scholarly journals Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates

2021 ◽  
Vol 17 (10) ◽  
pp. e1009966
Author(s):  
Derek R. Stein ◽  
Bryce M. Warner ◽  
Jonathan Audet ◽  
Geoff Soule ◽  
Vinayakumar Siragam ◽  
...  
Keyword(s):  
Animal Models ◽  
Lassa Fever ◽  
Geographic Region ◽  
World Health ◽  
Limiting Factor ◽  
Lassa Virus ◽  
African Countries ◽  
Animal Models Of Disease ◽  
Medical Countermeasures

Nigeria continues to experience ever increasing annual outbreaks of Lassa fever (LF). The World Health Organization has recently declared Lassa virus (LASV) as a priority pathogen for accelerated research leading to a renewed international effort to develop relevant animal models of disease and effective countermeasures to reduce LF morbidity and mortality in endemic West African countries. A limiting factor in evaluating medical countermeasures against LF is a lack of well characterized animal models outside of those based on infection with LASV strain Josiah originating form Sierra Leone, circa 1976. Here we genetically characterize five recent LASV isolates collected from the 2018 outbreak in Nigeria. Three isolates were further evaluated in vivo and despite being closely related and from the same spatial / geographic region of Nigeria, only one of the three isolates proved lethal in strain 13 guinea pigs and non-human primates (NHP). Additionally, this isolate exhibited atypical pathogenesis characteristics in the NHP model, most notably respiratory failure, not commonly described in hemorrhagic cases of LF. These results suggest that there is considerable phenotypic heterogeneity in LASV infections in Nigeria, which leads to a multitude of pathogenesis characteristics that could account for differences between subclinical and lethal LF infections. Most importantly, the development of disease models using currently circulating LASV strains in West Africa are critical for the evaluation of potential vaccines and medical countermeasures.

scholarly journals Community hygiene against lassa fever disease and its predictors in a Nigerian rural settlement

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
A A Gobir ◽  
C L Ejembi ◽  
A A Aliyu ◽  
M B Garba ◽  
C J C Igboanusi ◽  
...  
Keyword(s):  
Sampling Technique ◽  
Lassa Fever ◽  
West African ◽  
World Health ◽  
Food Storage ◽  
African Countries ◽  
Cross Sectional ◽  
Effective Prevention ◽  
Viral Haemorrhagic Fever ◽  
Hygiene Measures

Abstract Background Lassa fever disease (LFD) is a viral haemorrhagic fever that is endemic in some West african countries where an estimated 300,000 to 500,000 cases and 5000 deaths occur yearly. The World Health Organization described it as a global health threat. At community level, its prevention relies on promoting good “community hygiene”. This study was conducted to assess practice of community hygiene measures against LFD and its associated factors. Methods A cross-sectional, community based descriptive study conducted during a LFD epidemic in a a rural community of Nigeria. An interviewer-administered questionnaire was used to collect data from 556 adult respondents, selected using systematic random sampling technique. Data was analyzed using SPSS. Results A majority of the respondents were females (52.9%). Educational attainment was significantly associated with safe food storage at the multivariate level (aOR= 1.31, 95% CI: 1.10-1.54,P= 0.002) while having a good knowledge of LFD was a significant predictor of maintaining good housing standards (aOR= 3.73, 95% CI: 1.09-12.80,P=0.036). Conclusions Predictors of practice of community hygiene against LFD include education and having an excellent knowledge of LFD. To improve community hygiene practices in the community, there is need for a comprehensive LFD behavior change communication intervention. Key messages Cubing the global threat of LFD depends on its effective prevention in endemic West African communities. This study shows that such preventive measures are poor and there is need for more response to address the problem.

scholarly journals Lassa viral dynamics in non-human primates treated with favipiravir or ribavirin

2021 ◽  
Vol 17 (1) ◽  
pp. e1008535
Author(s):  
Guillaume Lingas ◽  
Kyle Rosenke ◽  
David Safronetz ◽  
Jérémie Guedj
Keyword(s):  
Mechanism Of Action ◽  
Ebola Virus ◽  
Antiviral Treatment ◽  
Antiviral Effect ◽  
Lassa Fever ◽  
Pharmacokinetic Data ◽  
Virus Infectivity ◽  
Lassa Virus ◽  
Viral Dynamics

