Avian Influenza viruses, drug resistance

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INFLUENZA VIRUSES, DRUG RESISTANCE

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[1]

Fri 30 Sep 2005

Cat Bachman <catbachman

Source: Reuters UK, Fri 30 Sep 2005 [edited]

<http://today.reuters.co.uk/news/newsArticle.aspx?type=scienceNews & storyID=2005-\

09-30T114757Z_01_YUE042474_RTRIDST_0_SCIENCE-BIRDFLU-TAMIFLU-DC.XML>

 

 

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.

 

[byline: Tan Ee Lyn]

 

--

Cat Bachman

<catbachman

 

******

[2]

Fri 30 Sep 2005

ProMED-mail <promed

Source: The Lancet 2005; 366:1175-1181, Fri 30 Sep 2005 [edited]

<http://www.thelancet.com/journals/lancet/article/PIIS0140673605673382

/abstract>

 

 

Cause for Concern: Incidence of Adamantane Resistance among Influenza A

(H3N2) Viruses Isolated Worldwide from 1994 to 2005

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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).

 

--

ProMED-mail

<promed

 

[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]

 

[see also:

Avian influenza, human - East Asia (120): Viet Nam 20050901.2589

Avian influenza, poultry - China: antiviral treatment 20050621.1740

2004

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Avian influenza - Eastern Asia (93): WHO statement 20040716.1935

Avian influenza A (H5N1) virus, human vaccine prospects 20040125.0300

Avian influenza A (H5N1) virus, drug resistance 20040125.0298

2001

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Influenza virus, neuraminidase inhibitor resistance (02) 20010928.2372

Influenza virus, neuraminidase inhibitor resistance 20010926.2350]

................................cp/pg/dk

 

 

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