Anti-viral resistance in 2009 A/H1N1 flu - historical compilation of news

[HenryN]

Re: Quebec man caught drug-resistant swine flu

>>This is the fourth case reported so far of Tamiflu resistance in H1N1 cases; earlier cases were reported from Denmark, Japan and Hong Kong. <<

Actually, the Quebec case is the fifth example of H274Y because the Yamaguchi case (second example from Japan) was reported July 17

http://www.flutrackers.com/forum/showpost.php?p=269852&postcount=16

[AlaskaDenise]

Re: Quebec man caught drug-resistant swine flu

Commentary

http://www.recombinomics.com/News/07...ada_Japan.html

Commentary

Tamiflu Resistant Pandemic H1N1 Spread to Canada and Japan

Recombinomics Commentary 04:15
July 22, 2009

"We know the exact, specific mutation, and this is a mutation that has been reported before in human viruses that were resistant to Tamiflu, so it's not totally unexpected," said Boivin.

Boivin said he suspects the Quebec father was already infected when he was given a low preventive dose of the antiviral drug Tamiflu.

The above comments describe another case of oseltamivir resistance in pandemic H1N1 swine flu. The description indicates the resistance is due to H274Y because all reported oseltamivir resistance since 2007 has been H274Y in H1N1. Earlier this month there were three cases described, and two of the three were also on prophylactic oseltamivir. However, since all cases have involved H274Y, the treatment may simply be aiding in the detection of H274Y, rather than selecting for de novo mutations. Sequence data reports consensus sequences, so a low level of H274Y would not be seen unless multiple clones were sequenced or levels increased due to the elimination of wild type H1N1 by oseltamivir treatment.

In addition to the H274Y in Quebec, a sequence released today from Yamaguchi Province in Japan also had H274Y. The characterization sheet provides little detail on the patient, but Yamaguchi Province gives detailed reports on each H1N1 confirmed case, and the reports give no support for the development of H1N1 in contacts under prophylactic treatment. Therefore, it is likely that the Yamguchi isolate is from a sample collected prior to Tamiflu treatment.

The sequence of A/Yamaguchi/22/2009 is distinct for the other two published sequences with H274Y. However, like A/Hong Kong/2369/2009, there are several NA sequences which are exact matches, other than position H274Y. These precursors are widespread, and the earliest isolate is from the United States (Sullivan county in New York), and all subsequent isolates are from other countries (Japan, China, Brazil) once again raising questions about surveillance of mild H1N1 cases in the United States. In Japan there have been no reported pandemic H1N1 deaths and most of the cases in in Yamaguchi province have been mild and patients have recovered without hospitalization.

These two cases of resistance raises the total to five and all involve H274Y, the same polymorphism reported in seasonal H1N1, where the level quickly rose to 100&#37; last season and is reported at 100% in the southern hemisphere this season. The presence of H274Y on seasonal H1N1, which is co-circulating with pandemic H1N1, offers the opportunity of recombination between seasonal and pandemic H1n1 to allow the H274Y to jump from seasonal H1N1 to pandemic H1N1.

The reports of H274Y in five patients this month raises concerns that the frequency will rise in the near term, with recombination and genetic hitchhiking driving the levels to 100%, due in part to widespread use of oseltamivir and in part to the large reservoir of H274Y in seasonal flu.


.

[Diane Morin]

Re: Qu?bec: un premier cas de r?sistance au Tamiflu

Published July 22, 2009 at 08h59 | Updated at 10:00
The CHUL first diagnosed cases of Tamiflu resistance in America

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Agrandir

Enlarge
A diagnosis of influenza A (H1N1) has been established for Quebecers aged 60 who took Tamiflu as a preventive measure and reduced dose. The man, however, developed flu-like symptoms or a cough, fever and muscle pain, while he was being processed. A sample was taken and a laboratory at the Hospital Center of Laval University has confirmed that the man had contracted the disease.
The Sun Photo Gallery



<table class="minithumb-auteurs" cellspacing="0"><tbody><tr><td> Canadian Press
</td></tr></tbody></table>
Quebec registered the first case in North America for resistance to Tamiflu, the main antiviral used to treat influenza A (H1N1).

