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Abstract Lassa virus, the cause of deadly Lassa fever, is endemic in West Africa, where thousands of cases occur on an annual basis. Nigeria continues to report increasingly severe outbreaks of Lassa Fever each year and there are currently no approved vaccines or therapeutics for the prevention or treatment of Lassa Fever. Given the high burden of disease coupled with the potential for further escalation due to climate change the WHO has listed Lassa virus as a priority pathogen with the potential to cause widespread outbreaks. Several candidate vaccines have received support and have entered clinical trials with promising early results. This review focuses on the current state of vaccine and therapeutic development for LASV disease and the potential of these interventions to advance through clinical trials. The growing burden of LASV disease in Africa highlights the importance of advancing preclinical and clinical testing of vaccines and therapeutics to respond to the growing threat of LASV disease.

Abstract Background Understanding the level of exposure to Lassa virus (LASV) in at-risk communities allows for the administration of effective preventive interventions to mitigate epidemics of Lassa fever. We assessed the seroprevalence of LASV antibodies in rural and semiurban communities of two cosmopolitan cities in Nigeria with poorly understood Lassa epidemiology. Methods A cross-sectional study was conducted in ten communities located in the Abuja Municipal Area Council (AMAC), Abuja, and Ikorodu Local Government Area (LGA), Lagos, from February 2nd to July 5th, 2022. Serum samples collected from participants were analyzed for IgG and IgM antibodies using a ReLASV® Pan-Lassa NP IgG/IgM enzyme-linked immunosorbent assay (ELISA) kit. A questionnaire administered to participants collected self-reported sociodemographic and LASV exposure information. Seroprevalence of LASV IgG/IgM was estimated overall, and by study site. Univariate and multivariate log-binomial models estimated unadjusted and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CI) for site-specific risk factors for LASV seropositivity. Grouped Least Absolute Shrinkage and Selection Operator (LASSO) was used for variable selection for multivariate analysis. Results A total of 628 participants with serum samples were included in the study. Most participants were female (434, 69%), married (459, 73%), and had a median age of 38 years (interquartile range 28–50). The overall seroprevalence was 27% (171/628), with a prevalence of 33% (126/376) in Abuja and 18% (45/252) in Lagos. Based on site-specific grouped LASSO selection, enrollment in the dry season (vs. wet; aPR, 95% CI: 1.73, 1.33–2.24), reported inconsistent washing of fruits and vegetables (aPR, 95% CI: 1.45, 1.10–1.92), and a positive malaria rapid test (aPR, 95% CI: 1.48, 1.09-2.00) were independently associated with LASV seropositivity in Abuja, whereas, only a self-reported history of rhinorrhea (PR, 95% CI: 2.21, 1.31–3.72) was independently associated with Lassa seropositivity in Lagos. Conclusions The LASV seroprevalence was comparable to that in other areas in Nigeria. Our findings corroborate those from other studies on the importance of limiting human exposure to rodents and focusing on behavioral factors such as poor hygiene practices to reduce exposure to LASV.

Lassa virus genome consists of two single-stranded, negative-sense RNA segments that lie in the genus Arenavirus. The disease associated with the Lassa virus is distributed all over the world, with approximately 3,000,000–5,000,000 infections diagnosed annually in West Africa. It shows high health risks to the human being. Previous research used the evolutionary time scale and adaptive evolution to describe the Lassa virus population pattern. However, it is still unclear how the Lassa virus takes advantage of synonymous codons. In this study, we analyzed the codon usage bias in 162 Lassa virus strains by calculating and comparing the nucleotide contents, effective number of codons (ENC), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and others. The results disclosed that LASV strains are rich in A/T. The average ENC value indicated a low codon usage bias in LASVs. The ENC-plot, neutrality plot and parity rule 2 plot demonstrated that, besides mutational pressure, other factors like natural selection also contributed to codon usage bias. This study is significant because it described the pattern of codon usage in the genomes of the Lassa viruses and provided the information needed for a fundamental evolutionary study of them.

Abstract This study aims to formulate a mathematical framework to examine how the Lassa virus spreads in humans of opposite genders. The stability of the model is analyzed at an equilibrium point in the absence of the Lassa fever. The model’s effectiveness is evaluated using real-life data, and all the parameters needed to determine the basic reproduction number are estimated. Sensitivity analysis is performed to pinpoint the crucial parameters significantly influencing the spread of the infection. The interaction between threshold parameters and the basic reproduction number is simulated. Control theory is employed to devise and evaluate strategies, such as awareness campaigns, advocating condom usage, and deploying rodenticides to reduce the possibility of virus transmission efficiently.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.

Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021–2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown – specifically relating to pathogen diversity, evolution, and transmission – the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the in vitro antiviral activity of Arevirumab-3 against LASV Togo was equivalent to lineage II and III strains, the reduced protection in macaques against Togo likely reflects the faster disease course of LASV Togo in macaques than other strains. This data causes concern regarding the ability of heterologous vaccines and treatments to provide cross protection against lineage VII LASV isolates.

The spread of Lassa virus (LASV) in Guinea, Liberia and Sierra Leone, which together are named the Mano River Union (MRU) area, was examined phylogeographically. To provide a reliable evolutionary scenario, new rodent-derived, whole LASV sequences were included. These were generated by metatranscriptomic next-generation sequencing from rodents sampled between 2003 and 2020 in 21 localities of Guinea and Sierra Leone. An analysis was performed using BEAST to perform continuous phylogeographic inference and EvoLaps v36 to visualize spatio-temporal spread. LASV was identified as expected in its primary host reservoir, the Natal multimammate mouse (Mastomys natalensis), and also in two Guinean multimammate mice (Mastomys erythroleucus) in northern Sierra Leone and two rusty-bellied brush-furred mice (Lophuromys sikapusi) in southern Sierra Leone. This finding is consistent with the latter two species being secondary host reservoirs. The strains in these three species were very closely related in LASV lineage IV. Phylogenetic analysis indicated that the most recent common ancestor of lineage IV existed 316–374 years ago and revealed distinct, well-supported clades from Sierra Leone (Bo, Kabala and Kenema), Guinea (Faranah, Kissidougou-Guekedou and Macenta) and Liberia (Phebe-Ganta). The phylogeographic scenario suggests southern Guinea as the point of origin of LASV in the MRU area, with subsequent spread to towards Mali, Liberia and Sierra Leone at a mean speed of 1.6 to 1.1 km/year.

