scholarly journals Acute Lassa Virus Encephalitis with Lassa Virus in the Cerebrospinal Fluid but Absent in the Blood: A Case Report with a Positive Outcome

2018 ◽  
Vol 10 (2) ◽  
pp. 150-158 ◽  
Author(s):  
Peter O. Okokhere ◽  
Cyril O. Erameh ◽  
Francis Alikah ◽  
Peter E. Akhideno ◽  
Christopher O. Iruolagbe ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurological Complication ◽  
Positive Outcome ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Rt Pcr ◽  
Nigerian Woman ◽  
The Central Nervous System ◽  
High Index Of Suspicion

It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of Lassa fever infection without associated bleeding, and to find Lassa virus (LAV) in the cerebrospinal fluid (CSF) but not in the serum. We report the case of a 38-year-old Nigerian woman with mainly CNS manifestation of Lassa fever. She was admitted twice within 11 days because of persistent fever. A clinical diagnosis of acute LAV encephalitis was made because of a high index of suspicion and CNS involvement confirmed by positive reverse transcriptase polymerase chain reaction (RT-PCR) for LAV in the CSF, while her blood was repeatedly negative for LAV by RT-PCR test. She recovered fully following supportive care coupled with treatment with an 18-day course of ribavirin, and suffered no long-term neurological complication or relapse. Post-treatment CSF examination by RT-PCR did not detect LAV.

scholarly journals A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs

npj Vaccines ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Derek R. Stein ◽  
Bryce M. Warner ◽  
Geoff Soule ◽  
Kevin Tierney ◽  
Kathy L. Frost ◽  
...  
Keyword(s):  
Virus Infection ◽  
Guinea Pigs ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Vesicular Stomatitis

scholarly journals Lassa Fever Encephalopathy: Lassa Virus in Cerebrospinal Fluid but Not in Serum

2001 ◽  
Vol 184 (3) ◽  
pp. 345-349 ◽  
Author(s):  
Stephan Günther ◽  
Boye Weisner ◽  
Andreas Roth ◽  
Thomas Grewing ◽  
Marcel Asper ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lassa Fever ◽  
Lassa Virus

scholarly journals Diagnosis and Clinical Virology of Lassa Fever as Evaluated by Enzyme-Linked Immunosorbent Assay, Indirect Fluorescent-Antibody Test, and Virus Isolation

2000 ◽  
Vol 38 (7) ◽  
pp. 2670-2677 ◽  
Author(s):  
D. G. Bausch ◽  
P. E. Rollin ◽  
A. H. Demby ◽  
M. Coulibaly ◽  
J. Kanu ◽  
...  
Keyword(s):  
Gold Standard ◽  
Virus Isolation ◽  
Fluorescent Antibody ◽  
Lassa Fever ◽  
Virus Antigen ◽  
Lassa Virus ◽  
Indirect Fluorescent Antibody ◽  
Rt Pcr ◽  
Prognostic Information ◽  
Course Of Illness

The Lassa virus (an arenavirus) is found in West Africa, where it sometimes causes a severe hemorrhagic illness called Lassa fever. Laboratory diagnosis has traditionally been by the indirect fluorescent-antibody (IFA) test. However, enzyme-linked immunosorbent assays (ELISAs) for Lassa virus antigen and immunoglobulin M (IgM) and G (IgG) antibodies have been developed that are thought to be more sensitive and specific. We compared ELISA and IFA testing on sera from 305 suspected cases of Lassa fever by using virus isolation with a positive reverse transcription-PCR (RT-PCR) test as the “gold standard.” Virus isolation and RT-PCR were positive on 50 (16%) of the 305 suspected cases. Taken together, Lassa virus antigen and IgM ELISAs were 88% (95% confidence interval [CI], 77 to 95%) sensitive and 90% (95% CI, 88 to 91%) specific for acute infection. Due to the stringent gold standard used, these likely represent underestimates. Diagnosis could often be made on a single serum specimen. Antigen detection was particularly useful in providing early diagnosis as well as prognostic information. Level of antigenemia varied inversely with survival. Detection by ELISA of IgG antibody early in the course of illness helped rule out acute Lassa virus infection. The presence of IFA during both acute and convalescent stages of infection, as well as significant interobserver variation in reading the slides, made interpretation difficult. However, the assay provided useful prognostic information, the presence of IFA early in the course of illness correlating with death. The high sensitivity and specificity, capability for early diagnosis, and prognostic value of the ELISAs make them the diagnostic tests of choice for the detection of Lassa fever.