This is the fourth case of Tamiflu resistance to be reported in the world since the discovery of this new virus (H1N1).

A diagnosis of influenza A (H1N1) has been established for Quebecers aged 60 who took Tamiflu as a preventive measure and a lower dose, because his son had contracted the virus influenza A (H1N1).

The man, however, developed flu-like symptoms or a cough, fever and muscle pain, while he was being processed. A sample was taken and a laboratory at the Hospital Center of Laval University has confirmed that the man had contracted the disease.

"It appears to be an isolated case, said the spokesman for the Agency of Health Canada Jirina Vlk. Although the strain (the virus) seems to have spread to other people, we continue to be vigilant. "

Cases of resistance have sometimes been noted during the use of Tamiflu to prevent infection - a procedure called prophylaxis.
"We knew it would happen and what happens is not good news," said Dr. Allison McGeer, an influenza expert from Mount Sinai Hospital in Toronto.

But she added that the number of such cases would increase because the amount of Tamiflu currently used worldwide.

Worldwide

In addition to Canada, cases of Tamiflu resistance have been reported in Denmark, Japan and Hong Kong. Three of the four cases involved people who took the drug.

The Agency for Health Canada said the man had recovered from influenza A (H1N1) without complications arise. The Qu&#233;b&#233;cois has also not been hospitalized.

[HenryN]

Re: Quebec man caught drug-resistant swine flu

Tamiflu-resistant strain rare: health officials

Last Updated: Wednesday, July 22, 2009 | 12:52 PM ET Comments0Recommend0

CBC News


There have been five documented cases of Tamiflu-resistant swine flu worldwide. (Michael Probst/Associated Press) Despite the appearance of a case of drug-resistant swine flu in Quebec, the resistant strain remains rare worldwide and there is no need to change Canada's approach to prescribing Tamiflu, health officials said Wednesday.
A 60-year-old Quebec man is one of five people around the world found to have a strain of H1N1 flu resistant to the antiviral drug Tamiflu (oseltamivir). The other cases occurred in Japan, Denmark and Hong Kong.
Dr. Guy Boivin, Canada Research Chair on emerging viruses and antiviral resistance in Quebec City, said he suspected the Quebec man was already infected when he was given a low preventive dose of Tamiflu as a precaution because he had a pulmonary condition. His son fell ill with the pandemic virus.
The man was given Tamiflu as post-exposure prophylaxis ? an attempt to prevent illness in someone exposed to the pandemic virus.
Boivin believes the man may have already been infected with the H1N1 virus. There is no evidence the man transmitted the resistant virus to anyone else. The man recovered and was never hospitalized.
Treat symptoms quickly

"In some cases, it's probably better to wait until we have the symptoms," said Boivin, who works at the Infectious Disease Research Centre in Quebec City. "But rapidly after symptom onset, treat with high doses of the anti-viral drug."
The man was never hospitalized and there are few cases of resistance worldwide, which means Canada's approach to swine flu should stay the same, Boivin said.
Health officials are watching for signs that the resistant strain might spread person-to-person or become more or less dangerous.
"Just because he ended up with a drug-resistant strain doesn't necessarily mean that that strain has the 'right stuff' to be able to go person to person to person," said Dr. Michael Gardam of the Ontario Agency for Health Protection and Promotion.
"Usually when you see Tamiflu-resistant strains, they actually aren't very good at spreading person to person. That isn't always the case. There is one strain that's out there that's very good at spreading person to person. But right now, we don't have any evidence that this strain is one of those strains that is able to do that."
Gardam said he and other health officials are watching closely for clusters of Tamiflu-resistant cases among people who hadn't been on the drug, which would indicate the resistant strain is starting to move from person to person.
Health officials also continue to take swabs of people sick enough to go to emergency to check for any mutations in the virus. Anyone who is sick enough to go to emergency should be treated with Tamiflu, Gardam said, adding the drug works best if given with the first 48 hours after showing symptoms.
The Public Health Agency of Canada recommends using Tamiflu for treatment only, to help stave off the development of resistance, said Jirina Vlk, a spokeswoman for the agency.
Stockpile still works

