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Lassa fever (LF) and yellow fever (YF) belong to a group of viral hemorrhagic fevers (VHFs). These viruses have common features and damages the organs and blood vessels; they also impair the body’s homeostasis. Some VHFs cause mild disease, while some cause severe disease and death such as in the case of Ebola or Marburg. LF virus and YF virus are two of the most recent emerging viruses in Africa, resulting in severe hemorrhagic fever in humans. Lassa fever virus is continuously on the rise both in Nigeria and neighboring countries in West Africa, with an estimate of over 500,000 cases of LF, and 5000 deaths, annually. YF virus is endemic in temperate climate regions of Africa, Central America (Guatemala, Honduras, Nicaragua, El Salvador), and South America (such as Brazil, Argentina, Peru, and Chile) with an annual estimated cases of 200,000 and 30,000 deaths globally. This review examines the impact of the COVID-19 pandemic on the trend in epidemiology of these two VHFs to delineate responses that are associated with protective or pathogenic outcomes.

Lassa fever is a viral zoonotic tropical disease endemic in parts of West Africa. It causes substantial mortality, morbidity and economic burdens on affected populations. The year 2019 marked the 50th anniversary of the first diagnosis of Lassa fever in Nigeria. Over the years, a few and sporadic intervention measures have been undertaken to control Lassa fever in Nigeria. However, the disease has remained a burden due to neglect, and apathy from the Government. Here we highlight the Lassa fever control efforts so far undertaken in Nigeria. We also point to some challenges and opportunities for effective Lassa fever control efforts. In addition, we proposed few Lassa fever control measures, which vary from advocacies, training of local communities and health workers in the use of rapid, cheap diagnostic tools. We also propose an integrated genomic surveillance platform that utilizes one health approach, in tracking and tackling Lassa fever, as the key future of Lassa fever control effort. In this review, we present IGOHRAL, an integrated genomic platform that utilizes clinical, genomic and epidemiological data in a one-health approach to tackle Lassa fever problem. Lassa fever (LF) is a serious viral hemorrhagic fever endemic in West Africa. The history of Lassa fever virus (LVS) in Nigeria is that of neglect, wickedness and apathy (Akpede et al., 2018). Lassa virus was first diagnosed in a missionary hospital in Nigeria in 1969 (Carey et al., 1972). There was an outbreak of a febrile illness involving hospital staff and those who visited the hospitals. The aetiology was later confirmed to be LVS. Prior to this outbreak, there have been several descriptions of illness resembling LF (Monath, 1975). However, a genomics study by Anderson et al. later confirmed that the LVS emerged in present day Nigeria over 1060 years ago (Andersen et al., 2015).

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.

Epidemic models have been broadly used to comprehend the dynamic behaviour of emerging and re-emerging infectious diseases, predict future trends, and assess intervention strategies. The symptomatic and asymptomatic features and environmental factors for Lassa fever (LF) transmission illustrate the need for sophisticated epidemic models to capture more vital dynamics and forecast trends of LF outbreaks within countries or sub-regions on various geographic scales. This study proposes a dynamic model to examine the transmission of LF infection, a deadly disease transmitted mainly by rodents through environment. We extend prior LF models by including an infectious stage to mild and severe as well as incorporating environmental contributions from infected humans and rodents. For model calibration and prediction, we show that the model fits well with the LF scenario in Nigeria and yields remarkable prediction results. Rigorous mathematical computation divulges that the model comprises two equilibria. That is disease-free equilibrium, which is locally-asymptotically stable (LAS) when the basic reproduction number, $ {\mathcal{R}}_{0} $, is $ < 1 $; and endemic equilibrium, which is globally-asymptotically stable (GAS) when $ {\mathcal{R}}_{0} $ is $ > 1 $. We use time-dependent control strategy by employing Pontryagin's Maximum Principle to derive conditions for optimal LF control. Furthermore, a partial rank correlation coefficient is adopted for the sensitivity analysis to obtain the model's top rank parameters requiring precise attention for efficacious LF prevention and control.

Objectives: Liberia is endemic to Lassa fever (LF) and has the largest reported per capita incidence of LF patients in the West African region. Cases of the disease increased unprecedentedly in 2019 and 2020, characterized by a geographical drift in epidemiology and seasonal variation of occurrence. This study aims to describe the epidemiological and clinical characteristics of LF in Liberia from 2019 to 2020. Methods: A retrospective study was conducted on cases of LF confirmed at the National Public Health Reference Laboratory from January 2019 to December 2020. Medical records were reviewed, and epidemiological and clinical data were collected in an organized manner. Descriptive and inferential statistics were carried out using Epi Info (version 7.2.5.0). Results: A total of 382 suspected LF cases were reported, of which 103 were laboratory-confirmed, yielding a case positivity rate of 27% (103/382). The median age of the LF cases was 20 (IQR: 9–30). Children younger than 18 years accounted for 40.8% (42/103) of the cases and healthcare workers’ cases constituted 7.7% of the cases. Bong, Nimba, and Grand Bass accounted for 87.4% of the cases with cases in new counties like Lofa, Margibi, and Grand Kru. Hemorrhage (aOR:10.2; 95% CI: 3.11–33.81), patients who did not receive ribavirin (aOR: 4.4; 95% CI: 1.12–17.57, P = 0.034), and patients aged 40 years or older (aOR: 6.2; 95% CI: 1.19–32.53, P = 0.049) were associated with LF mortality. Conclusion: The LF cases in 2019 and 2020 had a high case fatality rate and spread to new counties that had not previously reported LF. The disease occurred during most of the rainy season instead of the usual dry season. There is an urgent need to lower morbidity and mortality, improve early presentation to the hospital, and early initiation of appropriate medical care.

