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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Influenza A and B viruses belong to the Orthomyxoviridae family of viruses. These viruses are responsible for severe morbidity and significant excess mortality each year. Infection with influenza viruses usually leads to respiratory involvement and can result in pneumonia and secondary bacterial infections. Vaccine approaches to the prophylaxis of influenza virus infections have been problematic owing to the ability of these viruses to undergo antigenic shift by exchanging genomic segments or by undergoing antigenic drift, consisting of point mutations in the haemagglutinin (HA) and neuraminidase (NA) genes as a result of an error-prone viral polymerase. Historically, antiviral approaches for the therapy of both influenza A and B viruses have been largely unsuccessful until the elucidation of the X-ray crystallographic structure of the viral NA, which has permitted structure-based drug design of inhibitors of this enzyme. In addition, recent advances in the elucidation of the structure and complex function of influenza HA have resulted in the discovery of a number of diverse compounds that target this viral protein. This review article will focus largely on newer antiviral agents including those that inhibit the influenza virus NA and HA. Other novel approaches that have entered clinical trials or been considered for their clinical utility will be mentioned.
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PMID:Approaches and strategies for the treatment of influenza virus infections. 1048 Jul 36

Human parainfluenza viruses types 1, 2 and 3 (HPF 1, 2 and 3) are important pathogens in children. While these viruses share common structures and replication strategies, they target different parts of the respiratory tract; the most common outcomes of infection with HPF3 are bronchiolitis and pneumonia, while HPF 1 and 2 are associated with croup. While the HPF3 fusion protein (F) is critical for membrane fusion, our previous work revealed that the receptor binding hemagglutinin-neuraminidase (HN) is also essential to the fusion process; interaction between HN and its sialic acid-containing receptor on cell surfaces is required for HPF3 mediated cell fusion. Using our understanding of HPF3 HN's functions in the cell-binding and viral entry process, we are investigating the ways in which these processes differ in HPF 1 and 2, in part by manipulating receptor availability. Three experimental treatments were used to compare the HN-receptor interaction of HPF 1, 2 and 3: infection at high multiplicity of infection (m.o.i.); bacterial neuraminidase treatment of cells infected at low m.o.i.; and viral neuraminidase treatment of cells infected at low m.o.i. (using Newcastle disease virus [NDV] neuraminidase or UV irradiated HPF3 as sources of neuraminidase). In cells infected with HPF3, we have shown that infection with high m.o.i. blocks fusion, by removing sialic acid receptors for the viral HN. However, in cells infected with HPF 1 and 2, infection with high m.o.i. did not block fusion; the fusion increases with increasing m.o.i. In cells infected with HPF 1 and 2, neither bacterial nor NDV neuraminidase blocked cell fusion, using amounts of neuraminidase that completely block fusion of HPF3 infected cells. However, when inactivated HPF3 was used as a source of viral neuraminidase, the treatment inhibited fusion of cells infected with HPF 1 and 2 as well as 3. The differences found between these viruses in terms of their interaction with the cell, ability to modulate cell-cell fusion and response to exogenous neuraminidases of various specificities, may reflect salient differences in biological properties of the three viruses.
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PMID:Virus-receptor interactions of human parainfluenza viruses types 1, 2 and 3. 1054 58

The new neuraminidase inhibitors zanamivir and oseltamivir are important additions to the treatment of influenza, being the first class of agents active against both influenza A and influenza B. The decision to use these agents rather than amantadine or rimantadine, which are effective only against influenza A, should be based on the age of the patient, antiviral activity, side effect profile, ease of administration, drug interactions, and cost. All of these agents are effective only when started within 24 to 48 hours of onset of symptoms. To avoid inappropriate use of these agents, treatment should be continued only in patients with a confirmed diagnosis of influenza. Although effective in decreasing symptoms, none of these agents prevent pneumonia or hospitalization secondary to influenza.
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PMID:Antiviral agents for treating influenza. 1068 Feb 75