About 80 per cent of Canada's stockpile of antiviral medications consists of 50 million doses of Tamiflu, which remains effective. Boivin said he would like to see companies develop alternative antivirals in case more drug resistance occurs.
The other 20 per cent of Canada's stockpile is the antiviral drug Relenza (zanamivir), which is harder to administer than Tamiflu because it has to be inhaled into the lungs, Gardam said.
The company that manufactures Tamiflu, Roche, said its research shows a small percentage of people will not respond to the drug.
"We know that there are various reasons for the resistance. What we know is that it's not drug-induced, that it's some kind of natural mutation," said Laura Pagnotta, who speaks for Roche Canada.
Pagnotta said the World Health Organization still recommends Tamiflu for the prevention and treatment of swine flu, but says it should be prescribed on a case-by-case basis.
Health officials continue to recommend that people:

• Wash their hands often with warm, soapy water or hand sanitizer.
• Cough and sneeze into your arm, not your hand.
• Keep common surfaces and items clean and disinfected.
• Stay home if you're sick, unless directed to seek medical care.

The worldwide death toll from swine flu is more than 700, according to the World Health Organization, which recently stopped counting the number of cases worldwide.
As of last week, Canada was reporting more than 10,000 swine flu cases, with 45 deaths. Between 4,000 and 8,000 Canadians die of influenza and its complications annually, depending on the severity of the season, the Public Health Agency said.

http://www.cbc.ca/health/story/2009/07/22/swine-flu-tamiflu-resistance.html

[Chuck]

Tamiflu resistance in pandemic influenza - historical compilation of news

http://www.metronews.ca/calgary/canada/article/265992--tamiflu-resistant-strain-of-swine-flu-turns-up-in-quebec

Quebec finds first, Japan finds second cases of Tamiflu-resistant swine flu

HELEN BRANSWELL
July 22, 2009 11:50 a.m.

TORONTO - Canada has recorded a case of Tamiflu-resistant swine flu virus, in a Quebec man who had been given the drug to prevent infection.

Meanwhile, Japan revealed Tuesday it had found a second such case of Tamiflu resistance, in a person who has no ties to the country's earlier reported case.

The cases are the fourth and fifth globally since the new H1N1 virus was discovered in April.

The Quebec man, 60, was given the flu antiviral after his son fell ill with the pandemic virus. It's believed the resistance arose in the man and there is no evidence he transmitted resistant virus to anyone else.

"It appears to be an isolated case," said Jirina Vlk, spokesperson for the Public Health Agency of Canada.

"Although the strain does not appear to have spread beyond the reported individual case we continue to be vigilant on this front."

Use of Tamiflu to prevent infection - a procedure called prophylaxis - has been seen on occasion to give rise to resistant viruses.

"We know that it was going to happen and it's not good news that it's happening," said Dr. Allison McGeer, an influenza expert at Toronto's Mount Sinai Hospital.

But she said given the amount of Tamiflu being used in the world right now, such cases are bound to arise.

"It's the problem with influenza, right? Either we're going to see small numbers of these and they're just going to kind of appear periodically and we're all going to worry or it's going to go big," McGeer said.

"There's probably not going to be much in between."

Another such case cropped up in Japan, in the city of Yamaguchi. Japan's National Institute of Infectious Diseases logged genetic sequence data for the virus on Tuesday in Genbank, a repository for genetic sequences used by flu researchers.

The lab's director, Dr. Masato Tashiro, confirmed the case in an email containing details provided to the World Health Organization.

The new case was a person who had been given the antiviral drug as post-exposure prophylaxis - an attempt to prevent illness in a person exposed to the pandemic virus.

The person has since recovered, and it appears that there has been no spread, the email stated. The virus was sensitive to Relenza, a second drug in the same class as Tamiflu.

The earlier Japanese case had occurred in a person in the city of Osaka.

Other cases have been reported by Denmark and Hong Kong. Four of the five cases arose in people who had been taking the drug.

One, however, was recorded in a girl from San Francisco who travelled while sick to Hong Kong. Health inspectors at the airport there pulled her aside and tested her for swine flu.

