Incidence of symptomatic Lassa virus infection in West African countries (Enable 1.0 Lassa Research Study): a prospective, multisite, cohort study.

Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials. Here, we discuss several important aspects of LASV infection including immunobiology, immune evasion, and correlates of protection against LF, which have been identified through animal models and human infections. In addition, we discuss several vaccine candidates that have shown efficacy in animal models that could be advanced toward clinical trials. The increased fatality rate seen in the recent LASV outbreak in Nigeria highlights the importance of developing effective treatment and prevention strategies against LF. The spike in LASV cases seen in West Africa has the potential for increased mortality and human-to-human transmission, making the development and testing of effective vaccines for LASV critical.

BackgroundNo vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa. A replication-competent recombinant vesicular stomatitis virus–vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited.MethodsIn this phase 1, double-blind trial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly. Participants received a single vaccine dose of 2×104 plaque-forming units (PFU), 2×105 PFU, 2×106 PFU, or 2×107 PFU or placebo or received two vaccine doses of 2×107 PFU or placebo, within a window of 6 to 20 weeks. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural hearing loss, hearing acuity was measured before and after the injection. Secondary end points were levels of binding antibodies against LASV glycoprotein, neutralizing antibodies, and vaccine vector–derived viral RNA and PFU in plasma, urine, and saliva.ResultsA total of 114 adults were enrolled. No serious vaccine-related adverse events were reported. The vaccine caused minimal local reactions and dose-dependent, mild-to-severe early-onset systemic reactogenicity events that were transient. No hearing loss was detected. All doses induced robust long-lasting cellular and humoral (binding and neutralizing) responses that cross-reacted against common LASV lineages. No infectious vaccine virus particles were found in plasma, urine, or saliva.ConclusionsThe rVSVΔG-LASV-GPC vaccine resulted in transient local and systemic reactogenicity events but no hearing loss or serious adverse events. The vaccine had immunogenicity over a wide dose range in healthy adults in the United States and Liberia. (Funded by the Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04794218; Pan African Clinical Trials Registry number, PACTR2021106625781067.)

One-shot immunization using a Measles/Lassa vaccine fully protects cynomolgus monkeys against Lassa fever

Introduction Despite improved surveillance and case management practices, the case fatality rate (CFR) from Lassa fever (LF) remains high in Nigeria and other sub-Saharan African countries. Factors such as poor health-seeking behavior, denial, and stigma have been known to delay treatment initiation, thereby increasing fatality from LF. However, LF co-infection with malaria and arboviruses such as yellow fever (YF) and dengue, which are now occurring at epidemic thresholds in Nigeria, is poorly investigated. This study reviewed existing literature to determine the possible occurrence of LF, malaria, and arboviral co-infection. Methods The review focused on literature published between 2015 and 2025 from PubMed, Google Scholar, and Web of Science. Arksey and O’Malley’s methodological approach was adopted. Papers were selected following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. We identified 70 articles and screened them down to 15 for final review. Results LF- malaria, LF-YF, and LF- Dengue coinfection have been reported in Nigeria. Akhuemokhan et al. (2017) found that 30.8% of children with Lassa virus disease (LVD) also had malaria parasitemia. Animasaun et al. (2025) reported a single Lassa virus and dengue virus co-infection in Oyo State, Nigeria. Okwuraiwe et al. (2022) reported a single YF and LF co-infection in Ondo State, Nigeria. Cadmus et al. (2025) and the LASCOPE study reported that fever and digestive symptoms such as vomiting and abdominal pain were frequent in LF cases, suggesting possible malaria and arboviral coinfections. Triple co-infections involving LF, malaria, and arboviruses have not been documented. Multi-pathogen testing of fever cases is carried out for research purposes only. Conclusion Co-infections involving LF, malaria, and arboviruses are not routinely investigated in Nigeria, and may be responsible for high fatality from LF. Establishing a multi-pathogen testing for fever in LF endemic countries would improve detection and management of comorbidities that may impact fatality from LF.

