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New Strain Of H5N1 Resistant
To Tamiflu Anti-Virals
From Patricia Doyle, PhD
dr_p_doyle@hotmail.com
10-1-5
 
"A strain [isolate?] of the H5N1 avian influenza virus that may unleash the next global flu pandemic is showing resistance to Tamiflu,"
 
The above statement says it all. Tamiflu is not the panecea cure-all that we are being led to believe.
 
Patricia Doyle
 
Experts Warn Of Growing Resistance To Tamiflu
By Tan Ee Lyn
10-1-5
 
HONG KONG (Reuters) -- A strain [isolate?] of the H5N1 avian influenza virus that may unleash the next global flu pandemic is showing resistance to Tamiflu, the antiviral drug that countries around the world are now stockpiling to fend off the looming threat. Experts in Hong Kong said on Friday [30 Sep 2005] that the human H5N1 strain [isolate?] which surfaced in northern Viet Nam this year had proved to be resistant to Tamiflu, a powerful antiviral drug.
 
They urged drug manufacturers to make more effective versions of Relenza, another antiviral that is also known to be effective in battling the much-feared H5N1. Relenza is inhaled [whereas Tamiflu is taken orally]. "There are now resistant H5N1 strains [isolates] appearing, and we can't totally rely on one drug (Tamiflu)," William Chui, honorary associate professor with the Department of Pharmacology at the Queen Mary Hospital in Hong Kong, told Reuters. Chui was referring to the Tamiflu-resistant strain of H5N1 [avian influenza] in Viet Nam. Chui also said general viral resistance to Tamiflu was growing in Japan, where doctors habitually prescribe the drug to fight common influenza.
 
Switzerland's Roche Holdings AG makes Tamiflu, known generically as oseltamivir, and GalaxoSmithKline makes Relenza, or zanamivir. "Manufacturers should think about producing an injectable form of Relenza because resistance to Tamiflu has been seen in Japan and Viet Nam. Also with injections, high doses can be given where necessary and onset time is a lot faster," Chui said.
 
Drugs that are administered intravenously can be better absorbed in patients who have stomach and acidity problems, another expert said. "We don't have to worry about absorption, injections take drugs right in. But if the patient takes them orally, maybe some amounts won't be absorbed or some may be destroyed by stomach acids," said pharmacist Raymond Mak at Queen Mary Hospital. Intravenous Relenza would also ensure faster onset, which would be critical in patients who are seriously ill. "Orally taken drugs take 3-4 hours to reach maximum blood concentration and 3-4 hours is very critical in severe cases. But injectable Relenza takes only 30 minutes to reach maximum blood concentration, this is a huge difference," Chui said. With an intravenous antiviral, doctors can also vary the doses.
 
While the H5N1 virus is now mostly passed directly from bird to human, health experts have warned that it is just a matter of time before it mutates into a form that is easily transmissible between people. When that happens, it may result in as many as 150 million human deaths.
 
2 reports in The Lancet this month said that resistance to anti-influenza drugs was growing worldwide. In places such as China, drug resistance exceeded 70 percent, suggesting that drugs like amantadine and rimantadine will probably no longer be effective for treatment or as a preventive in a pandemic outbreak of flu, the reports said.
 
Abstract - The Lancet 2005; 366:1175-1181, Fri 30 Sep 2005
 
Cause for Concern: Incidence of Adamantane Resistance among Influenza A (H3N2) Viruses Isolated Worldwide from 1994 to 2005
 
Adamantanes have been used to treat influenza A virus infections for many years. Studies have shown a low incidence of resistance to these drugs among circulating influenza viruses; however, their use is rising worldwide and drug resistance has been reported among influenza A (H5N1) viruses isolated from poultry and human beings in Asia. We sought to assess adamantane resistance among influenza A viruses isolated during the past decade from countries participating in WHO's global influenza surveillance network.
 
We analysed data for influenza field isolates that were obtained worldwide and submitted to the WHO Collaborating Center for Influenza at the US Centers for Disease Control and Prevention between 1 Oct 1994, and 31 Mar 2005. We used pyrosequencing, confirmatory sequence analysis, and phenotypic testing to detect drug resistance among circulating influenza A H3N2 (n=6524), H1N1 (n=589), and H1N2 (n=83) viruses.
 
More than 7000 influenza A field isolates were screened for specific amino acid substitutions in the M2 gene known to confer drug resistance. During the decade of surveillance, a significant increase in drug resistance was noted, from 0.4 percent in 1994-1995 to 12.3 percent in 2003-2004. This increase in the proportion of resistant viruses was weighted heavily by those obtained from Asia, with 61 percent of resistant viruses isolated since 2003 being from people in Asia.
 
Our data raise concerns about the appropriate use of adamantanes and draw attention to the importance of tracking the emergence and spread of drug-resistant influenza A viruses.
 
(Authors: Rick A Bright a, Marie-jo Medina a, Xiyan Xu a, Gilda Perez-Oronoz a, Teresa R Wallis a, Xiaohong M Davis a, Laura Povinelli b, Nancy J Cox a, and Alexander I Klimov a: the Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Influenza Branch, Atlanta, GA, USA b: Wisconsin State Laboratory of Hygiene, Madison, WI, USA).
 
http://www.thelancet.com/journals/
lancet/article/PIIS0140673605673382/abstract
 
ProMED-mail
promed@promedmail.org
 
Resistance to amantadine and rimantadine has been recorded previously, but the high frequency of resistant virus where these drugs have been used extensively over a considerable period suggests that their future usefulness will be limited. Resistance to the neuraminidase inhibitors oseltamivir and zanamivir has generally not been observed. The recent appearance of a Tamiflu-resistant avian H5N1 influenza virus in Viet Nam is an alarming development. - Mod.CP
 
Patricia A. Doyle, PhD
Please visit my "Emerging Diseases" message board.
 
Zhan le Devlesa tai sastimasa
Go with God and in Good Health
 

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