She was positive, but told doctors there she hadn't taken Tamiflu. That suggests the virus that caused her infection was already resistant. U.S. officials have intensified surveillance for resistant viruses in the San Francisco area but say they have not found other cases.

The Public Health Agency says the Quebec man recovered from his bout of swine flu without complications and never needed hospitalization.

Vlk said the agency recommends using Tamiflu for treatment only, adding prudent use of the drug could stave off the development of resistance.

[ARR_309]

Re: Origins and evolutionary genomics of the 2009 swine origin H1N1 influenza A (pandemic)

Tamiflu resistance puzzle
Category: Antivirals • Influenza treatment • Swine flu
Posted on: July 23, 2009 7:00 AM, by revere

From:

http://scienceblogs.com/effectmeasure/2009/07/tamiflu_resistance_puzzle.php

"There have been three reported oseltamivir (Tamiflu) resistant isolates of H1N1 swine flu (added: and now a fourth in Canada) but with those exceptions all others have been sensitive to this oral antiviral. This is in marked contrast to the other H1N1 strain, the seasonal variety which is almost entirely resistant. The spread of Tamiflu resistance in the seasonal strain happened with dramatic suddenness in the winter of 2007 - 2008 and came as an unhappy surprise. People assume that a rapidly mutating virus would inevitably become resistant, but based on several laboratory studies there were reasons to believe the mutation or mutations conferring resistance also made the virus less fit to replicate, infect host cells or cause disease. Moreover the resistance developed and spread very rapidly in areas where the virus was under little antiviral pressure. But the resultant H1N1 seasonal viruses transmitted readily and caused a typical influenza illness. It was a public health problem, but also in interesting scientific one. Now a clue may be emerging in findings just published in a Letter in Emerging Infectious Diseases from scientists in Luxembourg.
Several mutations in the neuraminidase (NA) gene can cause Tamiflu to lose its effectiveness at blocking the virus's ability to detach its replicated progeny after infecting a host cell (and thus preventing further infection of other cells), but by far the most common is one designated H274Y. The 274 part is the amino acid location along the protein, while the H and Y say that Y has been substituted for H at that location. H is an abbreviation for the amino acid histidine, while Y is the abbreviation for tyrosine. In other words, in a resistant H1N1 virus, there is a change at a single place along the long string of amino acid beads that make up the N1 protein and it occurs 274 places down the line, substituting a tyrosine from a histidine building block. That's a pretty small change but it's enough to interfere with the docking of the Tamiflu to the neuriminidase enzyme on the virus's surface and allow it to perform its detaching function. But is this change all that's involved? Apparently not.
NA is not the only protein made by the virus. Also on its surface is hemagglutinin (HA, one version of which, H1, gives H1N1 part of its name), which is involved in viral attachment to the host cell (and other functions) and 6 other gene segments, most internal to the virus and involved in replication and other functions. Could it be that the virus with mutant NA had other less visible mutations that somehow "made up for" or corrected the lack of fitness found in resistant viruses with only H274Y? The scientists in Luxembourg compared sequences in all 8 gene segments in Tamiflu resistant versus sensitive H1N1s to see if there was another consistent change. They looked at 140 different isolates collected by Luxembourg's National Influenza Sentinel Surveillance System over the period when resistance emerged (December 2007 - March 2008). About a quarter of these isolates were Tamiflu resistant. They then searched for another genetic marker that accompanied H274Y but wasn't in H274 (the sensitive virus). No difference in most of the other genes -- PB1, polymerase A, hemagglutinin, nucleoprotein, matrix, nonstructural (NS) -- seemed to differentiate resistant from non-resistant. The exception was the PB2 gene, where a serine for proline change at position 453 (Pro453Ser) seemed to fit the bill. They looked at all published PB2 sequences to see if this was a common mutation and were able to find only three instances collected since 1918: one each in 1933, 1976 and 1988. The bottom line here is that these two genetic changes -- H274Y in NA and Pro453Ser -- are associated and seem to be related to the unexpected fitness of Tamiflu resistant seasonal H1N1."

[I]Sounds like a case of antagonistic epistasis to me![/I]

cont..

