases\/johnson-johnson-to-discontinue-phase-2-field-study-evaluating-investigational-antiviral-for-the-prevention-of-dengue. 2024. Accessed 2025 September 4."},{"issue":"1","key":"pntd.0014382.ref024","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1542\/peds.69.1.45","article-title":"Failure of hydrocortisone to affect outcome in dengue shock syndrome","volume":"69","author":"W Talogo","year":"1982","journal-title":"Pediatrics"},{"issue":"1","key":"pntd.0014382.ref025","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1542\/peds.92.1.111","article-title":"Failure of high-dose methylprednisolone in established dengue shock syndrome: A placebo-controlled, double-blind study","volume":"92","author":"S Tassniyom","year":"1993","journal-title":"Pediatrics"},{"issue":"4","key":"pntd.0014382.ref026","first-page":"573","article-title":"Hydrocortisone in the management of dengue shock syndrome","volume":"6","author":"MU Min","year":"1975","journal-title":"Southeast Asian J Trop Med Public Health"},{"issue":"1","key":"pntd.0014382.ref027","first-page":"6","article-title":"Studies on dengue hemorrhagic fever. Clinical study: An evaluation of steroids as a treatment","volume":"56","author":"B Pongpanich","year":"1973","journal-title":"J Med Assoc Thai"},{"issue":"7","key":"pntd.0014382.ref028","first-page":"1397","article-title":"Effect of high dose of steroid on plateletcount in acute stage of dengue Fever with thrombocytopenia","volume":"7","author":"KC Shashidhara","year":"2013","journal-title":"J Clin Diagn Res"},{"issue":"1008","key":"pntd.0014382.ref029","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1136\/pgmj.2008.078444","article-title":"Efficacy of low dose dexamethasone in severe thrombocytopenia caused by dengue fever: A placebo controlled study","volume":"85","author":"SAM Kularatne","year":"2009","journal-title":"Postgrad Med J"},{"key":"pntd.0014382.ref030","doi-asserted-by":"crossref","first-page":"242","DOI":"10.13181\/mji.v7i4.751","article-title":"The role of platelet antibody and bone marrow in adult dengue hemorrhagic fever with thrombocytopenia","author":"TM Waly","year":"1998","journal-title":"Med J Indones"},{"issue":"11","key":"pntd.0014382.ref031","article-title":"Role of corticosteroids in dengue fever in Pakistan","volume":"15","author":"H Aslam","year":"2021","journal-title":"PJMHS"},{"issue":"9","key":"pntd.0014382.ref032","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1093\/cid\/cis655","article-title":"Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: A randomized, placebo-controlled trial","volume":"55","author":"DTH Tam","year":"2012","journal-title":"Clin Infect Dis"},{"issue":"1","key":"pntd.0014382.ref033","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1038\/s41598-018-22285-x","article-title":"A preliminary study on efficacy of rupatadine for the treatment of acute dengue infection","volume":"8","author":"GN Malavige","year":"2018","journal-title":"Sci Rep"},{"issue":"6","key":"pntd.0014382.ref034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0010123","article-title":"Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial","volume":"16","author":"GN Malavige","year":"2022","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"pntd.0014382.ref035","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1093\/cid\/civ949","article-title":"Lovastatin for the treatment of adult patients with dengue: A randomized, double-blind, placebo-controlled trial","volume":"62","author":"J Whitehorn","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pntd.0014382.ref036","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0011927","article-title":"Effect of montelukast in preventing dengue with warning signs among patients with dengue: A multicenter, randomized, double-blind, placebo-controlled trial","volume":"18","author":"N Nitinai","year":"2024","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pntd.0014382.