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Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria. We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity. Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0–44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1–14) at 15 min and 10% (3–22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32–61] at 15 min and 50% [36–64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read. The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings. Médecins Sans Frontières. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Processes of self‐reflection and the learning they allow are crucial before, during, and after acute emergencies, including infectious disease outbreaks. Tools—such as Action Reviews—offer World Health Organization (WHO) member states a platform to enhance learning. We sought to better understand the value of these tools and how they may be further refined and better used.We searched the publicly available WHO Strategic Partnership for Health Security website for paired reports of Action Reviews, that is, reports with a comparable follow‐up report. We complemented the paired action reviews, with a literature search, including the gray literature. The paired action reviews were analyzed using the “Learning Health Systems” framework.We identified three paired action reviews: Lassa Fever After Action Reviews (AARs) in Nigeria (2017 and 2018), COVID‐19 Intra‐Action Reviews (IARs) in Botswana (2020 and 2021), and COVID‐19 IARs in South Sudan (2020 and 2021). Action Reviews allowed for surfacing relevant knowledge and, by engaging the right (in different contexts) actors, asking “are we doing things right?” (single loop learning) was evident in all the reports. Single loop learning is often embedded within examples of double loop learning (“are we doing the right things?”), providing a more transformative basis for policy change. Triple loop learning (“are we learning right”?) was evident in AARs, and less in IARs. The range of participants involved, the level of concentrated focus on specific issues, the duration available for follow through, and the pressures on the health system to respond influenced the type (i.e., loop) and the effectiveness of learning.Action Reviews, by design, surface knowledge. With favorable contextual conditions, this knowledge can then be applied and lead to corrective and innovative actions to improve health system performance, and in exceptional cases, continuous learning. [ABSTRACT FROM AUTHOR]

Lassa fever virus (LASV), a member of the Arenavirus family, is the etiological agent of Lassa fever, a severe hemorrhagic disease that causes considerable morbidity and mortality in the endemic areas of West Africa. LASV is a rodent-borne CDC Tier One biological threat agent and is on the World Health Organization's (WHO) Priority Pathogen list. Currently, no FDA-licensed vaccines or specific therapeutics are available. Here, we describe the efficacy of a deactivated rabies virus (RABV)-based vaccine encoding the glycoprotein precursor (GPC) of LASV (LASSARAB). Nonhuman primates (NHPs) were administered a two-dose regimen of LASSARAB or an irrelevant RABV-based vaccine to serve as a negative control. NHPs immunized with LASSARAB developed strong humoral responses to LASV-GPC. Upon challenge, NHPs vaccinated with LASSARAB survived to the study endpoint, whereas NHPs in the control group did not. This study demonstrates that LASSARAB is a worthy candidate for continued development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 N, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 N > L107F > K88E > H170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lassa virus (LASV) is the causative agent of human Lassa fever which in severe cases manifests as hemorrhagic fever leading to thousands of deaths annually. However, no approved vaccines or antiviral drugs are currently available. Recently, we screened approximately 2,500 compounds using a recombinant vesicular stomatitis virus (VSV) expressing LASV glycoprotein GP (VSV-LASVGP) and identified a P-glycoprotein inhibitor as a potential LASV entry inhibitor. Here, we show that another identified candidate, hexestrol (HES), an estrogen receptor agonist, is also a LASV entry inhibitor. HES inhibited VSV-LASVGP replication with a 50% inhibitory concentration (IC50) of 0.63 µM. Importantly, HES also inhibited authentic LASV replication with IC50 values of 0.31 µM–0.61 µM. Time-of-addition and cell-based membrane fusion assays suggested that HES inhibits the membrane fusion step during virus entry. Alternative estrogen receptor agonists did not inhibit VSV-LASVGP replication, suggesting that the estrogen receptor itself is unlikely to be involved in the antiviral activity of HES. Generation of a HES-resistant mutant revealed that the phenylalanine at amino acid position 446 (F446) of LASVGP, which is located in the transmembrane region, conferred resistance to HES. Although mutation of F446 enhanced the membrane fusion activity of LASVGP, it exhibited reduced VSV-LASVGP replication, most likely due to the instability of the pre-fusion state of LASVGP. Collectively, our results demonstrated that HES is a promising anti-LASV drug that acts by inhibiting the membrane fusion step of LASV entry. This study also highlights the importance of the LASVGP transmembrane region as a target for anti-LASV drugs. IMPORTANCE Lassa virus (LASV), the causative agent of Lassa fever, is the most devastating mammarenavirus with respect to its impact on public health in West Africa. However, no approved antiviral drugs or vaccines are currently available. Here, we identified hexestrol (HES), an estrogen receptor agonist, as the potential antiviral candidate drug. We showed that the estrogen receptor itself is not involved in the antiviral activity. HES directly bound to LASVGP and blocked membrane fusion, thereby inhibiting LASV infection. Through the generation of a HES-resistant virus, we found that phenylalanine at position 446 (F446) within the LASVGP transmembrane region plays a crucial role in the antiviral activity of HES. The mutation at F446 caused reduced virus replication, likely due to the instability of the pre-fusion state of LASVGP. These findings highlight the potential of HES as a promising candidate for the development of antiviral compounds targeting LASV. [ABSTRACT FROM AUTHOR]