"Science is a slow process and fitting all the pieces together takes even more time. There are false starts and backtracks and sometimes things that seem significant are only side tracks or misinterpretations. Whether this finding is indeed true, and if true, how it works mechanistically we don't know."

Yes we do...antagonistic epistasis and recombination fixing and spreading 'memory genomes' via the viral quasi-species complex..

cont...

"But it's a clue that might tell us something important about viral fitness and Tamiflu resistance. Could it affect the pandemic? "

Does the Pope wear a silly hat?


cont...

"Possibly, if the existence of Pro453Ser could be used as a marker or early warning of developing Tamiflu resistance. Another possibility, that it might provide information about a new therapeutic target, is probably too distant to have any application in the next year or two.

Science marches to its own rhythm."

The Emerg Infectious Disease paper summary can be found here:

http://www.cdc.gov/eid/content/15/9/pdfs/09-0452.pdf

[kiwibird]

Tamiflu resistance in pandemic influenza - historical compilation of news

http://www.scmp.com/portal/site/SCMP/menuitem.2af62ecb329d3d7733492d9253a0a0a0/?vgnextoid=cf2ee3aac18a2210VgnVCM100000360a0a0aRCRD&ss=China&s=News

Chinese medicine is curing swine flu, authorities claim
SWINE FLU OUTBREAK
Zhuang Pinghui
Jul 24, 2009

Traditional Chinese medicine had been more effective than Tamiflu in curing human infections of swine flu, and was expected to play an important role in case of a pandemic in autumn and winter, Beijing health authorities said.

Wang Yuguang , deputy dean of the Centre of Integrated Traditional and Western Medicine at Beijing's Ditan Hospital, which specialises in the treatment of infectious diseases, said swine flu patients treated with traditional Chinese medicine improved faster and tended to stay in hospital for a shorter time than patients using Tamiflu.

Click here to find out more!

It costs much less, too, Dr Wang said, with traditional treatments costing 10 to 13 yuan (HK$11-$15) a day, while Tamiflu cost 56 yuan a day.

The hospital allowed people in non-critical condition to be treated exclusively with traditional Chinese medicine from June 15, and by yesterday morning 88 of the 117 patients had been cured and discharged.

The hospital did not say how many of the 180 patients treated with Tamiflu had been discharged. The government has allocated 10 million yuan to research treatment of swine flu using traditional Chinese medicine, including one study comparing results with Tamiflu treatment.

Traditional medicine considers such factors as the level of virus infection, the condition of the body, age, season and climate. Treatment can be adjusted in the dose and types of herbs. Such personalised treatment seldom caused drug resistance, as Tamiflu could, Dr Wang said.

Tu Zhitao , director of the education department of the Beijing Administration of Traditional Chinese Medicine, said that traditional medicine "has achieved good results in treating swine flu in Ditan and Youan hospitals".

In total, 156 of Beijing's 327 swine flu patients have been treated with traditional medicine, and 125 have been cured and discharged.

He said hospitals were being advised to use traditional treatments first and resort to Western medicine only after Chinese medicine failed, a move intended to prepare for a possible pandemic late in the year.

[Chuck]

Tamiflu resistance in pandemic influenza - historical compilation of news

http://www.google.com/hostednews/ap/article/ALeqM5gfRaE_SJsou8txiDJekAEtjlZbHQD99KTVF00

AP Interview: Flu chief: Pandemic in early stages

By FRANK JORDANS (AP) ? 4 hours ago

GENEVA ? The global swine flu epidemic is still in its early stages, even though reports of over 100,000 infections in England alone last week are plausible, the World Health Organization's flu chief said Friday,

Keiji Fukuda, WHO's Assistant Director-General for Health Security and Environment, told The Associated Press that given the size of the world's population, the new H1N1 virus is likely to spread for some time.

WHO earlier estimated that as many as 2 billion people could become infected over the next two years ? nearly one-third of the world population.

"Even if we have hundreds of thousands of cases or a few millions of cases ... we're relatively early in the pandemic," Fukuda said in an interview at WHO's headquarters in Geneva.

The global health agency stopped asking governments to report new cases last week, saying the effort was too great now that the disease has become so widespread in some countries.