Intravenous delivery of adeno-associated viral gene therapy in feline GM1 gangliosidosis

Brain ◽  
2021 ◽  
Author(s):  
Amanda L Gross ◽  
Heather L Gray-Edwards ◽  
Cassie N Bebout ◽  
Nathan L Ta ◽  
Kayly Nielsen ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Galactosidase Activity ◽  
Gm1 Gangliosidosis ◽  
The Central Nervous System ◽  
Imaging And Spectroscopy ◽  
The Brain

Abstract GM1 gangliosidosis is a fatal neurodegenerative disease caused by a deficiency of lysosomal β-galactosidase. In its most severe form, GM1 gangliosidosis causes death by 4 years of age, and no effective treatments exist. Previous work has shown that injection of the brain parenchyma with an adeno-associated viral vector provides pronounced therapeutic benefit in a feline GM1 model. To develop a less invasive treatment for the brain and increase systemic biodistribution, intravenous injection of AAV9 was evaluated. AAV9 expressing feline β-galactosidase was intravenously administered at 1.5x1013 vector genomes/kilogram body weight to six GM1 cats at approximately 1 month of age. The animals were divided into two cohorts: 1) a long-term group, which was followed to humane endpoint, and 2) a short-term group, which was analyzed 16-weeks post treatment. Clinical assessments included neurological exams, cerebrospinal fluid and urine biomarkers, and 7-Telsa magnetic resonance imaging and spectroscopy. Postmortem analysis included β-galactosidase and virus distribution, histological analysis, and ganglioside content. Untreated GM1 animals survived 8.0 ± 0.6 months while intravenous treatment increased survival to an average of 3.5 years (n = 2) with substantial improvements in quality of life and neurologic function. Neurological abnormalities, which in untreated animals progress to the inability to stand and debilitating neurological disease by 8 months of age, were mild in all treated animals. Cerebrospinal fluid biomarkers were normalized, indicating decreased central nervous system cell damage in the treated animals. Urinary glycosaminoglycans decreased to normal levels in the long-term cohort. Magnetic resonance imaging and spectroscopy showed partial preservation of the brain in treated animals, which was supported by postmortem histological evaluation. β-galactosidase activity was increased throughout the central nervous system, reaching carrier levels in much of the cerebrum and normal levels in the cerebellum, spinal cord and cerebrospinal fluid. Ganglioside accumulation was significantly reduced by treatment. Peripheral tissues such as heart, skeletal muscle, and sciatic nerve also had normal β-galactosidase activity in treated GM1 cats. GM1 histopathology was largely corrected with treatment. There was no evidence of tumorigenesis or toxicity. Restoration of β-galactosidase activity in the central nervous system and peripheral organs by intravenous gene therapy led to profound increases in lifespan and quality of life in GM1 cats. This data supports the promise of intravenous gene therapy as a safe, effective treatment for GM1 gangliosidosis.

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.

scholarly journals Lassa Virus Diagnostic Platforms: Limitations and Prospects

2020 ◽  
pp. 5-17
Author(s):  
Yahaya Hassan ◽  
Abdulhadi Sale Kumurya ◽  
Ibrahim Aminu ◽  
Sanusi Rahinatu Sharfadi ◽  
Abdullahi Alhassan Sharif
Keyword(s):  
Point Of Care ◽  
Lassa Fever ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lassa Virus ◽  
Rt Pcr ◽  
Isothermal Method ◽  
Polymerase Chain ◽  
Thermal Cycler ◽  
Low Sensitivity ◽  
And Control

