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The Lancet. Infectious Diseases Apr 2018
Topics: Capital Financing; Centers for Disease Control and Prevention, U.S.; Communicable Disease Control; Global Health; Health Policy; Humans; Lassa Fever; United States; World Health Organization
PubMed: 29582756
DOI: 10.1016/S1473-3099(18)30179-8 -
Microorganisms Apr 2021Lassa fever causes an approximate 5000 to 10,000 deaths annually in West Africa and cases have been imported into Europe and the Americas, challenging public health.... (Review)
Review
Lassa fever causes an approximate 5000 to 10,000 deaths annually in West Africa and cases have been imported into Europe and the Americas, challenging public health. Although Lassa virus was first described over 5 decades ago in 1969, no treatments or vaccines have been approved to treat or prevent infection. In this review, we discuss current therapeutics in the development pipeline for the treatment of Lassa fever, focusing on those that have been evaluated in humans or animal models. Several treatments, including the antiviral favipiravir and a human monoclonal antibody cocktail, have shown efficacy in preclinical rodent and non-human primate animal models and have potential for use in clinical settings. Movement of the promising preclinical treatment options for Lassa fever into clinical trials is critical to continue addressing this neglected tropical disease.
PubMed: 33917071
DOI: 10.3390/microorganisms9040772 -
Biotechnology and Bioengineering Mar 2021Lack of experimental human models hinders research on Lassa hemorrhagic fever and the development of treatment strategies. Here, we report the first chip-based model for...
Lack of experimental human models hinders research on Lassa hemorrhagic fever and the development of treatment strategies. Here, we report the first chip-based model for Lassa hemorrhagic syndrome. The chip features a microvessel interfacing collagen network as a simple mimic for extracellular matrix, allowing for quantitative and real-time vascular integrity assessment. Luminal infusion of Lassa virus-like particles led to a dramatic increase in vascular permeability in a viral load-dependent manner. Using this platform, we showed that Fibrin-derived peptide FX06 can be used to suppress the vascular integrity loss. This simple chip-based model proved promising in the assessment of disease severity and provides an easy-to-use platform for future investigation of Lassa pathogenesis and drug development in a human-like setting.
Topics: Human Umbilical Vein Endothelial Cells; Humans; Lab-On-A-Chip Devices; Lassa Fever; Lassa virus; Microfluidic Analytical Techniques; Models, Biological; Shock, Hemorrhagic; Syndrome
PubMed: 33241859
DOI: 10.1002/bit.27636 -
Nature Reviews. Microbiology Feb 2023Lassa virus (LASV) is endemic in the rodent populations of Sierra Leone, Nigeria and other countries in West Africa. Spillover to humans occurs frequently and results in... (Review)
Review
Lassa virus (LASV) is endemic in the rodent populations of Sierra Leone, Nigeria and other countries in West Africa. Spillover to humans occurs frequently and results in Lassa fever, a viral haemorrhagic fever (VHF) associated with a high case fatality rate. Despite advances, fundamental gaps in knowledge of the immunology, epidemiology, ecology and pathogenesis of Lassa fever persist. More frequent outbreaks, the potential for further geographic expansion of Mastomys natalensis and other rodent reservoirs, the ease of procurement and possible use and weaponization of LASV, the frequent importation of LASV to North America and Europe, and the emergence of novel LASV strains in densely populated West Africa have driven new initiatives to develop countermeasures for LASV. Although promising candidates are being evaluated, as yet there are no approved vaccines or therapeutics for human use. This Review discusses the virology of LASV, the clinical course of Lassa fever and the progress towards developing medical countermeasures.
Topics: Humans; Lassa Fever; Lassa virus; Africa, Western; Viral Vaccines
PubMed: 36097163
DOI: 10.1038/s41579-022-00789-8 -
Current Opinion in Virology Aug 2019Lassa fever is a unique viral hemorrhagic fever that is endemic in parts of West Africa, primarily Sierra Leone, Guinea, Liberia, and Nigeria. The disease is caused by... (Review)
Review
Lassa fever is a unique viral hemorrhagic fever that is endemic in parts of West Africa, primarily Sierra Leone, Guinea, Liberia, and Nigeria. The disease is caused by the Lassa virus, an Old World arenavirus that has as primary reservoir host the multimammate rodent Mastomys nataliensis, which lives in association with humans. Recent estimates suggest LF causes two million cases and 5000-10000 deaths annually, mainly in West Africa. Clinical diagnosis and laboratory confirmation have always been major challenges for effective management and control of the disease in afflicted areas of West Africa. Recent advancements in molecular biology, recombinant DNA technology, and genomics sequencing has facilitated major advancement in development of better diagnostic and surveillance tools for Lassa fever virus. These include, the multiplex, magnetic bead-based immunodiagnostics for both Lassa virus antigens and antibodies; molecular probe-based quantitative real-time PCR for genomic signatures; rapid diagnostics tests that detects the most prevalent West African lineages; and the successful utilization of next-generation sequencing technology to diagnose and characterize Lassa virus in West Africa. These advances will continue to improve disease treatment, control, and prevention. In this review we will discuss progression of Lassa virus diagnostics from the past and into the future.