Authorities in Britain say there were over 100,000 infections in England alone last week, while U.S. health officials estimate the United States has passed the 1 million case mark. Those figures dwarf WHO's tally of 130,000 confirmed cases worldwide since the start of the outbreak last spring.

"We know that the total number of laboratory-confirmed cases is really only a subset of the total number of cases," Fukuda said.

Fukuda, the former chief of epidemiology at the U.S. Centers for Disease Control and Prevention, or CDC, also said there must be no doubt over the safety of swine flu vaccines before they are given to the public.

Health officials and drug makers are looking into ways of speeding up the production of the vaccine before the northern hemisphere enters its flu season in the fall.

The first vaccines are expected in September and October, said Fukuda. Other vaccines will take until December or January before they are released onto the market ? well into flu season when a further dramatic rise in swine flu cases is predicted.

"Everybody involved with the vaccine work, from manufacturers up to the regulatory agencies, are looking at what steps can be taken to make the process as streamlined as possible," Fukuda said. "One of the things which cannot be compromised is the safety of vaccines."

The search for an effective inoculation has taken on a new urgency as WHO announced that almost 800 people have died from the disease in the past four months. This is more than the H5N1 bird flu strain has killed in six years.

The CDC said Friday that ? based on the experience of the 1957 flu pandemic ? the number of Americans dying from swine flu over the next two years could range from 90,000 to several hundred thousand. That projection would drop if the vaccine campaign and other measures are successful, U.S. health officials said.

One question that scientists and health officials disagree on is whether pregnant women should be among the first to receive a vaccine ? after health workers, who make up about 1-2 percent of the world population and are considered indispensable.

A report by WHO experts found that pregnant women appear to be "at increased risk for severe disease, potentially resulting in spontaneous abortion and/or death, especially during the second and third trimesters of pregnancy."

Several women and their children have died in recent weeks, though obesity may have played a role in some of the deaths, the report says.

"Pregnant women have emerged as one of the groups that we are concerned about as being at higher risk than other people in terms of having the possibility of developing severe illness," said Fukuda.

But right now, WHO is holding back on recommending that pregnant women receive priority vaccinations. And the agency is not commenting on the contentious suggestion by British and Swiss health officials that women should consider delaying pregnancy if they can.

"WHO certainly has no recommendations on whether women should try to have children" now, Fukuda said.

The agency has been working hard to ensure that poor countries receive vaccines too, despite rich nations having pre-ordered most of the available stock. A WHO spokesman said Friday that two drug makers have pledged to donate 150 million doses of vaccine to poorer countries by the end of October.

"We're working with a range of partners to secure more vaccine for developing countries," WHO's Gregory Hartl said.

Fukuda, who is effectively in charge of WHO's pandemic response until mid-August while the agency's Hong Kong-born Director-General Margaret Chan is on home leave, also addressed the possibility that the virus might mutate and become resistant to anti-viral drugs such as Tamiflu.

Four separate Tamiflu-resistant cases have been reported recently from Denmark, Japan, Hong Kong and Canada.

"We haven't seen widespread emergence of resistance to the drug right now," Fukuda said, but added "this is something we're watching very carefully."

It is inevitable that over a long enough period of time the swine flu virus will mutate, he said.

"Unfortunately we can't predict in what direction," he said.

Associated Press Writer Bradley S. Klapper in Geneva and Mike Stobbe in Atlanta contributed to this report.

Copyright ? 2009 The Associated Press. All rights reserved.

[Treyfish]

Press Briefing Transcripts CDC Briefing on Investigation of Human Cases of H1N1 Flu

CDC Briefing on Investigation of Human Cases of H1N1 Flu
July 24, 2009, 11:30 a.m. ET


Anne Schuchat: Good morning, everyone. Thanks for joining us. You know, today I want to, again, give you a snapshot of what's going on with the new 2009 H1N1 influenza virus but also talk just a little bit about seasonal influenza as well. I'm planning to give you an assessment of what's going on and what we're doing to be better prepared for an increase of illness in the fall.