Background: There is limited epidemiological evidence on Lassa fever in pregnant women with acute gaps on prevalence, infection incidence, and risk factors. Such evidence would facilitate the design of therapeutic and vaccine trials and the design of control programs. Our study sought to address some of these gaps by estimating the seroprevalence and seroconversion risk of Lassa fever in pregnant women. Methodology/Principal findings: We conducted a prospective hospital-based cohort between February and December 2019 in Edo State, Southern Nigeria, enrolling pregnant women at antenatal clinic and following them up at delivery. Samples were evaluated for IgG antibodies against Lassa virus. The study demonstrates a seroprevalence of Lassa IgG antibodies of 49.6% and a seroconversion risk of 20.8%. Seropositivity was strongly correlated with rodent exposure around homes with an attributable risk proportion of 35%. Seroreversion was also seen with a seroreversion risk of 13.4%. Conclusions/Significance: Our study suggests that 50% of pregnant women were at risk of Lassa infection and that 35.0% of infections might be preventable by avoiding rodent exposure and conditions which facilitate infestation and the risk of human-rodent contact. While the evidence on rodent exposure is subjective and further studies are needed to provide a better understanding of the avenues of human-rodent interaction; public health measures to decrease the risk of rodent infestation and the risk of spill over events may be beneficial. With an estimated seroconversion risk of 20.8%, our study suggests an appreciable risk of contracting Lassa fever during pregnancy and while most of these seroconversions may not be new infections, given the high risk of adverse outcomes in pregnancy, it supports the need for preventative and therapeutic options against Lassa fever in pregnancy. The occurrence of seroreversion in our study suggests that the prevalence obtained in this, and other cohorts may be an underestimate of the actual proportion of women of childbearing age who present at pregnancy with prior LASV exposure. Additionally, the occurrence of both seroconversion and seroreversion in this cohort suggests that these parameters would need to be considered for the development of Lassa vaccine efficacy, effectiveness, and utility models. Author summary: Lassa virus is a viral haemorrhagic fever endemic to West Africa and yet to date there is limited information on its epidemiology in pregnancy. Information obtained from epidemiology studies is important because such information facilitates the design and costing of disease control programs and the design of clinical trials. Our study evaluated the epidemiology of Lassa fever in pregnant women specifically we looked at the prevalence, incidence, and risk factors for infection in pregnant women in South Nigeria. We found that 49.6% of pregnant women had antibodies to Lassa virus suggesting about 50% of pregnant women were at risk of Lassa infection. Additionally, while, the evidence was not conclusive, we found an appreciable risk of contracting Lassa fever during pregnancy. Given that, Lassa fever has high case fatality in pregnancy, our data supports the need for vaccines and drugs against Lassa fever. Our study also suggests that 35.0% of infections might be preventable by avoiding rodent exposure and conditions which facilitate rodent infestation and the risk of human-rodent contact. This suggests that public health measures such as proper sanitation and hygiene, improved housing and health education may be beneficial in reducing the risk of infection. [ABSTRACT FROM AUTHOR]

When it comes to human care service challenges, it is critical to understand the dynamic behavior of the associated contagious diseases because non-Markovian effects play a significant role in their spread. This investigation takes a look into an etiological model directly linked to the complexities of Lassa hemorrhagic fever disease in pregnant women in Africa. This is a bacteriostatic fever and an outbreak illness. The aforesaid ailment in expectant mothers has adverse implications that first popped up in Africa. The etiological model was constructed for the first time utilizing a recently designed fractal-fractional (FF) operator based on the power law, exponential decay, and Mittag-Leffler kernels with fractional order and fractal dimension. We construct three schemes of successive approximations based on FF operators using Lagrange polynomials, and the fundamental reproducing number is determined to be ℛ 0 . The existence and uniqueness of the suggested model's mathematical technique are examined. The endemic and disease-free equilibria are also calculated. Eventually, simulated results of the framework are performed using the suggested numerical approach, and the outcomes in graphical representations quantify the effects of the projected and integrated characteristics and demonstrate that the ailment can be considerably governed or exterminated if the outbreak propagation rate is lessened and the rate of intervention is improved. [ABSTRACT FROM AUTHOR]