Abstract Background Lassa fever (LF) presents significant public health challenges in Sierra Leone, particularly in the Lower Bambara Chiefdom. This study aims to deeply understand how knowledge and attitudes towards LF correlate with community-driven prevention and control measures. Methods A descriptive cross-sectional quantitative approach was used to conduct the research. Data from 2167 participants were collected using an Android-based survey from 1st February 2022 to 14th February 2022. Respondents' knowledge of LF causes, risk factors, transmission modes, and preventive measures were evaluated through a multiple-choice questionnaire, and attitudes toward prevention and control were measured on a 5-point Likert scale. Quantitative data were analyzed using SPSS version 26.0 and frequencies were presented in count, percentage, and table. Chi-square statistics were used to test for associations. Results Among the 2167 participants, over half were males (1184, 54.60%), farmers (1406, 64.90%), married (monogamous) (1428, 65.90%), and had never attended school (1336, 61.70%). Respondents demonstrated high knowledge levels of LF across socio-demographic groups (33% to 100%) and shared a positive attitude towards prevention and control (mean score of 26.77 on a 5–40 scale). Educational level, religious beliefs, and occupational status significantly influenced LF knowledge (p

Abu-Bakarr Steven Kamara, Patrick Fatoma, Andrew Moseray Department of Public Health, School of Community Health Sciences, Njala University Bo Campus, Bo City, Sierra LeoneCorrespondence: Abu-Bakarr Steven Kamara, Department of Public Health, School of Community Health Sciences, Njala University Bo Campus, Bo City, Sierra Leone, Tel +23276201595, Email abskamara@njala.edu.slBackground: Lassa fever is a critical public health issue in Sierra Leone that demands appropriate health system responses and interventions to mitigate infections and reduce mortality.Methods: A qualitative study was conducted to delve into healthcare workers’ experiences with Lassa fever management and interventions across diverse healthcare settings in Sierra Leone, including the Eastern Province and Freetown’s Directorate of Health Security and Emergency (DHSE). Engaging ten key informants through purposive sampling, the study employed NVivo version 10 for a detailed thematic analysis using Query and Coding to systematically identify, classify, and organize key themes regarding knowledge, diagnostics, management roles, and community impact.Results: The findings indicate a well-informed healthcare workforce but highlight gaps in early detection, diagnostic accuracy, and procedural standardization. Concerns were raised about the potential overestimation of disease incidence due to improved diagnostics, suggesting a historical under-detection of Lassa fever. The analysis underscores the need for a multifaceted management approach, emphasizing international collaboration and culturally sensitive community engagement to effectively tackle the disease. A significant concern identified is the high mortality rate resulting from delayed referrals and communication challenges within the health system, leading to actionable recommendations for enhancing Lassa fever response strategies. The study’s thematic analysis provides a nuanced understanding of the challenges and areas for improvement, emphasizing the critical role of healthcare professionals in combating Lassa fever.Conclusion: Combating Lassa fever in Sierra Leone demands an integrative strategy that extends beyond medical interventions to encompass educational and infrastructural enhancements. This research pays homage to the commitment of healthcare professionals, underscoring the importance of sustained support and recognition of their essential contributions to advancing Lassa fever management and interventions.Keywords: Lassa fever, Sierra Leone, healthcare professionals, health system response, community engagement, diagnostic challenges, mortality, communication strategies

Background: Lassa fever (LF) presents significant public health challenges in Sierra Leone, particularly in the Lower Bambara Chiefdom. This study aims to deeply understand how knowledge and attitudes towards LF correlate with community-driven prevention and control measures. Methods: A descriptive cross-sectional quantitative approach was used to conduct the research. Data from 2167 participants were collected using an Android-based survey from 1st February 2022 to 14th February 2022. Respondents' knowledge of LF causes, risk factors, transmission modes, and preventive measures were evaluated through a multiple-choice questionnaire, and attitudes toward prevention and control were measured on a 5-point Likert scale. Quantitative data were analyzed using SPSS version 26.0 and frequencies were presented in count, percentage, and table. Chi-square statistics were used to test for associations. Results: Among the 2167 participants, over half were males (1184, 54.60%), farmers (1406, 64.90%), married (monogamous) (1428, 65.90%), and had never attended school (1336, 61.70%). Respondents demonstrated high knowledge levels of LF across socio-demographic groups (33% to 100%) and shared a positive attitude towards prevention and control (mean score of 26.77 on a 5–40 scale). Educational level, religious beliefs, and occupational status significantly influenced LF knowledge (p < 0.05). Specifically, illiterates had a high knowledge score of 48.24%, while those with tertiary education had the highest score at 83.33%. Additionally, a Pearson correlation analysis revealed a positive linear relationship between the degree of knowledge and positive attitude towards LF infection and mortality risk factors (r = 0.090, p = 0.02). Conclusion: High LF knowledge in Lower Bambara Chiefdom positively influences prevention attitudes. Education, religion, and occupation are key factors. Tailored interventions enhance public health efforts. [ABSTRACT FROM AUTHOR]

