[Marburg, Ebole and Lassa virus infections].
Explore the source record for details and available documents.
Africa↗
SEARCH · Search PubMed
Results for “Lassa Fever”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The nasty viruses--Lassa, Marburg, and Ebola.
Explore the source record for details and available documents.
Africa↗
Evaluating the immunogenicity and protective efficacy of a DNA vaccine encoding Lassa virus nucleoprotein.
Several viruses in the Arenavirus genus of the family Arenaviridae cause severe, often fatal, hemorrhagic fever. One such virus, Lassa virus (LV), is a frequent cause of disease in Africa, and survivors often are left with substantial neurological impairment. The feasibility of protective immunization against LV infection, and the associated disease, has been demonstrated in animal models, using recombinant vaccinia viruses to deliver Lassa proteins. Circumstantial evidence implicates cellular immunity in this Lassa-induced protection, but this has not been confirmed. Here, we describe DNA vaccines that encode LV proteins. A single inoculation of a plasmid encoding full-length Lassa nucleoprotein (LNP) can induce CD8(+) T cell responses in mice and can protect against challenge with two arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PV). A DNA minigene vaccine encoding a 9 amino acid sequence from LNP also induces CD8(+) T cells and protects against arenavirus challenge, thus confirming prior speculation that protective cellular immunity is induced by LV proteins.
Amino Acid Sequence↗
Experimental study on the possibility of treatment of some hemorrhagic fevers.
After intracerebral challenge with 100 PFU of Lassa virus (strain Josiah), all infected mice (CBA/calac) died (control group). Production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) significantly increased in the blood of these mice during the infection. For neutralization of increasing concentrations of these cytokines recombinant IL-1RA was used intraperitonealy at a dose 100 microg kg(-1), everyday, within 5 days from the third day after the challenge. Injections of IL-1RA decreased the concentration of IL-1beta and TNF-alpha and resulted in survival of all infected mice (treatment group). Marburg fever (strain Popp) caused in guinea pigs by 5 LD(50) of virus lead to the significant increase of TNF-alpha in the animal's blood and caused a lethal outcome (control group). Treatment of infected guinea pigs by IL-1RA or anti-TNF serum decreased the concentration of TNF-alpha and resulted in survival of half of the animals (treatment group). For the treatment recombinant IL-1RA was used at a dose 100 microg kg(-1), intramuscularly, everyday, within 6 days from the third day after the challenge or anti-TNF serum, intramuscularly 0.5 ml (2000 U ml(-1); 1 U of the antiserum neutralises 0.03 ng of TNF-alpha), everyday, within 6 days from the third day after the challenge.
Animals↗
A comparison of indirect immunofluorescence and electron microscopy for the diagnosis of some haemorrhagic viruses in cell cultures.
Yellow fever, dengue (types 1, 2 and 4), Chikungunya, Rift Valley fever, Ebola, Marburg, and Lassa viruses were inoculated into susceptible cell cultures and daily investigated by indirect immunofluorescence (IFA) and electron microscopy (EM) with a view to achieve an early detection-identification of these agents. Compared to the other cell lines tested (Vero, BHK-21 and Aedes albopictus), CV-1 cells were found to be more sensitive. Viral antigens were detected by IFA from a few hours post inoculation (CHIK and RVF) to a maximum of 3 days (YF and EBO). For most of the viruses studied, the cytopathic effect (CPE) commenced 2-3 days after the detection of viral antigens. Virus particles were detected by EM only in the case of EBO, MBG and LAS, before any CPE was observed in cell cultures.
Animals↗
Human macrophages, but not dendritic cells, are activated and produce alpha/beta interferons in response to Mopeia virus infection.
Lassa virus (LV) and Mopeia virus (MV) are closely related members of the Arenavirus genus, sharing 75% amino acid sequence identity. However, LV causes hemorrhagic fever in humans and nonhuman primates, whereas MV cannot induce disease. We have previously shown that antigen-presenting cells (APC)-macrophages (MP) and dendritic cells (DC)-sustain high replication rates of LV but are not activated, suggesting that they play a role in the immunosuppression observed in severe cases of Lassa fever. Here, we infected human APC with MV and analyzed the cellular responses induced. MV infection was productive in MP and even more so in DC. Apoptosis was not induced in either cell type. Moreover, unlike DC, MP were early and strongly activated in response to MV, as shown by the increased surface expression of CD86, CD80, CD54, CD40, and HLA-abc and by the production of mRNA encoding alpha interferon (IFN-alpha), IFN-beta, tumor necrosis factor alpha and interleukin-6. In addition, MV-infected MP produced less of the virus than DC, which was related to the fact that these cells secreted IFN-alpha. Thus, the strong activation of MP is probably a major event in the control of MV infection and may be involved in the induction of an adaptive immune response in infected hosts. These results may explain the difference in pathogenicity between LV and MV.
Antigen-Presenting Cells↗
[Lassa, Marbourg and Ebola viruses: new features of African tropical pathology. II. Epidemiology. Public health problems (author's transl)].
