{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T05:18:06Z","timestamp":1772255886556,"version":"3.50.1"},"reference-count":37,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"2","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,7]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    A systematic review (SR) of published efficacy studies in visceral leishmaniasis (VL) was undertaken to describe methodological aspects of design, conduct, analysis, and reporting. Studies published during 2000\u20132021 and indexed in the Infectious Diseases Data Observatory VL library of clinical studies were eligible for inclusion (\n                    <jats:italic>N<\/jats:italic>\n                    = 89 studies). Of the 89 studies, 40 (44.9%) were randomized, 33 (37.1%) were single-armed, 14 (15.7%) were nonrandomized multiarmed studies, and randomization status was unclear in two (2.2%). After initial screening, disease confirmation was done by microscopy in 26 (29.2%) and by a combination of serology and microscopy in 63 (70.8%). Post-treatment follow-up duration was &lt;6 months in three (3.3%) studies, 6 months in 75 (84.3%), and &gt;6 months in 11 (12.4%) studies. Confirmation of relapse was solely based on clinical suspicion in four (4.5%) studies, parasitological demonstration in 64 (71.9%), using molecular\/serological\/parasitological method in 6 (6.7%), and there was no information in 15 (16.9%). Of the 40 randomized studies, sample size calculation was reported in only 22 (55.0%) studies. This review highlights substantial variations in definitions adopted for disease diagnosis and therapeutic outcomes suggesting a need for a harmonized trials protocol.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.23-0458","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T09:17:22Z","timestamp":1719911842000},"page":"365-376","source":"Crossref","is-referenced-by-count":1,"title":["Design, Conduct, Analysis, and Reporting of Therapeutic Efficacy Studies in Visceral Leishmaniasis: A Systematic Review of Published Reports, 2000\u20132021"],"prefix":"10.4269","volume":"111","author":[{"given":"Prabin","family":"Dahal","sequence":"first","affiliation":[{"name":"Infectious Diseases Data Observatory, Oxford, United Kingdom;"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sauman","family":"Singh-Phulgenda","sequence":"additional","affiliation":[{"name":"Infectious Diseases Data Observatory, Oxford, United Kingdom;"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Naylor","sequence":"additional","affiliation":[{"name":"Infectious Diseases Data Observatory, Oxford, United Kingdom;"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Brack","sequence":"additional","affiliation":[{"name":"Infectious Diseases Data Observatory, Oxford, United Kingdom;"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitali","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Institute of Postgraduate Medical Education & Research, Kolkata, India;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Alves","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe J.","family":"Guerin","sequence":"additional","affiliation":[{"name":"Infectious Diseases Data Observatory, Oxford, United Kingdom;"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasia","family":"Stepniewska","sequence":"additional","affiliation":[{"name":"Infectious Diseases Data Observatory, Oxford, United Kingdom;"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","year":"2023"},{"key":"b2","series-title":"PLoS Negl Trop Dis","first-page":"1","article-title":"Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform","volume":"11","author":"Bush","year":"2017"},{"key":"b3","series-title":"PLoS Negl Trop Dis","first-page":"e0009302","article-title":"Serious adverse events following treatment of visceral leishmaniasis: A systematic review and meta-analysis","volume":"15","author":"Singh-Phulgenda","year":"2021"},{"key":"b4","series-title":"Lancet Reg Heal Southeast Asia","first-page":"100317","article-title":"Estimating the proportion of relapse following treatment of Visceral Leishmaniasis: Meta-analysis using Infectious Diseases Data Observatory (IDDO) systematic review","volume":"22","author":"Chhajed","year":"2023"},{"key":"b5","series-title":"Clin Infect Dis","first-page":"409","article-title":"Designing and reporting clinical trials on treatments for cutaneous leishmaniasis","volume":"51","author":"Gonz\u00e1lez","year":"2010"},{"key":"b6","series-title":"Trop Med Int Health","first-page":"448","article-title":"Eligibility criteria and outcome measures adopted in clinical trials of treatments of cutaneous leishmaniasis: Systematic literature review covering the period 1991\u20132015","volume":"23","author":"L\u00f3pez-Carvajal","year":"2018"},{"key":"b7","year":"2022"},{"key":"b8","series-title":"Wellcome Open Res","first-page":"155","article-title":"Infectious diseases data observatory (IDDO) visceral leishmaniasis library of clinical therapeutic studies: A protocol for a living systematic review of clinical studies","volume":"7","author":"Singh-Phulgenda","year":"2022"},{"key":"b9","series-title":"Manson\u2019s Tropical Diseases","first-page":"631","author":"Boelaert"},{"key":"b10","series-title":"Eur J Clin Microbiol Infect Dis","first-page":"798","article-title":"Prospective evaluation and follow-up of European patients with visceral leishmaniasis and HIV-1 coinfection in the era of highly active antiretroviral therapy","volume":"19","author":"Villanueva","year":"2000"},{"key":"b11","series-title":"PLoS Negl Trop Dis","first-page":"e2613","article-title":"Safety and efficacy of single dose versus multiple doses of AmBisome\u00ae for treatment of visceral leishmaniasis in eastern Africa: A randomized trial","volume":"8","author":"Khalil","year":"2014"},{"key":"b12","series-title":"J Antimicrob Chemother","first-page":"1751","article-title":"Study of parasite kinetics with antileishmanial drugs using real-time quantitative PCR in Indian visceral leishmaniasis","volume":"66","author":"Sudarshan","year":"2011"},{"key":"b13","series-title":"Kala