"Pathological Insights into Lassa Virus-Induced Vestibular Dysfunction in Mice: Histopathological Analysis of the Inner Ear Vestibular Apparatus".

Lassa fever (LF), caused by Lassa virus (LASV) infection, typically leads to mild symptoms in humans, yet some survivors experience audiovestibular problems. Here we present vestibular histopathological insights in our LF model mice. We observed: 1) hemorrhage within the vestibular ganglion and stroma beneath the sensory epithelium, 2) preserved hair cells and supporting cells, 3) LASV antigen presence in the vestibular ganglion cells and the stroma beneath the sensory epithelium, and 4) CD3-positive T lymphocyte infiltration in the vestibular ganglion and the stroma underlying the sensory epithelium. LASV and/or its immune response likely contributes to the pathogenesis of vestibular dysfunction.

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.

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.

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.

Lassa Virus Replicon Particle Vaccine Protects Strain 13/N Guinea Pigs Against Challenge With Geographically and Genetically Diverse Viral Strains.

Lassa virus (LASV) causes mild to severe hemorrhagic fever disease in humans. Strain 13/N guinea pigs are highly susceptible to infection with LASV strain Josiah (clade IV), providing a critical model system for therapeutics and vaccine development. To develop additional models of disease, we detail the clinical course in guinea pigs infected with 5 geographically and genetically diverse LASV strains. Two of the developed models (LASV clades II and III) were then used to evaluate efficacy of a virus replicon particle vaccine against heterologous LASV challenge, demonstrating complete protection against clinical disease after a single vaccination dose.

Pathology and Pathogenesis of Lassa Fever: Novel Immunohistochemical Findings in Fatal Cases and Clinico-pathologic Correlation.

BACKGROUND: Lassa fever is a zoonotic, acute viral illness first identified in Nigeria in 1969. An estimate shows that the "at risk" seronegative population (in Sierra Leone, Guinea, and Nigeria) may be as high as 59 million, with an annual incidence of all illnesses of 3 million, and fatalities up to 67 000, demonstrating the serious impact of the disease on the region and global health. METHODS: Histopathologic evaluation, immunohistochemical assay, and electron microscopic examination were performed on postmortem tissue samples from 12 confirmed Lassa fever cases. RESULTS: Lassa fever virus antigens and viral particles were observed in multiple organ systems and cells, including cells in the mononuclear phagocytic system and other specialized cells where it had not been described previously. CONCLUSIONS: The immunolocalization of Lassa fever virus antigens in fatal cases provides novel insightful information with clinical and pathogenetic implications. The extensive involvement of the mononuclear phagocytic system, including tissue macrophages and endothelial cells, suggests participation of inflammatory mediators from this lineage with the resulting vascular dilatation and increasing permeability. Other findings indicate the pathogenesis of Lassa fever is multifactorial and additional studies are needed.

Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.

Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.

Two Cases of Lassa Fever Successfully Treated with Ribavirin and Adjunct Dexamethasone for Concomitant Infections.

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

Pathogens that Cause Illness Clinically Indistinguishable from Lassa Fever, Nigeria, 2018.

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

Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment.

Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.

Safety and Pharmacokinetics of LHF-535, a Potential Treatment for Lassa Fever, in Healthy Adults.

LHF-535 is a small-molecule antiviral currently under development as a therapeutic option to treat Lassa fever and other viral hemorrhagic fevers of arenavirus origin. The human safety and pharmacokinetics of LHF-535 were evaluated in two phase 1 trials in healthy volunteers. The first study was a double-blind, single ascending dose trial that evaluated weight-based oral doses ranging from 0.3 mg/kg in the first cohort to 40 mg/kg in the last cohort. The second study was a double-blind, multiple ascending dose trial that evaluated a 14-day oral dosing regimen, with three sequential cohorts receiving fixed doses of 450, 900, or 1,125 mg per day; the third cohort (1,125 mg/day) received a higher (loading) dose of 2,250 mg for the first dose. Each cohort in both studies consisted of eight participants randomized to either placebo (n = 2) or LHF-535 (n = 6). LHF-535 was well tolerated in both studies. Treatment-emergent adverse events were more frequent in placebo recipients than in LHF-535 recipients in both studies. LHF-535 exhibited rapid absorption, a long half-life, and exposures predicted to suppress viral replication.

