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PubMed1975

Recent isolations of Lassa virus from Nigerian rodents.

Rodents were trapped in the Benue-Plateau and North-Eastern States of Nigeria where Lassa fever had been reported in previous years. Eight Lassa virus strains were isolated from tissues and blood of rodents identified in the field as being of 3 different species: Mastomys natalensis, Rattus rattus, and Mus minutoides. All the infected rodents were collected in village habitats. These isolations indicate the presence of Lassa virus in wild rodents in Nigeria during periods when no human infections were evident.Prior studies in Sierra Leone have indicated that a single rodent species, M. natalensis, may be the important reservoir host of Lassa virus. Since the present study indicates that other rodent species may be involved as well, the ecology of Lassa virus may be more complicated than was heretofore supposed. In view of the importance of determining the geographic and species range of rodent hosts of Lassa virus, and because of the problems inherent in rodent identification under austere field conditions, it is urgent that further studies be conducted in the same areas of Nigeria to confirm these findings.

Animals↗

PubMed1987

[Clinico-epidemiologic and laboratory research on hemorrhagic fevers in Guinea].

In 1982-1983, were reported the cases of haemorrhagic fevers among populations living in the Madina-Ula district of Guinea. Clinico-epidemiological and serological studies (experimental studies) reveal into presumption of Ebola and Lassa fever viruses significance in the etiology of the disease outbreaks. Antibodies to Ebola virus were recognized in 19% from total number of sweating reconvalescent patients with the same clinical features, in order to 8% in healthy local populations. Antibodies to Lassa virus were detected in 3 cases, in 4 cases was revealed Lassa virus antigen in small rodents.

Antibodies, Viral↗

PubMed2005

Zidampidine, an aryl phosphate derivative of AZT: in vivo pharmacokinetics, metabolism, toxicity, and anti-viral efficacy against hemorrhagic fever caused by Lassa virus.

The pharmacokinetics, metabolism, and toxicity of Zidampidine, an aryl phosphate derivative of AZT, 3'-azidothymidine-5'-[p-bromophenyl methoxyalaninyl phosphate] were investigated in CD-1 mice. Following iv injection, Zidampidine was rapidly converted to its metabolites Ala-AZT-MP and AZT. Zidampidine was not toxic to mice at doses up to 250mg/kg. We next examined the therapeutic effect of Zidampidine in CBA mice challenged with intracerebral injections of the Josiah strain of Lassa virus. Mice were treated either with vehicle or non-toxic doses of Zidampidine administered intraperitoneally 24h prior, 1h prior, and 24, 48, 72, and 96h after virus inoculation. The probability of survival following the Lassa challenge was significantly improved for Zidampidine-treated mice (Kaplan Meier, Log-Rank p value<0.0001). This pilot study provides the basis for future preclinical evaluation of Zidampidine and its potential as a new agent for the treatment of viral hemorrhagic fevers caused by Lassa virus.

Animals↗

PubMed1998

[Viral contamination of food products: a poorly understood public health problem].

Throughout the world there have been several epidemics of food-borne diseases (FBD) about which there is lack of sufficient information for public health institutions to take appropriate measures. This study was conducted for the purpose of contributing to the dissemination of information on these diseases and their etiologic agents, epidemiology, and control. The study was based on data from 61 sources, including review articles, reports of outbreaks, and databases. Results reveal considerable underregistration and lack of data on FBD throughout the various countries, with viruses being the second most important cause of FBD in the United States of America. Two agents, Norwalk virus and hepatitis A virus, were the fifth and sixth most frequent causes, respectively, although the former was the single most frequent cause of FBD in 1982 and the second most frequent cause of water-borne diseases during the period from 1986 to 1988. Despite the scarcity of information on the problem, rotavirus, poliovirus, hepatitis E virus, astrovirus, and small gastroenteric viruses are also important causes of FBD. We also discuss the importance of viral zoonoses, especially hemorrhagic fevers transmitted by contact with rodent feces and tick-borne viral encephalitides (Lassa fever). There is discussion of the controversial mad cow disease and its potential transmission through food products, as well as of dietary aspects of the management of AIDS and other viral infections. Finally, measures for the prevention and control of FBD are described.

Brazil↗

PubMed2003

Molecular diagnostics of viral hemorrhagic fevers.