ABSTRACTThe Natal multimammate mouse (Mastomys natalensis) is the host of Lassa mammarenavirus, causing Lassa haemorrhagic fever in West Africa. As there is currently no operational vaccine and therapeutic drugs are limited, we explored rodent control as an alternative to prevent Lassa virus spillover in Upper Guinea, where the disease is highly endemic in rural areas. In a seven-year experiment, we distributed rodenticides for 10–30 days once a year and, in the last year, added intensive snap trapping for three months in all the houses of one village. We also captured rodents both before and after the intervention period to assess their effectiveness by examining alterations in trapping success and infection rates (Lassa virus RNA and IgG antibodies). We found that both interventions reduced the rodent population by 74–92% but swiftly rebounded to pre-treatment levels, even already six months after the last snap-trapping control. Furthermore, while we observed that chemical control modestly decreased Lassa virus infection rates annually (a reduction of 5% in seroprevalence per year), the intensive trapping unexpectedly led to a significantly higher infection rate (from a seroprevalence of 28% before to 67% after snap trapping control). After seven years, we conclude that annual chemical control, alone or with intensive trapping, is ineffective and sometimes counterproductive in preventing Lassa virus spillover in rural villages. These unexpected findings may result from density-dependent breeding compensation following culling and the survival of a small percentage of chronically infected rodents that may spread the virus to a new susceptible generation of mice.

Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we developed a novel LASV reverse genetics system which, to our knowledge, is the first to study the complete LASV life cycle under BSL-2 conditions. Viral particles can be produced efficiently when LASV minigenomic RNA harbouring minimal viral cis-elements and reporter genes is transfected into a helper cell line stably expressing viral NP, GP, Z and L proteins. The resulting defective virions, named LASVmg, can propagate only in the helper cell line, providing a BSL-2 model to study the complete LASV life cycle. Using this model, we found that a previously reported cellular receptor α-dystroglycan is dispensable for LASVmg infection. Furthermore, we showed that ribavirin can inhibit LASVmg infection by inducing viral mutations. This new BSL-2 system should facilitate studying the LASV life cycle and screening antivirals.

We evaluated the in vitro effects of lyophilization for 2 vesicular stomatitis virus–based vaccines by using 3 stabilizing formulations and demonstrated protective immunity of lyophilized/reconstituted vaccine in guinea pigs. Lyophilization increased stability of the vaccines, but specific vesicular stomatitis virus–based vaccines will each require extensive analysis to optimize stabilizing formulations.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome. Validation of docking protocols were achieved with reference inhibitors of the respective targets. Our in silico docking screen identified five drugs (dexamethasone, tadalafil, mefloquine, ergocalciferol, and flunarizine) with strong predicted binding affinity to LASV proteins involved in the formation of the vRNP. We used cell-based functional assays to evaluate the antiviral activity of the five selected drugs. We found that flunarizine, a calcium-entry blocker, inhibited the vRNP activity of LASV and LCMV and virus surface glycoprotein fusion activity required for mammarenavirus cell entry. Consistently with these findings, flunarizine significantly reduced peak titers of LCMV in a multi-step growth kinetics assay in human A549 cells. Flunarizine is being used in several countries worldwide to treat vertigo and migraine, supporting the interest in exploring its repurposing as a candidate drug to treat LASV infections.

Abstract Background Lassa fever is a hemorrhagic disease caused by Lassa virus (LASV), which has been classified by the World Health Organization as one of the top infectious diseases requiring prioritized research. Previous studies have provided insights into the classification and geographic characteristics of LASV lineages. However, the factor of the distribution and evolution characteristics and phylodynamics of the virus was still limited. Methods To enhance comprehensive understanding of LASV, we employed phylogenetic analysis, reassortment and recombination detection, and variation evaluation utilizing publicly available viral genome sequences. Results The results showed the estimated the root of time of the most recent common ancestor (TMRCA) for large (L) segment was approximately 634 (95% HPD: [385879]), whereas the TMRCA for small (S) segment was around 1224 (95% HPD: [10301401]). LASV primarily spread from east to west in West Africa through two routes, and in route 2, the virus independently spread to surrounding countries through Liberia, resulting in a wider spread of LASV. From 1969 to 2018, the effective population size experienced two significant increased, indicating the enhanced genetic diversity of LASV. We also found the evolution rate of L segment was faster than S segment, further results showed zinc-binding protein had the fastest evolution rate. Reassortment events were detected in multiple lineages including sub-lineage IIg, while recombination events were observed within lineage V. Significant amino acid changes in the glycoprotein precursor of LASV were identified, demonstrating sequence diversity among lineages in LASV. Conclusion This study comprehensively elucidated the transmission and evolution of LASV in West Africa, providing detailed insights into reassortment events, recombination events, and amino acid variations.

Odontogenic bone tumor (OT) is a rare pathology in the world, but it is very common in developing countries; its etiology is still unknown, and it causes serious deformities of the mandible and maxilla if it is not operated upon soon. Lassa virus (LASV) belongs to the Arenaviridae family, and its reservoir is a rodent of the genus Mastomys. The transmission of the LASV to humans can occur through ingestion or inhalation by contact with dirty objects, the consumption of contaminated food, or exposure to wounds, as rodents shed the virus in their urine and excrement. In this observational study, we aim to evaluate the presence of LASV in OT patient tissues collected in the Democratic Republic of the Congo. For this purpose, a group of nine patients affected by OT were enrolled, and the tissues derived from the surgery were collected. In total, 81.5% of the tissues were positive for LASV presence. Interestingly, we found that not only was the tumor LASV-positive, but in some cases, the bone was close to the tumor and the oral mucosa lining. These preliminary data could suggest the hypothesis that LASV may be involved with the onset of OT.

