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78 result(s) for "Lassa virus - isolation "
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New Hosts of The Lassa Virus
Lassa virus (LASV) causes a deadly haemorrhagic fever in humans, killing several thousand people in West Africa annually. For 40 years, the Natal multimammate rat, Mastomys natalensis , has been assumed to be the sole host of LASV. We found evidence that LASV is also hosted by other rodent species: the African wood mouse Hylomyscus pamfi in Nigeria, and the Guinea multimammate mouse Mastomys erythroleucus in both Nigeria and Guinea. Virus strains from these animals were isolated in the BSL-4 laboratory and fully sequenced. Phylogenetic analyses of viral genes coding for glycoprotein, nucleoprotein, polymerase and matrix protein show that Lassa strains detected in M. erythroleucus belong to lineages III and IV. The strain from H. pamfi clusters close to lineage I (for S gene) and between II & III (for L gene). Discovery of new rodent hosts has implications for LASV evolution and its spread into new areas within West Africa.
Lassa Fever in Post-Conflict Sierra Leone
Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.
CLASV: Rapid Lassa virus lineage assignment with random forest
Lassa fever, caused by the Lassa virus (LASV), is a deadly disease characterized by hemorrhages. Annually, it affects approximately 300,000 people in West Africa and causes about 5,000 deaths. It currently has no approved vaccine and is categorized as a top-priority disease. Apart from its endemicity to West Africa, there have been exported cases in almost all continents, including several European countries. Distinct Lassa virus lineages circulate in specific regions, and have been reported to show varying immunological behaviors and may contribute to differing disease outcomes. It is therefore important to rapidly identify which lineage caused an outbreak or an exported case. We present CLASV, a machine learning-based lineage assignment tool built using a Random Forest classifier. CLASV processes raw nucleotide sequences and assigns them to the dominant circulating lineages (II, III, and IV/V) rapidly and accurately. CLASV is implemented in Python for ease of integration into existing workflows and is freely available for public use.
A Case of Human Lassa Virus Infection With Robust Acute T-Cell Activation and Long-Term Virus-Specific T-Cell Responses
A nurse who acquired Lassa virus infection in Togo in the spring of 2016 was repatriated to the United States for care at Emory University Hospital. Serial sampling from this patient permitted the characterization of several aspects of the innate and cellular immune responses to Lassa virus. Although most of the immune responses correlated with the kinetics of viremia resolution, the CD8 T-cell response was of surprisingly high magnitude and prolonged duration, implying prolonged presentation of viral antigens. Indeed, long after viremia resolution, there was persistent viral RNA detected in the semen of the patient, accompanied by epididymitis, suggesting the male reproductive tract as 1 site of antigen persistence. Consistent with the magnitude of acute T-cell responses, the patient ultimately developed long-term, polyfunctional memory T-cell responses to Lassa virus.
Field validation of recombinant antigen immunoassays for diagnosis of Lassa fever
Lassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West Africa. It is difficult to distinguish febrile illnesses that are common in West Africa from Lassa fever based solely on a patient’s clinical presentation. The field performance of recombinant antigen-based Lassa fever immunoassays was compared to that of quantitative polymerase chain assays (qPCRs) using samples from subjects meeting the case definition of Lassa fever presenting to Kenema Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme-linked immunosorbant assay (ELISA) for detection of viral antigen in blood performed with 95% sensitivity and 97% specificity using a diagnostic standard that combined results of the immunoassays and qPCR. The ReLASV rapid diagnostic test (RDT), a lateral flow immunoassay based on paired monoclonal antibodies to the Josiah strain of LASV (lineage IV), performed with 90% sensitivity and 100% specificity. ReLASV immunoassays performed better than the most robust qPCR currently available, which had 82% sensitivity and 95% specificity. The performance characteristics of recombinant antigen-based Lassa virus immunoassays indicate that they can aid in the diagnosis of LASV Infection and inform the clinical management of Lassa fever patients.
Protection From Lethal Lassa Disease Can Be Achieved Both Before and After Virus Exposure by Administration of Single-Cycle Replicating Lassa Virus Replicon Particles
Lassa fever is a frequently severe human disease that is endemic to several countries in West Africa. To date, no licensed vaccines are available to prevent Lassa virus (LASV) infection, even though Lassa fever is thought to be an important disease contributing to mortality and both acute and chronic morbidity. We have previously described a vaccine candidate composed of single-cycle LASV replicon particles (VRPs) and a stable cell line for their production. Here, we refine the genetic composition of the VRPs and demonstrate the ability to reproducibly purify them with high yields. Studies in the guinea pig model confirm efficacy of the vaccine candidate, demonstrate that single-cycle replication is necessary for complete protection by the VRP vaccine, and show that postexposure vaccination can confer protection from lethal outcome.