Lassa fever is an haemorrhagic fever caused by Lassa virus (LASV). There is no vaccine approved against LASV and the only recommended antiviral treatment relies on ribavirin, despite limited evidence of efficacy. Recently, the nucleotide analogue favipiravir showed a high antiviral efficacy, with 100% survival obtained in an otherwise fully lethal non-human primate (NHP) model of Lassa fever. However the mechanism of action of the drug is not known and the absence of pharmacokinetic data limits the translation of these results to the human setting. Here we aimed to better understand the antiviral effect of favipiravir by developping the first mathematical model recapitulating Lassa viral dynamics and treatment. We analyzed the viral dynamics in 24 NHPs left untreated or treated with ribavirin or favipiravir, and we put the results in perspective with those obtained with the same drugs in the context of Ebola infection. Our model estimates favipiravir EC50 in vivo to 2.89 μg.mL-1, which is much lower than what was found against Ebola virus. The main mechanism of action of favipiravir was to decrease virus infectivity, with an efficacy of 91% at the highest dose. Based on our knowledge acquired on the drug pharmacokinetics in humans, our model predicts that favipiravir doses larger than 1200 mg twice a day should have the capability to strongly reduce the production infectious virus and provide a milestone towards a future use in humans.

scholarly journals Knowledge of Lassa Fever Disease and Its Risk Factors Among Rural People in a Nigerian Community

Proceedings ◽  
2020 ◽  
Vol 45 (1) ◽  
pp. 9
Author(s):  
Abdulrazaq Abdullahi Gobir ◽  
Clara Ladi Ejembi ◽  
Aliyu Abubakar Alhaji ◽  
Muhammad Bello Garba ◽  
Chinedu John -Camillus Igboanusi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rural Areas ◽  
Disease Transmission ◽  
Public Awareness ◽  
Lassa Fever ◽  
Lassa Virus ◽  
African Countries ◽  
Public Health Importance ◽  
Cross Sectional ◽  
Effective Prevention

Introduction: Lassa fever disease (LFD) is an acute viral haemorrhagic fever caused by Lassa virus. It is a disease of public health importance in West Africa and a global health threat. It is endemic in some West African countries like Benin, Ghana, Guinea, Liberia, Mali, Sierra Leone, and Nigeria, where an estimated 300,000 to 500,000 cases occur every year with an estimated 5000 annual deaths. Persons living in rural areas and health care workers are at greatest risk. Public awareness and knowledge of the LFD and its risk factors are some of the important factors that determine disease transmission and success of preventive/control efforts. This study was therefore conducted to assess LFD-related awareness and knowledge in Gangara, a rural agrarian community in Giwa Local Government Area of Kuduna State, NorthWest Nigeria. Methods: A cross-sectional, community based descriptive study conducted in Gangara community. An interviewer- administered questionnaire was used to collect data from 556 adult respondents, selected using systematic random sampling technique. Data was analyzed using SPSS (version 20). Results: A majority of the respondents were females (52.9%) with a mean age of 37.0 ± 15.2. The level of awareness of LFD was high (66.7%) among respondents and there was a statistically significant association between awareness of LFD and not having any form of education (P < 0.00). However, most of the respondents (79.0%) have poor knowledge of LFD. Knowledge of risk factors for LFD was also poor with 59.4% not knowing that drying grains and foodstuffs on the ground is a risk factor for LFD. Conclusions: Awareness of the disease was quite high but knowledge of the disease and its risk factors was poor. For effective prevention of future outbreaks, the community needs to be properly educated on LFD and its risk factors.