Azar in South Asia: Current Status and Sustainable Challenges","first-page":"125","author":"Rijal"},{"key":"b14","series-title":"Clin Infect Dis","first-page":"E1177","article-title":"Paromomycin and miltefosine combination as an alternative to treat patients with visceral leishmaniasis in eastern Africa: A randomized, controlled, multicountry trial","volume":"76","author":"Musa","year":"2023"},{"key":"b15","series-title":"Clin Diagn Lab Immunol","first-page":"951","article-title":"Laboratory diagnosis of visceral leishmaniasis","volume":"9","author":"Sundar","year":"2002"},{"key":"b16","series-title":"Trop Med Int Health","first-page":"31","article-title":"Field validity, reproducibility and feasibility of diagnostic tests for visceral leishmaniasis in rural Nepal","volume":"11","author":"Chappuis","year":"2006"},{"key":"b17","series-title":"Mol Diagn Ther","first-page":"443","article-title":"Molecular diagnosis of visceral leishmaniasis","volume":"22","author":"Sundar","year":"2018"},{"key":"b18","series-title":"PLoS Negl Trop Dis","first-page":"e0011231","article-title":"Evaluation of recombinase polymerase amplification assay for monitoring parasite load in patients with kala-azar and post kala-azar dermal leishmaniasis","volume":"17","author":"Roy","year":"2023"},{"key":"b19","series-title":"Acta Trop","first-page":"52","article-title":"PCR for diagnosis and assessment of cure in kala-azar patients in Bangladesh","volume":"113","author":"Salam","year":"2010"},{"key":"b20","series-title":"J Clin Microbiol","first-page":"2003","article-title":"Noninvasive molecular diagnosis of human visceral leishmaniasis","volume":"49","author":"Vaish","year":"2011"},{"key":"b21","series-title":"Diagn Microbiol Infect Dis","first-page":"40","article-title":"Parasite load estimation by qPCR differentiates between asymptomatic and symptomatic infection in Indian visceral leishmaniasis","volume":"80","author":"Sudarshan","year":"2014"},{"key":"b22","series-title":"J Clin Microbiol","first-page":"3905","article-title":"A correlative study of splenic parasite score and peripheral blood parasite load estimation by quantitative PCR in visceral leishmaniasis","volume":"53","author":"Sudarshan","year":"2015"},{"key":"b23","series-title":"Clin Infect Dis","first-page":"775","article-title":"Blood parasite load as an early marker to predict treatment response in visceral leishmaniasis in eastern Africa","volume":"73","author":"Verrest","year":"2021"},{"key":"b24","series-title":"PLoS Negl Trop Dis","first-page":"e0009650","article-title":"Visceral leishmaniasis in pregnancy and vertical transmission: A systematic literature review on the therapeutic orphans","volume":"15","author":"Dahal","year":"2021"},{"key":"b25","series-title":"J Clin Epidemiol","first-page":"173","article-title":"Series: Pragmatic trials and real world evidence: Paper 3. Patient selection challenges and consequences","volume":"89","author":"Oude Rengerink","year":"2017"},{"key":"b26","series-title":"PLoS Negl Trop Dis","first-page":"e0009598","article-title":"Improved kala-azar case management through implementation of health facility-based sentinel sites surveillance system in Bihar, India","volume":"15","author":"Das","year":"2021"},{"key":"b27","series-title":"PLoS Negl Trop Dis","first-page":"1","article-title":"Inequalities of visceral leishmaniasis case fatality in Brazil: A multilevel modeling considering space, time, individual and contextual factors","volume":"15","author":"Cota","year":"2021"},{"key":"b28","series-title":"PLoS Negl Trop Dis","first-page":"1","article-title":"Transmission dynamics of visceral leishmaniasis in the Indian subcontinent\u2014A systematic literature review","volume":"10","author":"Hirve","year":"2016"},{"key":"b29","series-title":"BMJ","first-page":"419","article-title":"Treatment of Indian visceral leishmaniasis with single or daily infusions of low dose liposomal amphotericin B: Randomized trial","volume":"323","author":"Sundar","year":"2001"},{"key":"b30"},{"key":"b31","series-title":"BMJ Open","first-page":"e074679","article-title":"Host, parasite and drug determinants of clinical outcomes following treatment of visceral leishmaniasis: A protocol for individual participant data meta-analysis","volume":"13","author":"Kumar","year":"2023"},{"key":"b32","series-title":"BMJ Open","first-page":"e075597","article-title":"Prognostic prediction models for clinical outcomes in patients diagnosed with visceral leishmaniasis: Protocol for a systematic review","volume":"13","author":"Wilson","year":"2023"},{"key":"b33","series-title":"Malar J","first-page":"4","article-title":"STARTER checklist for antimalarial therapeutic efficacy reporting","volume":"21","author":"Plucinski","year":"2022"},{"key":"b34","year":"2022"},{"key":"b35","series-title":"BMJ","first-page":"k5224","article-title":"Eliminating visceral leishmaniasis in South Asia: The road ahead","volume":"364","author":"Rijal","year":"2019"},{"key":"b36","series-title":"PLoS Negl Trop Dis","first-page":"e0011188","article-title":"Anticipating visceral leishmaniasis epidemics due to the conflict in northern Ethiopia","volume":"17","author":"Boodman","year":"2023"},{"key":"b37","series-title":"Malar J","first-page":"127","article-title":"Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malar","volume":"5","author":"Stepniewska","year":"2006"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/111\/2\/article-p365.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/111\/2\/article-p365.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/111\/2\/article-p365.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T08:42:18Z","timestamp":1723020138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/111\/2\/article-p365.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,7]]},"references-count":37,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.23-0458","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.09.06.23295148","asserted-by":"object"}]},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,7]]}}}