MV‐LASV is an investigational measles Schwarz‐based vaccine for the prevention of Lassa fever. A repeated‐dose toxicity study in cynomolgus macaques was performed to assess the biodistribution and local and systemic toxicological effects. Monkeys received three immunizations of MV‐LASV or saline intramuscularly with a 2‐week interval. An increase in anti‐measles antibodies confirmed the reaction of the immune system to the vaccine backbone. Clinical observations, body weight, body temperature, local tolerance, electrocardiogram parameters, various clinical pathology parameters (hematology, coagulation urinalysis, serum chemistry, and C‐reactive protein) were monitored. Gross pathology and histopathology of various tissues were evaluated. MV‐LASV induced a mild increase in fibrinogen and C‐reactive protein concentrations. This coincided with microscopic inflammation at the injection sites which partially or fully resolved following a 3‐week recovery period. Viral RNA was found in secondary lymphoid organs and injection sites and gall bladder. No viral shedding to the environment was observed. Overall, the vaccine was locally and systemically well tolerated, supporting a first‐in‐human study. MV‐LASV, a recombinant measles Schwarz‐based vaccine for the prevention of Lassa fever, was assessed in a repeated‐dose toxicity and biodistribution study. Cynomolgus monkeys received three immunizations of MV‐LASV or saline intramuscularly with a 2‐week interval. Viral RNA was found primarily in secondary lymphoid organs and injection sites. No viral shedding to the environment was observed. Overall, the vaccine was locally and systemically well tolerated, supporting a first‐in‐human study. [ABSTRACT FROM AUTHOR]

Lassa fever (LF) remains endemic in Nigeria with the country reporting the highest incidence and mortality globally. Recent national data suggests increasing incidence and expanding geographic spread. Predictors of LF case positivity in Nigeria have been sparsely studied. We thus sought to determine the sociodemographic and clinical determinants of LF positivity amongst suspected cases presenting to health facilities from 2018 to 2021. A secondary analysis of the national LF surveillance data between January 2018 and December 2021. Socio-demographic and clinical data of 20,027 suspected LF cases were analysed using frequencies and Chi-square statistics with significant p-value set at p < 0.05. The outcome variable was LF case status (positive or negative). Predictors of LF case positivity were assessed using multiple logistic regression models with 95% confidence intervals (CI). Case positivity rate (CPR) for the four years was 15.8% with higher odds of positivity among age group 40–49 years (aOR = 1.40; 95% CI 1.21–1.62), males (aOR = 1.11; 95% CI 1.03–1.20), those with formal education (aOR = 1.33; 95% CI 1.13–1.56), artisans (aOR = 1.70; 95% CI 1.28–2.27), religious leaders (aOR = 1.62; 95% CI 1.04–2.52), farmers (aOR = 1.48; 95% CI 1.21–1.81), and symptomatic individuals (aOR = 2.36; 95% CI 2.09–2.68). Being a health worker (aOR = 0.69; 95% CI 0.53–0.91), a teacher (aOR = 0.69; 95% CI 0.53–0.89) and cases reporting in the 3rd quarter (aOR = 0.79; 95% CI 0.69–0.92) had lower odds. In a sex-disaggregated analysis, female farmers had higher odds of positivity (aOR = 2.43; 95% CI 1.76–3.38; p < 0.001) than male farmers (aOR = 1.52; 95% CI 1.19–1.96; p < 0.01). Fever (aOR = 2.39; 95% CI 2.00–2.84) and gastrointestinal (GI) symptoms (aOR = 2.15; 95% CI 1.94–2.37) had the highest odds among symptoms. Combination of fever and GI symptoms (aOR = 2.15; 95% CI 1.50–3.10), fever and neurological symptoms (aOR = 6.37; 95% CI 1.49–27.16), fever and musculo-skeletal symptoms (aOR = 2.95; 95% CI 1.37–6.33), fever and cardiopulmonary symptoms (aOR = 1.81; 95% CI 1.24–2.64), and cardiopulmonary and general symptoms (aOR = 1.50; 95% CI 1.19–1.89) were also predictive. Cumulative LF CPR appears high with clearly identified predictors. Targeted interventions with heightened index of suspicion for sociodemographic categories predictive of LF in suspected cases are recommended. Ethnographic and further epidemiological studies could aid better understanding of these associations. [ABSTRACT FROM AUTHOR]