Influenza is an acute respiratory illness of global importance that causes considerable morbidity and mortality every year. At the beginning of the millennium, influenza will still be an emergent or re-emergent infection because of the viral ability to mutate. Global influenza surveillance indicates that influenza viruses may vary within a country and between countries and continents during an influenza season. Virologic surveillance is of critical importance in monitoring antigenic shift and drift. Disease surveillance is important in assessing the impact of the epidemics. Both types of information provide the basis of vaccine composition and the correct use of antivirals. Laboratory diagnosis is of critical importance for the global surveillance of influenza and may allow the timely use of antiviral drugs. Viral isolation remains the gold standard for laboratory diagnosis; however, several new rapid diagnostic tests are available or in development. The clinical spectrum of the disease varies from asymptomatic infection to the classic flu syndrome, and respiratory and nonrespiratory complications are observed particularly in high-risk groups. Current inactivated influenza vaccines have shown efficacy and effectiveness in preventing influenzalike illness, hospitalization for pneumonia, and death and in reducing health care costs. Because of the annual administration of the vaccine and the short period of time where it can be administered, strategies directed at improving vaccine coverage are of critical importance. In this sense, experiences obtained in different countries, such as with the National Immunization Campaigns developed in Argentina, provide one model of massive vaccine administration. In addition to current vaccines, new live attenuated vaccines will permit a most effective prevention of influenza in the community in the near future. A new type of antiviral, neuraminidase inhibitors, offers valuable benefits in the prevention and treatment of influenza A and B. A future pandemic of influenza seems inevitable. There is wide recognition that preparation for the next pandemic requires that infrastructure be in place during interpandemic periods for implementing preventive and therapeutic measures. The WHO has established a pandemic influenza task force, and a number of countries in Latin America have developed formal pandemic plans. These national and international efforts are essential to reduce the mortality and morbidity in the next influenza pandemic.
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PMID:Influenza. 1073 77

Antigenic variation is a strategy exploited by influenza viruses to promote survival in the face of the host adaptive immune response and constitutes a major obstacle to efficient vaccine development. Thus, variation in the surface glycoproteins hemagglutinin and neuraminidase is reflected by changes in susceptibility to antibody neutralization. This has led to the current view that antibody-mediated selection of influenza A viruses constitutes the basis for annual influenza epidemics and periodic pandemics. However, infection with this virus elicits a vigorous protective CD8(+) cytotoxic T lymphocyte (CTL) response, suggesting that CD8(+) CTLs might exert selection pressure on the virus. Studies with influenza A virus-infected transgenic mice bearing a T cell receptor (TCR) specific for viral nucleoprotein reveal that virus reemergence and persistence occurs weeks after the acute infection has apparently been controlled. The persisting virus is no longer recognized by CTLs, indicating that amino acid changes in the major viral nucleoprotein CTL epitope can be rapidly accumulated in vivo. These mutations lead to a total or partial loss of recognition by polyclonal CTLs by affecting presentation of viral peptide by class I major histocompatibility complex (MHC) molecules, or by interfering with TCR recognition of the mutant peptide-MHC complex. These data illustrate the distinct features of pulmonary immunity in selection of CTL escape variants. The likelihood of emergence and the biological impact of CTL escape variants on the clinical outcome of influenza pneumonia in an immunocompetent host, which is relevant for the design of preventive vaccines against this and other respiratory viral infections, are discussed.
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PMID:Viral escape by selection of cytotoxic T cell-resistant variants in influenza A virus pneumonia. 1083 2

The majority of influenza cases are not associated with complications. Secondary bacterial pneumonia, commonly caused by Streptococcus pneumoniae or Staphylococcus aureus, is well known to most clinicians. Primary influenza viral pneumonia, characterized by rapidly progressive hypoxia and respiratory insufficiency together with non-consolidating pulmonary infiltrates, has a high mortality rate. In 3 patients, a man aged 74 years, and two neonates aged 11 months and 4 weeks respectively, primary influenza A pneumonia was diagnosed. In the latter two patients the virus was cultivated from sputum. Despite intensive supporting and drug treatment, the first and the last patients died. In view of evolving therapeutic possibilities, notably regarding neuraminidase inhibitors, it is important that clinicians recognize this complication of influenza at an early stage.
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PMID:[Influenza A pneumonia]. 1104 55

