TY - JOUR
T1 - Clinical characterization of lassa fever
T2 - A systematic review of clinical reports and research to inform clinical trial design
AU - Merson, Laura
AU - Bourner, Josephine
AU - Jalloh, Sulaiman
AU - Erber, Astrid
AU - Salam, Alex Paddy
AU - Flahault, Antoine
AU - Olliaro, Piero L.
N1 - Funding Information:
This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] (PO, JB) and the Bill & Melinda Gates Foundation [OPP1209135] (PO, JB). This project is part of the EDCTP2 programme supported by the European Union [RIA2016E-1612 - African coaLition for Epidemic Research, Response and Training (ALERRT)] (LM, SJ). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2021 Merson et al.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - Background 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. Methodology 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. Results 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). Conclusion 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.
AB - Background 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. Methodology 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. Results 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). Conclusion 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.
UR - http://www.scopus.com/inward/record.url?scp=85116779771&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0009788
DO - 10.1371/journal.pntd.0009788
M3 - Review article
C2 - 34547033
AN - SCOPUS:85116779771
VL - 15
SP - 1
EP - 27
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
SN - 1935-2727
IS - 9
M1 - e0009788
ER -