1,723,899 research outputs found
Comparative studies on Mopeia viruses and other Arenaviridae, particularly Lassa virus
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Serologically related arenaviruses have been isolated from West Africa, Mozambique, Zimbabwe and the Central African Republic. Human disease is only associated with the West African isolates. The virulence of Mozambique, Zimbabwe and Central African Republic isolates in humans is not known.
This Thesis is an account of work carried out by the author to compare the biological characteristics of isolates from West Africa, Mozambique and Zimbabwe. It describes the successful isolation and identification of the aetiological agents, their physicochemical and antigenic characteristics and describes in vivo studies using mice, guinea pigs and Rhesus monkeys.
A direct comparison was made with a patient diagnosed as having Lassa fever. The disease in man and monkeys following infection with Lassa virus was similar. The Rhesus monkey and guinea pig proved suitable experimental models in which to study and compare the pathogenic responses and also to evaluate various aspects of protection. These animal models when immunised with the viruses from Mozambique and Zimbabwe were protected when subsequently challenged with Lassa virus.
The Mozambique and Zimbabwe isolates proved to have morphological and physicochemical characteristics not dissimilar from West African Lassa viruses and those members of the arenavirus family from South America. Serological and immunochemical investigations suggest the existence of both common and unique antigenic determinants on the viruses from Mozambique, -Zimbabwe and West Africa. This grouping also coincides with the geographic separation of the viruses, i.e. Lassa - West Africa and Mopeia -southeast Africa. Similar differences in host susceptibility have also been demonstrated. Lassa virus produces a fatal haemorrhagic disease while Mopeia isolates produce only an asymptomatic infection. The combined data suggests the possibility of two virus groups within the 'Old World' arenavirus classification. The proposed name, 'Mopeia', forms one group and includes the viruses from Mozambique and Zimbabwe. The Lassa strains from West Africa form the second group.
It is suggested that the Mopeia viruses are minor antigenic variants of Lassa and should be included within the arenavirus family
Structural and functional studies of novel mechanisms of Lassa fever virus nucleoprotein in immune suppression, viral RNA transcription and replication
No full textLassa fever virus is one of the most dangerous viruses of arenaviridae family,
causing more than 500,000 infections per year in Africa. The fatality rate for
hospitalized patients is as high as 20%. Due to the high fatality and lack of efficient licensed drugs and vaccines to treat and prevent, Lassa fever virus is classified as a Category A priority pathogen and biosafety level-4 agent by the Centers for Disease Control and Prevention of the USA. Cases were also found in the Americas and European countries, highlighting its potency to be a
bioterrorism weapon.
Like other areanaviruses, Lassa virus has developed a unique interferon suppression mechanism to evade from the host immune system, in which Lassa
nucleoprotein plays the key role. To understand the LASV nucleoprotein functions, we tried to determine the first arenaviral nucleoprotein structure, LASV nucleoprotein. The LASV nucleoprotein (NP) was overexpressed and purified. The NP protein was crystallized and the structure was determined to 1.80 Å resolution. The crystals belong to space group P3, with the unit cell parameters a = b = 177.16 Å, c = 56.49 Å, α= β= 90° and γ= 120°. The LASV NP
structure contains two domains, which are not similar to any reported viral nucleoprotein structures. The N-terminal domain has a novel structure with a
cavity, which we proposed for cap binding, and the C-terminus is a 3’-5' ribonuclease, which is responsible for suppressing interferon production. To characterize the possible interaction between NP and other arenaviral protein, we also overexpressed and purified LASV Z. Interestingly, both NP and Z proteins have two forms and the purified NP protein and monomeric Z protein bind RNA.