This study aims to analyze the dynamics of Lassa fever transmission and its impact on the brain and spinal cord then devise and analyze preventive actions. The stability of the infection-free equilibrium point is evaluated; the model’s precision is examined using empirical data; and all parameters are estimated and fitted. Subsequently, the basic reproductive number is determined, and subpopulation trends are observed over time. Sensitivity analysis is conducted to identify critical drivers influencing transmission dynamics. Two-dimensional plots visualize the impact of crucial parameters on the reproductive number. Through a comprehensive literature review and case analysis, an association between Lassa fever and various disabilities is established, including conditions such as encephalitis, hearing loss, ataxia, neuropsychiatric manifestations, meningitis, seizures, and coma. Solutions are devised and analyzed to enhance early detection, treatment, and mitigation of disease.

The article presents an analysis of studies assessing the effectiveness of new nonspecific medications against hemorrhagic fevers caused by arenaviruses. The possible targets for nonspecific medications, classes of researched antiviral preparations, methods of preclinical investigation of antiviral preparations in vitro and on laboratory animals, as well as prospects for their use in healthcare at present are considered. It has been shown that the level of development of nonspecific medications against hemorrhagic fevers caused by arenaviruses is significantly inferior to those against filovirus infections. Favipiravir should currently be considered as the most effective nonspecific medication against hemorrhagic fevers caused by arenaviruses.

Lassa fever, caused by Lassa virus (LASV), is endemic to West Africa, where ≈300,000 illnesses and ≈5,000 deaths occur annually. LASV is primarily spread by infected multimammate rats via urine and fomites, highlighting the need to understand the environmental fate of LASV. We evaluated persistence of LASV Josiah and Sauerwald strains on surfaces, in aqueous solutions, and with sodium hypochlorite disinfection. Tested strains were more stable in deionized water (first-order rate constant [k] for Josiah, 0.23 days; for Sauerwald, k = 0.34 days) than primary influent wastewater (Josiah, k = 1.3 days; Sauerwald, k = 1.9 days). Both strains had similar decay rates on high-density polyethylene (Josiah, k = 4.3 days; Sauerwald, k = 2.3 days) and stainless steel (Josiah, k = 5.3 days; Sauerwald, k = 2.7 days). Sodium hypochlorite was highly effective at inactivating both strains. Our findings can inform future risk assessment and management efforts for Lassa fever.

High-consequence pathogens such as the Ebola, Marburg, and Lassa viruses are handled in maximum-containment biosafety level 4 (BSL-4) laboratories. Genetic material is often isolated from such viruses and subsequently removed from BSL-4 laboratories for a multitude of downstream analyses using readily accessible technologies and equipment available at lower-biosafety level laboratories. However, it is essential to ensure that these materials are free of viable viruses before removal from BSL-4 laboratories to guarantee sample safety. This study details the in-house procedure used for validating the inactivation of Ebola, Marburg, and Lassa virus cultures after incubation with AVL lysis buffer (Qiagen) and ethanol. This study’s findings show that no viable virus was detectable when high-titer cultures of Ebola, Marburg, and Lassa viruses were incubated with AVL lysis buffer for 10 min, followed by an equal volume of 95% ethanol for 3 min, using a method with a sensitivity of ≤0.8 log10 TCID50 as the limit of detection.

There are currently no prophylactic vaccines licensed to protect against Lassa fever caused by Lassa virus (LASV) infection. The Emergent BioSolutions (EBS) vaccine candidate, EBS-LASV, is being developed for the prevention of Lassa fever. EBS-LASV is a live-attenuated recombinant Vesicular Stomatitis Virus (rVSV)-vectored vaccine encoding the surface glycoprotein complex (GPC) from LASV and has two attenuating vector modifications: a gene shuffle of the VSV N gene and a deletion of the VSV G gene. Preclinical studies were performed to evaluate EBS-LASV’s neurovirulence potential following intracranial (IC) injection and to determine the biodistribution and vector replication following intramuscular (IM) inoculation in mice. In addition, the potential EBS-LASV toxicity was assessed using repeated-dose IM EBS-LASV administration to rabbits. All mice receiving the IC injection of EBS-LASV survived, while mice administered the unattenuated control vector did not. The vaccine was only detected in the muscle at the injection site, draining lymph nodes, and the spleen over the first week following IM EBS-LASV injection in mice, with no detectable plasma viremia. No toxicity was observed in rabbits receiving a three-dose regimen of EBS-LASV. These studies demonstrate that EBS-LASV is safe when administered to animals and supported a first-in-human dose-escalation, safety, and immunogenicity clinical study.

Matriglycan, a recently characterized linear polysaccharide, is composed of alternating xylose and glucuronic acid subunits bound to the ubiquitously expressed protein α-dystroglycan (α-DG). Pathogenic arenaviruses, like the Lassa virus (LASV), hijack this long linear polysaccharide to gain cellular entry. Until recently, it was unclear through what mechanisms LASV engages its matriglycan receptor to initiate infection. Additionally, how matriglycan is synthesized onto α-DG by the Golgi-resident glycosyltransferase LARGE1 remained enigmatic. Recent structural data for LARGE1 and for the LASV spike complex informs us about the synthesis of matriglycan as well as its usage as an entry receptor by arenaviruses. In this review, we discuss structural insights into the system of matriglycan generation and eventual recognition by pathogenic viruses. We also highlight the unique usage of matriglycan as a high-affinity host receptor compared with other polysaccharides that decorate cells.