Background: Evidence from previous studies suggest that Lassa fever, a viral haemorrhagic fever endemic to West Africa has high case fatalities, particularly in pregnancy. While there have been remarkable innovations in vaccine development, with some Lassa vaccines undergoing early clinical trials. An understanding of Lassa antibody kinetics and immune responses will support vaccine design and development. However, there is currently no evidence on the antibody kinetics of Lassa (LASV) in pregnancy. Our study sought to estimate the efficiency of transplacental transfer of LASV IgG antibodies from the mother to the child. Methodology/Principal findings: The study made use of data from a prospective hospital-based cohort of pregnant women enrolled at the antenatal clinic and followed up at delivery between February and December 2019. Blood samples from mother-child pairs were evaluated for antibodies against Lassa virus. The study demonstrates a transplacental transfer of LASV IgG of 75.3% [60.0–94.0%], with a significant positive correlation between maternal and cord concentrations and a good level of agreement. The study also suggests that transfer may be more variable in women with 'de novo' antibodies compared to those with pre-existing antibodies. Conclusions/Significance: The study shows that maternal antibody levels play an important role in determining transfer efficiency of Lassa antibodies to the new-born; and while the evidence is preliminary, the study also suggests that transfer efficiency may be less stable in acute or recent infection, as such timing of vaccination before pregnancy, that is in women of childbearing age may be more appropriate for protection of both pregnant women and their neonates. Author summary: Lassa fever, an epidemic-prone viral infection which frequently occurs in West African countries has a high mortality in pregnant women and their new-borns. Vaccination is an ideal method for preventing infection and while there are currently no licensed vaccines for Lassa fever, there have been marked innovations in Lassa vaccine development with some vaccines currently in early trials. Vaccine development requires background information on disease prevalence, incidence, and antibody kinetics. Our study sought to understand the kinetics of Lassa antibodies in pregnant women and their new-borns. This is the first study to evaluate the transfer of Lassa antibodies between the mother and child. We found that maternal antibody levels play an important role in determining how well antibodies are transferred from the mother to the child and may be influenced by the time when antibodies developed, with transfer of antibodies being less stable in those with recent infection. This suggest that for protection of both pregnant women and their neonates, it may be more appropriate to vaccinate women before they become pregnant, that is women of child-bearing age. While, the evidence is not conclusive, it is an important first step to understanding the kinetics of Lassa antibodies. [ABSTRACT FROM AUTHOR]

Lassa fever is a substantial health burden in west Africa. We evaluated the safety, tolerability, and immunogenicity of a recombinant, live-attenuated, measles-vectored Lassa fever vaccine candidate (MV-LASV). This first-in-human phase 1 trial—consisting of an open-label dose-escalation stage and an observer-blinded, randomised, placebo-controlled treatment stage—was conducted at a single site at the University of Antwerp, Antwerp, Belgium, and involved healthy adults aged 18–55 years. Participants in the dose-escalation stage were sequentially assigned to a low-dose group (two intramuscular doses of MV-LASV at 2 × 104 times the median tissue culture infectious dose) or a high-dose group (two doses at 1 × 105 times the median tissue culture infectious dose). Participants in the double-blinded treatment stage were randomly assigned in a 2:2:1 ratio to receive low dose, high dose, or placebo. The primary endpoint was the rate of solicited and unsolicited adverse events up to study day 56 and was assessed in all participants who received at least one dose of investigational product. The trial is registered with ClinicalTrials.gov , NCT04055454 , and the European Union Drug Regulating Authorities Clinical Trials Database, 2018-003647-40, and is complete. Between Sept 26, 2019, and Jan 20, 2020, 60 participants were enrolled and assigned to receive placebo (n=12) or MV-LASV (n=48). All 60 participants received at least one study treatment. Most adverse events occurred during the treatment phase, and frequencies of total solicited or unsolicited adverse events were similar between treatment groups, with 96% of participants in the low-dose group, 100% of those in the high-dose group, and 92% of those in the placebo group having any solicited adverse event (p=0·6751) and 76% of those in the low-dose group, 70% of those in the high-dose group, and 100% of those in the placebo group having any unsolicited adverse event (p=0·1047). The only significant difference related to local solicited adverse events, with higher frequencies observed in groups receiving MV-LASV (24 [96%] of 25 participants in the low-dose group; all 23 [100%] participants in the high-dose group) than in the placebo group (6 [50%] of 12 participants; p=0·0001, Fisher-Freeman-Halton test). Adverse events were mostly of mild or moderate severity, and no serious adverse events were observed. MV-LASV also induced substantial concentrations of LASV-specific IgG (geometric mean titre 62·9 EU/ml in the low-dose group and 145·9 EU/ml in the high-dose group on day 42). MV-LASV showed an acceptable safety and tolerability profile, and immunogenicity seemed to be unaffected by pre-existing immunity against the vector. MV-LASV is therefore a promising candidate for further development. Coalition for Epidemic Preparedness Innovations. [ABSTRACT FROM AUTHOR]