And today we actually are releasing the influenza vaccine recommendations, so I want to mention those briefly. Those are available at our web at www.cdc.gov. We release every year at this time the seasonal vaccine recommendations. We look at the illness and you'll end up with updates to recommendations. And there are a few updates this year that differ from the past. So let me just highlight those.

First, I want to remind you that while we're focusing a lot of attention on the 2009 H1N1 influenza virus, we do expect seasonal influenza viruses to circulate as well, and we need to be prepared for both of them. The new seasonal influenza vaccine recommendation include a recommendation for annual vaccination for children age 6 months to 18 years. This past year's recommendations encouraged vaccination, and the plan has been that this year this would be a full recommendation. No longer just an encouragement or "where feasible," but a full-out recommendation. The update also includes the strains that are part of this year's flu vaccine and your, of course, new strains for the A H1N1, A H3N2 and B strains. They're all Brisbane source strains that are in the new flu virus vaccines. Vaccination against seasonal influenza should begin as soon as vaccine is available and continue throughout the influenza season. At this point, 83% of the population is recommended to get an annual flu vaccine and we recommend it for anyone who wants to reduce their risk of flu. Unfortunately, only about 40% of the U.S. population received the flu vaccine last year, so we're really recommending an intensifying use of this vaccine because it does protect against illness and complications like hospitalization and severe outcomes.

I want to make a special reminder to health care workers. We have recommended health care workers get the seasonal flu vaccine for years and we all need to be with vaccination coverage. This year in particular we want to keep health care workers healthy at work able to care for sick patients, and we don't want them to be spreading influenza to their patients. We recommend them strongly to receive the seasonal flu vaccine. And I'm expecting when H1N1 vaccine recommendations come out it's very, very likely health care workers will be in that group that ought to get vaccines as well.

Let me turn to the H1N1 situation and summarize where we are. We are continuing to see transmission here in The United States in places like summer camps, some military academies and similar settings where people from different parts of the country come together. You know, I think this is very unusual to have this much transmission of influenza during the season, and I think it's a testament to how susceptible people are to this virus.

We as a country or as a population have no protection.


So in these special circumstances, like camps or close quarters in the military academies, we're seeing the virus spread.

This week we have posted the latest numbers for case counts, but I want to mention this will be the last where you will see that kind of reporting. Our website shows, as of today, 43,771 laboratory identified cases of the new H1N1 virus. And 302 deaths that have been reported to us here from The United States. But as we've been saying, that's really just the tip of the iceberg, so we're no longer going to expect the states will continue this individual reporting and we're going to transition to other ways of describing the illness and the pattern.

On our website you can see something called "FluView," which goes through much more detail about what's happening in different parts of the country. We believe there have been well over a million cases of the new H1N1 virus so far in The United States. And the patterns that we're seeing right now are 20 states reporting widespread or regional influenza activity. As I said, it's very unusual for that kind of illness to be occurring at this time of the year. The Novel H1N1 viruses are making up 98% of all the subtyped viruses we have, subtype influenza A viruses, and we're seeing them dominate here in the U.S.

But I want to turn to the southern hemisphere where a lot is going on. You probably heard about this in the media. We're working closely with partners in the southern hemisphere and the Pan American Health Organization. The new H1N1 virus has been found in many countries, including the southern hemisphere. The specimens we have tested, including from southern hemisphere countries, have not changed. They're still the same strain we're seeing here, meaning that the vaccines we're working on preparing is directed against the strain that is still active both here in the U.S. and in the southern hemisphere countries. Of course in the southern hemisphere, they're having their regular flu season together with the new H1N1 virus, and we're seeing the strain circulate together with seasonal strains in some places and we're seeing it dominate in other places. We are in regular communication with our international field staff and partners in a number of places. There are variable reports about how bad are things in one country or another or in different parts of the country, and I want to mention why that is. Often there are differences in testing practices, in who is actually being confirmed to have this virus. There are differences in health care in terms of how people are managed in the hospital or intensive care unit and what kind of supports are available. There are differences in reporting. In some places, we're hearing about only the severe cases. In other places, we're hearing about illness that's in the community. Based on the information that's been shared with us and the laboratory findings and our people on the ground, we think that the circumstances are quite similar in different places and that this virus is capable of causing a range of illness. Severe life-threatening disease that requires intensive care unit and mechanical ventilation and also milder illness that gets better on its own. And this is really important for people to know this virus is out there, it's circulating, it causes a range of illness and we in The United States have to get ready for the fall.