Lassa virus (LASV) causes an acute multisystemic hemorrhagic fever in humans known as Lassa fever, which is endemic in several African countries. This manuscript focuses on the progression of disease in cynomolgus macaques challenged with aerosolized LASV and serially sampled for the development and progression of gross and histopathologic lesions. Gross lesions were first noted in tissues on day 6 and persisted throughout day 12. Viremia and histologic lesions were first noted on day 6 commencing with the pulmonary system and hemolymphatic system and progressing at later time points to include all systems. Immunoreactivity to LASV antigen was first observed in the lungs of one macaque on day 3 and appeared localized to macrophages with an increase at later time points to include immunoreactivity in all organ systems. Additionally, this manuscript will serve as a detailed atlas of histopathologic lesions and disease progression for comparison to other animal models of aerosolized Arenaviral disease.

Lassa fever virus (LASV) is the causative agent of Lassa fever, a disease endemic in West Africa. Exploring the relationships between environmental factors and LASV transmission across ecologically diverse regions can provide crucial information for the design of appropriate interventions and disease monitoring. We investigated LASV exposure in 2 ecologically diverse regions of Guinea. Our results showed that exposure to LASV was heterogenous between and within sites. LASV IgG seropositivity was 11.9% (95% CI 9.7%–14.5%) in a coastal study site in Basse-Guinée, but it was 59.6% (95% CI 55.5%–63.5%) in a forested study site located in Guinée Forestière. Seropositivity increased with age in the coastal site. We also found significant associations between exposure risk for LASV and landscape fragmentation in coastal and forested regions. Our study highlights the potential link between environmental change and LASV emergence and the urgent need for research on land management practices that reduce disease risks.

We phylogenetically compared sequences of the zoonotic Lassa virus (LASV) obtained from Mastomys rodents in seven localities across the highly endemic Edo and Ondo States within Nigeria. Sequencing 1641 nt from the S segment of the virus genome, we resolved clades within lineage II that were either limited to Ebudin and Okhuesan in Edo state (2g-beta) or along Owo-Okeluse-Ifon in Ondo state (2g-gamma). We also found clades within Ekpoma, a relatively large cosmopolitan town in Edo state, that extended into other localities within Edo (2g-alpha) and Ondo (2g-delta). LASV variants from M. natalensis within Ebudin and Ekpoma in Edo State (dated approximately 1961) were more ancient compared to those from Ondo state (approximately 1977), suggesting a broadly east-west virus migration across south-western Nigeria; a pattern not always consistent with LASV sequences derived from humans in the same localities. Additionally, in Ebudin and Ekpoma, LASV sequences between M. natalensis and M. erythroleucus were interspersed on the phylogenetic tree, but those from M. erythroleucus were estimated to emerge more recently (approximately 2005). Overall, our results show that LASV amplification in certain localities (reaching a prevalence as high as 76% in Okeluse), anthropogenically-aided spread of rodent-borne variants amidst the larger towns (involving communal accommodation such as student hostels), and virus-exchange between syntopic M. natalensis and M. erythroleucus rodents (as the latter, a savanna species, encroaches southward into the degraded forest) pose perpetual zoonotic hazard across the Edo-Ondo Lassa fever belt, threatening to accelerate the dissemination of the virus into non endemic areas.

The unrelenting menace of the Lassa virus, characterized by its high mortality rate and the potential for global dissemination, underscores an urgent call for its comprehensive eradication to safeguard global public health. In light of this, this research embarked on an extensive investigation of trans-N-feruloyltyramine (FLTM), a compound derived from Cissampelos pareira. This study encompassed a thorough examination of its structural characteristics, utilizing spectroscopic analyses including FT-IR, UV, and NMR, with the aim of elucidating its electronic, structural, and biological properties. Seamlessly integrating experimental and theoretical approaches at the DFT/B3LYP/def2SVP level of theory in FLTM_dmso, FLTM_gas, FLTM_H2O, and FLTM_MeOH solvation. Moreover, solvation dynamic simulation highlighted FLTM's heightened total energy and enhanced solubility across dimethyl sulfoxide (DMSO), water (H2O), and methanol (MeOH) phases, signifying efficient distribution to target sites and emphasizing its potential as a drug candidate. Conversely, FLTM_gas exhibited lower total energy. Electronic properties further elucidated FLTM's reactivity and kinetic stability, with FLTM_DMSO displaying the lowest energy gap among solvents and corresponding values of 1.4168, 4.2159, 4.2175, and 4.2749 eV. These findings mirrored the compound's higher reactivity and lower kinetic stability compared to FLTM_H2O, FLTM_gas, and FLTM_MeOH, aligning with principles of chemical hardness and softness. Results of the molecular docking introduced FLTM as a potential Lassa fever treatment candidate, surpassing Ribavirin in binding affinities with Lassa virus target receptors. FLTM exhibited binding energies of -6.5 kcal/mol, -7.2 kcal/mol, and -8.2 kcal/mol in 7UOT, 3MX5, and 3MX2, respectively, establishing interactions with crucial amino acid residues. These findings strongly advocate for FLTM's efficacy, meriting further in vitro and in vivo investigations for clinical validation.

ABSTRACTRecent viral hemorrhagic fever (VHF) disease outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV) in West Africa are unique and alarming. The intents of this editorial are to highlight what is known about these viruses and the disease outbreaks that they cause in the African continent and elsewhere and to raise awareness of a related virus called Lassa virus (LASV) that causes endemic viral hemorrhagic fever infections and frequent outbreaks in West Africa.

ABSTRACTMammarenaviruses, a genus of the family Arenaviridae, are capable of infecting mammals and are primarily found in rodent reservoirs worldwide. Mammarenaviruses can be transmitted to humans through contact with infected rodents, and though infection is often asymptomatic, some members of this genus can cause viral haemorrhagic fever which has mortality rates ranging from 1% to 50%. These viruses are typically restricted geographically, based on the geographical range of their host reservoirs. Lymphocytic choriomeningitis virus (LCMV) was previously thought to be the only mammarenavirus found across the globe. However, recent discoveries of two novel human mammarenaviruses, Wenzhou Virus (WENV) and Plateau Pika Virus (PPV), in Asia and Southeast Asia show that mammarenaviruses are more widespread than previously thought. This editorial article aims to raise awareness about these emerging viruses, their genetic and ecological diversities, and clinical significance, and to encourage further study of these emerging viruses.

