Lassa Fever Research Articles

Visuo-Spatial Impairment in Patients Who Recovered from Lassa Fever Infection: A 30 Day Follow Up Observatory Study

Visuo-Spatial Impairment in Patients Who Recovered from Lassa Fever Infection: A 30 Day Follow Up Observatory Study

Negative and ambisense RNA virus ribonucleocapsids: more than protective armor.

SUMMARYNegative and ambisense RNA viruses are the causative agents of important human diseases such as influenza, measles, Lassa fever, and Ebola hemorrhagic fever. The viral genome of these RNA viruses consists of one or more single-stranded RNA molecules that are encapsidated by viral nucleocapsid proteins to form a ribonucleoprotein complex (RNP). This RNP acts as protection, as a scaffold for RNA folding, and as the context for viral replication and transcription by a viral RNA polymerase. However, the roles of the viral nucleoproteins extend beyond these functions during the viral infection cycle. Recent advances in structural biology techniques and analysis methods have provided new insights into the formation, function, dynamics, and evolution of negative sense virus nucleocapsid proteins, as well as the role that they play in host innate immune responses against viral infection. In this review, we discuss the various roles of nucleocapsid proteins, both in the context of RNPs and in RNA-free states, as well as the open questions that remain.

An Analysis of the Hidden Markov Model for Surveilling the Transmission of Lassa Fever Epidemic Disease in Nigeria during Dry Season

Lassa fever is an infectious viral disease that is endemic in Nigeria and other West African countries. Early detection and response to outbreaks of the disease are critical to prevent its spread and reduce illnesses and death. Finding some mathematical patterns that explain the mechanisms of Lassa fever transmission, as well as a thorough understanding of the biological contributing to affecting the disease, are necessary in putting in place a surveillance system with a view to preventing further spread of the disease. In this study, we developed a Hidden Markov Model (HMM) approach to surveil the transmission of Lassa fever virus infections in Nigeria. The HMM was developed using the susceptible Infection recovered (SIR) model to formulate the transition matrix and data from past outbreaks of the disease to compute the observations. Our results showed that the dry season as the peak period for Lassa fever and recorded the lowest numbers during the rainy season. The transition matrix showed a 98% chance of transitioning to the infected state from being susceptible and a 96% chance of remaining infected. The stable probability resulted in a 97.9% probability of transitioning to the infected state and a 1.7% chance of transitioning to the susceptible state. The Empirical analysis using the proposed HMM approach does not only provide a valuable tool for public health officials to track and respond to outbreaks of Lassa fever, leading to more effective disease control strategies but also, establishes an efficient structure for other infectious diseases modeling to aid in early detection and response to epidemic outbreaks.

PH-dependent conformational change within the Lassa virus transmembrane domain elicits efficient membrane fusion

Lassa virus (LASV) is the most prevalent member of the arenavirus family and the causative agent of Lassa fever, a viral hemorrhagic fever. Although there are annual outbreaks in West Africa, and recently isolated cases worldwide, there are no current therapeutics or vaccines, which poses LASV as a significant global public health threat. One of the key steps in LASV infection is the delivery of its genetic material by fusing its viral membrane with the host cell membrane. This process is facilitated by significant conformational changes within glycoprotein 2 (GP2), yielding distinct prefusion and postfusion structural states. However, structural information is missing to understand the changes that occur in the transmembrane domain during the fusion process. Here, we used CD and NMR spectroscopy to show that the transmembrane domain has pH-dependent conformational changes that result in an extension of the alpha helix at the N-terminal end. Proline mutants of key residues in that region prevent the helical extension, as seen in CD and NMR. We developed a modified lipid mixing assay to study the importance of this extension on the function of GP2. Our assay shows that membrane fusion efficiency is optimal at low pH values but introducing the proline mutants results in lower fusion efficiency. These results indicate that these pH-dependent conformational changes are important to the fusion mechanism. This information can be used to design therapeutics to combat Lassa virus infections and prevent its potential spread.

