Study Finds Antivirals Effectively Curb Influenza Virus and Are Valuable in Managing Seasonal Flu in Households

Jan 16, 2007, 00:00 ET from Fred Hutchinson Cancer Research Center

    SEATTLE, Jan. 16 /PRNewswire/ -- Two antiviral drugs, oseltamivir and
 zanamivir, are highly effective when given as a preventive measure to
 reduce the spread of the influenza virus, according to an analysis of
 household-based studies by researchers at Fred Hutchinson Cancer Research
 Center, University of Michigan and University of Virginia, published in the
 current print edition of the American Journal of Epidemiology. The analysis
 also suggests that treatment with oseltamivir may reduce the infectiousness
 of influenza patients, although further studies are needed to provide a
 definitive conclusion.
     "Preventing the spread of influenza within families is an essential
 part of influenza management, regardless of the strain. This study shows
 that there is a clear benefit to be gained by giving antivirals to people
 who have been exposed to the virus to prevent the onset of symptomatic
 illness," said lead author M. Elizabeth (Betz) Halloran, M.D., D.Sc., a
 Hutchinson Center-based biostatistician.
     "While the efficacy of antivirals to protect against influenza is
 critical, the effect of these drugs on infectiousness also has important
 public-health consequences. Further studies to determine antiviral efficacy
 for reducing infectiousness would therefore be of great value," said
 Halloran, a member of the Hutchinson Center's Public Health Sciences
 Division and a professor of biostatistics at the University of Washington
 School of Public Health and Community Medicine.
     The report evaluated four household-based, randomized,
 placebo-controlled clinical trials, conducted from 2000 to 2004, which were
 designed to estimate the effect of post-exposure antiviral treatment on
 preventing influenza within households. Two of the trials were conducted
 with zanamivir and two with oseltamivir, permitting comparisons to be made
 between the two. The trials covered a total of 1,475 households. The
 majority of first household cases (53 percent to 70 percent) had influenza
 A (H3N2 or H1N1).
     The authors reviewed the effects of each antiviral on infectiousness
 and pathogenicity -- the ability of the influenza virus to cause overt
 disease. Pathogenicity in controls ranged from 44 percent to 66 percent.
 Efficacy in reducing pathogenicity for zanamivir was 52 percent and 56
 percent in the two zanamivir studies; for oseltamivir, it was 56 percent
 and 79 percent. The researchers found that both drugs were highly
 preventive against influenza illness, with oseltamivir at 81 percent
 efficacy and zanamivir at 75 percent. Thus, the preventive use of either
 product reduced by 75 percent to 81 percent the chance that an exposed
 person would become ill with influenza.
     The researchers' analysis found a significant reduction in
 infectiousness, as defined by reductions in influenza illnesses in
 household contacts, when oseltamivir was used for treatment of ill persons,
 but not when zanamivir was administered. Although these results are of
 interest, the authors stress that the numbers were small and combined
 estimates from two studies for each drug were used in both instances.
 Furthermore, oseltamivir treatment of ill persons did not appear to reduce
 the frequency of influenza infection in their contacts.
     In exploring the reasons for oseltamivir's greater effects on
 infectiousness, the authors speculated that the different modes of
 administration -- oral for oseltamivir and inhaled for zanamivir -- and
 resultant upper-respiratory viral levels could be the key, with zanamivir
 not reaching or affecting influenza virus in the nose. While both
 antivirals reduced cough, in earlier studies inhaled zanamivir did not
 significantly reduce nasal symptoms. In the paper the authors discussed the
 possibility that infectious droplets inhaled and exhaled from the nose may
 be important in viral transmission, thus orally administered oseltamivir
 might have an advantage in limiting spread.
     In addressing the limitations to their research, the authors call for
 further studies into antiviral efficacy. "Trials in non-household settings
 where influenza readily spreads -- such as schools, homes for the elderly
 and workplaces -- would be beneficial not only for planning management of
 seasonal influenza but also would be invaluable in pandemic planning.
 Additionally, simple solutions such as standardized randomization and study
 criteria would greatly facilitate trial comparison in the future. Such
 further studies will help us ensure we are better prepared not only for
 annual influenza seasons but also for the ultimate pandemic," said
 co-author Ira M. Longini, Jr., Ph.D., also a member of the Hutchinson
 Center's Public Health Sciences Division and a biostatistics professor at
 the University of Washington.
     This research was partially supported by a National Institute of
 Allergy and Infectious Disease grant and a National Institute of General
 Medical Sciences MIDAS grant. Roche and GlaxoSmithKline allowed access to
 the necessary data sets.
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     About influenza
     Influenza, commonly called the "flu," is a serious disease and annual
 outbreaks and epidemics are caused by influenza A and B viruses. Influenza
 is a highly contagious viral illness and is characterized by a sudden onset
 of debilitating clinical symptoms that affect the entire body. Up to 500
 million people are infected by influenza and up to 500,000 deaths are
 attributed to influenza each year. Influenza complications occur in all
 patient groups and include bronchitis, sinusitis, otitis media, and
     About oseltamivir and zanamivir
     Oseltamivir (brand name Tamiflu) and zanamivir (brand name Relenza) are
 neuraminidase inhibitors and are active against all clinically relevant
 influenza viruses. They work by blocking the action of the neuraminidase
 enzyme on the surface of the virus. When neuraminidase is inhibited, the
 virus is unable to spread to and infect other cells in the body.
 Oseltamivir is administered orally and is licensed for the treatment and
 prevention of influenza in adults and in children aged 1 year and above.
 Zanamivir is administered by oral inhalation. Zanamivir is registered in
 the United States for the treatment of influenza in adults and children
 aged 7 years or above, and for the prevention of influenza in adults and
 children aged 5 years or above.
     About the World Health Organization global influenza program:
     About the World Health Organization - avian flu:
     About the WHO Rapid Advice Guidelines on pharmacological management of
 humans infected with avian influenza A (H5N1) virus:
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     Kristen Woodward
     (206) 667-5095

SOURCE Fred Hutchinson Cancer Research Center