The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient T-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.

Lassa fever (LF) is endemic to broad regions of West Africa. Infection with Lassa virus (LASV), the etiologic agent of LF, results in a spectrum of clinical signs in humans, including severe and lethal hemorrhagic disease. Person-to-person transmission occurs through direct contact with body fluids or contaminated bedding and clothing. To investigate transmission risk in acute LASV infection, we evaluated viral RNA and infectious virus obtained from conjunctival, nasal, oral, genital, and rectal swab specimens from guinea pigs modelling lethal and non-lethal LF. Viral RNA and infectious virus were detected in all specimen types beginning 8 days post infection, prior to onset of fever. In the pre-clinical and clinical period, virus was isolated from a subset of nasal, oral, genital, and rectal swabs, and from all conjunctival swabs. Overall, conjunctival and nasal specimens most frequently yielded infectious virus. These findings indicate mucosal transmission risk based on virus isolation from various sites early in infection and support potential utility of minimally invasive specimen evaluation by RT-qPCR for LASV diagnostics.

Lassa fever (LF) is a neglected tropical disease that is caused by Lassa virus (LASV), a human hemorrhagic fever-causing mammarenavirus. A notable sequela of LF is sensorineural hearing loss (SNHL) that can develop in about 33% of the patients. Animal models of LF-associated SNHL have been limited in size and scope because LASV is a biosafety level 4 (BSL4) pathogen that requires its handling in a high biocontainment laboratory. In this report, we describe the development of an alternative arenavirus hearing loss model by infecting outbred Hartley guinea pigs with a virulent strain (rP18) of the Pichinde virus (PICV), which is a guinea pig-adapted mammarenavirus that has been used as a surrogate model of mammarenaviral hemorrhagic fevers in a conventional (BSL2) laboratory. By measuring auditory brainstem response (ABR) throughout the course of the virulent rP18 PICV infection, we noticed that some of the animals experienced an acute but transient level of hearing loss. Cochleae of hearing-impaired animals, but not of controls, had demonstrable viral RNA by quantitative RT-PCR, indicating the presence of virus in the affected inner ear with no overt histopathological changes. In contrast, neither the outbred Hartley guinea pigs infected with a known avirulent strain (rP2) of PICV nor those that were mock-infected showed any evidence of hearing loss or viral infection of the inner ear. This is the first report of an immunocompetent small animal model of mammarenavirus-induced hearing loss that can be used to evaluate potential therapeutics against virus-induced hearing impairment under a conventional laboratory setting.

Lassa fever is a viral hemorrhagic fever treated with supportive care and the broad-spectrum antiviral drug ribavirin. The pathophysiology, especially the role of hyperinflammation, of this disease is unknown. We report successful remission of complicated Lassa fever in 2 patients in Nigeria who received the antiinflammatory agent dexamethasone and standard ribavirin.

Arenaviruses are emerging enveloped negative-sense RNA viruses that cause neurological and hemorrhagic diseases in humans. Currently, no FDA-approved vaccine or therapeutic agent is available except for ribavirin, which must be administered early during infection for optimum efficacy. A hallmark of arenavirus infection is rapid and efficient immune suppression mediated by the exonuclease domain encoded by the nucleoprotein. This exonuclease is therefore an attractive target for the design of novel antiviral drugs since exonuclease inhibitors might not only have a direct effect on the enzyme but could also boost viral clearance through stimulation of the innate immune system of the host cell. Here, in silico screening and an enzymatic assay were used to identify a novel, specific but weak inhibitor of the arenavirus exonuclease, with IC50 values of 65.9 and 68.6 µM for Mopeia virus and Lymphocytic choriomeningitis virus, respectively. This finding was further characterized using crystallographic and docking approaches. This study serves as a proof of concept and may have assigned a new therapeutic purpose for the bisphosphonate family, therefore paving the way for the development of inhibitors against Arenaviridae.

Lassa fever is a natural focal disease dangerous for humans. In the larger part of sub-Saharan West Africa 37.7 million people in 14 countries live in areas where living conditions are suitable for zoonotic transmission of the virus from secretions of infected rodents of the species Mastomys natalensis. Routes of transmission can be via alimentary, airborne dust or airborne droplet pathways in case of accidental human contact with secretions of infected rodents. Mastomys natalensis penetrates into residence and place of storage of food and drinking water. In addition, the residents use such animals for food, so infection is also possible upon butchering carcasses. The etiological agent of this disease is the Lassa virus being one of the members of the Arenaviridae family. Unlike other arenavirus infections (e.g., Argentine and Bolivian fevers caused by Junin viruses and Machupo, respectively), human infection with Lassa virus can also occur from person to person. Cases of nosocomial infection among patients in conditions of poor hygiene and through contaminated medical equipment are described. Medical workers become infected during surgical operations or through contact with patients, because the pathogen can be transmitted via blood, saliva, vomiting, stool or urine. In endemic territories, Lassa fever is associated with significant morbidity, because 500 thousand clinical cases and due to 5 to 10 thousand fatal outcomes of this disease are registered annually (i.e. 12% mortality). The likelihood that this disease will become a more widespread threat worldwide may be associated with increased globalization as well as climate change leading to the expansion of the Lassa fever endemic zone into regions suitable for the settlement of M. natalensis and other rodent species capable of lifelong pathogen carriage. Among hospitalized persons with severe hemorrhagic symptoms, the mortality rate can be very high ranging from 14 to 89.5%. But in the majority of cases, the disease proceeds asymptomatically, and due to its long-term incubation period all ill subjects may be a source of infection, especially travelling at long distance by plane or train. Clinically evident disease occurs in the form of various nonspecific symptoms from malaise, fever, sore throat and chest, cough, myalgia and gastrointestinal disorders to signs of central nervous system disorders. The diagnosis of Lassa fever is often difficult due to the similarity of its course with other viral diseases common in Africa or malaria or typhoid fever. More specific symptoms for Lassa fever are revealed as conjunctivitis, hepatitis, pharyngitis, tonsillitis as well as developing oropharyngeal ulcers. Severe disease is complicated by abnormal bleeding, generalized edema, respiratory failure, hypotension, proteinuria, transaminitis, encephalopathy. Deafness develops in about 20% of cases. Multiple organ failure and open bleeding lead to death. The review is devoted to analyzing publications on the etiology, epidemiology and clinical picture of Lassa fever due to a threat of its importation with sick subjects to the territory of the Russian Federation.