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

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Liã Bárbara Arruda ◽  
Najmul Haider ◽  
Ayodeji Olayemi ◽  
David Simons ◽  
Deborah Ehichioya ◽  
...  
Keyword(s):  
Public Health ◽  
One Health ◽  
Population Expansion ◽  
Lassa Fever ◽  
West African ◽  
Lassa Virus ◽  
African Countries ◽  
Rodent Host ◽  
Public Health Burden ◽  
And Control

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

scholarly journals Lassa Virus Treatment Options

2021 ◽  
Vol 9 (4) ◽  
pp. 772
Author(s):  
Frederick Hansen ◽  
Michael A. Jarvis ◽  
Heinz Feldmann ◽  
Kyle Rosenke
Keyword(s):  
Animal Models ◽  
Treatment Options ◽  
Human Monoclonal Antibody ◽  
Lassa Fever ◽  
Clinical Settings ◽  
Lassa Virus ◽  
Preclinical Treatment ◽  
Development Pipeline ◽  
Antibody Cocktail ◽  
Human Primate

Lassa fever causes an approximate 5000 to 10,000 deaths annually in West Africa and cases have been imported into Europe and the Americas, challenging public health. Although Lassa virus was first described over 5 decades ago in 1969, no treatments or vaccines have been approved to treat or prevent infection. In this review, we discuss current therapeutics in the development pipeline for the treatment of Lassa fever, focusing on those that have been evaluated in humans or animal models. Several treatments, including the antiviral favipiravir and a human monoclonal antibody cocktail, have shown efficacy in preclinical rodent and non-human primate animal models and have potential for use in clinical settings. Movement of the promising preclinical treatment options for Lassa fever into clinical trials is critical to continue addressing this neglected tropical disease.

scholarly journals Predicting the evolution of Lassa Virus endemic area and population at risk over the next decades

2021 ◽  
Author(s):  
Raphaëlle Klitting ◽  
Liana E. Kafetzopoulou ◽  
Wim Thiery ◽  
Gytis Dudas ◽  
Sophie Gryseels ◽  
...  
Keyword(s):  
At Risk ◽  
West Africa ◽  
Endemic Area ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Environmental Data ◽  
World Health ◽  
Lassa Virus ◽  
Viral Genomes ◽  
Health Organization

AbstractLassa fever is listed among the diseases that pose the greatest risks to public health by the World Health Organization. This severe viral hemorrhagic fever is caused by Lassa virus, a zoonotic pathogen that repeatedly spills over to humans from its rodent reservoirs. It is currently not known how climate change, transformations in land use, and human population growth could affect the endemic area of this virus, currently limited to parts of West Africa. By exploring the environmental data associated with virus occurrence, we show how temperature, precipitation and the presence of pastures determine ecological suitability for virus circulation. We project that regions in Central and East Africa will likely become suitable for Lassa virus over the next decades and estimate that the total population living in areas suitable for Lassa virus may grow from about 100 million to 700 million by 2070. By analysing geotagged viral genomes, we find that in the event of Lassa virus being introduced into a new suitable region, its spread might remain spatially limited over the first decades. Our results highlight how the endemic area of Lassa virus may expand well beyond West Africa in the next decades due to human impact on the environment, putting hundreds of million more people at risk of infection.

scholarly journals Improving the Breadth of the Host’s Immune Response to Lassa Virus

Pathogens ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 84 ◽  
Author(s):  
Juan Zapata ◽  
Sandra Medina-Moreno ◽  
Camila Guzmán-Cardozo ◽  
Maria Salvato
Keyword(s):  
Immune Response ◽  
Vaccine Coverage ◽  
Virus Disease ◽  
West African ◽  
World Health ◽  
Lassa Virus ◽  
The West ◽  
African Patient ◽  
Health Organization ◽  
Medical Countermeasures

In 2017, the global Coalition for Epidemic Preparedness (CEPI) declared Lassa virus disease to be one of the world’s foremost biothreats. In January 2018, World Health Organization experts met to address the Lassa biothreat. It was commonly recognized that the diversity of Lassa virus (LASV) isolated from West African patient samples was far greater than that of the Ebola isolates from the West African epidemic of 2013–2016. Thus, vaccines produced against Lassa virus disease face the added challenge that they must be broadly-protective against a wide variety of LASV. In this review, we discuss what is known about the immune response to Lassa infection. We also discuss the approaches used to make broadly-protective influenza vaccines and how they could be applied to developing broad vaccine coverage against LASV disease. Recent advances in AIDS research are also potentially applicable to the design of broadly-protective medical countermeasures against LASV disease.

scholarly journals Dynamical System Analysis of a Lassa Fever Model with Varying Socioeconomic Classes