This review addresses the diagnostics of viral hemorrhagic fevers (VHFs). In the first part, an overview is given on classical methods of VHF diagnostics as well as novel molecular diagnostic tools. Currently available polymerase chain reaction (PCR) assays for diagnosis of VHF are summarized and discussed. In the second part, VHF diagnostics are described in particular for Lassa fever, yellow fever, and Crimean-Congo hemorrhagic fever, based on cases that were imported into or occurred within Europe. The third part is focussed on important differential diagnoses of VHF.

Adult↗

PubMed2006

A clinical guide to viral haemorrhagic fevers: Ebola, Marburg and Lassa.

The viral haemorrhagic fevers are a group of diseases that share many clinical features. Ebola, Marburg and Lassa are diseases that cause a relatively small number of deaths globally, but pose special risks to medical staff due to the ease of transmission, and can have a profound impact to the communities they affect. This article gives a brief overview of diseases caused by the Ebola, Marburg and Lassa viruses. It gives some practical advice to the clinician on the diagnosis and management of these diseases.

Animals↗

PubMedDate not supplied

Replication of hemorrhagic fever viruses in monocytic cells.

Monocytes play a central role in protection against many viruses. In some infections they are target cells for viral replication. There is increasing evidence that these cells may also be important in regulation of hemostasis. The part played by monocytic cells in the pathogenesis of hemorrhage in the viral hemorrhagic fevers is presently uncertain. Monocytes and monocytic cell lines have been used to investigate the ability of viruses to infect these cells in vitro. Several factors may affect the ability of a particular virus to infect monocytic cells, including specific antiserum to virus and the degree of cellular maturation. The effect of cellular maturation on the replication of Rift Valley fever virus in the U937 cell line is discussed in light of studies on the infectivity of other viruses for monocytic cells. Data supporting the ability of specific antibody to enhance the infectivity of Pichinde virus and Lassa fever virus for U937 cells are presented.

Antibodies, Viral↗

PubMed2004

Bichat guidelines for the clinical management of haemorrhagic fever viruses and bioterrorism-related haemorrhagic fever viruses.

Haemorrhagic fever viruses (HFVs) are a diverse group of viruses that cause a clinical disease associated with fever and bleeding disorder. HFVs that are associated with a potential biological threat are Ebola and Marburg viruses (Filoviridae), Lassa fever and New World arenaviruses (Machupo, Junin, Guanarito and Sabia viruses) (Arenaviridae), Rift Valley fever (Bunyaviridae) and yellow fever, Omsk haemorrhagic fever, and Kyanasur Forest disease (Flaviviridae). In terms of biological warfare concerning dengue, Crimean-Congo haemorrhagic fever and Hantaviruses, there is not sufficient knowledge to include them as a major biological threat. Dengue virus is the only one of these that cannot be transmitted via aerosol. Crimean-Congo haemorrhagic fever and the agents of haemorrhagic fever with renal syndrome appear difficult to weaponise. Ribavirin is recommended for the treatment and the prophylaxis of the arenaviruses and the bunyaviruses, but is not effective for the other families. All patients must be isolated and receive intensive supportive therapy.

Bioterrorism↗

PubMed1975

Lassa virus hepatitis. Observations on a fatal case from the 1972 Sierra Leone epidemic.

During a recent outbreak of Lassa fever in Sierre Leone, a 20-year-old woman developed an acute febrile disease with tonsillar exudates and hemorrhagic manifestations. Lassa virus was isolated in cell cultures from pharyngeal secretions and pleural fluid and was identified by complement fixation. Typical arenavirus particles were observed in these infected cell cultures. In a liver biopsy specimen, diffuse hepatocellular damage and focal necroses were evident, with a spectrum of liver cell change, ranging from slight vacuolizaiton to frank lysis. Virus was frequently observed in nearby extracellular spaces and was clearly associated with hepatocytes rather than sinusoidal cells. The demonstration for the first time of Lassa virus particules in human tissue provides direct evidence that the virus is responsible for the observed pathologic changes.

Disease Outbreaks↗

PubMed1994

[Virus diseases in patients returning from the tropics].

The high density of populations and insufficient sanitary conditions increases the risk to acquire viral diseases in tropical areas. This holds true for ubiquitous as well as for regional viral infections. Hepatitis and AIDS are found worldwide, but play a dominant role in tropical areas. Classical tropical viral infections are zoonoses. They are primarily infections of nonhuman vertebrates (e.g. rodents) and of arthropod vectors and can be transmitted to man. According to the clinical outcome these viral infections can be divided into three groups: influenza-like disease with arthralgia, encephalitis and hemorrhagic fevers. The majority of infections belong to the first group, followed by encephalitis cases. Viral hemorrhagic fevers are rare in visitors of tropical areas. Antibody detection is the method of choice in the diagnosis of tropical viral infections. In special situations (e.g. Lassa fever) the direct detection of the virus by PCR can be helpful. Tests for the detection of arboviruses, filoviruses and arenaviruses are only performed at a few centers worldwide.

