Prolonged excretion of amantadine-resistant influenza a virus quasi species after cessation of antiviral therapy in an immunocompromised patient.
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Phenotypic and molecular studies were conducted to characterize multiple influenza A isolates recovered from an immunocompromised patient who died of viral and fungal pneumonitis. The recovery of amantadine-resistant isolates was correlated with the detection of 2 drug-resistant M2 variants (codons 27 and 31) in combination with a wild-type virus. The mutant viruses persisted within the viral population in variable proportions >1 month after cessation of antiviral therapy. These results confirm animal studies reported elsewhere regarding the genetic stability of influenza M2 mutants and their potential for transmission in humans. (+info)
Conditional ablation of T-cell development by a novel viral ion channel transgene.
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A novel conditional-lethal transgene system is defined in which a mutated influenza A virus ion-channel protein, which is permeable to monovalent cations, is lethal to cells on heterotypic expression and whose activity can be blocked by an antiviral drug (amantadine), is used to reversibly disrupt T-cell development. In vivo expression of the M2 ion channel, as a transgene under control of the T-cell specific p56(Lck) proximal promoter, resulted in total ablation of T-cell development with the accumulation of three distinct populations of early progenitor cells (CD44(+) CD25(-); CD44(+) CD25(+); CD44(+) CD25(hi)) in the thymic rudiment. In vitro development of transgenic fetal thymic progenitors to single-positive T cells could be rescued by antiviral drug treatment. Moreover, there was a radical reduction in B-cell lymphopoiesis, evident at the pre-B-cell stage, with a twofold increase of lymphoid cells 'in cycle' in transgenic bone marrow, indicative of major changes in haematopoietic homeostasis. This system may provide a generic protocol for conditional, lineage-specific cell ablation with available tissue-specific promoters for any eukaryotic developmental system, and provide a window on early T-cell development. (+info)
Neuroleptic malignant syndrome presenting as pulmonary edema and severe bronchorrhea.
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Neuroleptic malignant syndrome is a rare (incidence, 0.02%-3.2%) but dangerous complication following the use of neuroleptic drugs. When not promptly recognized, this disease carries a high mortality (10%-20%) and morbidity rate. We report an unusual case of neuroleptic malignant syndrome that presented predominantly with autonomic instability in the form of recurrent episodes of respiratory distress. The respiratory distress was initially caused by pulmonary edema and later was caused by severe bronchorrhea. We propose that aspiration pneumonia resulting in respiratory failure, the leading cause of death in neuroleptic malignant syndrome, may be a result of a combination of altered mental status and bronchorrhea. This has therapeutic implications because early institution of bromocriptine/dantrolene can prevent aspiration pneumonia and, hence, mortality from respiratory failure. (+info)
Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP).
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This report updates the 2001 recommendations by the Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine and antiviral agents (MMWR 2001;50 [No. RR-4]:1-44). The 2002 recommendations include new or updated information regarding 1) the timing of influenza vaccination by risk group; 2) influenza vaccine for children aged 6-23 months; 3) the 2002-2003 trivalent vaccine virus strains: A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like strains; and 4) availability of certain influenza vaccine doses with reduced thimerosal content. A link to this report and other information related to influenza can be accessed at the website for the Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC, at http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm. (+info)
Nosocomial transmission of influenza.
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Influenza is a common nosocomial infection. Serious outbreaks occur typically in elderly long-term patients, but have also been reported in renal, transplant and oncology units, neonatal intensive care and paediatrics. It is likely that staff-patient cross-infection is common. Prompt diagnosis of an outbreak lies at the heart of an effective influenza control programme. This requires effective virological surveillance. There are a variety of strategies that can help to prevent spread of influenza in health care settings. Basic infection control should include isolating infected residents, restricting circulation of nursing staff between patients, and restriction of visitors. Annual influenza immunization should be offered to elderly patients, subjects with chronic disease, and those in long-term residential or nursing home care. Vaccination of health care workers has been shown to be effective in protecting elderly patients in long-term care. Use of oral amantadine or rimantadine is an additional possible strategy for prophylaxis or treatment during an outbreak. (+info)
The management of influenza in people of working age.
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Influenza is common, causing considerable morbidity and sickness absence from work in most winters. Influenza vaccines have been available for >40 years, but are not extensively used in the workforce (in the UK). Amantadine has been available for 25 years as a treatment and prophylactic against influenza A infection, but has scarcely been used. In the last 3 years, two neuraminidase inhibitor antivirals, zanamivir and oseltamivir, have been introduced to the market for the treatment and prophylaxis of influenza A and B infections. This review focuses on aspects of prevention and treatment of influenza appropriate to people of working age. Decisions based on the cost-effectiveness of prevention and treatment options differ when viewed from the perspective of the healthcare provider, the employer or the employee. Options currently available need to be directed to a wider range of people than those conventionally regarded as the target risk group. (+info)
Characterization of the 1918 "Spanish" influenza virus matrix gene segment.
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The coding region of influenza A virus RNA segment 7 from the 1918 pandemic virus, consisting of the open reading frames of the two matrix genes M1 and M2, has been sequenced. While this segment is highly conserved among influenza virus strains, the 1918 sequence does not match any previously sequenced influenza virus strains. The 1918 sequence matches the consensus over the M1 RNA-binding domains and nuclear localization signal and the highly conserved transmembrane domain of M2. Amino acid changes that correlate with high yield and pathogenicity in animal models were not found in the 1918 strain. Phylogenetic analyses suggest that both genes were mammalian adapted and that the 1918 sequence is very similar to the common ancestor of all subsequent human and classical swine matrix segments. The 1918 sequence matches other mammalian strains at 4 amino acids in the extracellular domain of M2 that differ consistently between avian and mammalian strains, suggesting that the matrix segment may have been circulating in human strains for at least several years before 1918. (+info)
Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus.
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The 1918 influenza pandemic caused more than 20 million deaths worldwide. Thus, the potential impact of a re-emergent 1918 or 1918-like influenza virus, whether through natural means or as a result of bioterrorism, is of significant concern. The genetic determinants of the virulence of the 1918 virus have not been defined yet, nor have specific clinical prophylaxis and/or treatment interventions that would be effective against a re-emergent 1918 or 1918-like virus been identified. Based on the reported nucleotide sequences, we have reconstructed the hemagglutinin (HA), neuraminidase (NA), and matrix (M) genes of the 1918 virus. Under biosafety level 3 (agricultural) conditions, we have generated recombinant influenza viruses bearing the 1918 HA, NA, or M segments. Strikingly, recombinant viruses possessing both the 1918 HA and 1918 NA were virulent in mice. In contrast, a control virus with the HA and NA from a more recent human isolate was unable to kill mice at any dose tested. The recombinant viruses were also tested for their sensitivity to U.S. Food and Drug Administration-approved antiinfluenza virus drugs in vitro and in vivo. Recombinant viruses possessing the 1918 NA or both the 1918 HA and 1918 NA were inhibited effectively in both tissue culture and mice by the NA inhibitors, zanamivir and oseltamivir. A recombinant virus possessing the 1918 M segment was inhibited effectively both in tissue culture and in vivo by the M2 ion-channel inhibitors amantadine and rimantadine. These data suggest that current antiviral strategies would be effective in curbing the dangers of a re-emergent 1918 or 1918-like virus. (+info)