Mortality Among Confirmed Lassa Fever Cases During the 2015–2016 Outbreak in Nigeria

Buba, Maryam Ibrahim; Dalhat, Mahmood; Nguku, Patrick; Waziri, Ndadilnasiya Endie; Mohammad, Jibreel Omar; Bomoi, Idriss Mohammed; Onyiah, Pamela; Onwujei, Jude; Balogun, Muhammad Shakir; Bashorun, Adebobola; Nsubuga, Peter; Nasidi, Abdulsalami

doi:10.2105/ajph.2017.304186

Cited by 44 publications

(47 citation statements)

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“…All LASV deaths have been recorded only in West Africa including Nigeria, Guinea, and Sierra Leone (Fig 6) [34,37,47,53,65,70,120,123]. Only the case fatality rate category in LASV suspected cases fulfilled the conditions for subgroup analyses (at least 3 studies divided into two or more categories).…”

Section: Subgroup Analysis and Metaregressionmentioning

confidence: 99%

“…Only the case fatality rate category in LASV suspected cases fulfilled the conditions for subgroup analyses (at least 3 studies divided into two or more categories). The case fatality rate was significantly higher in studies on community outbreak (p = 0.036), with a retrospective design (p = 0.018) [47,53,89,101,116,117], conducted in rural areas (p <0.001) [53], and in the community (p = 0.039) (S8 Table) [47]. S9 Table displayed the results of the meta-regression analysis.…”

Section: Subgroup Analysis and Metaregressionmentioning

confidence: 99%

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Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa

et al. 2020

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Accurate data on the Lassa virus (LASV) human case fatality rate (CFR) and the prevalence of LASV in humans, rodents and other mammals are needed for better planning of actions that will ultimately reduce the burden of LASV infection in sub-Saharan Africa. In this systematic review with meta-analysis, we searched PubMed, Scopus, Africa Journal Online, and African Index Medicus from 1969 to 2020 to obtain studies that reported enough data to calculate LASV infection CFR or prevalence. Study selection, data extraction, and risk of bias assessment were conducted independently. We extracted all measures of current, recent, and past infections with LASV. Prevalence and CFR estimates were pooled using a random-effect meta-analysis. Factors associated with CFR, prevalence, and sources of between-study heterogeneity were determined using subgroup and metaregression analyses. This review was registered with PROSPERO, CRD42020166465. We initially identified 1,399 records and finally retained 109 reports that contributed to 291 prevalence records from 25 countries. The overall CFR was 29.7% (22.3-37.5) in humans. Pooled prevalence of LASV infection was 8.7% (95% confidence interval: 6.8-10.8) in humans, 3.2% (1.9-4.6) in rodents, and 0.7% (0.0-2.3) in other mammals. Subgroup and metaregression analyses revealed a substantial statistical heterogeneity explained by higher prevalence in tissue organs, in case-control, in hospital outbreak, and surveys, in retrospective studies, in urban and hospital setting, in hospitalized patients, and in West African countries.

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Section: Subgroup Analysis and Metaregressionmentioning

confidence: 99%

Section: Subgroup Analysis and Metaregressionmentioning

confidence: 99%

Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa

et al. 2020

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“…We identified five retrospective cohort studies with 372 participants (Ajayi et al, 2013;Asogun et al, 2012;Buba et al, 2018;Dahmane et al, 2014;Shaffer et al, 2019) and one prospective clinical trial with 894 participants meeting our inclusion criteria (Final Report Analysis, 1992). Doses of intravenous ribavirin treatment varied slightly between studies (Supplementary Table S3).…”

Section: Efficacy Of Ribavirin For the Treatment Of Lfmentioning

confidence: 99%

Ribavirin for the treatment of Lassa fever: A systematic review and meta-analysis

