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Archive Number 20090706.2428
Published Date 06-JUL-2009
Subject PRO/AH/EDR> Influenza A (H1N1) - worldwide (84): Tamiflu resistance, China (HK)

INFLUENZA A (H1N1) - WORLDWIDE (84): TAMIFLU RESISTANCE, CHINA (HONG  
KONG S.A.R.)
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A ProMED-mail post
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ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

Date: Sat 4 Jul 2009
Source: 660News, All News Radio, The Canadian Press [edited]
<http://www.660news.com/news/national/more.jsp?content=n034881128>


All cases of Tamiflu resistance are not created equal. So while the  
1st 3 instances of swine flu infection with Tamiflu-resistant viruses  
were reported in the past week, it was Number 3, not Number 1 that put  
influenza experts on edge. Public health authorities in Hong Kong  
announced Friday [3 Jul 2009] they have found a case of Tamiflu  
resistance in a woman who hadn't taken the drug. That means she was  
infected with swine flu viruses that were already resistant to  
Tamiflu, the main weapon in most countries' and companies' pandemic  
drug arsenals.

The 2 earlier cases, reported from Denmark and Japan, involved people  
who had been taking the medication. While always unwelcome, that type  
of resistance is known to occur with seasonal [influenza virus]  
strains and may be less of a threat to the long-term viability of this  
key flu drug. "It was not at all surprising to see resistance in  
patients on treatment, but seeing it in someone who was not treated,  
it certainly is more concerning," says Dr. Malik Peiris, a flu expert  
at the University of Hong Kong.

There is currently no evidence Tamiflu-resistant viruses are spreading  
widely. Still, some experts see the Hong Kong case as a warning that  
Tamiflu's role in this pandemic may not be as long-lived as pandemic  
planners would like. "I think it's too early to judge," says Dr.  
Frederick Hayden, an expert on influenza antivirals who teaches at the  
University of Virginia. "But I think that possibility has existed from  
the beginning, and it's something that needs to be certainly  
considered in making determinations about things like antiviral  
stockpiling, management of patients with more serious illness in  
hospital and how the available drugs will be used."

Some experts say this early sign of resistance should prompt a rethink  
of how often and in which circumstances Tamiflu is used to battle the  
novel H1N1 virus. "It ... probably highlights the importance of not  
using these antiviral drugs indiscriminately, given that the disease  
is relatively mild," says Peiris, whose hospital monitored the woman  
who was found to be carrying the resistant virus. "In people who don't  
have underlying risk factors, they probably should not be treated with  
Tamiflu, basically."

Others suggest countries should limit how often they use the drug to  
prevent infection, a regimen known as prophylaxis. In prophylaxis,  
people who've been exposed to the virus are given one pill a day for  
10 days, compared to the treatment regime of 2 pills a day for 5 days.  
Some countries, including Canada, have been reserving prophylaxis for  
people at high risk from this flu, such as pregnant women. But others  
have taken a different approach, using Tamiflu to try to curb spread  
of the virus. For instance, Britain has made the drug widely available  
to contacts of confirmed cases, though it announced this past week it  
was changing that policy.

The World Health Organization is drafting guidance for countries on  
the use of antivirals. While the WHO advises rather than instructs, it  
has been stressing that saving these drugs for treatment makes the  
most sense, says Dr. Keiji Fukuda, the agency's top flu expert. "In  
general we have been pushing the advice that using these drugs for  
treatment is definitely the priority use of them," says Fukuda, the  
acting assistant director general for health security and environment.  
"And I think this is not just from a theoretical resistance  
perspective but also from the fact that if you have limited amounts of  
antiviral drugs, then you need to make some choices about how you use  
them."

