The anti-influenza virus drug rimantadine has trypanocidal activity.
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We report here that bloodstream forms of the African trypanosome, Trypanosoma brucei, are sensitive to the anti-influenza virus drug rimantadine (50% inhibitory concentration of 1.26 micrograms ml-1 at pH 7.4). The activity is pH dependent and is consistent with a mechanism involving inhibition of the ability to regulate internal pH. Rimantadine is also toxic to the trypanosomatid parasites Trypanosoma cruzi and Leishmania major. (+info)
Evidence for cytokine mediation of disease expression in adults experimentally infected with influenza A virus.
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The roles of interleukin (IL)-6 and IL-8 in mediating the symptoms and signs of influenza A infection were examined. Adults were intranasally inoculated with a rimantadine-sensitive strain of influenza A HlNl virus and treated with rimantadine or placebo. Viral shedding, secretion weights, symptom scores, and concentrations of IL-6 and IL-8 in nasal lavage fluids were compared between treatment groups. Viral shedding was associated with increases in local and systemic symptoms, in expelled secretion weights, and in levels of IL-6 and IL-8. Compared with placebo, rimantadine treatment reduced viral shedding, systemic symptoms, and levels of IL-8. Days of viral shedding and IL-6 but not IL-8 concentrations were significantly correlated with the other measures of symptoms and signs. These data support a causal relationship between viral replication, cytokine production, and symptom expression, and they suggest that IL-6 may have a role in mediating symptom and sign expression during influenza A infection. (+info)
Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP).
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This report updates 1998 recommendations by the Advisory Committee on Immunization Practices (ACIP) on the use of influenza vaccine and antiviral agents (MMWR 1998;47[No. RR-6]:1-26). The principal changes include a) information on the influenza virus strains included in the 1999-2000 trivalent vaccine; b) discussion of the potential expanded use of influenza vaccine; c) new background information on live-attenuated influenza vaccines (LAIVs), neuraminidase-inhibitor drugs, and rapid diagnostic tests; d) new information on the epidemiology of influenza among travelers; and e) the addition of referenced citations. This report and other information on influenza can be accessed at the website for the Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC at . (+info)
Low incidence of rimantadine resistance in field isolates of influenza A viruses.
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The spread of drug-resistant influenza viruses type A to close contacts in families, schools, and nursing homes has been well documented. To investigate whether drug-resistant influenza viruses circulate in the general population, 2017 isolates collected in 43 countries and territories during a 4-year period were tested for drug susceptibility in a bioassay. Drug resistance was confirmed by detection of specific mutations on the M2 gene that have been shown to confer resistance to amantadine or rimantadine. Sixteen viruses (0.8%) were found to be drug-resistant. Only 2 of these resistant viruses were isolated from individuals who received amantadine or rimantadine treatment at the time the specimens were collected. For 12 individuals use of amantadine or rimantadine could be excluded, and from the remaining 2 patients information about medication was unavailable. These results indicate that the circulation of drug-resistant influenza viruses is a rare event, but surveillance for drug resistance should be continued. (+info)
Amantadine and rimantadine have no direct inhibitory effects against hepatitis C viral protease, helicase, ATPase, polymerase, and internal ribosomal entry site-mediated translation.
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Amantadine, a drug known to inhibit influenza A viral matrix (M2) protein function, was reported to be an effective treatment in some patients with chronic hepatitis C virus (HCV) infection. Sequence comparison shows no homology between M2 and any of the HCV proteins. The effects of amantadine and a related analogue, rimantadine, on viral protease, helicase, ATPase, RNA-dependent RNA polymerase, and HCV internal ribosomal entry site (IRES) translation were tested by established in vitro biochemical assays. No inhibition (>15%) of HCV protease, helicase, ATPase, and polymerase was observed with concentrations up to 400 microgram/mL. IRES-specific inhibition was not observed at clinically relevant concentrations, but both cap and IRES reporter genes were suppressed at higher levels, suggesting nonspecific translation inhibition. In conclusion, amantadine and rimantadine have no direct and specific inhibitory effects against HCV protease, helicase, ATPase, polymerase, and IRES in vitro. (+info)
Updated treatment for influenza A and B.
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Influenza causes significant morbidity and mortality and is responsible for considerable medical expenditures. Vaccination is the most effective public health measure to combat this illness. Amantadine and rimantadine are older antiviral agents that have been important adjuncts in the prevention and treatment of influenza A outbreaks. Zanamivir and oseltamivir are newer agents indicated for the treatment of both influenza A and B. For antiviral agents to be effective, they must be used within 48 hours of the onset of influenza symptoms. Antiviral agents reduce the duration of fever and illness by one to two and one-half days and also reduce the severity of some symptoms. Use of amantadine or rimantadine is appropriate if influenza virus A is known to be the predominant agent in a particular year or location. Data need to be evaluated on the development of resistance and use of the newer antiviral agents in geriatric patients, high-risk patients and children. For optimal use of antiviral agents, patients with influenza symptoms must present early, and family physicians must accurately and rapidly diagnose the illness. (+info)
Definitive assignment of proton selectivity and attoampere unitary current to the M2 ion channel protein of influenza A virus.
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The viral ion channel protein M2 supports the transit of influenza virus and its glycoproteins through acidic compartments of the cell. M2 conducts endosomal protons into the virion to initiate uncoating and, by equilibrating the pH at trans-Golgi membranes, preserves the native conformation of acid-sensitive viral hemagglutinin. The exceptionally low conductance of the M2 channel thwarted resolution of single channels by electrophysiological techniques. Assays of liposome-reconstituted M2 yielded the average unitary channel current of the M2 tetramer--1.2 aA (1.2 x 10(-18) A) at neutral pH and 2.7 to 4.1 aA at pH 5.7--which activates the channel. Extrapolation to physiological temperature predicts 4.8 and 40 aA, respectively, and a unitary conductance of 0.03 versus 0.4 fS. This minute activity, below previous estimates, appears sufficient for virus reproduction, but low enough to avert abortive cytotoxicity. The unitary permeability of M2 was within the range reported for other proton channels. To address the ion selectivity of M2, we exploited the coupling of ionic influx and efflux in sealed liposomes. Metal ion fluxes were monitored by proton counterflow, employing a pH probe 1,000 times more sensitive than available Na+ or K+ probes. Even low-pH-activated M2 did not conduct Na+ and K+. The proton selectivity of M2 was estimated to be at least 3 x 10(6) (over sodium or potassium ions), in agreement with electrophysiological studies. The stringent proton selectivity of M2 suggests that the cytopathology of influenza virus does not involve direct perturbation of cellular sodium or potassium gradients. (+info)
Infection of a child in Hong Kong by an influenza A H3N2 virus closely related to viruses circulating in European pigs.
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Influenza virus A/Hong Kong/1774/99, isolated from a young child with mild influenza, was shown to be similar in its antigenic and genetic characteristics to H3N2 viruses circulating in pigs in Europe during the 1990s and in particular to be closely related to viruses isolated from two children in the Netherlands in 1993. Similar viruses had previously not been identified outside Europe. Although there is little evidence as to how the child contracted the infection, it appears likely that pigs in southern China were the source of infection. Characteristics shared with the European swine viruses include resistance to the anti-influenza drugs amantadine and rimantadine. Thus not only does this incident once again highlight the potential of pigs as a source of novel human influenza viruses, but also indicates the potential for emergence of amantadine-resistant human viruses. (+info)