The 2013–2016 West African Ebola outbreak was the largest, most geographically dispersed and deadliest on record. Since the West Africa outbreak began 4 independent outbreaks of Ebola have occurred, all in the Democratic Republic of the Congo (DRC). The last outbreak was detected only a week after the previous outbreak was declared over. Ebola is not the only global health challenge that is emerging with increasing frequency. During 2018 Nigeria experienced an unprecedented increase in Lassa fever cases. Nearly 500 cases have been diagnosed by August, more than reported in any previous year. While confirmed Lassa fever cases are concentrated in the southwest states of Edo (42%) and Ondo (24%), and the southeast state of Ebonyi (15%), additional cases have originated in 18 other states country-wide. Emerging viruses such as Ebola virus (EBOV) and Lassa virus (LASV) present enormous challenges to global public health. Numerous gaps exist in our understating of the factors that drive viral emergence and may be responsible for the increased frequency of Ebola outbreaks and the geographic expansion of LASV. For example, the EBOV strains that emerged in DRC in 2014 and during the latest 2018 outbreak in eastern DRC (North Kivu, virological.org/t/drc-2018-viral-genome-characterization/230) are phylogenetically most similar to EBOVs isolated during the 1995–1996 outbreaks in Middle Africa, rather than more recent isolates. EBOVs from the 2017 DRC outbreak in northern DRC (Yambuko) and 2018 outbreak in western DRC (Bikoro) also cluster in a manner that further challenges a simple monophyletic clock. The now uncertain evolutionary trajectory of EBOV is only one of many conundrums surrounding Ebola emergence. In contrast to EBOV whose reservoir is currently unknown, most LASV infections result from contact with Mastomys natalensis, the major natural reservoir. Previous phylogenetic investigations of LASV reported extensive viral genetic diversity and established the presence of at least 6 viral lineages across West Africa. The surge of Nigerian Lassa fever cases in 2018 is not attributable to a single Lassa virus strain, nor has it been sustained by human-to-human transmission (Siddle et al, accepted). Extensive viral diversity structured by geography, with major rivers appearing to act as barriers to migration of the rodent vector. Together these results suggest that the 2018 Lassa fever surge was driven by cross-species transmission of multiple viral strains from local rodent populations. The rapid availability of genomic sequence information for the recent Ebola outbreaks and the Lassa surge in Nigeria highlights the fact that there have been fundamental changes in the ways that the international community responds to outbreaks. At the beginning of the West African outbreak governments, often acting on the advice of outside “special” advisors, withheld information on actual numbers of cases. The threat of spread of the virus was minimized because it was felt that the outbreak would “burnout” within a timeframe of a few weeks, and that releasing actual case numbers would have a deleterious effect on the already fragile economies. Real-time case reporting has since become the norm. In prior outbreaks it was argued that no research, including genomic sequencing, should be done in an outbreak, so as not to impede the public health response. Promising experimental treatment and vaccines were withheld from Africans, including researchers with long experience with VHFs. While some trials of vaccines and drugs did occur late in the outbreak, in most cases definite results of effectiveness were not obtained due to diminishing case numbers. It is encouraging that a rVSV-ZEBOV vaccine is being rapidly deployed in the most recent outbreaks with apparent success. Experimental drugs, including monoclonal antibody therapies, are now being used in African patients. The World Health Organization (WHO) and the Coalition for Epidemic Preparedness Innovations (CEPI) have each now ranked LASV as a priority pathogen. These rankings are based on the potential for further geographic expansion of the rodent reservoirs, the ease of procurement and weaponization of the virus, the frequent importation to North America and Europe, and the emergence of novel strains in densely populated West Africa. The Food and Drug Administration recently recognized Lassa fever as a neglected tropical disease, which could also spur development of countermeasures. Reclassifying LASV as a Tier 1 Select Agent should now become a priority of the Centers for Disease Prevention and Control and the United States Department of Agriculture (USDA), a change which would also accelerate development of much needed vaccines and therapeutics. Lessons learned may improve the next response to an international health crisis caused by a viral pathogen that emerges in a region of the world with a severely limited health care infrastructure. However, predicting when the next new human viral pathogen will mutate or where it will emerge in people is not achievable. There are far too many possible pathogens and too little known about the changes that may determine the ability of animal viruses to jump to humans. Rather, the most effective way to prepare for the inevitable emergence of new pathogens is surveillance of humans, particularly those living in locations that are most vulnerable. Isolation of a novel pathogen from a person exhibiting symptoms or animals experiencing die-offs can occur in literally a matter of days. Scarce resources should be prioritized to surveillance efforts for known pathogens such as EBOV and LASV. Employing rapid and effective point-of-care diagnostics designed for environments that lack advanced laboratory infrastructure will greatly aid in early detection and containment efforts during future outbreaks.

