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Abstract：
BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform.
METHODS: A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology.
RESULTS: A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen.
CONCLUSIONS: Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.
METHODS: A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology.
RESULTS: A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen.
CONCLUSIONS: Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.
摘要：
背景：黑热病后真皮利什曼病（PKDL）是一种皮肤病，可在成功治疗内脏利什曼病（VL）后发生，是VL流行地区的公共卫生问题。我们进行了系统的范围审查，以评估已发表的PKDL临床研究的特征，了解研究范围，探索开发PKDL个体患者数据（IPD）平台的可行性和价值。
方法：通过搜索以下数据库，对已发表的文献进行了系统综述，以确定PKDL临床研究：PubMed，Scopus,OvidEmbase,WebofScience核心合集,世界卫生组织全球指数，帕斯卡尔,Clinicaltrials.gov,Ovid全球健康,Cochrane数据库和CENTRAL,和世卫组织国际临床试验注册平台。仅在患有PKDL诊断的人类中进行前瞻性研究，治疗,并纳入了1973年1月至2023年3月的后续测量.提取的数据包括患者特征的变量，治疗方案,诊断方法,地理位置,疗效终点，不良事件和统计方法。
结果：共筛选了3,418条记录，其中56项独特研究(n=2,486例患者)纳入本综述.在56项研究中，36人(64.3%)来自印度(1983-2022年)，12（21.4%）来自苏丹（1992-2021），6人（10.7%）来自孟加拉国（1991-2019年），2（3.6%）来自尼泊尔（2001-2007年）。1981年至1990年之间发表了5项（8.9％）研究（n=193例患者），10（17.9%）在1991-2000之间（n=230例），2001-2010年期间10人（17.9%）（n=198例），2011年起31例（55.4%）（n=1,865例）。8项（14.3%）是随机临床试验，48项(85.7%)为非随机研究.在8项随机对照研究中，中位治疗后随访时间为365天（范围：90-540天），在48项非随机研究中为360天（范围：28-2,373天）。疾病诊断基于3项(5.4%)研究的临床标准，在47项(83.9%)研究中，临床和寄生虫学方法混合使用，在6项(10.7%)研究中不清楚。用于治疗的主要药物是米替福辛（n=636例），脂质体两性霉素B（L-AmB）（n=508例），和反分裂方案（n=454例）。在270名患者中测试了10种其他药物方案，每个方案少于60名患者。
结论：我们的综述确定了三种主要药物（米替福辛，L-AmB,和五价锑)，而研究中合并的患者数量表明，IPD平台将是有价值的。在相关利益相关者的支持下，全球PKDL社区和充足的资金，可以实现PKDLIPD平台。这将允许探索治疗安全性和有效性的不同方面，这可能会指导未来的医疗保健决策和临床实践。
方法：通过搜索以下数据库，对已发表的文献进行了系统综述，以确定PKDL临床研究：PubMed，Scopus,OvidEmbase,WebofScience核心合集,世界卫生组织全球指数，帕斯卡尔,Clinicaltrials.gov,Ovid全球健康,Cochrane数据库和CENTRAL,和世卫组织国际临床试验注册平台。仅在患有PKDL诊断的人类中进行前瞻性研究，治疗,并纳入了1973年1月至2023年3月的后续测量.提取的数据包括患者特征的变量，治疗方案,诊断方法,地理位置,疗效终点，不良事件和统计方法。
结果：共筛选了3,418条记录，其中56项独特研究(n=2,486例患者)纳入本综述.在56项研究中，36人(64.3%)来自印度(1983-2022年)，12（21.4%）来自苏丹（1992-2021），6人（10.7%）来自孟加拉国（1991-2019年），2（3.6%）来自尼泊尔（2001-2007年）。1981年至1990年之间发表了5项（8.9％）研究（n=193例患者），10（17.9%）在1991-2000之间（n=230例），2001-2010年期间10人（17.9%）（n=198例），2011年起31例（55.4%）（n=1,865例）。8项（14.3%）是随机临床试验，48项(85.7%)为非随机研究.在8项随机对照研究中，中位治疗后随访时间为365天（范围：90-540天），在48项非随机研究中为360天（范围：28-2,373天）。疾病诊断基于3项(5.4%)研究的临床标准，在47项(83.9%)研究中，临床和寄生虫学方法混合使用，在6项(10.7%)研究中不清楚。用于治疗的主要药物是米替福辛（n=636例），脂质体两性霉素B（L-AmB）（n=508例），和反分裂方案（n=454例）。在270名患者中测试了10种其他药物方案，每个方案少于60名患者。
结论：我们的综述确定了三种主要药物（米替福辛，L-AmB,和五价锑)，而研究中合并的患者数量表明，IPD平台将是有价值的。在相关利益相关者的支持下，全球PKDL社区和充足的资金，可以实现PKDLIPD平台。这将允许探索治疗安全性和有效性的不同方面，这可能会指导未来的医疗保健决策和临床实践。