Lassa fever in pregnancy: Report of two maternal deaths in a tertiary center in the middle-belt region of Nigeria.

Lassa fever is endemic in West Africa, with an estimated 300,000 to 500,000 infections occurring annually and approximately 5,000 deaths. Two Lassa fever cases in pregnancy with maternal and fetal complications were presented. The age range was 20 to 30 years and the range of parity was 1 to 3. The duration of symptoms was 13 to 14 days. Clinical presentation and complications common to the two cases were fever, abnormal bleeding, cough/sore throat, anaemia, IUFD/Stillbirth, and maternal deaths. Others are vomiting, restlessness/confusion, hypotension and thrombocytopaenia. Major challenges encountered are late presentation, delay in confirming diagnosis and instituting definitive treatment, limited facility, and the impact of traditional and religious factors in safe burial for Lassa fever cases. In resource-constrained settings; diagnosis, treatment and surveillance for Lassa fever may be challenging. Early clinical suspicion and appropriate case management are critical for good reproductive outcome.

Tetravalent Rabies-Vectored Filovirus and Lassa Fever Vaccine Induces Long-term Immunity in Nonhuman Primates.

BACKGROUND: The objective of this study is to evaluate the immunogenicity of adjuvanted monovalent rabies virus (RABV)-based vaccine candidates against Ebola virus (FILORAB1), Sudan virus (FILORAB2), Marburg virus (FILORAB3), Lassa virus (LASSARAB1), and combined trivalent vaccine candidate (FILORAB1-3) and tetravalent vaccine candidate (FILORAB1-3 and LASSARAB) in nonhuman primates. METHODS: Twenty-four Macaca fascicularis were randomly assigned into 6 groups of 4 animals. Each group was vaccinated with either a single adjuvanted vaccine, the trivalent vaccine, or the tetravalent vaccine at days 0 and 28. We followed the humoral immune responses for 1 year by antigen-specific enzyme-linked immunosorbent assays and RABV neutralization assays. RESULTS: High titers of filovirus and/or Lassa virus glycoprotein-specific immunoglobulin G were induced in the vaccinated animals. There were no significant differences between immune responses in animals vaccinated with single vaccines vs trivalent or tetravalent vaccines. In addition, all vaccine groups elicited strong rabies neutralizing antibody titers. The antigen-specific immune responses were detectable for 1 year in all groups. CONCLUSIONS: In summary, this study shows the longevity of the immune responses up to 365 days for a pentavalent vaccine-against Ebola virus, Sudan virus, Marburg virus, Lassa virus, and RABV-using a safe and effective vaccine platform.

Evaluation of National Event-Based Surveillance, Nigeria, 2016-2018.

Nigeria Centres for Disease Control and Prevention established an event-based surveillance (EBS) system in 2016 to supplement traditional surveillance structures. The EBS system is comprised of an internet-based data mining tool and a call center. To evaluate the EBS system for usefulness, simplicity, acceptability, timeliness, and data quality, we performed a descriptive analysis of signals received during September 2017-June 2018. We used questionnaires, semistructured interviews, and direct observation to collect information from EBS staff. Amongst 43,631 raw signals detected, 138 (0.3%) were escalated; 63 (46%) of those were verified as events, including 25 Lassa fever outbreaks and 13 cholera outbreaks. Interviewees provided multiple examples of earlier outbreak detections but suggested notifications and logging could be improved to ensure action. EBS proved effective in detecting outbreaks, but we noted clear opportunities for efficiency gains. We recommend improving signal logging, standardizing processes, and revising outputs to ensure appropriate public health action.

Identification of Common CD8+ T Cell Epitopes from Lassa Fever Survivors in Nigeria and Sierra Leone.