Novel insights for a nonlinear deterministic-stochastic class of fractional-order Lassa fever model with varying kernels

Lassa fever is a hemorrhagic virus infection that is usually spread by rodents. It is a fatal infection that is prevalent in certain West African countries. We created an analytical deterministic-stochastic framework for the epidemics of Lassa fever employing a collection of ordinary differential equations with nonlinear solutions to identify the influence of propagation processes on infected development in individuals and rodents, which include channels that are commonly overlooked, such as ecological emergent and aerosol pathways. The findings shed light on the role of both immediate and subsequent infectiousness via the power law, exponential decay and generalized Mittag-Leffler kernels. The scenario involves the presence of a steady state and an endemic equilibrium regardless of the fundamental reproduction number, Re _{0}<1, making Lassa fever influence challenging and dependent on the severity of the initial sub-populations. Meanwhile, we demonstrate that the stochastic structure has an exclusive global positive solution via a positive starting point. The stochastic Lyapunov candidate approach is subsequently employed to determine sufficient requirements for the existence and uniqueness of an ergodic stationary distribution of non-negative stochastic simulation approaches. We acquire the particular configuration of the random perturbation associated with the model’s equilibrium Re _{0}^{s}<1 according to identical environments as the presence of a stationary distribution. Ultimately, modeling techniques are used to verify the mathematical conclusions. Our fractional and stochastic findings exhibit that when all modes of transmission are included, the impact of Lassa fever disease increases. The majority of single dissemination pathways are less detrimental with fractional findings; however, when combined with additional spread pathways, they boost the Lassa fever stress.

A review on Lassa fever

Lassa fever (LF) is indeed a significant public health concern, particularly in parts of Africa. This viral infection, caused by the Lassa virus (LASV), is known for its high prevalence and fatality rates in certain regions, including North Africa. Research indicates that the estimated case fatality rate of Lassa fever in North Africa ranges from 16.5% to as high as 50% in some areas. For example, in Plateau State, North Central Nigeria, the case fatality rate was reported to be 57%. Across Western Africa, up to 300,000 new infections and 5,000 deaths are estimated to occur annually, with fatality rates reaching up to 25.4% in recent Nigerian outbreaks. The high fatality rates, especially among hospitalized patients, highlight the severity of this disease. For instance, in Nigeria, the overall mortality rate has been reported to be around 19%, with higher rates among health workers.

Recurrent Lassa fever outbreak in Nigeria: current challenges and the strategies for control

Recurrent Lassa fever outbreak in Nigeria: current challenges and the strategies for control

Resurgence of Lassa fever in Nigeria: clinical features, epidemiology, pathogenesis, diagnostic methods, and treatment

Resurgence of Lassa fever in Nigeria: clinical features, epidemiology, pathogenesis, diagnostic methods, and treatment

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Lassa fever (LF) is endemic in West Africa and Nigeria in particular. Since 1969 when the disease was discovered, a seasonal outbreak is often reported in Nigeria. Many researchers have reported inconsistent or varying numbers of suspected, confirmed and death cases since 2012 to date. To enhance this reportage, and due to the high mortality rate associated with LF, it is pertinent to design a suitable and robust model that could predict or estimate the number of LF cases based on the onset data. To achieve these, we proposed a recursive prediction (RP) model that could do predictions with the onset data. The Pearson correlation coefficient (R) and R2 are applied to determine the performance analysis of the model. The RP model predicted 96.7% confirmed cases and 89.6% death cases for the first three months of 2022 based on the onset data. The model was also applied to predict COVID-19 death cases during the six weeks of the outbreak in India. The result showed a comparable prediction with the regression output for the COVID-19 death cases. This study demonstrated that the proposed model could be applied to perform prediction for any disease of unknown etiology during the onset of the disease outbreak without any treatment similar to the COVID-19 outbreak. The performance analysis of the RP showed that the model is useful to predict the increasing trend of an outbreak of a disease with unknown etiology without prior treatment experience and vaccines.

Public health interventions in the control of emerging diseases

There has been an unprecedented increase in the burden of emerging diseases in the recent past. This has been attributed to changes in environment, human behavior, increased travel and human intrusion into the sylvatic cycle which has facilitated the emergence of novel and resistant strains of pathogens. A public health intervention is any effort or policy that is designed to improve mental and physical health of the population. This article focusses on the various public health interventions like vaccination, nutritional intervention, hygiene and sanitation, health awareness which has been and can contribute immensely to curb the rising threat of emerging diseases. Much research has been going on regarding the vaccines against new emerging diseases like SARS-CoV, Ebola, Lassa fever, Nipah, Chikungunya and Rift valley fever. Nutritional interventions has proven to be of much benefit in low and middle income countries because of its synergistic effect with infections. Quarantine and sanitation measures were highly effective strategies for control of COVID-19 pandemic. These preventive interventions along with a robust public health infrastructure can serve as an effective barrier in the spread of many emerging strains of diseases.