Lassa virus is one of more than 25 causative viruses of viral hemorrhagic fever. Lassa fever was first recognized in Nigeria in 1969 and subsequently noted across West Africa. Unlike many viral hemorrhagic fevers, Lassa fever is not a rare disease that emerges only in outbreak form. Yearly infections may number in tens or even hundreds of thousands, with thousands of deaths. There is also concern of Lassa and other hemorrhagic fever viruses being used as bioweapons. Humans are infected through exposure to contaminated excreta of the rodent Mastomys natalensis, which is the natural reservoir, sometimes with secondary transmission between humans via contact with infected bodily fluids. In severe cases, patients progress to vascular instability and hemorrhage, with a case fatality in hospitalized cases of ≈25%. Treatment follows the guidelines for septic shock and as well as the administration of the antiviral drug ribavirin. Patients should be isolated under specialized viral hemorrhagic fever precautions and contacts monitored daily for 3 weeks. Prevention in the community is oriented toward limiting contact with rodents.

Lassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which is endemic in West African countries. The multimammate rat is the main animal reservoir and its geographic range is expected to expand due to influences like climate change and land usage, and this will place larger parts of Africa at risk. We conducted preclinical development on a promising experimental vaccine that allowed its advancement into human trials. The LF vaccine is based on a vesicular stomatitis virus (VSV) vector in which the VSV glycoprotein (G) was replaced with the LASV glycoprotein complex (GPC). Earlier studies showed that this vaccine (VSVΔG-LASV-GPC) was efficacious in macaques, thus we regenerated VSVΔG-LASV-GPC using laboratory and documentation practices required to support vaccine manufacturing and human trials. The efficacy of the clinical vaccine candidate was assessed in cynomolgus macaques and more extensive immunologic analysis was performed than previously to investigate immune responses associated with protection. A single VSVΔG-LASV-GPC vaccination elicited innate, humoural and cellular immune responses, prevented development of substantial LASV viraemia, and protected animals from disease. Vaccinated macaques developed polyfunctional antibodies and serum was shown to neutralize virus expressing GPCs representative of geographically diverse LASV lineages. The VSVΔG-LASV-GPC clinical candidate elicited immunity that protected 10 of 10 vaccinated macaques from disease supporting its use in a clinical development program, which recently progressed to phase 2 clinical trials. Moreover, immunologic analysis showed that virus-neutralizing serum antibodies likely played a role in preventing LASV disease in vaccinated macaques. This work was supported by the Coalition for Epidemic Preparedness Innovations (CEPI), The National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), The Bill and Melinda Gates Global Vaccine Accelerator Program, the Burroughs Wellcome Fund, and financial gifts and support by Nancy Zimmerman, Mark and Lisa Schwartz, and Terry and Susan Ragon.

Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with "flu-like" symptoms and may develop into lethal hemorrhagic disease in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few licensed vaccines or therapeutics against Lassa fever. The fact that animal models are limited and the fact that mostly laboratory-derived viruses are used for studies limit the successful development of countermeasures. In this study, we demonstrated that the LASV isolate LF2384-NS-DIA-1 (LF2384), which was directly isolated from a serum sample from a fatal human Lassa fever case in the 2012 Sierra Leone outbreak, causes uniformly lethal infection in outbred Hartley guinea pigs without virus-host adaptation. This is the first report of a clinically isolated strain of LASV causing lethal infection in outbred guinea pigs. This novel guinea pig model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.IMPORTANCE Lassa virus, the causative agent of Lassa fever, is a zoonotic pathogen causing annual outbreaks in West African countries. Human patients can develop lethal hemorrhagic fever in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few available countermeasures, such as antiviral drugs or vaccines. Moreover, the fact that animal models are not readily accessible and the fact that mostly laboratory viruses, which have been passaged many times after isolation, are used for studies further limits the successful development of countermeasures. In this study, we demonstrate that a human isolate of Lassa virus causes lethal infection uniformly in Hartley guinea pigs. This novel animal model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.

