Addressing bottlenecks in Lassa fever treatment: overcoming the ribavirin parenteral formulation challenge.

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.

Intrasegmental recombination as an evolutionary force of Lassa fever virus.

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.

LASSA FEVER IN INTERNALLY-DISPLACED PERSONS' CAMP: A CASE REPORT AT ZABARMARI, BORNO STATE, NIGERIA.

Introdution: Lassa fever is a viral hemorrhagic disease caused by the Lassa virus, a single stranded RNA virus of the Arenavirus family. It is a zoonotic illness spread by rats of the speciesMastomys natalensis . Between weeks 1 and 17, (2017), 242 suspected Lassa fever cases were reported in Nigeria, with 58 laboratory confirmed cases and 46 fatalities (CFR, 19.01%) from 50 Local Government Areas (LGAs) in 20 States. Methods: We conducted an outbreak investigation and gathered a thorough clinical history of the index case as well as contacts, who were then followed up using the standard viral hemorrhagic fever contact monitoring form. Following that, blood samples were collected from this patient. A total of 54 contacts were tracked for 21 days and their temperatures were recorded using a clinical thermometer. Furthermore, an environmental evaluation of the Zabarmari community and the Madinatu Internally-displaced persons' (IDP) camp was carried out. Results: The index case was a 32-year-old woman who was internallydisplaced in Zabarmari community. Her symptoms began with fever and vaginal bleeding and progressed to bleeding from the nose, mouth, and urethra. There was a history of rat exposure as well as inadequate environmental sanitation and hygiene. Real Time PCR detected Lassa fever in the blood sample. The Borno State Ministry of Environment, in partnership with the Ministry of Health, undertook public health education on Lassa fever prevention and implemented excellent sanitary measures. Conclusion: Increased awareness creation on good infection prevention and control practices is crucial among internally-displaced person and health care providers to prevent occurrence and spread of the disease.

Analysing the association between perceived knowledge, and attitudes on Lassa Fever infections and mortality risk factors in lower Bambara Chiefdom.

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.

The Perspectives of Healthcare Professionals on the Strategies, Challenges, and Community Responses to Health System Response and Interventions Towards Lassa Fever Infections and Mortality in Sierra Leone.

Background: 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.

Trend of Lassa fever cases and factors associated with mortality in Liberia, 2016 - 2021: a secondary data analysis.

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.

An atlas of gross and histologic lesions and immunohistochemical immunoreactivity during the temporal progression of aerosolized Lassa virus induced hemorrhagic fever in cynomolgus macaques.

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.

Knowledge and practices associated with Lassa fever in rural Nigeria: Implications for prevention and control.

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.

Re-emergence of Lassa fever in Nigeria: A new challenge for public health authorities.

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.

Combating the zoonotic trio of Ebola virus disease, Lassa fever, and COVID-19 in Nigeria: a retrospection of the challenges and lessons.

Various infectious disease outbreaks linked to zoonotic sources have been recorded over the years, some of which have resulted in epidemics on a national, regional, or global scale. In Africa, a number of such outbreaks occur intermittently, especially in countries like Nigeria with a high-risk of epidemiological transmission. Three viral outbreaks with zoonotic links have hit the Nigerian healthcare system hardest, which are the Ebola virus disease, Lassa fever and Coronavirus disease 2019. Due to the fragile nature of the Nigerian health system, several challenges were encountered in the process of responding to these viral outbreaks, some of which included inadequate healthcare infrastructure, limited diagnostic capacity, unfledged nature of emergency response, unsatisfactory remuneration of health workers, misinformation trends, amongst others. By reminiscing on the challenges and lessons learnt from these viral disease outbreaks, the Nigerian government and policymakers will be able to adopt more effective approaches towards emergency preparedness for future outbreaks of infectious diseases.

Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection.

BACKGROUND: Lassa virus (LASV) can cause severe acute systemic infection in humans. No approved antiviral drugs or vaccines are currently available. Antibody-based therapeutics are considered a promising treatment strategy in the management of LASV disease. METHODS: We used chimeric Ifnar-/- C57BL/6 (Ifnar-/- Bl6) mice, a lethal LASV mouse model, to evaluate the protective efficacy of polyclonal antibodies purified from sera of rabbits hyperimmunized with virus-like particles displaying native-like LASV glycoprotein GP spikes. RESULTS: Polyclonal anti-LASV GP antibodies provided 100% protection against lethal LASV infection in a pre- and post-exposure treatment setting and prevented LASV disease. Treatment also significantly lowered viremia level and virus load in organs. When treatment was initiated at the onset of symptoms, the hyperimmune antibodies provided partial protection and increased the survival rate by 80%. CONCLUSIONS: Our findings support the consideration of animal-derived hyperimmune antibodies targeting GP as an effective treatment option for highly pathogenic LASV.

Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents.

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

Inter-State Transmission of Lassa Fever during the 2015-2016 Lassa Outbreak in Nigeria: An Implication for Infection Prevention and Control Practices.

BACKGROUND: Lassa fever is an acute hemorrhagic viral disease caused by the Lassa virus. The Lassa virus belongs to the Arenaviridae family of RNA viruses. On 05/04/2016; two cases of Lassa fever were reported from Katsina State with the date of presentation of the first case on 23/03/2016 and 27/03/ 2016 for the second case. We investigated the outbreak to identify the agent and the source and propose recommendations as well as to assess the practice of infection, prevention and control (IPC). METHODS: We used descriptive study to describe contact tracing and facility assessment. We described the outbreak by time, place, and person. We defined a case using established guidelines and line-listed the contacts. We conducted IPC facility check in the state. Blood specimens were collected for Lassa fever detection. Microsoft Excel and Epi-info version 7.1.6 were used for data analysis. RESULTS: The index case of Lassa fever in Katsina State was seen on 23/03/2016 with a travel history from Kaduna State. The second case had contact with a positive Lassa fever case from Gwagwalada, Federal Capital Territory (FCT). A total of 82 contacts were line listed (9 developed Lassa fever). The case fatality rate was 27.3%. IPC checklist revealed 37.5% of the health facilities lacked personal protective equipment and safety boxes, 25% lacked isolation wards, and none had chlorine solution. Overall, 61% of personnel had poor knowledge of Lassa fever, 31% had fair knowledge and 8% had good knowledge. CONCLUSION: A multiple-source epidemic with sources of primary infection from outside Katsina state was noted. Most of the health facilities assessed lack basic IPC materials and knowledge on Lassa fever which should be addressed.

CONTEXTE: La fièvre de Lassa est une maladie virale hémorragique aiguë causée par le virus de Lassa. Le virus Lassa appartient à la famille des Arenaviridae, des virus à ARN. Le 05/04/2016 ; deux cas de fièvre de Lassa ont été signalés dans l'État de Katsina avec la date de présentation du premier cas le 23/03/2016 et le 27/03/2016 pour le second cas. Nous avons enquêté sur cette épidémie pour identifier l'agent et la source et proposer des recommandations ainsi que pour évaluer la pratique de l'infection, de la prévention et du contrôle (IPC). MÉTHODES: Nous avons utilisé une étude descriptive pour décrire la recherche des contacts et l'évaluation des installations. Nous avons décrit l'épidémie en fonction de la date, du lieu et de la personne. Nous avons défini un cas à l'aide de lignes directrices établies et dressé une liste des contacts. Nous avons vérifié les installations de CIP dans l'État. Des échantillons de sang ont été prélevés pour la détection de la fièvre de Lassa. Microsoft Excel et Epi-info version 7.1.6 ont été utilisés pour l'analyse des données. RÉSULTATS: Le cas index de fièvre de Lassa dans l'État de Katsina a été observé le 23/03/2016 avec des antécédents de voyage en provenance de l'État de Kaduna. Le deuxième cas a été en contact avec un cas positif de fièvre de Lassa à Gwagwalada, dans le Territoire de la capitale fédérale (FCT). Au total, 82 contacts ont été répertoriés (9 ont développé une fièvre de Lassa). Le taux de létalité était de 27,3%. La liste de contrôle IPC a révélé que 37,5 % des établissements de santé manquaient d'équipements de protection individuelle et de boîtes de sécurité, que 25 % n'avaient pas de salles d'isolement et qu'aucun n'avait de solution chlorée. Dans l'ensemble, 61 % du personnel avait une mauvaise connaissance de la fièvre de Lassa, 31 % une connaissance moyenne et 8 % une bonne connaissance. CONCLUSION: Une épidémie à sources multiples avec des sources d'infection primaire en dehors de l'État de Katsina a été observée. La plupart des établissements de santé évalués manquent de matériel IPC de base et de connaissances sur la fièvre de Lassa, ce qui devrait être corrigé. Mots clés: Épidémiologie, Contrôle des infections, Katsina, Épidémie, Fièvre de Lassa.