Lassa virus (LASV) is a zoonotic pathogen endemic throughout western Africa and is responsible for a human disease known as Lassa fever (LF). Historically, LASV has been emphasized as one of the greatest public health threats in West Africa, with up to 300,000 cases and 5000 associated deaths per year. This, and the fact that the disease has been reported in travelers, has driven a rapid production of various vaccine candidates. Several of these vaccines are currently in clinical development, despite limitations in understanding the immune response to infection. Alarmingly, the host immune response has been implicated in the induction of sensorineural hearing loss in LF survivors, legitimately raising safety questions about any future vaccines as well as efficacy in preventing potential hearing loss. The objective of this article is to revisit the importance and prevalence of LF in West Africa, with focus on Nigeria, and discuss current therapeutic approaches and ongoing vaccine development. In addition, we aim to emphasize the need for more scientific studies relating to LF-associated hearing loss, and to promote critical discussion about potential risks and benefits of vaccinating the population in endemic regions of West Africa.

Objectives: This summary on Lassa virus (LASV) infection and Lassa fever disease (LF) was developed from a clinical perspective to provide clinicians with a condensed, accessible understanding of the current literature. The information provided highlights pathogenesis, clinical features, and diagnostics emphasizing therapies and vaccines that have demonstrated potential value for use in clinical or research environments. Methods: We conducted an integrative literature review on the clinical and pathological features, vaccines, and treatments for LASV infection, focusing on recent studies and in vivo evidence from humans and/or non-human primates (NHPs), when available. Results: Two antiviral medications with potential benefit for the treatment of LASV infection and 1 for post-exposure prophylaxis were identified, although a larger number of therapeutic candidates are currently being evaluated. Multiple vaccine platforms are in pre-clinical development for LASV prevention, but data from human clinical trials are not yet available. Conclusion: We provide succinct summaries of medical countermeasures against LASV to give the busy clinician a rapid reference. Although there are no approved drugs or vaccines for LF, we provide condensed information from a literature review for measures that can be taken when faced with a suspected infection, including investigational treatment options and hospital engineering controls.

During the 2018 Lassa fever outbreak in Nigeria, samples from patients with suspected Lassa fever but negative Lassa virus PCR results were processed through custom gene expression array cards and metagenomic sequencing. Results demonstrated no single etiology, but bacterial and viral pathogens (including mixed co-infections) were detected.

Lassa fever is a fatal zoonotic hemorrhagic disease caused by Lassa virus carried by multimammate rats, which are widely spread in West Africa. In this work, a fractional-order model for Lassa fever transmission dynamics is developed and analysed. The model involves transmissions from rodents-to-human, person-to-person, as well as from Lassa virus infested environment/surfaces. The basic properties of the model such as positivity of solutions, and local stability of the disease-free equilibrium are determined. The reproduction number, $ \mathcal{R}_0 $, of the model is determined using the next generation method and it is used to determine the suitable conditions for disease progression as well as its containment. In addition, we performed sensitivity analysis of the model parameters using the Latin Hypercube Sampling (LHS) scheme to determine the most influential processes on the disease threshold, and determined the key processes to be focused on if the infection is to be curtailed. Moreover, fixed point theory was used to prove the existence and uniqueness of non-trivial solutions of the model. We used the Adams-Bashforth Moulton method to solve the model system numerically for different orders of the fractional derivative. Our results show that using various interventions and control measures such as controlling environmental contamination, reducing rodents-to-humans transmission and interpersonal contact, can significantly help in curbing new infections. Morestill, we observe that an increase in the memory effect, i.e. dependence on future values of the model on the previous states predicts lower peak values of infection cases in the short term, but higher equilibrium values in the long term.

Emergence and re-emergence of four types of severely infectious viruses have claimed significant numbers of lives when anthropogenic activities contribute to the mutagenesis of these pathogens and infectivity of these pathogens has been noticeably altered. However, both point and non-point sources can transport these viruses in water treatment and resource recovery facilities (RRF) where the presence of these pathogens in aerosolized form or in suspension can cause astronomical public health concerns. Hence, numerous scientific studies have been reviewed to comprehend the possible inactivation mechanisms of those viruses in aqueous phase where thermal-, photo-, and chemical-inactivation have confirmed their effectiveness in restraining those viruses and inactivation mechanisms are the major focuses to apprehend the quick and cost-effective virus removal process from water and RRF. Although practical applications of nano-sized disinfectants have challenged researchers, those disinfectants can completely kill the viruses and hamper RNA/DNA replication without any sign of reactivation or repair. Moreover, limitations and future research potential are discussed so that efficacious strategic management for a treatment facility can be developed at the forefront of fighting tactics against an epidemic or a pandemic. Enumerations, besides state-of-the-art detection techniques with gene sequences, are mentioned for these viruses. HIGHLIGHTS UV and FUVC can effectively inactivate corona- and ebolaviruses.; Nanostructured disinfectants have potential to inactivate the emerging viruses by forming ROSs in both solid and liquid phase.; Disintegration of capsid protein and nucleic acid is imperative to inactivate viruses.; A strategic framework to develop early warning in the community should be established.; This kind of review manuscript is extremely rare.;