Early and robust T cell responses have been associated with survival from Lassa fever (LF), but the Lassa virus-specific memory responses have not been well characterized. Regions within the virus surface glycoprotein (GPC) and nucleoprotein (NP) are the main targets of the Lassa virus-specific T cell responses, but, to date, only a few T cell epitopes within these proteins have been identified. We identified GPC and NP regions containing T cell epitopes and HLA haplotypes from LF survivors and used predictive HLA-binding algorithms to identify putative epitopes, which were then experimentally tested using autologous survivor samples. We identified 12 CD8-positive (CD8+) T cell epitopes, including epitopes common to both Nigerian and Sierra Leonean survivors. These data should be useful for the identification of dominant Lassa virus-specific T cell responses in Lassa fever survivors and vaccinated individuals as well as for designing vaccines that elicit cell-mediated immunity.IMPORTANCE The high morbidity and mortality associated with clinical cases of Lassa fever, together with the lack of licensed vaccines and limited and partially effective interventions, make Lassa virus (LASV) an important health concern in its regions of endemicity in West Africa. Previous infection with LASV protects from disease after subsequent exposure, providing a framework for designing vaccines to elicit similar protective immunity. Multiple major lineages of LASV circulate in West Africa, and therefore, ideal vaccine candidates should elicit immunity to all lineages. We therefore sought to identify common T cell epitopes between Lassa fever survivors from Sierra Leone and Nigeria, where distinct lineages circulate. We identified three such epitopes derived from highly conserved regions within LASV proteins. In this process, we also identified nine other T cell epitopes. These data should help in the design of an effective pan-LASV vaccine.

Severe Human Lassa Fever Is Characterized by Nonspecific T-Cell Activation and Lymphocyte Homing to Inflamed Tissues.

Lassa fever (LF) is a zoonotic viral hemorrhagic fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T-cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here, we present a multiparametric analysis of clinical immunology data collected during the 2017-2018 Lassa fever outbreak in Nigeria. During the acute phase of LF, we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific and antigenically unrelated T cells. However, severe and fatal LF cases were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of nonspecific T cells with homing capacity to inflamed tissues are associated with severe LF.IMPORTANCE Lassa fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa fever outbreak in Nigeria indicating that severe Lassa fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.

Lassa fever amidst the COVID-19 pandemic in Africa: A rising concern, efforts, challenges, and future recommendations.

Lassa fever, caused by the Lassa virus of the Arenaviruses family, is a re-emerging public health concern that has led to 300,000 infections and 5000 deaths annually in Africa. Highly prevalent in Sierra Leone, Liberia, Guinea, Nigeria, Côte d'lvoire, Ghana, Togo, and Benin, patients infected with the virus can manifest with cough, sore throat, headache, nausea, and vomiting among other symptoms. Coexisting with the coronavirus disease 2019 (COVID-19) pandemic and its impacts, cases of Lassa fever in the African population have been reported to decrease due to hesitancy in visiting clinics that leads to unreported cases-all contributing to a silent outbreak in West Africa. Thus, to overcome current burdens, gaps, and challenges caused by Lassa fever amidst COVID-19 in Africa, various recommendations for efficient control of transmission, measures for disease containment, and strategies to correct misperceptions were made.

Infection pattern, case fatality rate and spread of Lassa virus in Nigeria.

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

Factors associated with delayed presentation to healthcare facilities for Lassa fever cases, Nigeria 2019: a retrospective cohort study.

BACKGROUND: Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions. METHODS: We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation. RESULTS: Of 389 cases, median presentation time was 6 days (IQR 4-10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13-17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0-4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5-12 and 13-17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5-9 days and 20-60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41-95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time. CONCLUSIONS: Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.

The niche of One Health approaches in Lassa fever surveillance and control.

Lassa fever (LF), a zoonotic illness, represents a public health burden in West African countries where the Lassa virus (LASV) circulates among rodents. Human exposure hinges significantly on LASV ecology, which is in turn shaped by various parameters such as weather seasonality and even virus and rodent-host genetics. Furthermore, human behaviour, despite playing a key role in the zoonotic nature of the disease, critically affects either the spread or control of human-to-human transmission. Previous estimations on LF burden date from the 80s and it is unclear how the population expansion and the improvement on diagnostics and surveillance methods have affected such predictions. Although recent data have contributed to the awareness of epidemics, the real impact of LF in West African communities will only be possible with the intensification of interdisciplinary efforts in research and public health approaches. This review discusses the causes and consequences of LF from a One Health perspective, and how the application of this concept can improve the surveillance and control of this disease in West Africa.