Lassa, Marbourg and Ebola viruses are characterised by their endemo-epidemicity in tropical Africa, by their potential of inter-human transmission, by their gravity (30 to 50% mortality in cases admitted to hospital) and by the difficulty of their aetiological diagnosis. This results in a public health problem for countries in non-endemic regions receiving travellers coming from Africa. This problem is related to the risk of importation of cases, a risk which should not be exaggerated but nor should it be underestimated. Appropriate measures may be suggested in the light of assessment of the risk: organisation of specialised hospital facilities, laboratory and coordination service.
Africa↗
Taking down Goliaths: new vaccines may spell the end for Ebola, Marburg and Lassa virus infections.
Explore the source record for details and available documents.
Canada↗
Viral hemorrhagic fever antibodies in Nigerian populations.
Using the immunofluorescence test, a serosurvey for antibodies to five viral agents associated with hemorrhagic febrile infections was conducted with 1,677 human sera from different parts of Nigeria. Three hundred fifty-seven (21.3%) were positive for Lassa virus antibody, while antibodies to Rift Valley fever virus were detected in 42 (2.5%) of the sera. Testing for Rift Valley fever virus antibody was confirmed by plaque reduction neutralization test. Antibodies to Ebola and Marburg viruses were detected in 30 and 29 sera, respectively. Of the 357 Lassa virus antibody-positive sera, 297 (83.2%) were positive for Lassa only. In contrast, sera positive for Marburg were positive in combination with Lassa, Ebola, or Rift Valley fever viruses. Antibodies to Lassa and Rift Valley fever viruses were found in all locations in Nigeria, whereas Ebola and Marburg antibodies were found mainly in the northern savanna zones of Benue and Gongola, but not in the rain forest area of Ondo.
Adolescent↗
The model of response to viral haemorrhagic fevers of the National Institute for Infectious Diseases "Lazzaro Spallanzani".
Viral haemorrhagic fevers (VHF) are severe and life-threatening diseases caused by a range of viruses. However, only four agents of VHF are known to be readily capable of person-to-person spread: Lassa virus, Crimean/Congo haemorrhagic fever virus, Ebola and Marburg viruses. Diseases caused by these viruses are endemic only in few areas in the world, most notably Africa and some rural parts of the Middle East and Eastern Europe. Nonetheless, the increasing volume of international travel presents a greater likelihood for the importation of these infections or of suspected cases in non endemic countries. Four conditions can lead to the importation and to the subsequent recognition of VHF within Europe: 1) patients arriving as a result of a planned medical evacuation; 2) persons who became sick on route to their destination; 3) persons discovered ill when entering a country, for example during routine clinical examination at the airport; 4) persons becoming sick after their arrival. Public health implications and the risk of secondary spread of pathogens in the above reported circumstances are very different. Similarly, preparedness and response should vary. This paper summarizes the present knowledge on the four VHF capable of person-to-person spread, describes the high isolation area constructed at the Italian National Institute for Infectious Diseases Lazzaro Spallanzani in Rome to respond to the occurrence of VHF. A brief overview of procedures and equipment adopted is provided.
Disease Outbreaks↗
Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.
Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.
Antigen Presentation↗
Haemorrhagic fever virus activity in equatorial Africa: distribution and prevalence of filovirus reactive antibody in the Central African Republic.
Seroepidemiological surveys were conducted to determine the frequency and distribution of haemorrhagic fever virus (HFV) activity in the Central African Republic. Human serum specimens (4295) were collected from 5 ecologically distinct zones. Serological evidence of HFV activity was found in all the zones. The filovirus antibody prevalence (24.4%, 1051/4295) was greater than the combined prevalence for Lassa virus, Rift Valley fever virus and Crimean-Congo HFV antibody (1.1%, 45/4295; P < 0.01). Evidence of filovirus activity was found in all zones: 21.3% (914/4295) of the population were seropositive for Ebola virus antibody while only 3.2% (137/4295) were seroreactive with Marburg viral antigens. Age and sex were important host-related factors influencing filovirus activity, particularly in dry grassland and moist forest communities. These communities shared many factors, but differences, such as agricultural practices and ethnic backgrounds, may also affect the risk of infection. Filovirus infections appear to occur without apparent disease. Continued investigations are needed to evaluate the true pathogenicity of the African filoviruses and the likelihood that unidentified serologically cross-reacting and non-pathogenic members of the filovirus family are active in equatorial Africa.
Adolescent↗
Viral haemorrhagic fever antibodies in Zimbabwe schoolchildren.
Explore the source record for details and available documents.
Animals↗
Recent advances in vaccines against viral haemorrhagic fevers.
Development of vaccines against viral haemorrhagic fevers is a public health priority. Recent advances in our knowledge of pathogenesis and of the immune responses elicited by these viruses emphasize the crucial role of the immune system in the control of infection, but also its probable involvement in pathogenesis. Several vaccine candidates against viral haemorrhagic fevers have been evaluated in animals during the past year. Together, these data suggest that a vaccine approach against viral haemorrhagic fevers is feasible, should induce well-balanced immune responses with cellular and humoral components, and should avoid the potential deleterious effects that are associated with such immune responses.