Lassa virus (LASV) is the most prevalent arenavirus afflicting humans and has high potential to become a threat to global public health. The transmembrane domain (TM) of the LASV glycoprotein complex forms critical interactions with the LASV stable signal peptide that are important for the maturation and fusion activity of the virus. A further study of the structure-based molecular mechanisms is required to understand the role of the TM in the lifecycle of LASV in greater detail. However, it is challenging to obtain the TM in high quantity and purity due to its hydrophobic nature which results in solubility issues that makes it prone to aggregation in typical buffer systems. Here, we designed a purification and detergent screen protocol for the highly insoluble TM to enhance the yield and purity for structural studies. Based on the detergents tested, the TM had the highest incorporation in LMPG. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were utilized to confirm the best detergent system for structural studies. Through CD spectroscopy, we were able to characterize the secondary structure of the TM as largely alpha-helical, while NMR spectroscopy showed a well-structured and stable TM in LMPG. From these results, LMPG was determined to be the optimal detergent for further structural studies.

The rate at which zoonotic viruses spill over into the human population varies significantly over space and time. Remarkably, we do not yet know how much of this variation is attributable to genetic variation within viral populations. This gap in understanding arises because we lack methods of genetic analysis that can be easily applied to zoonotic viruses, where the number of available viral sequences is often limited, and opportunistic sampling introduces significant population stratification. Here, we explore the feasibility of using patterns of shared ancestry to correct for population stratification, enabling genome-wide association methods to identify genetic substitutions associated with spillover into the human population. Using a combination of phylogenetically structured simulations and Lassa virus sequences collected from humans and rodents in Sierra Leone, we demonstrate that existing methods do not fully correct for stratification, leading to elevated error rates. We also demonstrate, however, that the Type I error rate can be substantially reduced by confining the analysis to a less-stratified region of the phylogeny, even in an already-small dataset. Using this method, we detect two candidate single-nucleotide polymorphisms associated with spillover in the Lassa virus polymerase gene and provide generalized recommendations for the collection and analysis of zoonotic viruses.

Lassa fever (LF) is a deadly viral hemorrhagic disease that is endemic to West Africa. The causative agent of LF is Lassa virus (LASV), which causes approximately 300,000 infections and 5,000 deaths annually. There are currently no approved therapeutics or FDA-approved vaccines against LASV. The high genetic variability between LASV strains and immune evasion mediated by the virus complicate the development of effective therapeutics and vaccines. Here, we aim to provide a comprehensive review of the basic biology of LASV and its mechanisms of disease pathogenesis and virulence in various animal models, as well as an update on prospective vaccines, therapeutics, and diagnostics for LF. Until effective vaccines and/or therapeutics are available for use to prevent or treat LF, a better level of understanding of the basic biology of LASV, its natural genetic variations and immune evasion mechanisms as potential pathogenicity factors, and of the rodent reservoir-vector populations and their geographical distributions, is necessary for the development of accurate diagnostics and effective therapeutics and vaccines against this deadly human viral pathogen.

Background: Lassa virus disease (LVD) is of public health concern in endemic countries of Africa. Majority of Lassa virus infections are asymptomatic while symptomatic cases can mimic other infections. This study was aimed at determining the clinical features seen in children with positive Lassa virus PCR and symptoms that determine outcome of LVD in an endemic community, Southeast Nigeria. Materials and methods: It was a prospective observational study that enrolled 183 children that met the criteria for LVD suspects. These were subjected to the Lassa virus polymerase chain reaction test (PCR). Structured questionnaire was used to obtain relevant information from suspects. Results: Twenty-four out of the 183 were positive to Lassa virus PCR, giving a positivity rate of 13.1%. The odds of having a positive Lassa PCR result was about 4 times in children with history of abdominal pain (OR= 3.65, p= 0.010) and about 3 times in Lassa fever suspects with vomiting (OR= 2.63, p= 0.040). However these symptoms had low sensitivity and positive predictive values of 42% and 28% for abdominal pain, and 42%, 23% for vomiting respectively. Seven out of 24 children died during the study period, giving a case fatality rate of 29.2%, with bleeding (83.3%) and poor urine volume (83.3%) as major causes of case fatality. Conclusion: Vomiting and abdominal pain though were common presentations besides fever, had low sensitivity and positive predictive values for LVD, therefore cannot predict a positive Lassa PCR result. Awareness creation for a Lassa virus PCR test after 2 days of treatment of febrile illness is advocated.

The Lassa virus one of the main etiological agent of hemorrhagic fevers in the world: according to WHO estimates, it affects 100,000 to 300,000 people annually, which results in up to 10,000 deaths [1]. Although expansion of Lassa fever caused by this pathogen is mostly limited to the West African countries: Sierra Leone, Liberia, Guinea and Nigeria, imported cases have been historically documented in Europe, the United States of America (USA), Canada, Japan, and Israel [2]. In 2017, WHO included the Lassa virus in the list of priority pathogens in need of accelerated research, development of vaccines, therapeutic agents and diagnostic tools regarding infections they cause [3]. This review describes main technological platforms used for the development of vaccines for the prevention of Lassa fever.