The mammarenavirus Lassa virus (LASV) causes the life-threatening hemorrhagic fever disease, Lassa fever. The lack of licensed medical countermeasures against LASV underscores the urgent need for the development of novel LASV vaccines, which has been hampered by the requirement for a biosafety level 4 facility to handle live LASV. Here, we investigated the efficacy of mRNA-lipid nanoparticle (mRNA-LNP)- based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), in mice. Two doses of LASgpc- or LCMnp-mRNA-LNP administered intravenously (i.v.) protected C57BL/6 mice from a lethal challenge with a recombinant (r) LCMV expressing a modified LASgpc (rLCMV/LASgpc2m) inoculated intracranially. Intramuscular (i.m.) immunization with two doses of LASgpc- or LCMnp-mRNA-LNP significantly reduced the viral load in C57BL/6 mice inoculated i.v. with rLCMV/LASgpc2m. High levels of viremia and lethality were observed in CBA mice inoculated i.v. with rLCMV/LASgpc2m, which were abrogated by i.m. immunization with two doses of LASgpc-mRNA-LNP. The protective efficacy of two i.m. doses of LCMnp-mRNA-LNP was confirmed in a lethal hemorrhagic disease model of FVB mice i.v. inoculated with wild-type rLCMV. In all conditions tested, negligible and high levels of LASgpc- and LCMnp-specific antibodies were detected in mRNA-LNP-immunized mice, respectively, but robust LASgpc- and LCMnp-specific CD8+ T cell responses were induced. Accordingly, plasma from LASgpcmRNA-LNP-immunized mice did not exhibit neutralizing activity. Our findings and surrogate mouse models of LASV infection, which can be studied at a reduced biocontainment level, provide a critical foundation for the rapid development of mRNA-LNPbased LASV vaccines. IMPORTANCE Lassa virus (LASV) is a highly pathogenic mammarenavirus responsible for several hundred thousand infections annually in West African countries, causing a high number of lethal Lassa fever (LF) cases. Despite its significant impact on human health, clinically approved, safe, and effective medical countermeasures against LF are not available. The requirement of a biosafety level 4 facility to handle live LASV has been one of the main obstacles to the research and development of LASV countermeasures. Here, we report that two doses of mRNA-lipid nanoparticle-based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of lymphocytic choriomeningitis virus (LCMV), a mammarenavirus genetically closely related to LASV, conferred protection to recombinant LCMV-based surrogate mouse models of lethal LASV infection. Notably, robust LASgpc- and LCMnp-specific CD8+ T cell responses were detected in mRNA-LNP-immunized mice, whereas no virus-neutralizing activity was observed. [ABSTRACT FROM AUTHOR]

Lassa fever (LF), caused by Lassa virus (LASV), is one of the most dangerous diseases to public health. Homologous recombination (HR) is a basic genetic power driving biological evolution. However, as a negative-stranded RNA virus, it is unknown whether HR occurs between LASVs and its influence on the outbreak of LF. In this study, after analyzing 575 S and 433 L segments of LASV collected in Africa, we found that LASV can achieve HR in both of its segments. Interestingly, although the length of S segment is less than half of the L segment, the proportion of LASVs with S recombinants is significantly higher than that with L recombinants. These results suggest that HR may be a feature of LASV, which can be set by natural selection to produce beneficial or eliminate harmful mutations for the virus, so it plays a role in LASV evolution during the outbreak of LF. [ABSTRACT FROM AUTHOR]

Infectious diseases pose a very significant threat to development of the society and the world at large. With several outbreaks of diseases like Monkeypox, Lassa fever, SARS, COVID-19, etc, the global economy was grossly affected. The rate of transfer and mortality associated with similar outbreaks is alarming. This research presents a novel approach utilizing the Internet of Medical Things (IoMT) to develop a third-party notification model. This model uses IoMT's ubiquitous connectivity to notify even ordinary individuals of the presence of an infectious disease vector within a specified range. A four-tier architecture, including cloud and web API blocks, healthcare provider management, IoT sensory, and notification blocks forms the bedrock of the model. The research focuses on developing a Location Tracking Device (LTD) prototype that incorporates the Haversine formula for real-time distance calculation between individuals performed at the edge using the location data supplied by the LTDs as input parameters. The optimization of data reception rates was based on the average human walking speed in order to enhance response time of the system. Results from testing the prototype demonstrate an average of 4.68s response delay which corresponds to an offset of about 6.85m from the real vector distance calculation. The research implementation challenges include the internet connection speed, network availability, and topography. Despite these challenges, the IoMT-enabled model introduces a promising approach to infectious disease-carrier monitoring, integrating personalized carrier/vectorpresence awareness with associated risks within the disease control ecosystem. Hence, every user can use the LTD during an epidemic to help track the user’s nearness to a symptomatic person thereby helping to control the spread of infectious diseases during epidemics. [ABSTRACT FROM AUTHOR]