Dengue Virus↗
Arenavirus chemotherapy--retrospect and prospect.
Two groups of compounds, identifiable by structural similarity, have been found to interfere with the in vitro replication of arenaviruses. All 4 members of the benzimidazole group contain dipolar fused benzene and 5-membered nitrogen-containing rings and share potential chelating ability through the different bidentate structures formed with their side-chains. The biological activity of one of these compounds, metisazone, has been shown to depend on the presence of divalent metals of the first transition series, Cu(++) being the most effective. Furthermore, whereas metisazone inactivates cell-free virus, two other members of the group, HBB and 1,2-bis(5-methoxy-1H-benzimidazol-2-yl)-1,2-ethanediol, act intracellularly. The site of action of the fourth member, SKF 30097, is not known. Using murine lymphocytic choriomeningitis infections as an in vivo model, the bisbenzimidazole derivative has been found to increase life-span without interfering with virus replication. Medication with SKF 30097 or metisazone and copper (2(+)) sulfate did not significantly or reproducibly change the expected day of death of the animals. The amantadine compounds of the second group have unusual symmetric structures with a 10-carbon cage. The parent compound acts intracellularly, while the site of action of an octachloro derivative is not known. Medication with the parent compound, but not the derivative, shortened the interval between LCM infection and death of the mouse. Tissue culture and animal screening of the many available derivatives in these two groups may uncover compounds more efficacious than those already examined.
Amantadine↗
[Serological study of the virus responsible for hemorrhagic fever in an urban population of Cameroon].
A sero-epidemiological study of Hemorrhagic Fever Viruses in a urban population of Cameroon. The authors report the results of a sero-epidemiological survey undertaken in a urban population of Cameroon and concerning Congo, Rift (RVF), Lassa, Ebola, Marburg and Yellow Fever Viruses. On 375 human sera tested, 1.06% show antibodies against RVF virus and 1.87% are positive for anti-Ebola antibodies thus yielding evidence that these two viruses are present in this area of Cameroon. 33.75% have antibodies against Yellow Fever Virus as determined with an Hemagglutination-inhibition test. This quite high percentage, in spite of the weak specificity of the method for this virus, could raise the problem of the opportunity of a vaccination campaign. No antibody to Marburg, Lassa or Congo viruses is detected.
Adolescent↗
Viral hemorrhagic fever--a vascular disease?
The syndrome of "viral hemorrhagic fever" in man caused by certain viruses, such as Ebola, Lassa, Dengue, and Crimean-Congo hemorrhagic fever viruses, is often associated with a shock syndrome of undetermined pathogenesis. However, the vascular system, particularly the vascular endothelium, seems to be directly and indirectly targeted by all these viruses. Here we briefly summarize the current knowledge on Marburg and Ebola virus infections, the prototype viral hemorrhagic fever agents, and formulate a working hypothesis for the pathogenesis of viral hemorrhagic fever. Infections with filoviruses show lethality up to 89% and in severe cases lead to a shock syndrome associated with hypotension, coagulation disorders and an imbalance of fluid distribution between the intravascular and extravascular tissue space. The primary target cells for filoviruses are mononuclear phagocytotic cells which are activated upon infection and release certain cytokines and chemokines. These mediators indirectly target the endothelium and are thought to play a key role in the pathogenesis of filoviral hemorrhagic fever. In addition, direct infection and subsequent destruction of endothelial cells might contribute to the pathogenesis. Filoviruses, particularly Ebola virus, encode nonstructural glycoproteins which are released from infected host cells. Their function as potential determinants in pathogenicity remains to be investigated.
Endothelium, Vascular↗
Epidemiology of hemorrhagic fever viruses.
Twelve distinct viruses associated with hemorrhagic fever in humans are classified among four families: Arenaviridae, which includes Lassa, Junin, and Machupo viruses; Bunyaviridae, which includes Rift Valley fever, Crimean-Congo hemorrhagic fever, and Hantaan viruses; Filoviridae, which includes Marburg and Ebola viruses; and Flaviviridae, which includes yellow fever, dengue, Kyasanur Forest disease, and Omsk viruses. Most hemorrhagic fever viruses are zoonoses, with the possible exception of the four dengue viruses, which may continually circulate among humans. Hemorrhagic fever viruses are found in both temperate and tropical habitats and generally infect both sexes and all ages, although the age and sex of those infected are frequently influenced by the possibility of occupational exposure. Transmission to humans is frequently by bite of an infected tick or mosquito or via aerosol from infected rodent hosts. Aerosol and nosocomial transmission are especially important with Lassa, Junin, Machupo, Crimean-Congo hemorrhagic fever, Marburg, and Ebola viruses. Seasonality of hemorrhagic fever among humans is influenced for the most part by the dynamics of infected arthropod or vertebrate hosts. Mammals, especially rodents, appear to be important natural hosts for many hemorrhagic fever viruses. The transmission cycle for each hemorrhagic fever virus is distinct and is dependent upon the characteristics of the primary vector species and the possibility for its contact with humans.
Animals↗