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0010051","article-title":"Effect of oseltamivir phosphate versus placebo on platelet recovery and plasma leakage in adults with dengue and thrombocytopenia; A phase 2, multicenter, double-blind, randomized trial","volume":"16","author":"RN Tunjungputri","year":"2022","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"pntd.0014382.ref038","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1097\/INF.0b013e3182575e6a","article-title":"Use of pentoxifylline in treatment of children with dengue hemorrhagic fever","volume":"31","author":"D Salgado","year":"2012","journal-title":"Pediatr Infect Dis J"},{"issue":"4","key":"pntd.0014382.ref039","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0022-3476(97)70055-6","article-title":"Failure of carbazochrome sodium sulfonate (AC-17) to prevent dengue vascular permeability or shock: A randomized, controlled trial","volume":"131","author":"S Tassniyom","year":"1997","journal-title":"J Pediatr"},{"issue":"2","key":"pntd.0014382.ref040","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4103\/ijccm.IJCCM_386_16","article-title":"Safety and efficacy of a single dose of anti-D (WinRho\u00ae) in severe thrombocytopenia secondary to dengue virus infection","volume":"21","author":"AK Pannu","year":"2017","journal-title":"Indian J Crit Care Med"},{"key":"pntd.0014382.ref041","doi-asserted-by":"crossref","first-page":"100624","DOI":"10.1016\/j.eclinm.2020.100624","article-title":"Investigation of the efficacy and safety of eltrombopag to correct thrombocytopenia in moderate to severe dengue patients - 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randomized open label comparative clinical study","volume":"8","author":"P Hans","year":"2018","journal-title":"Ann Med Health Sci Res"},{"issue":"1","key":"pntd.0014382.ref054","first-page":"483","article-title":"A prospective open labelled clinical study to evaluate the efficacy and safety of novel herbal formula denpap in patients with dengue fever","volume":"10","author":"S Ns","year":"2021","journal-title":"IjpsrInfo"},{"issue":"2","key":"pntd.0014382.ref055","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0228699","article-title":"Efficacy & safety of Carica papaya leaf extract \u03bc l) in adult dengue \u2013 Results of a pilot study","volume":"15","author":"DT Sathyapalan","year":"2020","journal-title":"PLoS One"},{"issue":"6","key":"pntd.0014382.ref056","first-page":"22","article-title":"Effect of carica papaya leaf extract capsule on platelet count in patients of dengue fever with thrombocytopenia","volume":"64","author":"AK Gadhwal","year":"2016","journal-title":"J Assoc Physicians India"},{"key":"pntd.0014382.ref057","article-title":"To evaluate the efficacy of Carica papaya leaf extract on platelet count in dengue induced thrombocytopenia: A randomized controlled trial","volume":"47","author":"S Dharani","year":"2015","journal-title":"Indian J Pharmacol"},{"issue":"1","key":"pntd.0014382.ref058","first-page":"725","article-title":"Effect of vitamin E & vitamin C supplementation on thrombocytopenia in dengue fever - 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Report of a pilot study","volume":"51","author":"JI Cabrera-Cortina","year":"2008","journal-title":"Proc West Pharmacol Soc"},{"issue":"11","key":"pntd.0014382.ref062","doi-asserted-by":"crossref","first-page":"645","DOI":"10.12980\/apjtd.7.2017D7-176","article-title":"Effects of vitamin E supplementation on the clinical outcome of dengue fever and dengue haemorrhagic fever in children","volume":"7","author":"PWP Chathurangana","year":"2017","journal-title":"Asian Pac J Trop Dis"},{"issue":"11","key":"pntd.0014382.ref063","article-title":"The efficacy of vitamin c on hemoglobin levels and white blood cell count as an adjuvant in the treatment of dengue fever","volume":"11","author":"S Rammohan","year":"2018","journal-title":"Asian Journal of Pharmaceutical and Clinical Research"},{"key":"pntd.0014382.ref064","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2147\/IDR.S71505","article-title":"The effect of a unique propolis compound (Propoelix) on clinical outcomes in patients with dengue hemorrhagic fever","author":"S Lardo","year":"2014","journal-title":"Infect Drug Resist"},{"issue":"1","key":"pntd.0014382.ref065","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.homp.2006.10.004","article-title":"The use of homeopathic combination remedy for dengue fever symptoms: A pilot RCT in Honduras","volume":"96","author":"J Jacobs","year":"2007","journal-title":"Homeopathy"},{"key":"pntd.0014382.ref066","first-page":"6","article-title":"Management of thrombocytopenia and flu-like symptoms in dengue patients with herbal water of Euphorbia hirta","volume":"24","author":"M Mir","year":"2012","journal-title":"J Ayub