Assay validation is an essential component of disease surveillance testing, but can be problematic in settings where access to positive control material is limited and a safety risk for handlers. Here we describe a single non-infectious synthetic control that can help develop and validate the PCR based detection of the viral causes of Crimean-Congo hemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease and Rift Valley fever. We designed non-infectious synthetic DNA oligonucleotide sequences incorporating primer binding sites suitable for five assays, and a T7 promotor site which was used to transcribe the sequence. Transcribed RNA was used as template in a dilution series, extracted and amplified with RT-PCR and RT-qPCR to demonstrate successful recovery and determine limits of detection in a range of laboratory settings. Our results show this approach is adaptable to any diagnostic assay requiring validation of nucleic acid extraction and/or amplification, particularly where sourcing reliable, safe material for positive controls is infeasible. Author summary: The majority of zoonoses originate in wildlife and tend to emerge from biodiverse regions in low to middle income countries, frequently among deprived populations of at-risk people with a lack of access to diagnostic capacity or surveillance. Diseases such as Crimean-Congo hemorrhagic fever, Rift Valley fever, Ebola virus disease, Marburg virus disease and Lassa fever are viral hemorrhagic fevers (VHFs) and rank among the most neglected and serious threats to global public health. This threat is partly due to the severity of disease caused by these pathogens, but also because their geographical distribution is close to human populations with often limited access to medical or diagnostic laboratory services. In our study we describe techniques for PCR based detection of five VHF viruses using a synthetic, multi-target non-infectious positive control. Our work has applications in assay design and optimization, particularly where access to source material is problematic or requires high level biosafety containment, as is the case with VHF viruses. This approach can help learners train in techniques used in nucleic acid extraction, amplification, and sequencing of VHF viruses and can be used for any targets, with potential for multiplexing from a single positive control. [ABSTRACT FROM AUTHOR]

Lassa haemorrhagic fever (LHF) is a disease that is mainly transmitted among humans by rodents. To discuss the effects due to the spatial heterogeneous structure, periodic incubation period, and periodicity of weather on the spread of LHF, we formulate a nonlocal reactiondiffusion model with periodic delays. We develop a way to calculate the basic reproduction number R0 and study global dynamics of the model. Our simulations show that (i) it is possible to overestimate R0 if a spatial average system is used, and underestimate spreading risk of the disease if the seasonality of LHF is ignored; (ii) LHF transmission can be reduced by increasing the diffusion rate of the hosts; (iii) shortening the incubation periodmay reduce the risk of disease transmission. [ABSTRACT FROM AUTHOR]

IntroductionLassa fever is a zoonotic infectious disease endemic in West Africa with a high case-fatality rate and reported stigmatization of surviving patients. This study examines discrimination among survivors of Lassa fever (LF) complicated by hearing loss (HL).MethodsThis cross-sectional qualitative study used an in-depth interview guide to collect information from patients with HL about their experience of stigma. Interviews were conducted by a trained team of interviewers at the Jos University Teaching Hospital between January and April 2022 in Hausa language after informed consent was obtained. Recordings of the interviews were transcribed and translated from Hausa to English. Data analysis was conducted using NVivo software using a thematic framework approach.ResultsMost (73%) respondents were male (n = 11); 27% were female (n = 4). The median age was 35 years (interquartile range, 16.5). Some Lassa fever patients experienced stigma and discrimination (53%) including isolation and withdrawal of family and community support during and after illness. HL increased stigma, as some patients were labeled “deaf” by other community members, increasing perceived stigma and devaluation. HL affected the socio-economic wellbeing of some who could not communicate well with their families and customers and constrained social interactions, evoking pain and apathy. Some survivors of LF and victims of its sequelae of HL experienced double stigmatization. While they were ill with LF, a third of respondents reported avoidance and isolation by family and community members who withdrew care and support both to them and their close family members. These forms of stigmatization strained their relationships.ConclusionThere is a need to address stigma in LF survivors who develop HL through concerted community-owned awareness to improve their quality of life along with a robust social support system to aid prevention.