Animals↗

PubMedDate not supplied

Pirital virus (Arenaviridae) infection in the syrian golden hamster, Mesocricetus auratus: a new animal model for arenaviral hemorrhagic fever.

Adult Syrian golden hamsters inoculated intraperitoneally with Pirital virus, a recently discovered member of the Tacaribe complex of New World arenaviruses, developed a progressively severe, fatal illness with many of the pathologic features observed in fatal human cases of Lassa fever and other arenaviral hemorrhagic fevers. Most of the animals became moribund by Day 5 and were dead by Day 7 after inoculation. The most consistent histopathologic changes included interstitial pneumonitis, splenic lymphoid depletion and necrosis, and multifocal hepatic necrosis without significant inflammatory cell infiltration. The liver changes ranged from single cell death by apoptosis to coagulative necrosis of clusters of hepatocytes. Immunohistochemical studies of the liver demonstrated the presence and accumulation ot Pirital virus antigen within hepatocytes as well as Kupffer cells. An in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay showed progressively increasing apoptotic activity in the liver of infected hamsters. A human hepatoblastoma cell line (Hep G2/C3A) inoculated with Pirital virus also developed progressive cell destruction and accumulation of viral antigen, as demonstrated by immunofluorescence. Results of this pilot study suggest that the Pirital virus-hamster model is a very promising new small animal model for studying the pathogenesis of arenavirus infections, particularly, the mechanism of direct virus-induced hepatic injury. It may also be useful for testingantiviral agents for treatment of arenaviral hemorrhagic fevers.

Animals↗

PubMedDate not supplied

Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug.

Ribavirin, a broad-spectrum antiviral drug, is active against hemorrhagic fever viruses (with the exception of Ebola virus) in cell culture systems. In model infections with arenaviruses in guinea pigs and monkeys, ribavirin has demonstrated both prophylactic and therapeutic efficacy. In therapeutic studies it has not prevented late-onset neurologic disease. In human cases of Lassa fever, it significantly reduces mortality when administered before day 7 of illness to persons at high risk. In rodents and monkeys infected with Rift Valley fever virus, ribavirin therapy resulted in reduced mortality; prophylactic administration to volunteers infected with sandfly fever virus, Sicilian strain, prevented development of illness. Ribavirin increased the number of survivors and the mean time to death in suckling mice infected with Crimean-Congo hemorrhagic fever virus and in suckling mice infected with Hantaan virus. In the People's Republic of China, ribavirin significantly reduced mortality in patients with hemorrhagic fever with renal syndrome. Ribavirin has not been effective in animal models of filoviral and flaviviral infections. The only important adverse effect of ribavirin in humans is manageable, reversible anemia.

Anemia↗

PubMedDate not supplied

[The cultivation and physicochemical properties of the Josiah strain of the Lassa virus].

Data on the stability of Lassa virus, Josia strain, isolated from man to the effect of physicochemical factors (heating at 50 degrees C, solutions of urea and formalin of various concentrations, UV irradiation) as well as on the time course of this strain reproduction in cell lines of different origins are presented. Recommendations for lowering of reactogenicity of the virus-containing material are given. The experimental results must be taken into consideration in the development and manufacture of diagnostic and therapeutic-prophylactic preparations for Lassa fever.

Animals↗

PubMed1980

Monoclonal antibodies to lymphocytic choriomeningitis virus react with pathogenic arenaviruses.

Certain arenaviruses have become widely recognized as important human pathogens, the most notable among these being Lassa virus, the causative agent of Lassa fever. Two other members of the group, Junin and Machupo virus, are the aetiological agents of Argentine and Bolivian haemorrhagic fevers, respectively. All these agents share both morphological features and to varying degrees serological cross-reactivity with other non-pathogenic arenaviruses. Despite the evident clinical importance of these viruses, work to define their physiochemical structure and to develop rapid and precise diagnostic techniques has been slow. Consequently, the definitive relationships among West African Lassa strains, strains of a related agent from Mozambique and of an Old World arenavirus, lymphocytic choriomeningitis (LCM), have not been established. This problem is of more than simple taxonomic importance in view of the fact that a Mozambique virus strain produced subclinical infection in experimental monkeys which were then resistant to challenge with monkey and human virulent Lassa virus from Sierra Leone. We have explored the use of monoclonal hybridoma antibodies generated against relatively less hazardous arenaviruses to define antigens cross-reactive with the important human pathogens of the group. Here we describe the use of monoclonal antibodies directed against LCM, virus to define antigenic specificities shared among LCM, Lassa and Mozambique viruses.