Lassa fever is a severe public health problem in Nigeria with far-reaching political, social, cultural, and religious ramifications. Thus, a further understanding of the disease is critical. Despite attempts to end the viral epidemic, the illness has persisted, leading to several major outbreaks in decades. Additionally, the country's epidemic in 2019-2020 set a new global record for the number of Lassa fever cases. This year, 244 cases and 37 deaths had been reported as of January 2023. To identify gaps and provide recommendations for the complete eradication of Lassa fever in the country. This paper investigates the underlying causes of the continuous outbreaks of the illness in Nigeria and the measures to prevent it. The frequent outbreaks of Lassa fever in Nigeria have been linked to several factors, including inadequate waste management, poor sanitation, restricted access to healthcare, and abject poverty. The reoccurring outbreaks are also attributed to a lack of political will, funding, poor coordination and communication, and low public awareness of the illness and its prevention. To effectively stop outbreaks of Lassa fever in Nigeria, the government and partners must continuously put into practice tried-and-true prevention measures such as improved surveillance to detect outbreaks earlier, increased funding and resources to support effective control measures, better primary healthcare facilities and training for healthcare professionals, heightened community engagement and education to raise awareness, and more effective vector control methods to reduce rodent populations, while looking for innovative approaches and dealing with the underlying social and economic problems contributing to the viral persistence. [ABSTRACT FROM AUTHOR]

Lassa fever, a viral hemorrhagic fever caused by the Lassa virus (LASV), is endemic in West Africa and is associated with high morbidity and mortality. At least three of the four proposed seven lineages of LASV are found in Nigeria, where the multimammate rat, Mastomys natalensis, serves as the primary reservoir. Endemic countries report approximately 200,000 infections and 5,000 deaths annually, with Nigeria experiencing thousands of infections and hundreds of deaths including healthcare workers. The aim of this review is to provide scientific information for better understanding of the evolutionary biology, molecular epidemiology, pathogenesis, diagnosis, and prevention of Lassa fever in Nigeria and other endemic regions worldwide, which can lead to improved control efforts and reduce morbidity and mortality from recurrent epidemics. To achieve this aim, observational studies such as case series, cross-sectional and cohort studies published between December 2017 and September 2022 were searched for on various online databases including Google Scholar, Africa Journals Online (AJOL), Research Gates, PubMed, PMIC, NCDC, and WHO websites. Although the origin and evolutionary history, and the transmission dynamics of Lassa virus have been revealed through recent molecular epidemiological studies, the factors that drive the evolution of the virus remain unclear. Genetic changes in the viral genome may have enabled the virus to adapt to humans. Diagnosis of Lassa fever has also advanced from basic serological tests to more sophisticated methods such as quantitative real time polymerase chain reaction (qRT-PCR) and sequencing, which are particularly useful for identifying outbreak strains. Several vaccines, including recombinant vesicular stomatitis virus (rVSV), virus-like particle (VLP), and DNA-based vaccines, have shown promise in animal models and some have progressed to phase 2 clinical trials. Preventing and controlling Lassa fever is critical to safeguard the health and well-being of affected communities. Effective measures such as rodent control, improved sanitation, and early detection and isolation of infected individuals are essential for reducing transmission. Ongoing research into the genetic and ecological factors that drive the evolution of Lassa virus is necessary to reduce the impacts of Lassa fever. [ABSTRACT FROM AUTHOR]

Background: Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses. Method: We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (nmin = 1000 per site) will be drawn from the LF cohort (nmin = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM). Discussion: Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates. [ABSTRACT FROM AUTHOR]

Lassa fever hits West African countries annually in the absence of licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine protecting cynomolgus monkeys against divergent strains one month or more than a year before Lassa virus infection. Given the limited dissemination area during outbreaks and the risk of nosocomial transmission, a vaccine inducing rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. Here, we test whether the time to protection can be reduced after immunization by challenging measles virus pre-immune male cynomolgus monkeys sixteen or eight days after a single shot of MeV-NP. None of the immunized monkeys develop disease and they rapidly control viral replication. Animals immunized eight days before the challenge are the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated one hour after the challenge, but was not protected and succumbed to the disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in the presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine. Lassa virus vaccination is impeded by the limited capacity of vaccine candidates to induce rapid protection. In this study, the authors found that a single shot of a measles-based Lassa vaccine protected nonhuman primates 16 or 8 days after vaccination. [ABSTRACT FROM AUTHOR]

Nigeria experiences annual outbreaks of Lassa fever (LF) with high case numbers. At least three clades of Lassa virus (LASV) have been documented in Nigeria, though recent outbreaks are most often associated with clade II or clade III viruses. Using a recently isolated clade III LASV from a case of LF in Nigeria in 2018, we developed and characterized a guinea pig adapted virus capable of causing lethal disease in commercially available Hartley guinea pigs. Uniform lethality was observed after four passages of the virus and was associated with only two dominant genomic changes. The adapted virus was highly virulent with a median lethal dose of 10 median tissue culture infectious doses. Disease was characterized by several hallmarks of LF in similar models including high fever, thrombocytopenia, coagulation disorders, and increased inflammatory immune mediators. High viral loads were noted in all solid organ specimens analyzed. Histological abnormalities were most striking in the lungs and livers of terminal animals and included interstitial inflammation, edema, and steatosis. Overall, this model represents a convenient small animal model for a clade III Nigeria LASV with which evaluation of specific prophylactic vaccines and medical countermeasures can be conducted. [ABSTRACT FROM AUTHOR]