A co-infection model for onchocerciasis and Lassa fever (OLF) with periodic variational vectors and optimal control is studied and analyzed to assess the impact of controls against incidence infections. The model is qualitatively examined in order to evaluate its asymptotic behavior in relation to the equilibria. Employing a Lyapunov function, we demonstrated that the disease-free equilibrium (DFE) is globally asymptotically stable; that is, the related basic reproduction number is less than unity. When it is bigger than one, we use a suitable nonlinear Lyapunov function to demonstrate the existence of a globally asymptotically stable endemic equilibrium (EE). Furthermore, the necessary conditions for the presence of optimum control and the optimality system for the co-infection model are established using Pontryagin’s maximum principle. The model is quantitatively analyzed by studying how sensitive the basic reproduction number is to the model parameters and the model simulation using Runge–Kutta technique of order 4 is also presented to study the effects of the treatments. We deduced from the quantitative analysis that, if there is an effective treatment and diagnosis of those exposed to and infected with the disease, the spread of the viral disease can be effectively managed. The results presented in this work will be useful for the proper mitigation of the disease.

Background Lassa fever is an endemic and immediately notifiable disease in Liberia, and one laboratory confirmed case constitutes an outbreak. We described the epidemiological characteristics and hospital outcome of Lassa fever cases hospitalized during the 2022-2023 outbreak in Liberia. Methods A cohort study was conducted using routine Lassa fever surveillance data from the 2022-2023 outbreak in Liberia. Descriptive statistics were used to summarize the data and log binomial regression to assess the association between epidemiological characteristics and mortality. Results A total of 439 suspected Lassa fever cases were reported. The median age was 22 (interquartile range: 10-33) years and 233 (53%) were women. The median number of days between symptom onset and admission was 4 (IQR 2-7). Of the 439 cases, 416 (95%) were tested for Lassa fever and 138 were confirmed with 33% positivity rate. The majority, 290 (69%), of confirmed cases were Conclusions The outbreak highlighted a high disease burden of Lassa fever with young adults disproportionately infected, and substantial mortality, even among those who tested negative for the virus. This underscores the urgent need for preventive measures like vaccines and health education campaigns.

Abstract Ribavirin ampoule formulation remains a major challenge in managing Lassa fever disease. Lassa fever is an endemic viral hemorrhagic fever in the West Africa subregion, which has high-dose ribavirin as the standard of care. The high-dose therapy required makes the 200 mg/ml ampoule dosing of ribavirin a daunting task to administer, especially during disease outbreaks. This commentary highlights the challenges and makes a passionate call for vial dosage adjustment to fit the high-dose requirement of Lassa fever disease.

Lassa fever (LF) is a zoonotic viral hemorrhagic disease endemic to several West African countries. Approximately 300–500,000 cases occur annually across all ages with 10–20% case fatality rates. A LF vaccine is a recognized public health priority, with several candidates entering clinical trials. However, the perspectives of regional experts regarding critical vaccine properties, ideal delivery methods, and priority target populations remain unclear. Using a mixed methods approach with a standardized questionnaire, we individually interviewed 8 West African stakeholders, each with extensive knowledge and experience of LF. They strongly favored the use of a mass, proactive campaign strategy to immunize a wide age range of people in high-risk areas, including pregnant women and health care workers. We estimated that these and other plausible delivery scenarios could result in an initial demand of anywhere from 1 to 100 million doses, with most demand coming from Nigeria. These findings may help inform LF vaccine development and deployment efforts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A co-infection model for onchocerciasis and Lassa fever (OLF) with periodic variational vectors and optimal control is studied and analyzed to assess the impact of controls against incidence infections. The model is qualitatively examined in order to evaluate its asymptotic behavior in relation to the equilibria. Employing a Lyapunov function, we demonstrated that the disease-free equilibrium (DFE) is globally asymptotically stable; that is, the related basic reproduction number is less than unity. When it is bigger than one, we use a suitable nonlinear Lyapunov function to demonstrate the existence of a globally asymptotically stable endemic equilibrium (EE). Furthermore, the necessary conditions for the presence of optimum control and the optimality system for the co-infection model are established using Pontryagin's maximum principle. The model is quantitatively analyzed by studying how sensitive the basic reproduction number is to the model parameters and the model simulation using Runge–Kutta technique of order 4 is also presented to study the effects of the treatments. We deduced from the quantitative analysis that, if there is an effective treatment and diagnosis of those exposed to and infected with the disease, the spread of the viral disease can be effectively managed. The results presented in this work will be useful for the proper mitigation of the disease. [ABSTRACT FROM AUTHOR]

