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 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 Genome Sequence of Lassa Virus Isolated from the First Domestically Acquired Case in Germany

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Svenja Wolff ◽  
Tilman Schultze ◽  
Sarah Katharina Fehling ◽  
Jan Philipp Mengel ◽  
Gerrit Kann ◽  
...  
Keyword(s):  
West Africa ◽  
Genome Sequence ◽  
Treatment Options ◽  
Specific Treatment ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Lassa Virus ◽  
First Case

Lassa virus (LASV) is a zoonotic, hemorrhagic fever-causing virus endemic in West Africa, for which no approved vaccines or specific treatment options exist. Here, we report the genome sequence of LASV isolated from the first case of acquired Lassa fever disease outside of Africa.

scholarly journals Animal Models of Lassa Fever

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 197 ◽  
Author(s):  
Rachel A. Sattler ◽  
Slobodan Paessler ◽  
Hinh Ly ◽  
Cheng Huang
Keyword(s):  
Animal Model ◽  
Hearing Loss ◽  
Animal Models ◽  
Sensorineural Hearing Loss ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Disease Pathogenesis ◽  
Western Africa ◽  
Socioeconomic Burden

Lassa virus (LASV), the causative agent of Lassa fever, is estimated to be responsible for up to 300,000 new infections and 5000 deaths each year across Western Africa. The most recent 2018 and 2019 Nigerian outbreaks featured alarmingly high fatality rates of up to 25.4%. In addition to the severity and high fatality of the disease, a significant population of survivors suffer from long-term sequelae, such as sensorineural hearing loss, resulting in a huge socioeconomic burden in endemic regions. There are no Food and Drug Administration (FDA)-approved vaccines, and therapeutics remain extremely limited for Lassa fever. Development of countermeasures depends on relevant animal models that can develop a disease strongly mimicking the pathogenic features of Lassa fever in humans. The objective of this review is to evaluate the currently available animal models for LASV infection with an emphasis on their pathogenic and histologic characteristics as well as recent advances in the development of a suitable rodent model. This information may facilitate the development of an improved animal model for understanding disease pathogenesis of Lassa fever and for vaccine or antiviral testing.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone
Keyword(s):  
Drug Resistance ◽  
Animal Models ◽  
Carbonic Anhydrase ◽  
Drug Target ◽  
Treatment Options ◽  
Parasitic Diseases ◽  
Carbonic Anhydrases ◽  
Extensive Drug Resistance ◽  
Protozoan Infections

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

cccccImmunological screening of Lassa Virus among Health workers and Contacts of patients of Lassa fever in Ondo State

Immunobiology ◽  
2021 ◽  
pp. 152076
Author(s):  
Joseph Ojonugwa Shaibu ◽  
Olumuyiwa Babalola Salu ◽  
Olufemi Samuel Amoo ◽  
Ifeoma Idigbe ◽  
Adesola Zaidat Musa ◽  
...  
Keyword(s):  
Health Workers ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Ondo State

scholarly journals Lassa Virus Circulation in Small Mammal Populations in Bo District, Sierra Leone

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 28
Author(s):  
Umaru Bangura ◽  
Jacob Buanie ◽  
Joyce Lamin ◽  
Christopher Davis ◽  
Gédéon Ngiala Bongo ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Sierra Leone ◽  
Small Mammal ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Sierra Leonean ◽  
Bayesian Phylogenetic Analysis ◽  
Prevalent Species ◽  
Lineage Iv

Lassa fever is a viral hemorrhagic fever caused by the Lassa virus LASV, which was first isolated in the rodent Mastomys natalensis in 1974 in Kenema, Sierra Leone. As little is known about the abundance and the presence of LASV in rodents living in the Bo area, we carried out a small mammal longitudinal population survey. A standardized trapping session was performed in various habitats and seasons in six villages over two years (2014–2016) and samples collected were tested for arenavirus IgG and LASV. A Bayesian phylogenetic analysis was performed on sequences identified by PCR. A total of 1490 small mammals were collected, and 16 rodent species were identified, with M. natalensis (355, 24%) found to be the most prevalent species. Forty-one (2.8%) samples were IgG positive, and 31 of these were trapped in homes and 10 in surrounding vegetation. Twenty-nine of 41 seropositive rodents were M. natalensis. We detected four LASV by PCR in two villages, all found in M. natalensis. Phylogenetic analysis showed that the sequences were distributed within the Sierra Leonean clade within lineage IV, distinguishing a Bo sub-clade older than a Kenema sub-clade. Compared to other settings, we found a low abundance of M. natalensis and a low circulation of LASV in rodents in villages around Bo district.

