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Abstract：
Research is urgently needed to reduce the morbidity and mortality of Lassa fever (LF), including clinical trials to test new therapies and to verify the efficacy and safety of the only current treatment recommendation, ribavirin, which has a weak clinical evidence base. To help establish a basis for the development of an adaptable, standardised clinical trial methodology, we conducted a systematic review to identify the clinical characteristics and outcomes of LF and describe how LF has historically been defined and assessed in the scientific literature.
Primary clinical studies and reports of patients with suspected and confirmed diagnosis of LF published in the peer-reviewed literature before 15 April 2021 were included. Publications were selected following a two-stage screening of abstracts, then full-texts, by two independent reviewers at each stage. Data were extracted, verified, and summarised using descriptive statistics.
147 publications were included, primarily case reports (36%), case series (28%), and cohort studies (20%); only 2 quasi-randomised studies (1%) were found. Data are mostly from Nigeria (52% of individuals, 41% of publications) and Sierra Leone (42% of individuals, 31% of publications). The results corroborate the World Health Organisation characterisation of LF presentation. However, a broader spectrum of presenting symptoms is evident, such as gastrointestinal illness and other nervous system and musculoskeletal disorders that are not commonly included as indicators of LF. The overall case fatality ratio was 30% in laboratory-confirmed cases (1896/6373 reported in 109 publications).
Systematic review is an important tool in the clinical characterisation of diseases with limited publications. The results herein provide a more complete understanding of the spectrum of disease which is relevant to clinical trial design. This review demonstrates the need for coordination across the LF research community to generate harmonised research methods that can contribute to building a strong evidence base for new treatments and foster confidence in their integration into clinical care.
Primary clinical studies and reports of patients with suspected and confirmed diagnosis of LF published in the peer-reviewed literature before 15 April 2021 were included. Publications were selected following a two-stage screening of abstracts, then full-texts, by two independent reviewers at each stage. Data were extracted, verified, and summarised using descriptive statistics.
147 publications were included, primarily case reports (36%), case series (28%), and cohort studies (20%); only 2 quasi-randomised studies (1%) were found. Data are mostly from Nigeria (52% of individuals, 41% of publications) and Sierra Leone (42% of individuals, 31% of publications). The results corroborate the World Health Organisation characterisation of LF presentation. However, a broader spectrum of presenting symptoms is evident, such as gastrointestinal illness and other nervous system and musculoskeletal disorders that are not commonly included as indicators of LF. The overall case fatality ratio was 30% in laboratory-confirmed cases (1896/6373 reported in 109 publications).
Systematic review is an important tool in the clinical characterisation of diseases with limited publications. The results herein provide a more complete understanding of the spectrum of disease which is relevant to clinical trial design. This review demonstrates the need for coordination across the LF research community to generate harmonised research methods that can contribute to building a strong evidence base for new treatments and foster confidence in their integration into clinical care.
摘要：
迫切需要研究以降低拉沙热（LF）的发病率和死亡率，包括临床试验，以测试新疗法，并验证目前唯一的治疗建议的疗效和安全性，利巴韦林,临床证据基础薄弱。为了帮助建立适应发展的基础，标准化临床试验方法，我们进行了系统评价,以确定LF的临床特征和结局,并描述了LF在科学文献中的定义和评估.
纳入2021年4月15日前发表在同行评审文献中的疑似和确诊LF患者的主要临床研究和报告。出版物是在对摘要进行两阶段筛选后选出的，然后全文，在每个阶段由两名独立审稿人。数据被提取，已验证,并使用描述性统计数据进行总结。
包括147种出版物，主要是病例报告(36%)，案例系列(28%)，和队列研究（20％）；仅发现2项准随机研究（1％）。数据主要来自尼日利亚(52%的个人，41%的出版物)和塞拉利昂(42%的个人，31%的出版物)。结果证实了世界卫生组织对LF表现的表征。然而,更广泛的症状表现是显而易见的，如胃肠道疾病和其他神经系统和肌肉骨骼疾病，通常不包括作为LF的指标。实验室确诊病例的总病死率为30％（在109份出版物中报告了1896/6373）。
系统评价是在出版物有限的疾病的临床表征中的重要工具。本文的结果提供了对与临床试验设计相关的疾病谱的更完整的理解。这篇综述表明，需要在LF研究界进行协调，以产生协调的研究方法，这有助于为新疗法建立强有力的证据基础，并培养将其纳入临床护理的信心。
纳入2021年4月15日前发表在同行评审文献中的疑似和确诊LF患者的主要临床研究和报告。出版物是在对摘要进行两阶段筛选后选出的，然后全文，在每个阶段由两名独立审稿人。数据被提取，已验证,并使用描述性统计数据进行总结。
包括147种出版物，主要是病例报告(36%)，案例系列(28%)，和队列研究（20％）；仅发现2项准随机研究（1％）。数据主要来自尼日利亚(52%的个人，41%的出版物)和塞拉利昂(42%的个人，31%的出版物)。结果证实了世界卫生组织对LF表现的表征。然而,更广泛的症状表现是显而易见的，如胃肠道疾病和其他神经系统和肌肉骨骼疾病，通常不包括作为LF的指标。实验室确诊病例的总病死率为30％（在109份出版物中报告了1896/6373）。
系统评价是在出版物有限的疾病的临床表征中的重要工具。本文的结果提供了对与临床试验设计相关的疾病谱的更完整的理解。这篇综述表明，需要在LF研究界进行协调，以产生协调的研究方法，这有助于为新疗法建立强有力的证据基础，并培养将其纳入临床护理的信心。