It is surprising that only the oligomeric Z protein interacts with NP protein but
the monomeric Z protein does not as determined by Isothermal Titration
Calorimetry (ITC). Our studies have reported the first arenaviral nucleoprotein
structure, revealed the novel mechanism for the cap binding and immune
suppression, which set up a platform for the development of novel drugs and vaccines
to treat deadly arenaviral infections
C-Reactive Protein and Association with Disease Severity in Hospitalized Adult Lassa Fever Patients in Nigeria
No full textBackground : Lassa fever poses a significant health burden in west Africa. The pathophysiology of Lassa fever and determinants of clinical spectrum of disease remain poorly understood. We performed a study to understand the correlation of blood Inflammatory marker C-reactive protein (CRP), with Lassa fever disease severity. Methods : A cross-sectional controlled study of adult Lassa fever patients presenting to the Institute of Lassa Fever Research and Control at Irrua Specialist Teaching Hospital, Nigeria, between January and April 2023. Lassa fever was confirmed using real-time PCR. Disease severity classified as: Severe disease= Blood urea level >100 mg/dL; Moderate categorized <100 mg/dL. CRP was measured using Tecan Infinite F50 ELISA system Disease severity was correlated with CRP levels. Results : 64 adult patients with Lassa fever and 60 healthy controls were enrolled. There was no difference in mean age (37.6 vs. 35.2 years, p=0.10) and gender (male 53% vs 56%, p=0.82). CRP levels were significantly elevated in Lassa fever patients (mean: 36.23 mg/L, SD: 4.56, %CV: 12.59) compared to controls (mean: 5.42 mg/L, SD: 0.53, %CV: 9.78) (p=0.000). CRP levels varied with disease severity, being significantly higher in patients with severe disease (28.57 mg/L, SD = 2.34; %CV = 8.19) compared to those with moderately severe disease (12.34 mg/L, SD = 0.98; %CV = 7.94);(p = 0.001). Conclusions : Lassa fever inpatients showed significant inflammation and elevated CRP levels which correlated with disease severity. CRP could serve as a potential baseline marker in outbreak situations to trigger management decision making to treat or not to treat in light of limited Ribavirin supplies. Given the inflammatory changes and correlation of elevated CRP levels with LF disease severity, larger controlled studies during outbreaks are required to assess use of CRP for more accurate triaging, including commencement of treatment
Lassa fever
No full textLassa fever is an acute viral illness that occurs in west Africa. The illness was discovered in 1969 when two missionary nurses died in Nigeria. The virus is named after the town in Nigeria where the first cases occurred. The virus, a member of the virus family Arenaviridae, is a single-stranded RNA virus and is zoonotic, or animal-borne.Lassa fever is endemic in parts of west Africa including Sierra Leone, Liberia, Guinea and Nigeria; however, other neighboring countries are also at risk, as the animal vector for Lassa virus, the "multimammate rat" (Mastomys natalensis) is distributed throughout the region. In 2009, the first case from Mali was reported in a traveler living in southern Mali; Ghana reported its first cases in late 2011. Isolated cases have also been reported in Co\ucc\u201ate d\ue2\u20ac\u2122Ivoire and Burkina Faso and there is serologic evidence of Lassa virus infection in Togo and Benin.The number of Lassa virus infections per year in west Africa is estimated at 100,000 to 300,000, with approximately 5,000 deaths. Unfortunately, such estimates are crude, because surveillance for cases of the disease is not uniformly performed. In some areas of Sierra Leone and Liberia, it is known that 10%-16% of people admitted to hospitals every year have Lassa fever, which indicates the serious impact of the disease on the population of this region.Transmission -- Signs and symptoms -- Risk of exposure \ue2\u20ac\u201c Diagnosis \ue2\u20ac\u201c Treatment \ue2\u20ac\u201c Prevention -- References.Health EducationInfectious Diseas
Lassa Fever
No full textLassa virus causes Lassa fever disease in several countries in West Africa, where it is estimated to infect up to half million people causing roughly five thousand deaths each year. This deadly virus has also been introduced in multiple occasions into the western world, including the United States, United Kingdom, Netherlands, Sweden, and Germany. Lassa virus infection, which is often misdiagnosed, can lead to a wide range of disease symptoms ranging from mild flu-like symptoms to bleeding disorders, multi-organ failure, and death. Despite some major discoveries made in recent years of research on Lassa fever, there are still many unresolved key issues that hamper the development of effective vaccines and therapies. Some of these issues include a detailed understanding of the viral and participating host factors in completing the virus life cycle, in mediating disease pathogenesis or protection, and in activating or suppressing host immune responses against virus infection. This book is devoted to understanding some of these important issues. Expert and timely contributions in the form of editorial and original research and review articles on Lassa fever viral replication, disease pathogenesis and protection, host immune modulations, and other related hot topics are presented in this publication