Approximately one-third of Lassa virus (LASV)-infected patients develop sensorineural hearing loss (SNHL) in the late stages of acute disease or in early convalescence. With 500,000 annual cases of Lassa fever (LF), LASV is a major cause of hearing loss in regions of West Africa where LF is endemic. To date, no animal models exist that depict the human pathology of LF with associated hearing loss. Here, we aimed to develop an animal model to study LASV-induced hearing loss using human isolates from a 2012 Sierra Leone outbreak. We have recently established a murine model for LF that closely mimics many features of human disease. In this model, LASV isolated from a lethal human case was highly virulent, while the virus isolated from a nonlethal case elicited mostly mild disease with moderate mortality. More importantly, both viruses were able to induce SNHL in surviving animals. However, utilization of the nonlethal, human LASV isolate allowed us to consistently produce large numbers of survivors with hearing loss. Surviving mice developed permanent hearing loss associated with mild damage to the cochlear hair cells and, strikingly, significant degeneration of the spiral ganglion cells of the auditory nerve. Therefore, the pathological changes in the inner ear of the mice with SNHL supported the phenotypic loss of hearing and provided further insights into the mechanistic cause of LF-associated hearing loss. Sensorineural hearing loss is a major complication for LF survivors. The development of a small-animal model of LASV infection that replicates hearing loss and the clinical and pathological features of LF will significantly increase knowledge of pathogenesis and vaccine studies. In addition, such a model will permit detailed characterization of the hearing loss mechanism and allow for the development of appropriate diagnostic approaches and medical care for LF patients with hearing impairment.

Lassa virus (LASV) is the causative agent of Lassa fever (LF), an often-fatal hemorrhagic disease. LF is endemic in Nigeria, Sierra Leone and other West African countries. Diagnosis of LASV infection is challenged by the genetic diversity of the virus, which is greatest in Nigeria. The ReLASV Pan-Lassa Antigen Rapid Test (Pan-Lassa RDT) is a point-of-care, in vitro diagnostic test that utilizes a mixture of polyclonal antibodies raised against recombinant nucleoproteins of representative strains from the three most prevalent LASV lineages (II, III and IV). We compared the performance of the Pan-LASV RDT to available quantitative PCR (qPCR) assays during the 2018 LF outbreak in Nigeria. For patients with acute LF (RDT positive, IgG/IgM negative) during initial screening, RDT performance was 83.3% sensitivity and 92.8% specificity when compared to composite results of two qPCR assays. 100% of samples that gave Ct values below 22 on both qPCR assays were positive on the Pan-Lassa RDT. There were significantly elevated case fatality rates and elevated liver transaminase levels in subjects whose samples were RDT positive compared to RDT negative.

Lassa fever symptomatology, viral dynamics, and host immune response (PREPARE): a prospective, observational cohort study in Liberia.

Lassa virus is endemic in many West African countries and has significant epidemic/pandemic potential. The Coalition for Epidemic Preparedness Innovations (CEPI) Centralized Laboratory Network (CLN) is developing validated, harmonized methods to support and accelerate vaccine development in the event of an outbreak. We present here the development and validation of an assay to quantify anti-Lassa virus neutralizing antibodies. As the method uses a pseudotyped virus (PV) instead of authentic Lassa virus-a pathogen listed as hazard group 4-it can be performed at a lower containment level, making it widely accessible especially in those regions where Lassa fever is circulating. A recombinant vesicular stomatitis virus (rVSV)-based pseudotyped virus neutralization assay (PVNA) was developed. A working standard was prepared and calibrated against the International Standard (IS) for Lassa virus neutralizing antibodies, enabling results to be expressed in International Units. The method was validated according to the International Council for Harmonisation (ICH) Q2(R2) guidelines. The rVSV-based PVNA was successfully developed and validated. The analytical range of the assay was established as 10-100 IU/mL, and seropositive samples from a Lassa vaccine clinical trial fell within this range. Results from the PVNA showed direct correlation with results obtained from authentic virus neutralization methods. The method was, therefore, concluded to be fit-for-purpose. We have successfully developed and validated a PVNA for the quantification of neutralizing antibodies against Lassa virus. We have also provided a practical example of how to calibrate a serological method to the WHO International Standard to achieve greater harmonization and comparability between studies. The method is now being transferred to partner laboratories within the CLN to enable harmonized testing of clinical trial samples and support the development and evaluation of Lassa vaccine candidates.