The unusual finding of peripheral lymphadenopathy among confirmed Lassa fever patients in Nigeria.

Lassa fever is a viral haemorrhagic fever belonging to the arenaviridae family that is well known to be endemic to West Africa. The clinical presentation of the disease ranges from asymptomatic to fulminant illness. Lymphadenopathy a clinical manifestation of inflammation, infection, or malignancy has not been widely reported in Lassa fever disease. We report two cases of Lassa fever disease presenting with lymphadenopathy.

Enlargement of lymph nodes, is a common symptom of many infections, however it is not commonly mentioned in patients with Lassa fever, a viral hemorrhagic fever that is endemic in West Africa. However, recent research suggests that lymphadenopathy may be underreported in Lassa fever patients. This new finding could have important implications for the diagnosis and treatment of the disease, as well as for our understanding of how it spreads.

Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies.

Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.

Focussed Assessment with Sonography in acute Lassa Fever (FASLa): Development of a point-of-care protocol and description of common ultrasound findings.

BACKGROUND: Managing Lassa fever (LF) patients is challenging because of the complexity of this life-threatening infectious disease, the necessary isolation measures, and the limited resources in countries where it is endemic. Point-of-care ultrasonography (POCUS) is a promising low-cost imaging technique that may help in guiding the management of patients. METHODS: We conducted this observational study at the Irrua Specialist Teaching Hospital in Nigeria. We developed a POCUS protocol, trained local physicians who applied the protocol to LF patients and recorded and interpreted the clips. These were then independently re-evaluated by an external expert, and associations with clinical, laboratory and virological data were analyzed. FINDINGS: We developed the POCUS protocol based on existing literature and expert opinion and trained two clinicians, who then used POCUS to examine 46 patients. We observed at least one pathological finding in 29 (63%) patients. Ascites was found in 14 (30%), pericardial effusion in 10 (22%), pleural effusion in 5 (11%), and polyserositis in 7 (15%) patients, respectively. Eight patients (17%) showed hyperechoic kidneys. Seven patients succumbed to the disease while 39 patients survived, resulting in a fatality rate of 15%. Pleural effusions and hyper-echoic kidneys were associated with increased mortality. INTERPRETATION: In acute LF, a newly established POCUS protocol readily identified a high prevalence of clinically relevant pathological findings. The assessment by POCUS required minimal resources and training; the detected pathologies such as pleural effusions and kidney injury may help to guide the clinical management of the most at-risk LF patients.

Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives.

Lassa fever (LF) is a rodent-borne disease that threatens human health in the sub-region of West Africa where the zoonotic host of Lassa virus (LASV) is predominant. Currently, treatment options for LF are limited and since no preventive vaccine is approved for its infectivity, there is a high mortality rate in endemic areas. This narrative review explores the transmission, pathogenicity of LASV, advances, and challenges of different treatment options. Our findings indicate that genetic diversity among the different strains of LASV and their ability to circumvent the immune system poses a critical challenge to the development of LASV vaccines/therapeutics. Thus, understanding the biochemistry, physiology and genetic polymorphism of LASV, mechanism of evading host immunity are essential for development of effective LASV vaccines/therapeutics to combat this lethal viral disease. The LASV nucleoprotein (NP) is a novel target for therapeutics as it functions significantly in several aspects of the viral life cycle. Consequently, LASV NP inhibitors could be employed as effective therapeutics as they will potentially inhibit LASV replication. Effective preventive control measures, vaccine development, target validation, and repurposing of existing drugs, such as ribavirin, using activity or in silico-based and computational bioinformatics, would aid in the development of novel drugs for LF management.

Understanding the transmission pathways of Lassa fever: A mathematical modeling approach.