Lassa fever situation report for week 1 to week 15 from 2021 to 2023 in Nigeria: a review

Lassa fever is a viral hemorrhagic fever caused by Lassa virus. The Lassa virus is an enveloped single-stranded, non-lytic bi-segmented negative-stranded RNA virus belonging to the family Arenaviridae. Lassa fever is relatively common or endemic in West Africa or particularly in countries such as Benin, Ghana, Guinea, Liberia, Mali, Sierra Leone, and Nigeria. Humans usually become infected with the virus through exposure to food or household items contaminated with the urine or faeces of infected multimammate rat while spread of the disease between or among persons is by direct contact. The disease cases rises to the peak during the dry season particularly between December to April and falls in May annually. The incubation period for the disease is between 1 – 3 weeks, which can lead to spread from region to region. This review focuses on the secondary data for the epidemiological trend of the Lassa fever disease in Nigeria. The rodent host and reservoir is the primary driver of the Lassa fever seasonal trends. Therefore, to control the disease, it is necessary to control the rodent host by killing it. This can be achieved through the use of trap,poisoned bait and interference with their breeding by killing the newly born off springs.

Community-Directed Educational Intervention for Lassa Fever Prevention Practices Among Nursing Mothers Attending Primary Health Care Centres in Akinyele, Ibadan, Oyo State, Nigeria: A Quasi-Experimental Study

Community-Directed Educational Intervention for Lassa Fever Prevention Practices Among Nursing Mothers Attending Primary Health Care Centres in Akinyele, Ibadan, Oyo State, Nigeria: A Quasi-Experimental Study

Allosteric inhibition mechanism of targeted covalent inhibitors, PCMPS and PCMB, on Lassa fever virus NP exonuclease

Allosteric inhibition mechanism of targeted covalent inhibitors, PCMPS and PCMB, on Lassa fever virus NP exonuclease

A human monoclonal antibody combination rescues nonhuman primates from advanced disease caused by the major lineages of Lassa virus

There are no approved treatments for Lassa fever (LF), which is responsible for thousands of deaths each year in West Africa. A major challenge in developing effective medical countermeasures against LF is the high diversity of circulating Lassa virus (LASV) strains with four recognized lineages and four proposed lineages. The recent resurgence of LASV in Nigeria caused by genetically distinct strains underscores this concern. Two LASV lineages (II and III) are dominant in Nigeria. Here, we show that combinations of two or three pan-lineage neutralizing human monoclonal antibodies (8.9F, 12.1F, 37.D) known as Arevirumab-2 or Arevirumab-3 can protect up to 100% of cynomolgus macaques against challenge with both lineage II and III LASV isolates when treatment is initiated at advanced stages of disease on day 8 after LASV exposure. This work demonstrates that it may be possible to develop postexposure interventions that can broadly protect against most strains of LASV.

Efficacy of microbicidal actives and formulations for inactivation of Lassa virus in suspension

The World Health Organization’s R&D Blueprint list of priority diseases for 2022 includes Lassa fever, signifying the need for research and development in emergency contexts. This disease is caused by the arenavirus Lassa virus (LASV). Being an enveloped virus, LASV should be susceptible to a variety of microbicidal actives, although empirical data to support this expectation are needed. We evaluated the virucidal efficacy of sodium hypochlorite, ethanol, a formulated dual quaternary ammonium compound, an accelerated hydrogen peroxide formulation, and a p-chloro-m-xylenol formulation, per ASTM E1052-20, against LASV engineered to express green fluorescent protein (GFP). A 10-μL volume of virus in tripartite soil (bovine serum albumin, tryptone, and mucin) was combined with 50 μL of disinfectant in suspension for 0.5, 1, 5, or 10 min at 20–25 °C. Neutralized test mixtures were quantified by GFP expression to determine log10 reduction. Remaining material was passaged on Vero cells to confirm absence of residual infectious virus. Input virus titers of 6.6–8.0 log10 per assay were completely inactivated by each disinfectant within 1–5 min contact time. The rapid and substantial inactivation of LASV suggests the utility of these microbicides for mitigating spread of infectious virus during Lassa fever outbreaks.