Background: Lassa virus (LASV) is the cause of lassa fever (LF) belonging to the Arenaviridae family. Clinical diagnosis is often difficult because of symptoms commonality with other infectious diseases. Early and rapid diagnosis is critical for therapy initiation and LF transmission prevention and control. Aims: This review aims to highlight current diagnostic platforms and prospects of new emerging sensitive platforms. Methodology: Available published articles on LASV diagnostics with a focus on current methods: virus culture, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT – PCR) and rapid diagnostic tests (RDT) were reviewed based on their performances and limitations. Prospects of new diagnostic platforms: mobile health, microfluidic, clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas), Loop-mediated isothermal amplification (LAMP) for LASV diagnosis were also reviewed. Results: Low sensitivity of the ELISA platform during the window period of LASV infection was observed. Moreover, RT – PCR findings indicated limitation of expertise necessity, cost of thermal cycler, and dedicated facility. Molecular-based point-of-care (POC) diagnostic development should be prioritized to increase speed and sensitivity. Conclusion: The integration of POC device into molecular isothermal method against LASV scourge will be a success story in curving intermittent outbreaks in endemic areas and prompt clinical management.

scholarly journals Case series of outcome of newborn babies exposed to Lassa fever virus infection

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Dorathy Chinwe Obu ◽  
Obumneme Benaianh Ezeanosike ◽  
Samuel Amechi Nwukor
Keyword(s):  
Horizontal Transmission ◽  
Case Series ◽  
Hemorrhagic Fever ◽  
Positive Outcome ◽  
Lassa Fever ◽  
West African ◽  
Lassa Virus ◽  
African Countries ◽  
Lassa Fever Virus ◽  
Prompt Diagnosis

Lassa fever (LF) is an acute viral hemorrhagic fever caused by the Lassa virus, a zoonotic infection transmitted by the infected multimammate mouse which is endemic in West African countries. It affects all ages contributing to high maternal and neonatal mortality rates. Neonates are at risk of vertical and horizontal transmission of Lassa virus. We report a series of six newborns, three of whom were delivered to Lassa fever positive mothers and were managed as exposed babies while the remaining three were diagnosed with neonatal Lassa fever. None of the babies exposed to the virus became infected and two of these exposed babies had a positive outcome. All the babies with neonatal Lassa fever died days after birth even before confirming the diagnosis and initiating ribavirin treatment. This highlights the need for prompt diagnosis in utero with treatment of mother before delivery to improve the neonatal outcome. Also, the need to commence intravenous ribavirin treatment in highly suspicious cases of neonatal Lassa fever while awaiting confirmation of the diagnosis is emphasized.

CHAPTER 9: Immunology of TBEV-Infections

2020 ◽  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Sample Collection ◽  
Tick Borne Encephalitis ◽  
Viral Infectious Disease ◽  
The Central Nervous System

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

Herbal Medicine for Glioblastoma: Current and Future Prospects

2020 ◽  
Vol 16 (8) ◽  
pp. 1022-1043
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mustafa A. Hatiboglu
Keyword(s):  
Cell Proliferation ◽  
Survival Rates ◽  
Standard Of Care ◽  
Natural Compounds ◽  
Treatment Modalities ◽  
Normal Brain ◽  
The Central Nervous System ◽  
Cycle Regulation ◽  
Immense Potential

Background: Glioblastoma is one of the most aggressive and devastating tumours of the central nervous system with short survival time. Glioblastoma usually shows fast cell proliferation and invasion of normal brain tissue causing poor prognosis. The present standard of care in patients with glioblastoma includes surgery followed by radiotherapy and temozolomide (TMZ) based chemotherapy. Unfortunately, these approaches are not sufficient to lead a favorable prognosis and survival rates. As the current approaches do not provide a long-term benefit in those patients, new alternative treatments including natural compounds, have drawn attention. Due to their natural origin, they are associated with minimum cellular toxicity towards normal cells and it has become one of the most attractive approaches to treat tumours by natural compounds or phytochemicals. Objective: In the present review, the role of natural compounds or phytochemicals in the treatment of glioblastoma describing their efficacy on various aspects of glioblastoma pathophysiology such as cell proliferation, apoptosis, cell cycle regulation, cellular signaling pathways, chemoresistance and their role in combinatorial therapeutic approaches was described. Methods: Peer-reviewed literature was extracted using Pubmed, EMBASE Ovid and Google Scholar to be reviewed in the present article. Conclusion: Preclinical data available in the literature suggest that phytochemicals hold immense potential to be translated into treatment modalities. However, further clinical studies with conclusive results are required to implement phytochemicals in treatment modalities.

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