Review of treatment and therapeutic targets in brain arteriovenous malformation

2021 ◽  
pp. 0271678X2110267
Author(s):  
Peipei Pan ◽  
Shantel Weinsheimer ◽  
Daniel Cooke ◽  
Ethan Winkler ◽  
Adib Abla ◽  
...  
Keyword(s):  
Animal Models ◽  
De Novo ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Therapeutic Targets ◽  
Current Treatment ◽  
Mitogen Activated Protein Kinase ◽  
De Novo Mutations ◽  
Genetic Syndromes ◽  
Mitogen Activated Protein

Brain arteriovenous malformations (bAVM) are an important cause of intracranial hemorrhage (ICH), especially in younger patients. The pathogenesis of bAVM are largely unknown. Current understanding of bAVM etiology is based on studying genetic syndromes, animal models, and surgically resected specimens from patients. The identification of activating somatic mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene and other mitogen-activated protein kinase ( MAPK) pathway genes has opened up new avenues for bAVM study, leading to a paradigm shift to search for somatic, de novo mutations in sporadic bAVMs instead of focusing on inherited genetic mutations. Through the development of new models and understanding of pathways involved in maintaining normal vascular structure and functions, promising therapeutic targets have been identified and safety and efficacy studies are underway in animal models and in patients. The goal of this paper is to provide a thorough review or current diagnostic and treatment tools, known genes and key pathways involved in bAVM pathogenesis to summarize current treatment options and potential therapeutic targets uncovered by recent discoveries.

Animal Experiments and their Alternatives in Psychiatry

1988 ◽  
Vol 15 (4) ◽  
pp. 313-318
Author(s):  
Anthony Stevens
Keyword(s):  
Animal Models ◽  
Human Study ◽  
Animal Experiments ◽  
Experimental Production ◽  
Potential Utility ◽  
Pharmacological Agents ◽  
Wide Range ◽  
Influential Paper ◽  
Adequate Data ◽  
Human Primate

During the last twenty years, the most enthusiastic advocates of the use of animal models in the study of human psychiatric dysfunction have been Harlow and Suomi. In an influential paper, Induced Depression in Monkeys (1974), they argued that more extensive use of non-human primates “would have great potential utility since many manipulations and measurements presently prohibited in human study by ethical and practical considerations could be readily performed on non-human primate subjects in well-controlled experimental environments.” Harlow & Suomi concluded this paper with the following statement: “The results obtained to date on induced depression in monkeys show that proper and profound depressions can be produced relatively easily by a variety of techniques. These induced depressions either bear a close resemblance to human depression or have such similarity as to suggest that closely correlated human and animal depressive patterns may be achieved with refined techniques. The results to date also provide adequate data for the conduct of meaningful researches on the effects of pharmacological agents which either enhance, inhibit or preclude the experimental production of depression. Further, the existence of firm and fast monkey depression syndromes offers vast opportunities for testing a wide range of therapeutic techniques, either behavioural or biochemical.”

Kolaviron, a Biflavonoid Compound: Pharmacological activity and Therapeutic Efficacy

2021 ◽  
Vol 18 ◽  
Author(s):  
Damilare Rotimi ◽  
Jennifer Chidubem Amanze ◽  
Adebola Busola Ojo ◽  
Matthew Iyobhebhe ◽  
Tobiloba Christiana Elebiyo ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Treatment Options ◽  
Herbal Remedies ◽  
Clinical Settings ◽  
Garcinia Kola ◽  
Anti Cancer ◽  
The World ◽  
Health Promoting ◽  
Grown Plant ◽  
Viable Treatment

Abstract: The use of herbal remedies for medicinal purposes is becoming more popular around the world. As a result, plants have become viable treatment options for a variety of diseases. Garcinia kola (bitter kola) is a perennially grown plant in the Guttiferae family that has been evaluated and reported to have numerous health-promoting properties. Kolaviron is a biflavanoid and major phytochemical found in Garcinia kola that includes Garcinia Biflavanoid-1 (GB-1), kolaflavanone, and Garcinia Biflavanoid-2 (GB-2). It is obtained as a fraction extracted from Garcinia kola. Kolaviron's pharmacological properties include anti-inflammatory, anti-spasmodic, ameliorative, anti-asthmatic, anti-cancer, anti-malarial, hepatoprotective, antioxidant, anti-atherogenic, neuroprotective, anti-diabetic, and anti-amnesic properties. Kolaviron is recommended for use in clinical settings because it has been shown to have a high therapeutic efficacy in clinical trials. The purpose of this review is to assess the therapeutic efficacy of kolaviron.

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