Topics: Africa, Western; Antigens, Viral; Clinical Laboratory Techniques; Genomics; Humans; Lassa Fever; Lassa virus; Molecular Diagnostic Techniques; Serologic Tests
PubMed: 31518896
DOI: 10.1016/j.coviro.2019.08.002 -
Journal of Clinical Microbiology Jun 2017Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa... (Review)
Review
Lassa virus remains an important cause of illness in West Africa and among the travelers returning from this region with an acute febrile illness. The symptoms of Lassa fever can be nonspecific and mimic those of other endemic infections, especially early in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to confirm the diagnosis. An early identification of Lassa fever is crucial for maximizing the benefit of available antiviral therapy, as treatment efficacy rapidly decreases following the clinical onset of the disease. This minireview provides an overview of the currently available diagnostic tests for Lassa fever and their strengths and weaknesses.
Topics: Africa, Western; Clinical Laboratory Techniques; Diagnostic Tests, Routine; Humans; Lassa Fever; Lassa virus
PubMed: 28404674
DOI: 10.1128/JCM.00170-17 -
Annals of Clinical Microbiology and... Apr 2021Lassa fever (LF), a zoonotic illness, represents a public health burden in West African countries where the Lassa virus (LASV) circulates among rodents. Human exposure... (Review)
Review
Lassa fever (LF), a zoonotic illness, represents a public health burden in West African countries where the Lassa virus (LASV) circulates among rodents. Human exposure hinges significantly on LASV ecology, which is in turn shaped by various parameters such as weather seasonality and even virus and rodent-host genetics. Furthermore, human behaviour, despite playing a key role in the zoonotic nature of the disease, critically affects either the spread or control of human-to-human transmission. Previous estimations on LF burden date from the 80s and it is unclear how the population expansion and the improvement on diagnostics and surveillance methods have affected such predictions. Although recent data have contributed to the awareness of epidemics, the real impact of LF in West African communities will only be possible with the intensification of interdisciplinary efforts in research and public health approaches. This review discusses the causes and consequences of LF from a One Health perspective, and how the application of this concept can improve the surveillance and control of this disease in West Africa.
Topics: Africa, Western; Animals; Disease Reservoirs; Humans; Lassa Fever; Lassa virus; One Health; Public Health; Rodentia
PubMed: 33894784
DOI: 10.1186/s12941-021-00431-0 -
African Journal of Infectious Diseases 2022Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to...
BACKGROUND
Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to approximately 5000 deaths annually. The development of the LASV vaccine has been listed as a priority by the World Health Organization since 2018. Considering the accelerated development and availability of vaccines against COVID-19, we set out to assess the prospects of LASV vaccines and the progress made so far.
MATERIALS AND METHODS
We reviewed the progress made on twenty-six vaccine candidates listed by Salami . (2019) and searched for new vaccine candidates through Google Scholar, PubMed, and DOAJ from June to July 2021. We searched the articles published in English using keywords that included "vaccine" AND "Lassa fever" OR "Lassa virus" in the title/abstract.
RESULTS
Thirty-four candidate vaccines were identified - 26 already listed in the review by Salami et al. and an additional 8, which were developed over the last seven years. 30 vaccines are still in the pre-clinical stage while 4 of them are currently undergoing clinical trials. The most promising candidates in 2019 were vesicular stomatitis virus-vectored vaccine and live-attenuated MV/LASV vaccine; both had progressed to clinical trials.
CONCLUSIONS
Despite the focus on COVID-19 vaccines since 2020, LASV vaccine is under development and continues to make impressive progress, hence more emphasis should be put into exploring further clinical studies related to the most promising types of vaccines identified.
PubMed: 36124324
DOI: 10.21010/Ajid.v16i2S.6 -
Viruses Oct 2012Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000... (Review)
Review
Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host's immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Genome, Viral; Humans; Immune Evasion; Lassa Fever; Lassa virus; Liver; Necrosis; Viral Load; Viremia; Virus Replication
PubMed: 23202452
DOI: 10.3390/v4102031 -
Cell Reports May 2023Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for...
Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.
Topics: Humans; Lassa virus; Antibodies, Neutralizing; Lassa Fever; Glycoproteins; Antigens, Viral
PubMed: 37209096
DOI: 10.1016/j.celrep.2023.112524