Eberhardt

Mischlinger

Jordan

et al. 2019

International Journal of Infectious Diseases

107

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Objectives: Lassa fever (LF) causes annual outbreaks in endemic regions with high mortality of symptomatic patients. Ribavirin is recommended as standard treatment for LF in national and international guidelines but the evidence base for this recommendation has been questioned recently. Methods: We conducted a systematic review and included 6 studies providing efficacy data of ribavirin treatment for LF (PROSPERO protocol CRD42018103994). Results: Besides retrospective case series, the evidence mostly relies on a single prospective clinical trial with critical risk of bias. In this trial, LF associated mortality is reduced for patients with elevated aspartate aminotransferase (AST) when treated with ribavirin (OR 0.41, 95% CI 0.23-0.73), while mortality is higher for patients without elevated AST (OR 2.37, 95% CI 1.07-5.25). Conclusions: Based on the available data, current treatment guidelines may therefore put patients with mild LF at increased risk of death. The role of ribavirin in the treatment of LF requires urgent reassessment.

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“…L assa virus (LASV), the causative agent of Lassa fever (LF), is endemic in Western Africa (1). LASV is estimated to infect hundreds of thousands of individuals annually, with about 20% of infected individuals developing clinical symptoms and signs, and is associated with a high case-fatality rate (CFR) (2). The majority of human infections occur after direct contact with infected rodents (predominantly Mastomys spp.)…”

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confidence: 99%

A Lassa Fever Live-Attenuated Vaccine Based on Codon Deoptimization of the Viral Glycoprotein Gene

Caì

Cheng

et al. 2020

mBio

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Lassa virus (LASV) is endemic in Western Africa and is estimated to infect hundreds of thousands of individuals annually. A considerable number of these infections result in Lassa fever (LF), which is associated with significant morbidity and a case-fatality rate as high as 69% among hospitalized confirmed patients. U.S. Food and Drug Administration-approved LF vaccines are not available. Current antiviral treatment is limited to off-label use of a nucleoside analogue, ribavirin, that is only partially effective and associated with significant side effects. We generated and characterized a recombinant LASV expressing a codon-deoptimized (CD) glycoprotein precursor gene (GPC), rLASV-GPC/CD. Comparison of growth kinetics and peak titers showed that rLASV-GPC/CD is slightly attenuated in cell culture compared to wild-type (WT) recombinant LASV (rLASV-WT). However, rLASV-GPC/CD is highly attenuated in strain 13 and Hartley guinea pigs, as reflected by the absence of detectable clinical signs in animals inoculated with rLASV-GPC/CD. Importantly, a single subcutaneous dose of rLASV-GPC/CD provides complete protection against an otherwise lethal exposure to LASV. Our results demonstrate the feasibility of implementing a CD approach for developing a safe and effective LASV live-attenuated vaccine candidate. Moreover, rLASV-GPC/CD might provide investigators with a tool to safely study LASV outside maximum (biosafety level 4) containment, which could accelerate the elucidation of basic aspects of the molecular and cell biology of LASV and the development of novel LASV medical countermeasures. IMPORTANCE Lassa virus (LASV) infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever (LF) cases. Licensed LF vaccines are not available, and anti-LF therapy is limited to off-label use of the nucleoside analog ribavirin with uncertain efficacy. We describe the generation of a novel live-attenuated LASV vaccine candidate. This vaccine candidate is based on mutating wild-type (WT) LASV in a key region of the viral genome, the glycoprotein precursor (GPC) gene. These mutations do not change the encoded GPC but interfere with its production in host cells. This mutated LASV (rLASV-GPC/CD) behaves like WT LASV (rLASV-WT) in cell culture, but in contrast to rLASV-WT, does not cause disease in inoculated guinea pigs. Guinea pigs immunized with rLASV-GPC/CD were protected against an otherwise lethal exposure to WT LASV. Our results support the testing of this candidate vaccine in nonhuman primate models ofLF.

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Mortality Among Confirmed Lassa Fever Cases During the 2015–2016 Outbreak in Nigeria

Abstract: Effective, coordinated response reduces mortality from public health events. Attention to vulnerable groups during disasters is essential. Public Health Implications. Activating an incident command system improves the outcome of disasters in resource-constrained settings.

Cited by 44 publications

References 10 publications

Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa

Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa

Ribavirin for the treatment of Lassa fever: A systematic review and meta-analysis

A Lassa Fever Live-Attenuated Vaccine Based on Codon Deoptimization of the Viral Glycoprotein Gene

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