Modelling the Transmission Dynamics of the Lassa Fever Infection

Lassa fever is an acute hemorrhagic zoonotic illness that usually last for days duration occurring mostly in West African countries. Lassa virus being zoonotic means that, transmission of the disease from infected animal to human is possible with the animal reservoir or host being a rodent of the genus Mastomys. Currently, an ongoing outbreak in Nigeria has spread to 19 States of the country. Statistical figures indicated that, out of suspected cases, has been confirmed with deaths of infected persons from Lassa fever in less than two months, giving a case fatality rate of..... More details can be found in the full paper

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4+ T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models

Knowledge, Attitudes, And Practices (kap) About Lassa Fever Prevention And Control: A Survey Of Three Rural Communities In Central Liberia-Epidemiology Of Microbial Diseases

Introduction: Since the discovery of Lassa fever in 1969 in Nigeria, the disease has become endemic in many West African countries. An estimated 500,000 cases of Lassa fever virus occur each year, leading to approximately 5,000 deaths annually. Liberia continues to record outbreaks almost every subsequent year in regions once considered non-endemic. With no effective vaccines, many studies have underscored the importance for residents in Lassa-endemic regions to have good knowledge and good prevention practices in place to prevent Lassa fever. Methods: A cross-sectional data extracted from a longitudinal, observational, cohort study conducted using voluntary participant self-reported and study visits data from the ENABLE study in central Liberia. Generalized Estimating Equation (GEE) model was used to perform a regression analysis to measure the association between 1,700 adult participants’ Lassa fever knowledge and Lassa fever infection, and between Lassa fever prevention practices and Lassa fever infection, considering correlations among family members in the same household. Results: Univariate regression analyses were performed to measure the association between knowledge and infection and between practices and infection. The study found no significant association between response and the outcome (Lassa fever infection), which indicates that people\u27s knowledge and prevention practices of Lassa fever did not have a significant association with their likelihood of acquiring Lassa fever infection. However, formal education and community were found to be significantly associated with the outcome. Significant findings were defined by p \u3c0.05. Conclusion: The study’s findings emphasized the importance of conducting KAP evaluations in rural communities to generate and improve evidence-based knowledge and proper prevention practices to prevent and control Lassa fever outbreaks. Further, the study demonstrates that while good knowledge and prevention practices are integral to preventing Lassa fever in rural communities, KAP studies should seek to understand the impacts of other factors including poverty and socioeconomic status, overcrowding, environmental sanitation, and housing characteristics

Fatal case of newborn Lassa fever virus infection mimicking late onset neonatal sepsis: a case report from northern Nigeria

BACKGROUND: Lassa fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa fever infections are rare in scientific literature. We report a fatal case of Lassa fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis. CASE PRESENTATION: The patient is a 26-day-old neonate who was admitted with a day history of fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting the need to evaluate for Lassa fever using reverse transcription polymerase chain reaction (RT-PCR). He died 31 h into admission and RT-PCR result was positive for Lassa fever. CONCLUSIONS: Neonatal Lassa fever infection is highly fatal and can mimic neonatal sepsis. High index of suspicion is needed particularly for atypical presentations of neonatal sepsis in Lassa fever endemic areas

Review of Lassa fever, an emerging old world haemorrhagic viral disease in sub-Saharan Africa

Lassa fever is an acute immunosuppressive illness of increasing public health concern causing severe morbidity and significant mortality (Case fatality rate (CFR) ≥ 50%) especially in epidemic cases. Although Lassa fever has emerged (following its first detection (1969) in Lassa town, Nigeria) as one of the most prevalent and debilitating viral haemorrhagic fevers endemic in West Africa region (Nigeria inclusive), yet, the control/prevention of the regular outbreak of the disease has become an herculean task in the areas affected; there is inadequate healthcare facility (including Laboratory/diagnostic and care centres), poor socioeconomic environment, lack of awareness among the populace and presence of favourable ecologic niche for the survival and propagation of the natural host and reservoir mouse (Mastomys natalensis) of Lassa virus . Lassa fever is mainly transmitted by contact with excretions and secretions of infected rats via foods and water as well as exposure to other contaminated items. Lassa virus is a member of an Old World Arenariruses, of family Arenaviridae. It is an enveloped, single-stranded (SS) bisegmented RNA virus with ability to replicate very rapidly. It consists of 4 lineages; 3 members are identified as ancenstral strains found in Nigeria, while the fourth is domiciled in other West Africa Countries. Lassa virus infects almost every tissue in human body resulting in multisystemic dysfunction. The incubation period is generally between 6 to 21 days resulting in 3 stages of clinical manifestation viz: Acute phase characterized by flu-like, non-specific illness; haemorrhagic phase accompanied with gastrointestinal symptoms and cardiovascular/neurologic complications. Currently, there is no clinically certified Lassa fever vaccine thus complicating deterrent or preventive measures. Hence, there is need for intensification of educational programs for the populace on the useful control measures against Lassa fever. The stakeholders need to prioritize intervention and support program and also speed up the processes leading to the production of effective vaccine to limit the menace of Lassa fever outbreak and associated morbidity, fatality and high socio-economic cost.Keywords: Lassa fever, endemic, epidemic, reservoir rodent, West Afric

Taking forward a 'One Health' approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a 'One Health' approach to control such zoonotic pathogens with epidemic potential

Crystal structure of Schmallenberg orthobunyavirus nucleoprotein-RNA complex reveals a novel RNA sequestration mechanism

Schmallenberg virus (SBV) is a newly emerged orthobunyavirus (family Bunyaviridae) that has caused severe disease in the offspring of farm animals across Europe. Like all orthobunyaviruses, SBV contains a tripartite negative-sense RNA genome that is encapsidated by the viral nucleocapsid (N) protein in the form of a ribonucleoprotein complex (RNP). We recently reported the three-dimensional structure of SBV N that revealed a novel fold. Here we report the crystal structure of the SBV N protein in complex with a 42-nt-long RNA to 2.16 Å resolution. The complex comprises a tetramer of N that encapsidates the RNA as a cross-shape inside the protein ring structure, with each protomer bound to 11 ribonucleotides. Eight bases are bound in the positively charged cleft between the N- and C-terminal domains of N, and three bases are shielded by the extended N-terminal arm. SBV N appears to sequester RNA using a different mechanism compared with the nucleoproteins of other negative-sense RNA viruses. Furthermore, the structure suggests that RNA binding results in conformational changes of some residues in the RNA-binding cleft and the N- and C-terminal arms. Our results provide new insights into the novel mechanism of RNA encapsidation by orthobunyaviruses

Envelope Exchange for the Generation of Live-Attenuated Arenavirus Vaccines

Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell–mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates