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http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/1781
Common Flu Drugs Meet Growing Resistance
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Rubeen K. Israni, M.D., Fellow, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine
September 21, 2005
Also covered by: MSN, MSNBC
MedPage Today Action Points
Be aware that in the event of a global influenza pandemic, the agents amantadine and rimantadine may be ineffective at preventing influenza A infections or ameliorating their severity.
Understand that influenza vaccines are modestly effective at protecting elderly patients in long-term care settings, but are less effective at protecting community-based elderly.
Review
ATLANTA, Sept. 21-About 12% of influenza A strains worldwide have developed resistance to the most commonly used antiflu drugs, including avian flu strains found in poultry and people in Asia.
"We were alarmed to find such a dramatic increase in drug resistance in circulating human influenza viruses in recent years," said Rick A. Bright, Ph.D., of the National Center for Infectious Diseases at the CDC here in a special online edition of The Lancet.
"Our report has broad implications for agencies and governments planning to stockpile these drugs for epidemic and pandemic strains of influenza," said Dr. Bright and colleagues at the CDC and the Wisconsin State Laboratory of Hygiene in Madison.
"With the increasing rates of resistance shown here, amantadine and rimantadine will probably no longer be effective for treatment or prophylaxis in the event of a pandemic outbreak of influenza."
To make matters worse, researchers from a collaborative vaccine evaluation group reported in the same online issue of Lancet said that flu vaccines appear to work pretty well at protecting the elderly in long-term care facilities, but come up short when it comes to preventing the spread of influenza in the community.
In susceptible influenza strains, adamantane drugs such as amantadine and rimantadine are about 80% to 90% effective at preventing infection, and can reduce the duration of the flu by about one to five days, if they are given within 48 hours of infection.
Their mechanism of action is blocking the M2 protein ion channel, which prevents fusion of the viral and host-cell membranes, and stops release of viral RNA into the cytoplasm, thereby inhibiting viral replication.
As with other antiviral drugs, the target virus can develop resistant mutations, particularly when the virus circulates among people living in close quarters such as nursing homes, hospital pediatric wards and households where antiviral therapy has been used, the authors noted.
Although surveillance for drug resistant influenza A strains has been carried out since 1991, more than a decade has passed since the last comprehensive global survey of influenza A resistance to adamantanes was published. At that time, the incidence of resistance among circulating viruses was about 1%.
In the intervening years, however, there have been reports of growing adamantane resistance, including H5N1 avian strains isolated from both humans and birds in southeast Asia, the authors noted.
The current study summarized surveillance for resistance to admantanes from Oct. 1994 through Mar. 2005.
The investigators analyzed data on influenza field isolates that were collected worldwide and submitted to the World Health Organization Collaboration Center for Influenza at the CDC.
They screened more than 7,000 isolates for specific amino acid substitutions in the M2 gene that are known to confer drug resistance. The isolates were primarily H3N2 viruses (n=6524), but also H1N1 (n=589) and H1N2 (n=83) strains.
They found that resistance to amantadine and rimantadine increased from 0.4% in 1994-1995 to 12.3% in 2003-2004 for H3N2 strains.
Of particular concern was the fact that 61% of resistant viruses isolated since 2003 were from people in Asia. In China, the incidence of drug-resistant strains in 2004 was 73.8%. In contrast, the incidence in Japan was 4.3%, and in the United States 1.9%.
"The trend of a rising incidence of resistant viruses isolated from Asian countries compared with the lower incidence in the Americas during the period studied might be a consequence of differences in the procurement of amantadine and rimantadine in these countries," Dr. Bright and colleagues wrote.
In the U.S., adamantanes are licensed as anti-influenza drugs that are prescribed for influenza or influenza-like illness only by licensed physicians.
However, in China, Russia, and some other countries, amantadine or rimantadine are available in over-the-counter formulations and are included in various cold remedies that do not need a prescription.
The authors warned that in the event of a global influenza pandemic -- an event which many infectious disease experts view as inevitable -- rimantadine and amantadine will probably not be effective for prevention or treatment of infection.
The authors also pointed out that a significant increase in resistance rates has occurred in the last two to three years. In China, the rates spiked in 2002-2003 which were followed by spikes in Taiwan, Hong Kong, and South Korea in 2003. The U.S. rates have increased from 1.9% in 2004 to 15% during the first six months of 2005.
The separate study suggesting that vaccines against influenza are modestly effective at protecting the elderly in long-term care settings, but less so for those in the community was by Professor Tom Jefferson and colleagues at Cochrane Vaccines Field, a collaborative evaluation group based in Alessandrina, Italy.
They performed meta-analyses of 64 comparative studies on the effectiveness of influenza vaccines in people 65-years old and up.
Looking at pooled data from 29 studies, they found that among elderly residents of long-term care facilities, inactivated influenza vaccines prevented up to 42% of influenza- and pneumonia-related deaths.
But when they looked at combined data from 15 other studies, they found that vaccines did not protect community-based elderly individuals against the development of influenza-like illnesses, influenza, or pneumonia, although they did prevent up to 30% of hospitalizations for pneumonia.
"We need a more comprehensive and perhaps more effective strategy in controlling acute respiratory infections, relying on several preventive interventions that take into account the multi-agent nature of infectious respiratory disease and its context (such as personal hygiene, provision of electricity and adequate food, water and sanitation)," Dr. Jefferson said in a statement.
Primary source: The Lancet
Source reference:
Bright RA et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Published online Sept. 22, 2005 DOI:10.1016/S0140-6736(05) 67338-2
Additional source: ,The Lancet
Source reference:
Jefferson T et al. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Published online Sept. 22, 2005 DOI:10.1016/S0140-6736(05) 67339-4
http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/1781
Common Flu Drugs Meet Growing Resistance
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Rubeen K. Israni, M.D., Fellow, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine
September 21, 2005
Also covered by: MSN, MSNBC
MedPage Today Action Points
Be aware that in the event of a global influenza pandemic, the agents amantadine and rimantadine may be ineffective at preventing influenza A infections or ameliorating their severity.
Understand that influenza vaccines are modestly effective at protecting elderly patients in long-term care settings, but are less effective at protecting community-based elderly.
Review
ATLANTA, Sept. 21-About 12% of influenza A strains worldwide have developed resistance to the most commonly used antiflu drugs, including avian flu strains found in poultry and people in Asia.
"We were alarmed to find such a dramatic increase in drug resistance in circulating human influenza viruses in recent years," said Rick A. Bright, Ph.D., of the National Center for Infectious Diseases at the CDC here in a special online edition of The Lancet.
"Our report has broad implications for agencies and governments planning to stockpile these drugs for epidemic and pandemic strains of influenza," said Dr. Bright and colleagues at the CDC and the Wisconsin State Laboratory of Hygiene in Madison.
"With the increasing rates of resistance shown here, amantadine and rimantadine will probably no longer be effective for treatment or prophylaxis in the event of a pandemic outbreak of influenza."
To make matters worse, researchers from a collaborative vaccine evaluation group reported in the same online issue of Lancet said that flu vaccines appear to work pretty well at protecting the elderly in long-term care facilities, but come up short when it comes to preventing the spread of influenza in the community.
In susceptible influenza strains, adamantane drugs such as amantadine and rimantadine are about 80% to 90% effective at preventing infection, and can reduce the duration of the flu by about one to five days, if they are given within 48 hours of infection.
Their mechanism of action is blocking the M2 protein ion channel, which prevents fusion of the viral and host-cell membranes, and stops release of viral RNA into the cytoplasm, thereby inhibiting viral replication.
As with other antiviral drugs, the target virus can develop resistant mutations, particularly when the virus circulates among people living in close quarters such as nursing homes, hospital pediatric wards and households where antiviral therapy has been used, the authors noted.
Although surveillance for drug resistant influenza A strains has been carried out since 1991, more than a decade has passed since the last comprehensive global survey of influenza A resistance to adamantanes was published. At that time, the incidence of resistance among circulating viruses was about 1%.
In the intervening years, however, there have been reports of growing adamantane resistance, including H5N1 avian strains isolated from both humans and birds in southeast Asia, the authors noted.
The current study summarized surveillance for resistance to admantanes from Oct. 1994 through Mar. 2005.
The investigators analyzed data on influenza field isolates that were collected worldwide and submitted to the World Health Organization Collaboration Center for Influenza at the CDC.
They screened more than 7,000 isolates for specific amino acid substitutions in the M2 gene that are known to confer drug resistance. The isolates were primarily H3N2 viruses (n=6524), but also H1N1 (n=589) and H1N2 (n=83) strains.
They found that resistance to amantadine and rimantadine increased from 0.4% in 1994-1995 to 12.3% in 2003-2004 for H3N2 strains.
Of particular concern was the fact that 61% of resistant viruses isolated since 2003 were from people in Asia. In China, the incidence of drug-resistant strains in 2004 was 73.8%. In contrast, the incidence in Japan was 4.3%, and in the United States 1.9%.
"The trend of a rising incidence of resistant viruses isolated from Asian countries compared with the lower incidence in the Americas during the period studied might be a consequence of differences in the procurement of amantadine and rimantadine in these countries," Dr. Bright and colleagues wrote.
In the U.S., adamantanes are licensed as anti-influenza drugs that are prescribed for influenza or influenza-like illness only by licensed physicians.
However, in China, Russia, and some other countries, amantadine or rimantadine are available in over-the-counter formulations and are included in various cold remedies that do not need a prescription.
The authors warned that in the event of a global influenza pandemic -- an event which many infectious disease experts view as inevitable -- rimantadine and amantadine will probably not be effective for prevention or treatment of infection.
The authors also pointed out that a significant increase in resistance rates has occurred in the last two to three years. In China, the rates spiked in 2002-2003 which were followed by spikes in Taiwan, Hong Kong, and South Korea in 2003. The U.S. rates have increased from 1.9% in 2004 to 15% during the first six months of 2005.
The separate study suggesting that vaccines against influenza are modestly effective at protecting the elderly in long-term care settings, but less so for those in the community was by Professor Tom Jefferson and colleagues at Cochrane Vaccines Field, a collaborative evaluation group based in Alessandrina, Italy.
They performed meta-analyses of 64 comparative studies on the effectiveness of influenza vaccines in people 65-years old and up.
Looking at pooled data from 29 studies, they found that among elderly residents of long-term care facilities, inactivated influenza vaccines prevented up to 42% of influenza- and pneumonia-related deaths.
But when they looked at combined data from 15 other studies, they found that vaccines did not protect community-based elderly individuals against the development of influenza-like illnesses, influenza, or pneumonia, although they did prevent up to 30% of hospitalizations for pneumonia.
"We need a more comprehensive and perhaps more effective strategy in controlling acute respiratory infections, relying on several preventive interventions that take into account the multi-agent nature of infectious respiratory disease and its context (such as personal hygiene, provision of electricity and adequate food, water and sanitation)," Dr. Jefferson said in a statement.
Primary source: The Lancet
Source reference:
Bright RA et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Published online Sept. 22, 2005 DOI:10.1016/S0140-6736(05) 67338-2
Additional source: ,The Lancet
Source reference:
Jefferson T et al. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Published online Sept. 22, 2005 DOI:10.1016/S0140-6736(05) 67339-4