Antibodies, Viral↗

PubMed1987

Occupational hazards in hospitals: risk of infection.

In this review of the risk of infection to hospital staff, attention is drawn to the continuing risk presented by hepatitis B and pulmonary tuberculosis, which are more common than diseases such as typhoid fever, brucellosis, histoplasmosis, whooping cough, infectious gastroenteritis, measles, and parotiditis. Other items considered include the susceptibility of female hospital staff to rubella and the importance of their undergoing screening and vaccination; the risks currently presented by epidemic keratoconjunctivitis and by herpes viruses (herpes simplex, varicella zoster, and cytomegalovirus); and the risk of contracting the new infectious diseases (Legionnaires' disease, Marburg disease, Lassa fever, and the acquired immune deficiency syndrome).

Allied Health Personnel↗

PubMedDate not supplied

A survey for antibodies to Lassa virus among health workers in Nigeria.

A study was conducted among 552 health workers at 6 health facilities in Nigeria. Lassa virus immunoglobulin (Ig) G antibody was detected in 12.3%, using an enzyme-linked immunosorbent assay. Antibody prevalence in the 6 health centres ranged from 1.2% to 27.3%. Prevalences were higher in primary and secondary health facilities than in tertiary centres. Seroprevalences ranged from 1.7% to 23.7% among different occupational groups of health workers; the highest observed antibody prevalence was among ward aids. Lassa virus IgM antibody, indicating recent infection, was present in 6 of the health workers, 5 of whom were ward aids and one was a nurse. All of the health workers with specific IgM came from a single facility in Lafia, sampled during an outbreak of Lassa fever.

Antibodies, Viral↗

PubMed1975

Antigenic properties of the arenaviruses.

Arenaviruses are known to show antigenic relationships in the complement-fixation (CF) and fluorescent antibody tests but not in the neutralization test. The humoral response to some of the arenaviruses is characterized by a dissociation between the antibodies determined by the CF test and those determined by the neutralization test and also by its late appearance following natural infection. Investigations are reported showing that, as regards the CF test, Junin, Machupo, Amapari, and Tacaribe viruses are closely related, while LCM and Lassa viruses are distantly related to each other and to the remaining viruses in the group. Studies by agar gel diffusion and precipitation have shown complete specificity except among viruses that are very closely related in the CF test. Observations with sera from persons infected with Lassa fever virus show that CF antibodies rarely appear before the 18th day after onset; they can persist, with diminishing titres, for up to 6 years.

Animals↗

PubMed1991

Simultaneous expression of the Lassa virus N and GPC genes from a single recombinant vaccinia virus.

A new transfer vector was constructed that directs the insertion of two heterologous genes into the vaccinia virus thymidine kinase (TK) gene during a single recombination event. This vector, pDAVAC2, contains bidirectional vaccinia P7.5 early/late promoter elements and two unique cloning sites. cDNA clones containing the complete coding sequences for the Lassa virus (Josiah strain) nucleoprotein (N) and glycoprotein (GPC) genes were inserted into the vaccinia TK gene using this transfer vector. The recombinant virus, V-LSGN-II, expressed proteins in cell culture that appeared to be authentic with respect to electrophoretic mobility, glycosylation, and post-translational cleavage. Indirect immunofluorescence (IFA) of recombinant virus-infected cells demonstrated both the bright granular and diffuse patterns of staining characteristic of the Lassa nucleoprotein and glycoprotein, respectively. Electron-dense inclusion bodies typical of arenavirus-infected cells were observed by electron microscopy in V-LSN and V-LSGN-II-infected cells, but not in V-LSGPC-infected cells. Mice inoculated with V-LSGN-II by intraperitoneal injection developed serum antibodies that reacted with authentic Lassa proteins in immunofluorescence and radioimmune precipitation assays. This recombinant virus represents an additional candidate for a Lassa fever vaccine and demonstrates the feasibility of expressing any two genes of interest in a single recombinant vaccinia virus through the use of the transfer vector pDAVAC2.

Animals↗