Metagenomic surveillance uncovers diverse and novel viral taxa in febrile patients from Nigeria

Effective infectious disease surveillance in high-risk regions is critical for clinical care and pandemic preemption; however, few clinical diagnostics are available for the wide range of potential human pathogens. Here, we conduct unbiased metagenomic sequencing of 593 samples from febrile Nigerian patients collected in three settings: i) population-level surveillance of individuals presenting with symptoms consistent with Lassa Fever (LF); ii) real-time investigations of outbreaks with suspected infectious etiologies; and iii) undiagnosed clinically challenging cases. We identify 13 distinct viruses, including the second and third documented cases of human blood-associated dicistrovirus, and a highly divergent, unclassified dicistrovirus that we name human blood-associated dicistrovirus 2. We show that pegivirus C is a common co-infection in individuals with LF and is associated with lower Lassa viral loads and favorable outcomes. We help uncover the causes of three outbreaks as yellow fever virus, monkeypox virus, and a noninfectious cause, the latter ultimately determined to be pesticide poisoning. We demonstrate that a local, Nigerian-driven metagenomics response to complex public health scenarios generates accurate, real-time differential diagnoses, yielding insights that inform policy.

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

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

Lassa fever: knowledge deficits among nurses and non-nurses at a tertiary hospital in Ondo, southwest Nigeria

Introduction: Lassa fever is endemic to many African countries with knowledge deficit linked to increased exposure, morbidity and mortality among healthcare workers. Objectives: To assess knowledge deficit among nurses and non-nurses. Materials and methods: This was a descriptive, cross-sectional study conducted at the University of Medical Sciences Teaching Hospital, Ondo State, Nigeria. Results: There were 59 (48.8%) nurses and 62 (51.2%) non-nurses with a male to female ratio of 1:2.9. Their mean age was 34.2±8.0 years. Nurses and non-nurses performed well in 30 (62.5%) and 26 (54.2%) out of 48 knowledge domains respectively. Participants performed poorly in (i) early identification of disease such as negative malaria test in a feverish patient (32.2%) and role of high index of suspicion (34.7%); (ii) knowledge of transmission via body fluid {sweat (43%), saliva (28.9%), semen (21.5%)}, and (iii) decontamination with methylated spirit (22.3%), chlorine (32.2%) and formalin (20.7%)}. Nurses performed better than non-nurses in identifying (i) Mastomys natalensis as carrier for Lassa fever virus (p=0.049) (ii) deafness as a Lassa fever sequelae (p=0.041) (iii) semen (p=0.008) and vagina secretion (p=0.035) as routes of transmission (iv) nurses being directly at risk of Lassa fever (p = &lt;0.01) (v) patient avoidance (p=0.004), hand washing (p=0.004), use of hand sanitizer (p=0.046) and safe waste disposal (p=0.047) as helpful in reducing Lassa fever infection. Conclusion: Knowledge of Lassa fever among healthcare workers in the tertiary hospital was generally unsatisfactory with serious knowledge deficits in many domains.

An Epidemiological Analysis of Lassa Fever Outbreak in Nigeria from January 2019 to June 2023

Lassa Fever (LF) is an acute viral haemorrhagic zoonotic disease, is endemic in some parts of Nigeria. The disease alert and outbreak threshold are known; however, there has been a shift from the previous seasonal transmission pattern to an all year-round transmission. The aim of this study was to carry out the analysis on LF and highlight the magnitude of the disease over a five-year period. We described data on Lassa fever and highlighted the magnitude of the disease over a five-year period. We conducted a secondary data analysis of LF with specific surveillance data from the NCDC for five years period (January 2019 to June 2023). A total of 29347 suspected cases were reported within the study period; of these, 4469 were confirmed cases, 861 were dead cases by NCDC. However, highest percentage for the case fatality rate/ratio was recorded in the year 2019 with 20.9% and lowest was recorded in the year 2023 with 17.3%. The highest percentage case positive rate was recorded in the year 2023 with 18.7% and lowest was recorded in the year 2021 with 11.0%.

Perceived public alarm and comprehension of risk communication messages about Lassa fever in Nigeria: a gauge of the risk communication model

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 &amp;lt; 0.05 but not in Edo state at r2 = 0.010, at p &amp;gt; 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.