A rapid LASV detection method based on CRISPR-Cas13a and recombinase aided amplification with special lateral-flow test strips
Lassa virus (LASV) is a high-risk pathogen associated with severe viral hemorrhagic fever in both humans and animals. Owing to its significant treatment challenges and high infectivity, LASV is classified as a biosafety level 4 (BSL-4) pathogen. It is essential to establish a rapid LASV detection method to prevent and control the disease. To address the biosecurity threats caused by LASV, in this study, we developed a new test method for LASV detection by combining the recombinase-mediated isothermal amplification (RAA) and CRISPR-Cas13a detection technology. The detection efficiency of this method was evaluated and compared with existing methods. The results demonstrate that this new detection maintains relatively high sensitivity and specificity, while having excellent simplicity and rapidity. The sensitivity of the method for detecting the LASV can achieve a threshold of 10 1 copies/µL using fluorescence detection in 90 min and 10 2 copies/µL with lateral flow strip detection in just an hour, which only needs a simple constant temperature equipment to achieve. The application of this detection method holds substantial biosecurity significance for underdeveloped regions (e.g., West Africa), as well as for countries like China, which have a vast territory and uneven development of medical testing levels in various regions.
Serological Evidence of Lassa Virus Exposure in Non-Mastomys Small Mammals Within a Hyperendemic Region of North-Central Nigeria: A Pilot Study
Lassa fever (LF), a severe hemorrhagic disease endemic to West Africa, is primarily transmitted by rodents of the genus Mastomys, particularly Mastomys natalensis, which serve as the main reservoirs of Lassa virus (LASV). There have been reports of high prevalence of LF in Nigeria, and outbreaks tend to be recurrent yet geographically restricted, implying that additional ecological or epidemiological factors influence the distribution of the disease beyond the mere presence of M. natalensis. However, national-scale data on LASV prevalence in rodent populations remain scarce. To address this gap, a targeted small mammal survey was conducted over a four-month period (May to August 2024) in Otukpo Local Government Area (LGA) of Benue State, north-central Nigeria. Rodents and other small mammals were trapped across three purposively selected wards identified as high-risk areas based on prior reports of occurrence of such small mammals in the areas and the informal settlements in which the selected wards were located in in Otukpo LGA. Analysis of the samples revealed no statistically significant variation in LASV prevalence among the study sites, indicating a relatively uniform, low-level exposure risk across the LGA and region. However, a marginally significant difference in LASV detection between plasma and serum samples suggests that sample type and storage conditions may influence serological sensitivity. These findings highlight the importance of refining diagnostic protocols, broadening surveillance to include additional rodent hosts, and integrating ecological data with public health strategies to improve early warning systems and strengthen Lassa fever control efforts.
An Outbreak of Ebola Virus Disease in the Lassa Fever Zone
Background. Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs. Methods. Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities. Results. Augustine Goba, director of the KGH Lassa laboratory, diagnosed the first documented case of EVD in Sierra Leone, on 25 May 2014. Thereafter, KGH received and cared for numbers of patients with EVD that quickly overwhelmed the capacity for safe management. Numerous healthcare workers contracted and lost their lives to EVD. The vast majority of subsequent EVD cases in West Africa can be traced back to a single transmission chain that includes this first diagnosed case. Conclusions. Responding to the challenges of confronting 2 hemorrhagic fever viruses will require continued investments in the development of countermeasures (vaccines, therapeutic agents, and diagnostic assays), infrastructure, and human resources.
Rapid diagnostic tests for Lassa fever: what do we aim for?
Lassa virus (LASV) is a high-consequence pathogen endemic to west Africa that causes annual outbreaks with substantial mortality. Besides transmission from the rodent reservoir to humans, human-to-human transmission can occur through contact with blood and other bodily fluids.1,2 To date, people in endemic regions presenting with the initially unspecific clinical symptoms of Lassa fever are mostly tested for LASV only after empirical treatment with antimalarials and antibiotics has failed. The sensitivity of the test was poorly correlated with viral load, as false-negative test results also occurred in highly viraemic individuals.3 Based on the understanding that RDTs are often imperfect diagnostic tools, they could still have a highly positive impact on patient management when used wisely. [...]to correctly interpret the results of this study, we need to first ask what the minimum acceptable test performance characteristics of an RDT are for this high-consequence pathogen. [...]tests have proven sufficiently accurate in the field, we must continue to rely on an accelerated implementation of molecular diagnostic assays for Lassa fever diagnosis.