Lassa fever is a deadly viral illness that is endemic in some parts of West Africa, including Nigeria. A deterministic model in the form of a non-linear system of differential equations is developed to analyse the dynamics and possible control of the disease. The model is tested by fitting it to data from Nigeria's Lassa fever outbreak using a least-squares fitting routine and the model is shown to provide a reasonable fit to the data. Parameters representing various control measures in the model are estimated using the model fitting. Important epidemiological features of the model such as the basic reproduction number (R 0) , the disease-free equilibrium, and the endemic equilibrium are determined and analysed. The disease-free equilibrium is shown to be asymptotically stable when R 0 < 1 . A bifurcation about R 0 = 1 was determined using the Center Manifold Theorem. Using numerical simulations of the model future dynamics of Lassa fever disease in Nigeria are predicted and the impact of control measures on the disease determined. The use of approved rodenticides is shown to be the most effective control followed by reducing person-to-person and rodent-to-person contacts, respectively. Isolation and treatment of infected individuals are shown to be less effective when compared with the other control measures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Investigating the interplay of factors that result in a viral zoonotic outbreak is difficult, though it is increasingly important. As anthropogenic influences shift the delicate balance of ecosystems, new zoonoses emerge in humans. Sub-Saharan Africa is a notable hotspot for zoonotic disease due to abundant competent mammalian reservoir hosts. Furthermore, poverty, corruption, and an overreliance on natural resources play considerable roles in depleting biological resources, exacerbating the population's susceptibility. Unsurprisingly, viral zoonoses have emerged in Africa, including HIV/AIDS, Ebola, Avian influenza, Lassa fever, Zika, and Monkeypox. These diseases are among the principal causes of death in endemic areas. Though typically distinct in their manifestations, viral zoonoses are connected by underlying, definitive factors. This review summarises vital findings on viral zoonoses in Africa using nine notable case studies as a benchmark for future studies. We discuss the importance of ecological recuperation and protection as a central strategy to control zoonotic diseases. Emphasis was made on moderating key drivers of zoonotic diseases to forestall future pandemics. This is in conjunction with attempts to redirect efforts from reactive to pre-emptive through a multidisciplinary “one health” approach.

IntroductionLassa fever constitutes a threat to the public health system in Nigeria with the reoccurring annual epidemics and its attendant risk communication intervention challenges.ObjectiveThis study examined the influence of public alarm (if any) on respondents' comprehension of risk communication messages about the most common host of the Lassa virus, modes of transmission, risk factors, and protective measures for Lassa fever. The risk communication model (mental noise hypothesis) served as the benchmark for measuring respondents' perceptions in the most endemic states in Nigeria.MethodThe study adopted a quantitative approach, using the survey method. Data for this study were collected from 653 respondents through a structured questionnaire. Respondents were selected through a multi-stage sampling technique. Frequency tables were used to profile the respondents' characteristics and key variables while regression coefficients were used to draw inferences.ResultsThe study found a high level of perceived public alarm among the respondents but maximum attention was paid to risk communication messages amid the high level of anxiety. Knowledge of the common Lassa virus-host, modes of transmission, risk factors, and risk reduction measures was adequate irrespective of the high level of perceived public alarm. Public alarm significantly influenced audience comprehension of the risk information about Lassa fever in Ebonyi and Ondo at r2 = 0.040 and 0.076, at p < 0.05 but not in Edo state at r2 = 0.010, at p > 0.05.ConclusionThe authors conclude that devoting adequate attention to outbreak communication messages amid a high level of anxiety could lead to improved knowledge of infectious diseases.

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.

Background: This is a standardized, pre-positioned protocol for the coordinated evaluation of Lassa fever therapeutics. The protocol is the product of discussions that took place in 2021 and 2022 among international investigators from a wide range of scientific and medical disciplines working together within the West Africa Lassa fever Consortium (WALC). Methods: This is a clinical Phase II/III multicentre randomised controlled platform trial using a superiority framework with an equal allocation ratio and a composite primary endpoint of all-cause mortality OR new onset of i) acute kidney failure (AKF), OR ii) acute respiratory failure (ARF), OR iii) shock assessed from enrolment (D0) to D28. Discussion: This pre-positioned protocol was developed by the WALC and made available for adaptation and implementation by the wider Lassa fever research community in order to generate efficient, reliable, and comparable evidence for Lassa fever therapeutics.

Background Lassa fever is a viral haemorrhagic fever endemic to eight West African countries. Symptomatic disease is expected to occur in 20% of those infected and transmission typically occurs from viral spillover from rodent hosts. The combination of limited access to diagnostics and healthcare means the true burden of this disease is unknown. Methods The case fatality rate among confirmed, probable and possible cases of Lassa fever in endemic regions is expected to be ≈15%. Here, annual reported cases and deaths have been used to estimate the case fatality rate, using three subsets of available data, to understand the scale of underreporting of severe human cases. Results The literature review produced 38 records of cases and fatalities, comprising 5230 reported cases and 1482 reported deaths in seven countries. The estimated case fatality rate ranges from 16.5 to 25.6% (standard deviation 11.5–32.2). The expected number of severe cases between 2012 and 2022 is 8995, with current reported numbers 58% of what is expected. Conclusion This analysis highlights current uncertainty and systemic underreporting of the morbidity and mortality burden of Lassa fever in its endemic region and must be considered when discussing the epidemiology of this neglected tropical disease. [ABSTRACT FROM AUTHOR]

The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.