 From their 1st sighting, the new H1N1 viruses have been resistant to  
2 older flu drugs, amantadine and rimantadine. That left the only 2  
other influenza drugs, oseltamivir (Tamiflu) and zanamivir (Relenza),  
as the sole options for treatment and prophylaxis. There is a risk  
inherent in using the drug to prevent illness. If people who are  
already infected but aren't yet experiencing symptoms are put on  
prophylaxis, there won't be enough drug in their systems to kill all  
the viruses they house. Those that survive develop resistance to the  
drug. And that, it appears, may be what happened in the resistance  
cases in Denmark and Japan. In both instances the women involved had  
been given Tamiflu prophylaxis after a contact developed swine flu.

But the Hong Kong case was different. A 16-year-old girl travelling  
from San Francisco was stopped in Hong Kong's airport in mid-June  
[2009] after setting off a fever detection device. She was taken to  
hospital where she tested positive for swine flu. She had not been  
taking antivirals and declined to be treated with the drug. She was  
kept in isolation until she recovered.

Dr. Jennifer McKimm-Breschkin, an influenza expert from Australia and  
a member of the team that developed Relenza, says this case shows  
resistant swine flu viruses can spread. It was previously thought flu  
viruses that developed resistance to the drug would be crippled in the  
process and would not transmit to others. But that belief was  
shattered in 2008 when it was discovered Tamiflu-resistant versions of  
the seasonal H1N1 viruses were spreading rapidly around the globe.  
They have since all but wiped out [replaced] Tamiflu-susceptible  
seasonal H1N1 viruses. "This is a patient that hasn't been treated who  
has gone from San Francisco to Hong Kong. What that means is that she  
has caught a resistant virus in San Francisco," says McKimm-  
Breschkin, virology project leader at the Commonwealth Science and  
Research Organization -- known as CSIRO -- in Melbourne. "So that  
means this virus has been transmitted from somebody who's presumably  
been treated. Which means it's been fit enough to transmit -- and that  
is of a lot more concern than just resistance in a treated patient."  
Experts have worried the seasonal H1N1 viruses might reassort or swap  
genes with the swine H1N1. If swine flu picked up the neuraminidase  
gene -- the N in a flu virus' name -- from the seasonal H1N1, it would  
acquire the resistance its seasonal cousin has developed.

Authorities in Hong Kong have not yet told the WHO whether that is  
what has happened in this case. But whether the Hong Kong resistance  
case is due to reassortment, or from the fact that some swine flu  
viruses have developed resistance on their own, the situation demands  
careful monitoring, Fukuda and others say. "The really big question  
for any finding of antiviral drug resistance with these viruses is  
whether it's an isolated event or whether it's a tip of a larger  
phenomenon," he explains. "The bottom line, as is so often the bottom  
line with influenza, is that the real answer to the current situation  
is monitoring as closely as possible, which in this instance is really  
being done, since an extraordinary number of viruses are being  
collected and looked at."

[Byline: Helen Branswell]

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[The identification in Hong Kong (S.A.R.) of a patient arriving from  
the USA harboring Tamiflu-resistant A (H1N1) pandemic influenza virus,  
who had not previously received Tamiflu treatment, is a disturbing but  
not unexpected development in view of the often indiscriminate use of  
the antiviral in some countries. It remains to be seen whether this  
Tamiflu-resistant virus will be transmitted more or less efficiently  
than Tamiflu-sensitive virus. It may be that Tamiflu will become  
largely ineffective in the control and treatment of the A (H1N1)  
pandemic virus sooner rather than later. Restriction in future use of  
Tamiflu should be considered.