West African Mastomys rodents are the primary reservoir of the zoonotic Lassa virus (LASV). The virus causes haemorrhagic Lassa fever and considerable mortality in humans. To date, the role of Mastomys immunogenetics in resistance to, and persistence of, LASV infections is largely unknown. Here, we investigated the role of Major Histocompatibility Complex class I (MHC-I) on LASV infection status (i.e., active vs. cleared infection, determined via PCR and an immunofluorescence assay on IgG antibodies, respectively) in Mastomys natalensis and M. erythroleucus sampled within southwestern Nigeria. We identified more than 190 and 90 MHC-I alleles by Illumina high throughput-sequencing in M. natalensis and M. erythroleucus, respectively, with different MHC allele compositions and frequencies between LASV endemic and non-endemic sites. In M. natalensis, the MHC allele ManaMHC-I*006 was negatively associated with active infections (PCR-positive) and positively associated with cleared infections (IgG-positive) simultaneously, suggesting efficient immune responses that facilitate LASV clearance in animals carrying this allele. Contrarily, alleles ManaMHC-I*008 and ManaMHC-I*021 in M. natalensis, and MaerMHC-I*008 in M. erythroleucus, were positively associated with active infection, implying susceptibility. Alleles associated with susceptibility shared a glutamic acid at the positively selected codon 57, while ManaMHC-I*006 featured an arginine. There was no link between number of MHC alleles per Mastomys individual and LASV prevalence. Thus, specific alleles, but not MHC diversity per se, seem to mediate antibody responses to viremia. We conclude that co-evolution with LASV likely shaped the MHC-I diversity of the main LASV reservoirs in southwestern Nigeria, and that information on reservoir immunogenetics may hold insights into transmission dynamics and zoonotic spillover risks. Author summary: The Lassa virus is passed from rodents to humans, causing a disease that kills thousands of people every year in West Africa. To control spread, scientists are trying to understand why some rodents are more susceptible to the virus than others. One factor they are studying is the genetic makeup of the rodents' immune systems. They found that a specific allele of the Major Histocompatibility Complex (MHC I), called ManaMHC-I*006, was associated with resistance to and clearance of the virus, while other alleles were associated with susceptibility. They also found that the immunogenetic composition of rodents differed between areas where Lassa virus is endemic or non-endemic. These findings can help predict where the virus might emerge and can help researchers develop a vaccine to protect the rodents from getting the virus, which can ultimately help prevent the spread of the disease to humans. The authors emphasize the significance of adopting a One-Health approach in thinking about wildlife and human health. [ABSTRACT FROM AUTHOR]

The article offers information on the prevalence and impact of Lassa fever in Nigeria, highlighting the challenges of diagnosis and treatment. Topics include the severity of Lassa fever; its impact on communities; and the efforts to raise awareness and develop countermeasures. The disease, although often mild or asymptomatic, can be fatal in severe cases, posing a significant public health threat, especially in rural areas where access to healthcare is limited.

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. [ABSTRACT FROM AUTHOR]

Lassa fever is an acute viral hemorrhagic disease that affects humans and is endemic in various West African nations. In this study, a fractional-order model is constructed using the Caputo operator for SEIR-type Lassa fever transmission, including the control strategy. The proposed model examines the dynamics of Lassa fever transmission from rodents to humans and from person to person and in territories with infection in society. The model is analyzed both qualitatively and quantitatively. We examine the positively invariant area and demonstrate positive, bounded solutions to the model. We also show the equilibrium states for the occurrence and extinction of infection. The proposed nonlinear system is verified to be present, and a unique solution is shown to exist using fixed point theorems. Using the Volterra-type Lyapunov function, we investigate the global stability of the suggested system with a fractional Caputo derivative. To study the impact of the fractional operator through computational simulations, results are generated employing a two-step Lagrange polynomial in the generalized version of the power law kernel. A graphical evaluation is provided to show the simplicity and dependability of the model, and all rodents that could be source viruses are important in ecological research. The findings with a value equal to 1 are stronger, according to the comparison of outcomes with different fractional orders. The adverse effect of Lassa fever increases when all modes of transmission are taken into account, according to the study, with fractional-order findings indicating less detrimental effects on specific transmission routes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Lassa fever (LF) is endemic in Liberia and is immediately reportable. Suspected cases are confirmed at the National Public Health Reference Laboratory. However, there is limited information on the trend and factors associated with mortality. We described the epidemiological characteristics of LF cases and determined factors associated with mortality in Liberia from 2016 to 2021. Methods: we reviewed 867 case-based LF surveillance data from 2016 to 2021 obtained from the National Public Health Institute of Liberia (NPHIL). The cases that met the suspected LF case definition were tested with RT-PCR. Using Epi Info 7.2.5.0. We conducted univariate, bivariate, and multivariate and analysis. We calculated frequencies, proportions. Positivity rate, case fatality rate, and factors associated with LF mortality using chi-square statistics and logistics regression at 5% level of significance. Results: eighty-five percent (737/867) of the suspected cases were tested and 26.0% (192/737) were confirmed LF positive. The median age of confirmed LF cases was 21(IQR: 12-34) years. Age 10-19 years accounted for 24.5% (47/192) and females 54.2% (104/192). Bong 33.9% (65/192), Grand Bassa 31.8% (61/192), and Nimba counties, 21.9% (42/192) accounted for most of the cases. The median duration from symptom onset to hospital admission was 6 (IQR: 3-9) days. A majority, 66% (126/192) of the cases were reported during the dry season (October-March) and annual incidence was highest at 12 cases per 1,000,000 population in 2019 and 2020. The overall case fatality rate was 44.8%. Non-endemic counties, Margibi, 77.8% and Montserrado, 66.7% accounted for the highest case fatality rate (CFR), while 2018, 66.7% and 2021, 60.0% recorded the highest CFR during the period. Age =30 years (aOR=2.1,95% CI: 1.08-4.11, p=0.027) and residing in Grand Bassa County (aOR=0.3, 95% CI: 0.13-0.73, p=0.007) were associated with LF mortality. Conclusion: Lassa fever was endemic in three of the fifteen counties of Liberia, case fatality rate remained generally high and widely varied. The high fatality of LF has been reported to the NPHIL and is currently being further investigated. There is a need to continuously train healthcare workers, especially in non-endemic counties to improve the LF treatment outcome. [ABSTRACT FROM AUTHOR]