The spread of Lassa fever infection is increasing in West Africa over the last decade. The impact of this can better be understood when considering the various possible transmission routes. We designed a mathematical model for the epidemiology of Lassa Fever using a system of nonlinear ordinary differential equations to determine the effect of transmission pathways toward the infection progression in humans and rodents including those usually neglected such as the environmental surface and aerosol routes. We analyzed the model and carried out numerical simulations to determine the impact of each transmission routes. Our results showed that the burden of Lassa fever infection is increased when all the transmission routes are incorporated and most single transmission routes are less harmful, but when in combination with other transmission routes, they increase the Lassa fever burden. It is therefore important to consider multiple transmission routes to better estimate the Lassa fever burden optimally and in turn determine control strategies targeted at the transmission pathways.

Pharmacokinetics of Ribavirin in the Treatment of Lassa Fever: An Observational Clinical Study at the Irrua Specialist Teaching Hospital, Edo State, Nigeria.

BACKGROUND: Lassa fever is endemic in large parts of West Africa. The recommended antiviral treatment is ribavirin. Two treatment regimens are currently endorsed in Nigeria: the "McCormick regimen" based on a study published in 1986 and the "Irrua regimen" constituting a simplified schedule developed at the Irrua Specialist Teaching Hospital, Nigeria. Evidence for the safety and efficacy of ribavirin in Lassa fever patients is poor and pharmacokinetic data for both regimens are lacking. METHODS: Polymerase chain reaction-confirmed Lassa fever patients with mild to moderate disease severity were invited to participate in this prospective, observational pharmacokinetic study. Pharmacokinetics of ribavirin, clinical, virologic, and clinical laboratory parameters were assessed. RESULTS: Using a population pharmacokinetic approach, plasma concentrations of ribavirin were best described by a 3-compartment model. Drug exposure was remarkably consistent between participants. Overall, drug clearance was 28.5% lower in female compared with male participants. Median (5th-95th percentile) time above half maximal inhibitory concentration (IC50) was 37.3% (16.9%-73.1%), 16.7% (8.2%-58.5%), and 9.6% (4.9%-38.4%) on days 1, 7, and 8, respectively. Clinical laboratory parameters indicated reduction of cell damage and development of hemolytic anemia in the course of the treatment period. CONCLUSIONS: This observational study characterizes the pharmacokinetics of ribavirin in the treatment of Lassa fever indicating consistent exposure across patients. Whereas only a short time interval of concentrations above the IC50 implies rather low antiviral efficacy in vivo, the prominent reduction of cell damage markers might point to indirect-potentially anti-inflammatory-effects of ribavirin. The role of ribavirin in the treatment of Lassa fever requires further scrutiny.

Lassa fever cases and mortality in Nigeria: Quantile Regression vs. Machine Learning Models.

Lassa fever (LF) is caused by the Lassa fever virus (LFV). It is endemic in West Africa, of which % of the infections are ascribed to Nigeria. This disease affects mostly the productive age and hence a proper understanding of the dynamics of this disease will help in formulating policies that would help in curbing the spread of LF. The objective of this study is to compare the performance of quantile regression models with that of Machine Learning models in. Data between between 7th January 2018 2018 and 17th December, 2022 on suspected cases, confirmed cases and deaths resulting from LF were retrieved from the Nigeria Centre for Disease Control (NCDC). The data obtained were fitted to quantile regression models (QRM) at 25, 50 and 75% as well as to Machine learning models. The response variable being confirmed cases and mortality due to Lassa fever in Nigeria while the independent variables were total confirmed cases, the week, month and year. Result showed that the highest monthly mean confirmed cases (56) and mortality (9) from LF were reported in February. The first quarter of the year reported the highest cases of both confirmed cases and deaths in Nigeria. Result also revealed that for the confirmed cases, quantile regression at 50% outperformed the best of the MLM, Gaussian-matern5/2 GPR (RMSE=10.3393 vs. 11.615), while for mortality, the medium Gaussian SVM (RMSE=1.6441 vs. 1.8352) outperformed QRM. Quantile regression model at 50% better captured the dynamics of the confirmed cases of LF in Nigeria while the medium Gaussian SVM better captured the mortality of LF in Nigeria. Among the features selected, confirmed cases was found to be the most important feature that drive its mortality with the implication that as the confirmed cases of Lassa fever increases, is a significant increase in its mortality. This therefore necessitates a need for a better intervention measures that will help curb Lassa fever mortality as a result of the increase in the confirmed cases. There is also a need for promotion of good community hygiene which could include; discouraging rodents from entering homes and putting food in rodent proof containers to avoid contamination to help hart the spread of Lassa fever in Nigeria.