Influenza is a highly contagious, acute illness which has afflicted humans and animals since ancient times. Influenza viruses are part of the Orthomyxoviridae family and are grouped into types A, B and C according to antigenic characteristics of the core proteins. Influenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals and birds, occasionally producing devastating pandemics in humans, such as in 1918, when over twenty million deaths occurred world-wide. The two surface glycoproteins of the virus, haemagglutinin (HA) and neuraminidase (NA), are the most important antigens for inducing protective immunity in the host and therefore show the greatest variation. For influenza A viruses, fifteen antigenically distinct HA subtypes and nine NA subtypes are recognised at present; a virus possesses one HA and one NA subtype, apparently in any combination. Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. In the 20th Century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, has occurred on four occasions, as follows, in 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each resulting in a pandemic. Frequent epidemics have occurred between the pandemics as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Currently, epidemics occur throughout the world in the human population due to infection with influenza A viruses of subtypes H1N1 and H3N2 or with influenza B virus. The impact of these epidemics is most effectively measured by monitoring excess mortality due to pneumonia and influenza. Phylogenetic studies suggest that aquatic birds could be the source of all influenza A viruses in other species. Human pandemic strains are thought to have emerged through one of the following three mechanisms: genetic reassortment (occurring as a result of the segmented genome of the virus) of avian and human influenza A viruses infecting the same host direct transfer of whole virus from another species the re-emergence of a virus which may have caused an epidemic many years earlier. Since 1996, the viruses H7N7, H5N1 and H9N2 have been transmitted from birds to humans but have apparently failed to spread in the human population. Such incidents are rare, but transmission between humans and other animals has also been demonstrated. This has led to the suggestion that the proposed reassortment of human and avian viruses occurs in an intermediate animal with subsequent transference to the human population. Pigs have been considered the leading contender for the role of intermediary because these animals may serve as hosts for productive infections of both avian and human viruses and, in addition, the evidence strongly suggests that pigs have been involved in interspecies transmission of influenza viruses, particularly the spread of H1N1 viruses to humans. Global surveillance of influenza is maintained by a network of laboratories sponsored by the World Health Organization. The main control measure for influenza in human populations is immunoprophylaxis, aimed at the epidemics occurring between pandemics.
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PMID:Recent zoonoses caused by influenza A viruses. 1118 16

Influenza is a serious disease for the elderly. Influenza causes high fever in the elderly, similar as in healthy adults. Cough lasts longer, but frequency and degree of sore throat and coryza is lower in the elderly. Rapid diagnosis kits based on enzyme-linked immunoassay contribute to quick diagnosis, improving treatment of the elderly. Amantadine can mitigate various symptoms and hastens recovery. Other newly developed neuraminidase inhibitors are also hopeful for treatment. The poor prognosis of influenza in the elderly is associated with a high frequency of pneumonia complications. Decreased serum albumin level is a risk factor for post-influenza pneumonia. To reduce excess influenza death in the elderly, prophylaxis and management of the general health condition of elderly patients may be most important.
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PMID:[Clinical features of influenza in the aged]. 1122 12

Influenza infection is a serious problem in institutions for the elderly and those with increased risk factors because of the high pneumonia complication rate and a significant increase in mortality. An outbreak of influenza is mainly caused by contact from the staff to residents, therefore the health care of the staffs and prevention of influenza should be a high priority in institutions such as nursing homes. To prevent influenza epidemics, institutionalised elderly and high risk groups should be vaccinated more actively. The rapid test for diagnosis of influenza viral infection permits the timely administration of antiviral agents and infection control among institutionalised elderly and high risk groups. Amantadine and neuraminidase inhibitors could be used for treatment and prophylaxis of influenza among institutionalised elderly and high risk group patients.
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PMID:[Prevention and care management of influenza infection in institutions for the elderly and high risk groups]. 1122 25

The overall goal for this review is to summarize the current body of knowledge about the structure and function of major known antigens of Streptococcus pneumoniae, a major gram-positive bacterial pathogen of humans. This information is then related to the role of these proteins in pneumococcal pathogenesis and in the development of new vaccines and/or other antimicrobial agents. S. pneumoniae is the most common cause of fatal community-acquired pneumonia in the elderly and is also one of the most common causes of middle ear infections and meningitis in children. The present vaccine for the pneumococcus consists of a mixture of 23 different capsular polysaccharides. While this vaccine is very effective in young adults, who are normally at low risk of serious disease, it is only about 60% effective in the elderly. In children younger than 2 years the vaccine is ineffective and is not recommended due to the inability of this age group to mount an antibody response to the pneumococcal polysaccharides. Antimicrobial drugs such as penicillin have diminished the risk from pneumococcal disease. Several pneumococcal proteins including pneumococcal surface proteins A and C, hyaluronate lyase, pneumolysin, autolysin, pneumococcal surface antigen A, choline binding protein A, and two neuraminidase enzymes are being investigated as potential vaccine or drug targets. Essentially all of these antigens have been or are being investigated on a structural level in addition to being characterized biochemically. Recently, three-dimensional structures for hyaluronate lyase and pneumococcal surface antigen A became available from X-ray crystallography determinations. Also, modeling studies based on biophysical measurements provided more information about the structures of pneumolysin and pneumococcal surface protein A. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines as an alternative to polysaccharide-based vaccines for the treatment of pneumococcal disease.
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PMID:Pneumococcal virulence factors: structure and function. 1138 Oct 99


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