ABSTRACT The dynamics of Lassa virus (LASV) infections in rodent reservoirs and their endemic human caseloads remain poorly understood. During the endemic period, human infections are believed to be associated with the seasonal migration of Mastomys natalensis, thought to be the primary reservoir that triggers multiple spillovers of LASV to humans. It has become imperative to improve LASV diagnosis in rodents while updating their prevalence in two regions of Lassa fever endemicity in Nigeria. Rodents (total, 942) were trapped in Ondo (531) and Ebonyi (411) states between October 2018 and April 2020 for detection of LASV using various tissues. Overall, the LASV prevalence was 53.6%. The outbreak area sampled in Ondo had three and two times higher capture success and LASV prevalence, respectively, than Ebonyi State. This correlated with the higher number of annual cases of Lassa fever (LF) in Ondo State versus Ebonyi State. All rodent genera (Mastomys, Rattus, Crocidura, Mus, and Tatera) captured in both states showed slightly variable LASV positivity, with Rattus spp. being the most predominantly infected (77.3%) rodents in Ondo State versus Mastomys spp. (41.6%) in Ebonyi State. The tissues with the highest LASV positivity were the kidneys, spleen, and testes. The finding of a relatively high LASV prevalence in all of the rodent genera captured highlights the complex interspecies transmission dynamics of LASV infections in the reservoirs and their potential association with increased environmental contact, as well as the risk of zoonotic spillover in these communities, which have the highest prevalence of Lassa fever in Nigeria. IMPORTANCE Our findings show the highest LASV positivity in small rodents ever recorded and the first direct detection of LASV in Tatera spp. Our findings also indicate the abundance of LASV-infected small rodents in houses, with probable interspecies transmission through vertical and horizontal coitus routes. Consequently, we suggest that the abundance of different reservoir species for LASV may fuel the epizootic outbreaks of LF in affected human communities. The high prevalence of LASV with the diversity of affected rodents has direct implications for our understanding of the transmission risk, mitigation, and ultimately, the prevention of LF in humans. Optimal tissues for LASV detection in rodents are also presented.

ABSTRACT Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is particularly resistant to antibody neutralization. Lineage I LASV evades neutralization by half of known antibodies in the GPC-A antibody competition group and all but one of the antibodies in the GPC-B competition group. Here, we solve two cryo-electron microscopy (cryo-EM) structures of LI GP in complex with a GPC-A and a GPC-B antibody. We used complementary structural and biochemical techniques to identify single-amino-acid substitutions in LI that are responsible for immune evasion by each antibody group. Further, we show that LI infection is more dependent on the endosomal receptor lysosome-associated membrane protein 1 (LAMP1) for viral entry relative to LIV. In the absence of LAMP1, LI requires a more acidic fusion pH to initiate membrane fusion with the host cell relative to LIV. IMPORTANCE No vaccine or therapeutics are approved to prevent LASV infection or treat LF. All vaccine platforms currently under development present only the LIV GP sequence. However, our data suggest that the high genetic diversity of LASV may be problematic for designing both a broadly reactive immunogen and therapeutic. Here, we examine antibodies that are highly potent against LIV yet are ineffective against LI. By pinpointing LI mutations responsible for this decrease in antibody efficacy, we suggest that future vaccine platforms may need to incorporate specific LI-like mutations in order to generate a broadly neutralizing antibody response against all LASV lineages.

Abstract Background Lassa fever (LF) is a zoonotic infectious disease of public concern in Nigeria. The infection dynamics of the disease is not well elucidated in Nigeria. This study was carried out to describe the pattern of infection, case fatality rate and spread of lassa virus (LASV) from 2017 to 2020. Methods Weekly epidemiological data on LF from December, 2016 to September, 2020 were obtained from Nigeria Centre for Disease Control. The number of confirmed cases and deaths were computed according to months and states. Descriptive statistics was performed and case fatality rate was calculated. Distribution and spread maps of LF over the four years period was performed on ArcMap 10.7. Results A total of 2787 confirmed cases and 516 deaths were reported in Nigeria from December, 2016 to September, 2020. Increase in number of cases and deaths were observed with 298, 528, 796 and 1165 confirmed cases and 79, 125, 158 and 158 deaths in 2017, 2018, 2019 and 2020 respectively. Over 60% of the cases were reported in two states, Edo and Ondo states. The LF cases spread from 19 states in 2017 to 32 states and Federal Capital Territory (FCT) in 2020. Ondo state (25.39%) had the highest of deaths rate from LF over the four years. Case fatality rate (CFR) of LF was highest in 2017 (26.5%) with CFR of 23.7, 19.6 and 13.4% in 2018, 2019 and 2020 respectively. The peak of infection was in the month of February for the four years. Infections increases at the onset of dry season in November and decline till April when the wet season sets-in. Conclusion There is an annual increase in the number of LASV infection across the states in Nigeria. There is need to heighten control strategies through the use of integrated approach, ranging from vector control, health education and early diagnosis.

Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.

Arenaviruses, such as Lassa virus (LASV), can cause severe and fatal hemorrhagic fevers (e.g., Lassa fever, LF) in humans with no vaccines or therapeutics. Research on arenavirus-induced hemorrhagic fevers (AHFs) has been hampered by the highly virulent nature of these viral pathogens, which require high biocontainment laboratory, and the lack of an immune-competent small animal model that can recapitulate AHF disease and pathological features. Guinea pig infected with Pichinde virus (PICV), an arenavirus that does not cause disease in humans, has been established as a convenient surrogate animal model for AHFs as it can be handled in a conventional laboratory. The PICV strain P18, derived from sequential passaging of the virus 18 times in strain 13 inbred guinea pigs, causes severe febrile illness in guinea pigs that is reminiscent of lethal LF in humans. As inbred guinea pigs are not readily available and are difficult to maintain, outbred Hartley guinea pigs have been used but they show a high degree of disease heterogeneity upon virulent P18 PICV infection. Here, we describe an improved outbred guinea-pig infection model using recombinant rP18 PICV generated by reverse genetics technique followed by plaque purification, which consistently shows >90% mortality and virulent infection. Comprehensive virological, histopathological, and immunohistochemical analyses of the rP18-virus infected animals show similar features of human LASV infection. Our data demonstrate that this improved animal model can serve as a safe, affordable, and convenient surrogate small animal model for studying human LF pathogenesis and for evaluating efficacy of preventative or therapeutic approaches.

Lassa fever is a disease that is not well-known worldwide, particularly due to the inability of the multimammate rat, the primary vector of the Lassa virus, to breed in temperate regions. The aim of this review is to provide an overview of the disease and its modus operandi while also providing information about trends in the past decade, as well as proven strategies that have been used to manage its spread.