Lassa fever is a deadly viral disease whose incubation period ranges from six to twenty-one days and about eighty percent of Lassa virus infection is asymptomatic. A deterministic model was formulated to quantify the transmission dynamics of the disease under isolation and treatment of the isolated asymptomatic and symptomatic humans for effective management and possible elimination of the disease. The solutions of the model were shown to be positive and bounded. Equilibrium analysis was conducted and both the disease-free and the endemic equilibria were derived. The threshold quantity for disease elimination, R0, was also obtained and used to derive conditions for the existence of stability of the eqilibria. The quantity was also employed to examine the sensitivity of the model parameters to disease propagation and reduction. The theoretical analysis was then complemented with the quantitative analysis by adopting a set of realistic values for the model parame- ters in order to show the effect of isolation and treatment on the spread and fatality of Lassa fever. Results from the quantitative study showed that death and infection from Lassa fever fell continuously as more and more exposed individuals were detected and isolated for treatment. The study therefore suggested that any measure taken to eradicate or curtail Lassa fever spread should include detection and isolation of the exposed humans for prompt treatments. [ABSTRACT FROM AUTHOR]

This paper aims to investigate various epidemiological aspects of Lassa fever viral infection using a fractional-order mathematical model so as to assess the impacts of treatment and vaccination on the spread of Lassa fever transmission dynamics. Initially, the model employs integer-order nonlinear differential equations, incorporating imperfect vaccination and treatment as control measures for the human population. Subsequently, the model is redefined using a fractional order derivative with power law to enhance understanding of disease dynamics. The paper establishes conditions ensuring the existence and uniqueness of the model’s solution in the fractional case, alongside presenting stability analysis of the endemic equilibrium using the Lyapunov function approach. Numerical simulations are performed using the fractional Adams–Bashforth–Moulton method, shedding light on the influence of model parameters and fractional order values on Lassa fever dynamics and control. Additional numerical simulations conducted utilizing surface and contour plots revealed that elevating the contact rates and diminishing the efficacy of vaccines would escalate the prevalence of Lassa fever among the human populace. It was also observed that optimizing treatment and enhancing vaccination strategies would ultimately mitigate the prevalence of Lassa fever within the human population.

This study aims to develop a mathematical model for analyzing Lassa fever transmission dynamics and proposing effective control measures. The stability of the Lassa fever-free equilibrium point is examined and the model's accuracy is assessed using real-world data. Additionally, the parameter values and the basic reproduction number are estimated. A sensitivity analysis is also conducted, which identifies the key drivers influencing transmission dynamics. Moreover, the impact of model parameters on basic reproduction numbers is investigated. Multiple control methodologies including use of Ribavirin, implementing mobile health technology and incorporating natural predators are devised and analyzed using optimal control theory to curtail virus transmission.

Lassa Fever is a deadly viral haemorrhagic disease, causing annually several hundreds of deaths in West Africa. This zoonotic disease is primarily transmitted to humans by rodents of the genus Mastomys, even though other rodents reportedly carry the Lassa virus, while secondary interhuman transmission accounts for approximately 20% of cases. Although this disease has been endemic in rural zones of Nigeria, Sierra Leone, Liberfia, and Guinea for hundreds of years, it is also characterised by epidemic outbreaks in the dry season, responsible for heavy death tolls. No licensed vaccine or satisfying treatment is currently available. Disease management is hindered by the incomplete knowledge of the epidemiology and distribution of the disease, resulting from an inadequate health and surveillance system. Additional scientific constraints such as the genetic diversity of the virus and the lack of understanding of the mechanisms of immune protection complexify the development of a vaccine. The intricate socio-economic context in the affected regions, and the lack of monetary incentive for drug development, allow the disease to persist in some of West Africa’s poorest communities. The increase in the number of reported cases and in the fatality rate, the expansion of the endemic area, as well as the threat Lassa Fever represents internationally should urge the global community to work on the disease control and prevention. The disease control requires collaborative research for medical countermeasures and tailored public health policies. Lassa Fever, created by the interconnection between animals, humans, and ecosystems, and embedded in an intricate social context, should be addressed with a ‘One Health’ approach. This article provides an overview of Lassa Fever, focusing on Nigeria, and discusses the perspectives for the control of disease.