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.

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

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

The Lassa virus (LASV) causes Lassa fever, a highly infectious and lethal agent of acute viral hemorrhagic fever. At present, there are still no effective treatments available, creating an urgent need to develop novel therapeutics. Some benzimidazole compounds targeting the arenavirus envelope glycoprotein complex (GPC) are promising inhibitors of LASV. In this study, we synthesized two series of LASV inhibitors based on the benzimidazole structure. Lentiviral pseudotypes bearing the LASV GPC were established to identify virus entry inhibitors. Surface plasmon resonance (SPR) was further used to verify the binding activities of the potential compounds. Compounds 7d−Z, 7h−Z, 13c, 13d, and 13f showed relatively excellent antiviral activities with IC50 values ranging from 7.58 to 15.46 nM and their SI values above 1251. These five representative compounds exhibited stronger binding affinity with low equilibrium dissociation constants (KD < 8.25 × 10−7 M) in SPR study. The compound 7h−Z displayed the most potent antiviral activity (IC50 = 7.58 nM) with a relatively high SI value (2496), which could be further studied as a lead compound. The structure–activity relationship indicated that the compounds with lipophilic and spatially larger substituents might possess higher antiviral activity and a much larger safety margin. This study will provide some good guidance for the development of highly active compounds with a novel skeleton against LASV. [ABSTRACT FROM AUTHOR]

Background: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The prevalence of exposure to LASV in Sierra Leone is crudely estimated and largely unknown. This cross-sectional study aimed to establish a baseline point seroprevalence of IgG antibodies to LASV in three administrative districts of Sierra Leone and identify potential risk factors for seropositivity and LASV exposure. Methodology and principal findings: Between 2015 and 2018, over 10,642 participants from Kenema, Tonkolili, and Port Loko Districts were enrolled in this cross-sectional study. Previous LASV and LF epidemiological studies support classification of these districts as "endemic," "emerging," and "non-endemic", respectively. Dried blood spot samples were tested for LASV antibodies by ELISA to determine the seropositivity of participants, indicating previous exposure to LASV. Surveys were administered to each participant to assess demographic and environmental factors associated with a higher risk of exposure to LASV. Overall seroprevalence for antibodies to LASV was 16.0%. In Kenema, Port Loko, and Tonkolili Districts, seroprevalences were 20.1%, 14.1%, and 10.6%, respectively. In a multivariate analysis, individuals were more likely to be LASV seropositive if they were living in Kenema District, regardless of sex, age, or occupation. Environmental factors contributed to an increased risk of LASV exposure, including poor housing construction and proximity to bushland, forested areas, and refuse. Conclusions and significance: In this study we determine a baseline LASV seroprevalence in three districts which will inform future epidemiological, ecological, and clinical studies on LF and the LASV in Sierra Leone. The heterogeneity of the distribution of LASV and LF over both space, and time, can make the design of efficacy trials and intervention programs difficult. Having more studies on the prevalence of LASV and identifying potential hyper-endemic areas will greatly increase the awareness of LF and improve targeted control programs related to LASV. Author summary: Lassa fever (LF), an acute viral hemorrhagic fever, is a major public health threat in West Africa. Lassa virus (LASV), the cause of LF, is transmitted to humans from the infected excrement or urine of the rodent-host, Mastomys natalensis. The true prevalence of LASV in Sierra Leone remains unknown. Working with the LF research program at Kenema Government Hospital (KGH), this study sought to establish a baseline seroprevalence of antibodies to LASV in Sierra Leone, targeting three administrative districts. Previous studies suggest LF and the presence of LASV is more widespread in Sierra Leone than previously recognized. This study corroborated these suggestions and revealed potential demographic and environmental factors that could increase the risk of exposure to LASV. As the largest epidemiological study conducted on LASV to-date in Sierra Leone, it will help inform future public health interventions and improve epidemiological, ecological, and clinical studies on LF and LASV. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Lassa fever (LF), a haemorrhagic fever disease caused by Lassa virus (LASV), is a serious public health burden in West Africa. The Mano River region (Sierra Leone, Guinea, Liberia, and Côte d'Ivoire) has been an endemic focus of the disease over the past decades. Here, we deciphered the genetic basis underlying LF endemics in this region. Clade model and type I functional divergence analyses revealed that the major LASV group, Kenema sub-clade, which is currently circulating in the Eastern Province of Sierra Leone, has been affected by different selective pressure compared to isolates from the other areas with effects on the viral RNA-dependent RNA polymerase (L protein) and probably nucleoprotein (NP). Further, contingency analysis showed that, in the early endemic, the sub-clade has undergone adaptive diversification via acceleration of amino acid substitutions in L protein. These findings highlight the key viral factor and local adaptation regarding the endemicity of LF. • A molecular study was conducted on LF endemics in the Mano River region. • The major viral group, Kenema sub-clade, has been under local selection. • Viral L protein and probably NP have been the targets of the local selection. • In the early endemic, the Kenema sub-clade has experienced local adaptation. • The amino acid changes through the adaptation have accumulated on L protein. [ABSTRACT FROM AUTHOR]