Med Coll Abbottabad"},{"issue":"03","key":"pntd.0014382.ref067","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1055\/s-0038-1676953","article-title":"Effect of adjuvant homeopathy with usual care in management of thrombocytopenia due to dengue: A comparative cohort study","volume":"108","author":"D Nayak","year":"2019","journal-title":"Homeopathy"},{"issue":"1","key":"pntd.0014382.ref068","first-page":"1","article-title":"A pilot study examining the effect of kelulut honey in dengue infected patients by examining clinical, hemodynamic and biochemical parameters","volume":"4","author":"N Muhamad","year":"2020","journal-title":"Japanese Journal of Gastroenterology and Hepatology"},{"issue":"2","key":"pntd.0014382.ref069","first-page":"377","article-title":"A comparative clinical study of Guduchi Kwath and Kiratatikta Kwath to increase the platelet count in dengue fever","volume":"23","author":"V Pawar","year":"2024","journal-title":"Empirical Economics Letters"},{"issue":"7","key":"pntd.0014382.ref070","first-page":"6465","article-title":"Safety and efficacy of nilavembu kudineer in dengue fever","volume":"13","author":"R Maignana Kumar","year":"2022","journal-title":"Journal of Pharmaceutical Negative Results"},{"key":"pntd.0014382.ref071","unstructured":"NAVIPP. Novel Antivirals for Infections of Pandemic Potential webpage, Work Package 6. https:\/\/www.navipp.eu\/project\/ Accessed 11\/11\/2025."},{"key":"pntd.0014382.ref072","unstructured":"Rapidly Emerging Antiviral Drug Development Initiative. READDI webpage. https:\/\/readdi.org\/our-approach\/readdis-role\/ Accessed 11\/11\/2025."},{"key":"pntd.0014382.ref073","unstructured":"DNDi. Drugs for Neglected Diseases initiative. https:\/\/dndi.org\/diseases\/dengue\/. Accessed 2025 November 11."},{"issue":"49","key":"pntd.0014382.ref074","first-page":"2","article-title":"Expert opinion: Dengue burden and prevention in Vietnam","volume":"1","author":"NT Ph\u1ea1m","year":"2025","journal-title":"T\u1ea1p ch\u00ed Truy\u1ec1n nhi\u1ec5m Vi\u1ec7t Nam"},{"issue":"12","key":"pntd.0014382.ref075","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1136\/archdischild-2025-329078","article-title":"Role of anakinra in the management of children with severe dengue","volume":"110","author":"C Bhat","year":"2025","journal-title":"Arch Dis Child"},{"issue":"6","key":"pntd.0014382.ref076","first-page":"496","article-title":"Dengue associated hemophagocytic lymphohistiocytosis: A case series","volume":"51","author":"P Pal","year":"2014","journal-title":"Indian Pediatr"},{"issue":"1","key":"pntd.0014382.ref077","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jcv.2012.06.005","article-title":"Hemophagocytosis in dengue: Comprehensive report of six cases","volume":"55","author":"LH Tan","year":"2012","journal-title":"J Clin Virol"},{"issue":"10434","key":"pntd.0014382.ref078","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1016\/S0140-6736(23)02882-9","article-title":"High-dose corticosteroid therapy in COVID-19: The RECOVERY trial","volume":"403","author":"Z Hashim","year":"2024","journal-title":"The Lancet"},{"key":"pntd.0014382.ref079","doi-asserted-by":"crossref","unstructured":"World Health Organization WHO. Dengue guidelines for diagnosis, treatment, prevention and control: new edition. 2009. https:\/\/doi.org\/10.1176\/pn.41.1.0029b","DOI":"10.1176\/pn.41.1.0029b"},{"issue":"10","key":"pntd.0014382.ref080","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0006497","article-title":"Development of standard clinical endpoints for use in dengue interventional trials","volume":"12","author":"KM Tomashek","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014382.ref081","unstructured":"Chan XH. WHO target product profiles for treatments for dengue fever. https:\/\/cdn.who.int\/media\/docs\/default-source\/ntds\/dengue\/draft-who-tpps-for-treatments-for-dengue-fever.pdf?sfvrsn=6af53f12_3. Accessed 2026 April 13."}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014382","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:49:28Z","timestamp":1780681768000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014382"}},"subtitle":[],"editor":[{"given":"Kentaro","family":"Iwata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":81,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0014382","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}