This study aims to develop a mathematical model for analyzing Lassa fever transmission dynamics and proposing effective control measures. The stability of the Lassa fever-free equilibrium point is examined and the model's accuracy is assessed using real-world data. Additionally, the parameter values and the basic reproduction number are estimated. A sensitivity analysis is also conducted, which identifies the key drivers influencing transmission dynamics. Moreover, the impact of model parameters on basic reproduction numbers is investigated. Multiple control methodologies including use of Ribavirin, implementing mobile health technology and incorporating natural predators are devised and analyzed using optimal control theory to curtail virus transmission. [ABSTRACT FROM AUTHOR]

Lassa fever (Lf) is a viral haemorrhagic disease endemic to West Africa and is caused by the Lassa mammarenavirus. The rodent Mastomys natalensis serves as the primary reservoir and its ecology and behaviour have been linked to the distinct spatial and temporal patterns in the incidence of Lf. Nigeria has experienced an unprecedented epidemic that lasted from January until April of 2018, which has been followed by subsequent epidemics of Lf in the same period every year since. While previous research has modelled the case seasonality within Nigeria, this did not capture the seasonal variation in the reproduction of the zoonotic reservoir and its effect on case numbers. To this end, we introduce an approximate Bayesian computation scheme to fit our model to the case data from 2018–2020 supplied by the NCDC. In this study we used a periodically forced seasonal nonautonomous system of ordinary differential equations as a vector model to demonstrate that the population dynamics of the rodent reservoir may be responsible for the spikes in the number of observed cases in humans. The results show that in December through to March, spillover from the zoonotic reservoir drastically increases and spreads the virus to the people of Nigeria. Therefore to effectively combat Lf, attention and efforts should be concentrated during this period. Author summary: Lassa fever is a viral disease prevalent in West Africa, with Mastomys natalensis serving as the primary reservoir. In Nigeria, annual outbreaks occur from December to March. Using a novel model and data from 2018–2020, we demonstrate that the population dynamics of the reservoir contribute to spikes in human cases. Specifically, spillover transmission increases drastically during this period, highlighting the need for concentrated efforts and interventions. Understanding the seasonal dynamics of the reservoir is crucial for effective Lassa fever control and prevention strategies in Nigeria. [ABSTRACT FROM AUTHOR]

Lassa fever (LF) is a haemorrhagic illness endemic in West Africa, which can be attributed to poor rat control and poor sanitation, especially in the rural communities. Increasing awareness and education about LF has been advocated for its prevention and control. This study investigated the level of awareness and knowledge associated with LF among the residents of Iwo and Oluponna areas of Osun State, southwest Nigeria. A descriptive cross-sectional study was carried out among the adult residents using a structured questionnaire. Descriptive and inferential statistics were used in analysing the data. In total, 534 (79.11%) respondents had heard about LF, but only 15.4% had good knowledge of the disease. Their main source of information was the media (46.3%, P=0.002, P<0.01), while only 21.2% got information from health workers. About 45% of respondents have rats in their houses. Respondents from Iwo were better informed than Oluponna. Multiple logistic regression analysis indicated location to be significantly associated with awareness (OR=1.62, C.I=1.078-2.433, P<0.05), knowledge of prevention (OR=5.88, C.I=2.807-12.317, P=0.000, P<0.01) and treatment (OR=1.648, C.I=1.122-2.420, P=0.011, P<0.05). Although the residents of Iwo are better informed about LF than Oluponna residents, the knowledge of the disease is poor in both areas. Health workers should be well informed, and the government should increase enlightenment programmes about LF, especially in rural communities of Nigeria, so as to curtail the spread and prevent outbreaks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Lassa virus is an RNA virus belonging to the Arenaviridae family. It is responsible for Lassa fever, an acute viral zoonosis of the severe hemorrhagic fever type with manifestations of fever, muscle pain, sore throat, nausea, vomiting, and chest and abdominal pain. Lassa fever is endemic in West Africa, where the first case was reported in 1969 in Lassa, a town in Nigeria, more than 50 years ago, and it is estimated that nearly 5000 deaths occur in West Africa each year. Nigeria is one of the endemic hotspots and has experienced numerous recurrent outbreaks of Lassa fever due to the increased multiplication of the host reservoir, Mastomys natalensis. For the Lassa epidemics in 2022 and January 2023 alone, Nigeria accounts for a quarter of the annual deaths from this disease. Poor lifestyle and hygiene, difficulty in diagnosis due to nonspecific symptomatology, lack of effective treatment based on clinical evidence, an ineffective human immunization program combined with a health system that is not adapted or equipped to control and prevent recurrent deadly epidemics, and an outdated regional disease surveillance system in West Africa are some of the challenges that must be overcome to rapidly and effectively eradicate this disease, whose area of spread is constantly expanding as a result of the movement of populations in the context of economic and socio‐cultural activities. [ABSTRACT FROM AUTHOR]