Unlike Tamiflu, which is administered orally in tablet form, the  
alternate neuraminidase inhibiter Zanamivir (Relenza) is an antiviral  
that must be administered twice a day in powder form through a special  
inhaler, with treatment continuing for up to 5 days. This may be an  
advantage in reducing the indiscriminate use of the drug. Relenza can  
be used by people over 12 years of age who are known or suspected to  
have influenza A or influenza B virus infection. - Mod.CP]

[see also:
Influenza A (H1N1) - worldwide (83): antiviral resistance 20090705.2417
Influenza A (H1N1) - worldwide (82): transmission 20090704.2402
Influenza A (H1N1) - worldwide (81): epidemic analysis 20090703.2391
Influenza A (H1N1) - worldwide (80): Argentina, human to pig 20090701.2376
Influenza A (H1N1) - worldwide (79): case count 20090701.2372
Influenza A (H1N1) - worldwide (78): Tamiflu resistance, DK 20090630.2359
Influenza A (H1N1) - worldwide (76): comments on 1918 virus (03) 20090625.2309
Influenza A (H1N1) - worldwide (74): susp. origin 20090624.2303
Influenza A (H1N1) - worldwide (73): case count, epidemiology 20090622.2288
Influenza A (H1N1) - worldwide (72): case count, epidemiology 20090619.2261
Influenza A (H1N1) - worldwide (70): risk factors 20090619.2260
Influenza A (H1N1) - worldwide (69): other viral infections 20090618.2254
Influenza A (H1N1) - worldwide (68): southern hemisphere 20090618.2253
Influenza A (H1N1) - worldwide (65): antivirals in pregnancy 20090616.2224
Influenza A (H1N1) - worldwide (64): case count, pandemic 20090616.2221
Influenza A (H1N1) - worldwide (62): Egypt, Lebanon 20090611.2150
Influenza A (H1N1) - worldwide (62): Egypt, Lebanon 20090611.2150
Influenza A (H1N1) - worldwide (60): Egypt (Cairo) 20090608.2117
Influenza A (H1N1) - worldwide (59): Worldwide 20090608.2117
Influenza A (H1N1) - worldwide (58): USA, Africa 20090607.2109
Influenza A (H1N1) - worldwide (57): Brazil, USA 20090605.2090
Influenza A (H1N1) - worldwide (55) 20090603.2056
Influenza A (H1N1) - worldwide (47): China, epidemiology 20090526.1962
Influenza A (H1N1) - worldwide (45) 20090525.1951
Influenza A (H1N1) - worldwide (42) 20090523.1929
Influenza A (H1N1) - worldwide (39) 20090521.1903
Influenza A (H1N1) - worldwide (37) 20090520.1893
Influenza A (H1N1) - worldwide (34) 20090518.1863
Influenza A (H1N1) - worldwide (31) 20090516.1835
Influenza A (H1N1) - worldwide (29) 20090515.1824
Influenza A (H1N1) - worldwide (26) 20090514.1798
Influenza A (H1N1) - worldwide (23) 20090511.1764
Influenza A (H1N1) - worldwide (21) 20090510.1749
Influenza A (H1N1) - worldwide (19) 20090509.1733
Influenza A (H1N1) - worldwide (17) 20090508.1722
Influenza (H1N1) - worldwide (15) 20090507.1709
Influenza A (H1N1) - worldwide (13) 20090506.1695
Influenza A (H1N1) - worldwide (11): coincident H3N2 variation 20090505.1679
Influenza A (H1N1) - worldwide 20090430.1636
Influenza A (H1N1) "swine flu": worldwide (07), update, pandemic 5  
20090429.1622
Influenza A (H1N1) "swine flu": Worldwide 20090427.1583
Influenza A (H1N1) virus, human: worldwide 20090426.1577
Influenza A (H1N1) virus, human - New Zealand, susp 20090426.1574
Influenza A (H1N1) virus, human - N America (04) 20090426.1569
Influenza A (H1N1) virus, human - N America 20090425.1552
Acute respiratory disease - Mexico, swine virus susp 20090424.1546
Influenza A (H1N1) virus, swine, human - USA (02): (CA, TX) 20090424.1541
Influenza A (H1N1) virus, swine, human - USA: (CA) 20090422.1516
Influenza A (H1N1) virus, swine, human - Spain 20090220.0715]
...........................................................cp/msp/jw
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