Background: The recent outbreaks of Marburg virus disease (MVD) in Guinea and Ghana have become a major public health concern not only to the West African sub-region but a threat to global health. Given the poorly elucidated ecological and epidemiological dynamics of the Marburg virus, it would be imprudent to preclude the possibility of another pandemic if urgent efforts are not put in place. However, the prior emergence and impact of COVID-19 and other co-occurring epidemics may add 'noise' to the epidemiological dynamics and public health interventions that may be required in the advent of a MVD outbreak in Nigeria. Short conclusion: Paying attention to the lessons learned from previous (and current) multiple epidemics including Avian Influenza, Yellow fever, Ebola virus disease, Monkeypox, Lassa fever, and COVID-19 could help avoid a potentially devastating public health catastrophe in Nigeria. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Lassa fever is a viral haemorrhagic fever endemic in Nigeria. Improved surveillance and testing capacity have revealed in an increased number of reported cases and apparent geographic spread of Lassa fever in Nigeria. We described the recent four-year trend of Lassa fever in Nigeria to improve understanding of its epidemiology and inform the design of appropriate interventions. Methods: We analysed the national surveillance data on Lassa fever maintained by the Nigeria Centre for Diseases Control (NCDC) and described trends, sociodemographic, geographic distribution, and clinical outcomes. We compared cases, positivity, and clinical outcomes in the period January 2018 to December 2021. Results: We found Lassa fever to be reported throughout the year with more than half the cases reported within the first quarter of the year, a recent increase in numbers and geographic spread of the virus, and male and adult (>18 years) preponderance. Case fatality rates were worse in males, the under-five and elderly, during off-peak periods, and among low reporting states. Conclusion: Lassa fever is endemic in Nigeria with a recent increase in numbers and geographical distribution. Sustaining improved surveillance, enhanced laboratory diagnosis and improved case management capacity during off-peak periods should remain a priority. Attention should be paid to the very young and elderly during outbreaks. Further research efforts should identify and address specific factors that determine poor clinical outcomes. [ABSTRACT FROM AUTHOR]

Elucidating the adaptive immune characteristics of natural protection to Lassa fever (LF) is vital in designing and selecting optimal vaccine candidates. With rejuvenated interest in LF and a call for accelerated research on the Lassa virus (LASV) vaccine, there is a need to define the correlates of natural protective immune responses to LF. Here, we describe cellular and antibody immune responses present in survivors of LF (N = 370) and their exposed contacts (N = 170) in a LASV endemic region in Nigeria. Interestingly, our data showed comparable T cell and binding antibody responses from both survivors and their contacts, while neutralizing antibody responses were primarily seen in the LF survivors and not their contacts. Neutralizing antibody responses were found to be cross-reactive against all five lineages of LASV with a strong bias to Lineage II, the prevalent strain in southern Nigeria. We demonstrated that both T cell and antibody responses were not detectable in peripheral blood after a decade in LF survivors. Notably LF survivors maintained high levels of detectable binding antibody response for six months while their contacts did not. Lastly, as potential vaccine targets, we identified the regions of the LASV Glycoprotein (GP) and Nucleoprotein (NP) that induced the broadest peptide-specific T cell responses. Taken together this data informs immunological readouts and potential benchmarks for clinical trials evaluating LASV vaccine candidates. [ABSTRACT FROM AUTHOR]

Lassa fever (LF) and yellow fever (YF) belong to a group of viral hemorrhagic fevers (VHFs). These viruses have common features and damages the organs and blood vessels; they also impair the body's homeostasis. Some VHFs cause mild disease, while some cause severe disease and death such as in the case of Ebola or Marburg. LF virus and YF virus are two of the most recent emerging viruses in Africa, resulting in severe hemorrhagic fever in humans. Lassa fever virus is continuously on the rise both in Nigeria and neighboring countries in West Africa, with an estimate of over 500,000 cases of LF, and 5000 deaths, annually. YF virus is endemic in temperate climate regions of Africa, Central America (Guatemala, Honduras, Nicaragua, El Salvador), and South America (such as Brazil, Argentina, Peru, and Chile) with an annual estimated cases of 200,000 and 30,000 deaths globally. This review examines the impact of the COVID-19 pandemic on the trend in epidemiology of these two VHFs to delineate responses that are associated with protective or pathogenic outcomes. [ABSTRACT FROM AUTHOR]

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.