Tamiflu Resistant Pandemic H1N1 in Asymptomatic Traveler from San Francisco

[HenryN]

98

F/36

Asymptomatic

Returned from San Francisco with mother and

Imported

Singapore Airlines(flight no SQ1) Arrived on June 11

Daughter (confirmed patient), mother, two sisters , a brother

Ping Tin Estate Kwun Tong

[HenryN]

The above description matches the 16 year old patient from San Franciso who arrived in Hong Kong on June 11. The patient above was asymptomatic.

Flight SQ1 is a direct flight from San Francisco to Hong Kong.

[HenryN]

03rd July 2009 - Friday - Flight Number SQ1 / Aircraft (B777-300ER)

Airport Scheduled Time Actual Time Estimated Time Status Departure From San Francisco (SFO) 01:05 (-1) 00:58 (-1) Departed Arrival In Hong Kong (HKG) 06:35 05:57 Arrived

[HenryN]

Tin Ping Estate

http://www.housingauthority.gov.hk/e...1_4930,00.html

[AlaskaDenise]

That flight has 349 seats total (42 FC, 307 econ).

A singapore airlines flight (#1) arriving on the same day, is on a 77W.

.

[HenryN]

Based on the fact that the traveler "returned" to Hong Kong with her family and went to Hong Kong housing compex via public transportation suggest she is a Hong Kong resident.

[HenryN]

Commentary

[ironorehopper]

This case detected in Spain: a US military camp resident tested positive after returning from US; the patient was under antiviral since early this week; despite this, he needs to be hospitalized.

http://www.flutrackers.com/forum/sho...d.php?t=114194

[AlaskaDenise]

Originally Posted by niman

Commentary

Commentary

Asymptomatic Traveler With Tamiflu Resistant Pandemic H1N1

Recombinomics Commentary 20:20
July 4, 2009

Asymptomatic

Returned from San Francisco with mother and daughter (confirmed patient) on June 11

Admitted to United Christian Hospital (UCH) on June 12

Imported

Singapore Airlines (flight no SQ1) Arrived on June 11

Daughter (confirmed patient), mother, two sisters , a brother

The above data, from a Hong Kong DOH report describing pandemic H1N1 confirmed cases, is the only entry that matches reports on the 16 year old who was intercepted at the airport on June 11 and was subsequently found to be infected with Tamiflu resistant H1N1. The patient's flight had originated in San Francisco, and Singapore Airlines flight SQ1 is a nonstop flight from San Francisco to Hong Kong, providing additional evidence for Tamiflu resistant H1N1 in northern California.

The above description indicates the confirmed patient was the daughter in the traveling family described above. The case is also described as asymptomatic, in contrast to media reports which indicated where was identified because of a fever. The cause of the discrepancy remains unclear, although the above report lists the age of the female patient as 36 instead of 16 and admission into United Christian Hospital instead of Queen Mary Hospital although transfer from one hospital to another could explain that discrepancy.

In any event, the above description is the only patient listed who flew into Hong Kong from San Francisco on June 11, and likely represents the case who had mild symptoms or was asymptomatic on arrival. Since the patient was not taking Tamiflu, the resistance would represent a fit pandemic H1N1 which is likely circulating in the United States.

Currently, efforts in the United States are directed toward severe cases and would likely miss either mild or asymptomatic individuals, allowing for silent spread of Tamiflu resistant pandemic H1N1.

The other two reported cases with H274Y (Denmark and Japan) were from patients who were on a prophylactic dose. Although agencies have focused on a spontaneous mutation selected by the Tamiflu treatment, the reports do not exclude a mixture, with the H274Y on a minor population. A mixture would also raise concerns of silent spread of H274Y. The presence of H274Y in a treated patient may also be present in India, where a patient is asymptomatic, but shedding pandemic H1n1 in spite of a full course of Tamiflu treatment. The emergence of H274Y in treatment patients may simply reflect selection of this minor population. However, the presence of H274Y in a minor population could lead to a jump onto another variant of pandemic H1H1, as was seen in seasonal H1N1. The fixing of H274Y in seasonal flu was preceded by H274Y in a number of clades and sub-clades, signaling multiple dependent introductions into hosts not taking Tamiflu.

The fixing of H274Y in seasonal flu has led to predictions that pandemic H1N1 with H274Y would emerge due to recombination between seasonal and pandemic H1N1. Others expected such dual infections to lead to acquisition of H274Y by reassortment, but none of the examples describe to date have involved reassortment and acquisition of human N1.

The reports of three examples of H274Y this week supports acquisition via recombination, and more such examples are expected in the near term, as more labs focus on H274Y in pandemic H1N1.

.

[HenryN]

INFLUENZA A (H1N1) - WORLDWIDE (84): TAMIFLU RESISTANCE, CHINA (HONG
KONG S.A.R.)
***********************************************
A ProMED-mail post
<http://www.promedmail.org>
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

[HenryN]

Originally Posted by niman

INFLUENZA A (H1N1) - WORLDWIDE (84): TAMIFLU RESISTANCE, CHINA (HONG
KONG S.A.R.)
***********************************************
It remains to be seen whether this
Tamiflu-resistant virus will be transmitted more or less efficiently
than Tamiflu-sensitive virus. cp/msp/jw

More lessons NOT learned.

[Nika]

Originally Posted by niman

More lessons NOT learned.

Does this statement indicate that you think that they will not ration tamiflu effectively to minimize encouraging further resistance or is there another action you think they need to take in light of the seasonal flu resistance experience?

It seems like, until we find a foolproof mechanism that we can raise a med against that can not be side stepped by the pathogen, resistance (esp in flu) is a high likelihood at some point, no?

[sharon sanders]

Welcome Nika!

[Nika]

Florida:

Goodness your fast! Thanks for the lovely welcome! Have learned a lot in cruising here, about time I registered.

[HenryN]

Originally Posted by Nika

Does this statement indicate that you think that they will not ration tamiflu effectively to minimize encouraging further resistance or is there another action you think they need to take in light of the seasonal flu resistance experience?

It seems like, until we find a foolproof mechanism that we can raise a med against that can not be side stepped by the pathogen, resistance (esp in flu) is a high likelihood at some point, no?

A fit pandemic H1N1 with H274Y virtially ensures that resistance will spread, and widespread Tamiflu use will accellerate that spread.

[Vibrant62]

Dr. Niman. On the basis of current knowledge, how long would you estimate before such resistance is widespread?

[HenryN]

Originally Posted by Vibrant62

Dr. Niman. On the basis of current knowledge, how long would you estimate before such resistance is widespread?

It will be quicker than seasonal flu, because of more Tamiflu usage, but more sequence data is required before realistic estimates can be made. So far only Hong Kong has released NA sequences with H274Y.