Introduction: Lassa viral hemorrhagic fever is caused by the Lassa virus. The aim of our study is to describe the therapeutic itinerary of the 4 cases of Lassa virus hemorrhagic of February-March 2017 epidemic that occurred in Mango. Methodology: Our study is a transverse retro-prospective and descriptive study from February, 1st to March, 31st 2017 that dealt with 4 confirmed Lassa fever cases declared positive on the PCR basis; hospitalized or deceased at the hospital “Esperance” of Mango; support center of Lassa viral hemorrhagic fever. Results: we reported 4 clinical observations of Lassa viral hemorrhagic fever diagnosed on the PCR basis during the Lassa fever epidemic. Patients came from Benin (2 cases) or from Burkina-Faso (1 case) and were 25, 60, 52 years old and a premature baby of 13 days. The reasons for admission were external hemorrhage, a pultated tonsillitis and abdominal pains. Fever was observed for all the cases. Complications were marked by hemorrhages and shocks. Only two patients benefitted from Antiviral therapy with Ribavirin and were declared healed. The other two patients did not benefit from the treatment due to diagnostic and therapeutic delays. Lethality was 75% (3 cases) with a highly secured burial. Effective management of contacts was established. Conclusion: Diagnostic and therapeutic delays of patients are responsible of the Dark Prognosis of Lassa fever during the epidemic.

Introduction: Lassa fever is endemic in West Africa, with an estimated 100,000 to 300,000 infections and 5,000 deaths annually. On February 1, 2023, the Bo District Surveillance Team received a notification from a community in the district about suspected Lassa fever deaths. Trainees of the Sierra Leone Field Epidemiology Training Program were deployed to confirm the diagnosis, assess the magnitude, and identify possible sources of infection and routes of transmission. Methods: We adapted the Lassa fever surveillance case definition, and a suspected case of Lassa Fever was any person who presented with gradual onset of one or more of the following: malaise, fever, headache, cough, nausea, vomiting, myalgia, chest pain, hearing loss and either history of contact with excreta or urine of rodents or history of contact with confirmed Lassa fever case from January 1 to March 14, 2023. A probable case was any suspected case who died before specimens for laboratory testing were collected or any suspected case with an epidemiological link to a confirmed case. A confirmed case was any suspected case that was laboratory confirmed for Lassa fever virus. We collected demographic, clinical, and exposure data from all suspected and confirmed cases through interviews and a review of clinical records. Blood samples were collected from six suspected cases and tested using Reverse transcription polymerase chain reaction (RT-PCR) to confirm Lassa fever infection. An active case search was conducted in the affected communities and eight health facilities. Contacts were line-listed, followed up, and monitored for 21 days. We conducted environmental assessments; seven rodents were trapped using Sharman trap and bait, and samples of the trapped rodents were tested by RT-PCR. Results: Eight suspected cases of Lassa fever were identified in Selenga Chiedom, Bo district, from January 1 to March 14, 2023. There were two probable cases and both died. Two of the suspected cases were confirmed as Lassa fever cases, and both died, making the case fatality rate 100% (2/2). All the confirmed cases were females aged 21 and 57. No additional cases were identified. Thirty contacts were identified, and two of them developed Lassa fever signs or symptoms but tested negative for Lassa fever. Rodent droppings were found in the case patient's residence. Three of seven rodents trapped tested positive for Lassa fever. Conclusion: A Lassa fever outbreak was confirmed in Bo District with a high case fatality rate. The sources of infection for this outbreak are likely infected rodents residing in the case patient's residence. However, sequencing was not done to establish the genetic link between the viruses detected from the rodents and the cases. The high case fatality rate could be due to late detection and delayed clinical care and treatment. We sensitized clinicians on the early diagnosis of Lassa fever and raised awareness among affected communities about keeping their homes clean and storing meals in rodent-proof containers. Following this investigation, the Lassa fever surveillance systems were enhanced to improve early case detection and notification.

Lassa Fever, Nigeria, 2005–2008