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ifeanyi Sunday Onah ◽  
Obiora Cornelius Collins
Keyword(s):  
Disease Transmission ◽  
System Analysis ◽  
Lassa Fever ◽  
West African ◽  
Sensitivity Analyses ◽  
Model Parameters ◽  
Lassa Virus ◽  
African Countries ◽  
Patch Model ◽  
Viral Illness

Lassa fever is an animal-borne acute viral illness caused by Lassa virus. It poses a serious health challenge around the world today, especially in West African countries like Ghana, Benin, Guinea, Liberia, Mali, Sierra Leone, and Nigeria. In this work, we formulate a multiple-patch Lassa fever model, where each patch denotes a socioeconomic class (SEC). Some of the important epidemiological features such as basic reproduction number of the model were determined and analysed accordingly. We further investigated how varying SECs affect the transmission dynamics of Lassa fever. We analysed the required state at which each SEC is responsible in driving the Lassa fever disease outbreak. Sensitivity analyses were carried out to determine the importance of model parameters to the disease transmission and prevalence. We carried out numerical simulation to support our analytical results. Finally, we extend some of the results of the 2-patch model to the general n -patch model.

scholarly journals Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Junki Maruyama ◽  
John T. Manning ◽  
Elizabeth J. Mateer ◽  
Rachel Sattler ◽  
Natalya Bukreyeva ◽  
...  
Keyword(s):  
Public Health ◽  
Sierra Leone ◽  
Guinea Pigs ◽  
Lassa Fever ◽  
West African ◽  
Lassa Virus ◽  
African Countries ◽  
Successful Development ◽  
Public Health Perspective ◽  
Lethal Infection

ABSTRACT 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.

scholarly journals Inhibition of Different Lassa Virus Strains by Alpha and Gamma Interferons and Comparison with a Less Pathogenic Arenavirus

2004 ◽  
Vol 78 (6) ◽  
pp. 3162-3169 ◽  
Author(s):  
Marcel Asper ◽  
Thomas Sternsdorf ◽  
Meike Hass ◽  
Christian Drosten ◽  
Antje Rhode ◽  
...  
Keyword(s):  
Vero Cells ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
High Pathogenicity ◽  
Ifn Γ ◽  
Virus Strains

ABSTRACT The high pathogenicity of Lassa virus is assumed to involve resistance to the effects of interferon (IFN). We have analyzed the effects of alpha IFN (IFN-α), IFN-γ, and tumor necrosis factor alpha (TNF-α) on replication of Lassa virus compared to the related, but less pathogenic, lymphocytic choriomeningitis virus (LCMV). Three low-passage Lassa virus strains (AV, NL, and CSF), isolated from humans with mild to fulminant Lassa fever, were tested. Lassa virus replication was inhibited by IFN-α and IFN-γ, but not TNF-α, in Huh7 and Vero cells. The degree of IFN sensitivity of a Lassa virus isolate did not correlate with disease severity in human patients. Furthermore, cytokine effects observed for Lassa virus and LCMV (strains CH-5692, Armstrong, and WE) were similar. To address the mechanisms involved in the IFN effect, we used cell lines in which overexpression of IFN-stimulated proteins promyelocytic leukemia protein (PML) and Sp100 could be induced. Both proteins reside in PML bodies, a cellular target of the LCMV and Lassa virus Z proteins. Overexpression of PML or Sp100 did not affect replication of either virus. This, together with the previous finding that PML knockout facilitates LCMV replication in vitro and in vivo (M. Djavani, J. Rodas, I. S. Lukashevich, D. Horejsh, P. P. Pandolfi, K. L. Borden, and M. S. Salvato, J. Virol. 75:6204-6208, 2001; W. V. Bonilla, D. D. Pinschewer, P. Klenerman, V. Rousson, M. Gaboli, P. P. Pandolfi, R. M. Zinkernagel, M. S. Salvato, and H. Hengartner, J. Virol. 76:3810-3818, 2002), describes PML as a mediator within the antiviral pathway rather than as a direct effector protein. In conclusion, the high pathogenicity of Lassa virus compared to LCMV is probably not due to increased resistance to the effects of IFN-α or IFN-γ. Both cytokines inhibit replication which is relevant for the design of antiviral strategies against Lassa fever with the aim of enhancing the IFN response.

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