Lassa fever [French]
No full textLassa fever [French]La fi\ue8vre de Lassa est une maladie virale aig\ufce pr\ue9sente en Afrique de l\u2019Ouest. Cette maladie a \ue9t\ue9 d\ue9couverte en 1969 lorsque deux infirmi\ue8res missionnaires sont mortes au Nigeria. Le virus tire son nom de la ville du Nigeria dans laquelle les premiers cas sont apparus. Appartenant \ue0 la famille du virus Arenaviridae, ce virus \ue0 ARN \ue0 simple brin est zoonotique, c\u2019est-\ue0-dire transmis par les animaux.La fi\ue8vre de Lassa est end\ue9mique dans certaines r\ue9gions d\u2019Afrique de l\u2019Ouest, notamment en Sierra Leone, au Liberia, en Guin\ue9e et au Nig\ue9ria ; toutefois, d\u2019autres r\ue9gions sont \ue9galement expos\ue9es du fait que l\u2019animal vecteur du virus de Lassa, le \uab rat plurimammaire \ubb (Mastomys natalensis) est pr\ue9sent dans toute la r\ue9gion. En 2009, le premier cas au Mali a \ue9t\ue9 signal\ue9 par un voyageur vivant dans le sud du pays ; le Ghana a d\ue9clar\ue9 les premiers cas sur son territoire fin 2011. Des cas isol\ue9s ont \ue9galement \ue9t\ue9 signal\ue9s en C\uf4te d\u2019Ivoire et au Burkina Faso, et il existe des signes s\ue9rologiques d\u2019infection au virus de Lassa au Togo et au B\ue9nin.Le nombre annuel de cas d\u2019infection au virus de Lassa en Afrique de l\u2019Ouest est estim\ue9 entre 100.000 et 300.000, avec pr\ue8s de 5.000 d\ue9c\ue8s. Il s\u2019agit malheureusement d\u2019estimations brutes car la surveillance des cas de la maladie n\u2019est pas r\ue9alis\ue9e de fa\ue7on uniforme. Dans certaines r\ue9gions de Sierra Leone et du Liberia, il est \ue9tabli qu\u2019entre 10 et 16 % des personnes admises \ue0 l\u2019h\uf4pital chaque ann\ue9e sont atteintes de la fi\ue8vre de Lassa, et cela met en \ue9vidence le grave impact de la maladie sur les habitants de cette r\ue9gion.Publication date from document properties.factsheet.pdf20161149
Prevalence and risk factors of Lassa seropositivity in inhabitants of the forest region of Guinea: a cross-sectional study.
No full textBACKGROUND: Lassa fever is a viral hemorrhagic fever endemic in West Africa. The reservoir host of the virus is a multimammate rat, Mastomys natalensis. Prevalence estimates of Lassa virus antibodies in humans vary greatly between studies, and the main modes of transmission of the virus from rodents to humans remain unclear. We aimed to (i) estimate the prevalence of Lassa virus-specific IgG antibodies (LV IgG) in the human population of a rural area of Guinea, and (ii) identify risk factors for positive LV IgG. METHODS AND FINDINGS: A population-based cross-sectional study design was used. In April 2000, all individuals one year of age and older living in three prefectures located in the tropical secondary forest area of Guinea (Gueckedou, Lola and Yomou) were sampled using two-stage cluster sampling. For each individual identified by the sampling procedure and who agreed to participate, a standardized questionnaire was completed to collect data on personal exposure to potential risk factors for Lassa fever (mainly contact with rodents), and a blood sample was tested for LV IgG. A multiple logistic regression model was used to determine risk factors for positive LV IgG. A total of 1424 subjects were interviewed and 977 sera were tested. Prevalence of positive LV Ig was of 12.9% [10.8%-15.0%] and 10.0% [8.1%-11.9%] in rural and urban areas, respectively. Two risk factors of positive LV IgG were identified: to have, in the past twelve months, undergone an injection (odds ratio [OR] = 1.8 [1.1-3.1]), or lived with someone displaying a haemorrhage (OR = 1.7 [1.1-2.9]). No factors related to contacts with rats and/or mice remained statistically significant in the multivariate analysis. CONCLUSIONS: Our study underlines the potential importance of person-to-person transmission of Lassa fever, via close contact in the same household or nosocomial exposure
What you need to know about Lassa fever
No full textLassa fever is caused by a virus that is found in West Africa. It was first discovered in 1969 in Lassa, Nigeria when two missionary nurses died.Lassa fever is mainly found in Sierra Leone, Liberia, Guinea, and Nigeria and is spread by rats. Other neighboring countries are also at risk because the type of rat that spreads the virus is also found throughout the West African region.Lassa fever is different from Ebola, the disease that is responsible for the current outbreak in West Africa. Although Lassa fever and Ebola can result in similar symptoms, Lassa fever is less likely than Ebola to spread from person to person and is far less deadly. The death rate from Lassa fever is approximately 1% versus approximately 70% from Ebola. While both diseases are viral hemorrhagic fevers, bleeding and severe symptoms are not common in cases of Lassa fever.CS25728
What you need to know about Lassa fever
No full textLassa fever is caused by a virus that is found in West Africa. It was first discovered in 1969 in Lassa, Nigeria when two missionary nurses died.Lassa fever is mainly found in Sierra Leone, Liberia, Guinea, and Nigeria and is spread by rats. Other neighboring countries are also at risk because the type of rat that spreads the virus is also found throughout the West African region.CS330933-A April 19, 2022What-you-need-to-know-about-Lassa-508.pdf20221149
- …