I want to mention a few words about summer camps because a lot of folks have kids in summer camps right now. We hope parents send their children to sleepaway camps for their children to be looking forward to. A lot of camps have been reporting outbreaks. We've been working closely with camp organizations and state and local health departments to provide assistance to camps to make sure they have good plans in place to keep sick children away from others, to communicate frequently with parents about what's going on, to make sure kids are able to wash their hands often, which is so important in keeping infections from spreading, and that they have good notification processes. Now, in the media there have been reports of some places offering a lot of the Tamiflu or anti-viral prophylactics. I just want to remind you we have guidance about anti-viral medicines on our website. We greatly value the anti-viral drugs. At this point we're strongly recommending them for treatment rather than for prevention. And for treatment of people with complicated influenza, severe presentations or people with underlying factors like asthma or pregnancy that might give them a much harder time battling influenza. There is a place for preventive use of these drugs, mainly for the very high-risk people who are in extremely close contact with someone with the virus. So the anti-viral drugs are one part of our armamentarium for influenza, including the H1N1 virus, but there are other steps that are more important, like keeping sick people home or separated from other people and making sure there's good hand washing and hygiene.

Yesterday we provided a little update about the clinical patterns that we were seeing with the H1N1 virus. There was a report about four children who had severe neurologic complications. Fortunately, most of these children have done well. But it's just a reminder that seizure, encephalitis and other neurologic complications can occur in influenza. This is reported in the literature -- quite a bit for seasonal influenza -- and now it's also occurring with this new H1N1 virus. We don't know whether neurologic problems will be more common with this virus, but we want clinicians to be on the lookout for that and to think about testing and treating for influenza in such circumstances. We know that neurologic problems like seizures are very concerning for parents and we want them to have this conversation that that is one more thing to be on the lookout for in conjunction with influenza. And another reason that we're taking this new H1N1 virus so seriously, in terms of what we're working on and the things that we're busy preparing for, there's a lot of work going on at CDC, HHS and across the government to be ready for the fall.

One area that we're working closely on is school guidance. We had issued school guidance last spring about the approaches to managing influenza in schools, and we're working now to update that guidance. And so I just want to let you know to look forward to formally updated guidance in the next few weeks. We're in the process of reviewing all the information learned from the spring and what are the benefits and unintended consequences of school dismissals, and what are the best ways to keep kids healthy and learning and to minimize disruption, as well as to minimize the real impact that this new virus can have.

A second area that's very active is the efforts around vaccines. I think the media heard yesterday from the FDA and the NIH about efforts being carried out around clinical trials and vaccine development. And I want to remind you that next Wednesday, July 29th, CDC's Advisory Committee On Immunization Practices will be convening here in Atlanta. They will be deliberating recommendations for which populations should be targeted for the H1N1 vaccine and whether prioritization is going to be appropriate. We also provided planning scenarios to the state and local health departments so that they can be working carefully with the private sector, with the health systems, with communities and communicators about vaccination preparations. At this point the secretary has announced that we are planning for a voluntary vaccination program in the fall, assuming availability of appropriate vaccines and that the virus hasn't changed so substantially that a vaccine wouldn't work. So there's a lot going on to be ready for such an effort. And this ACIP committee meeting next week will be a key step in that process. At this point I want to stop and be able to answer the questions that you have which we can go to now.

Tom Skinner: This will start the question and answer period.

Operator: Thank you. At this time if you would like to ask a question, please press star 1 on your touch-tone phone. Please announce your name.

Our first question is from Marian Falco, CNN Medical News. Your line is open.

Miriam Falco: Hi. Dr. Schuchat, thanks for taking the questions. Would you say that, especially given the information we got from NOWR on the neurological problems, would you still characterize this strain of flu being mild, causing mild and moderate illness, or is it more severe than that?

Anne Schuchat: I don't like to use the word "mild" for the new H1N1 influenza virus. I actually think this is a virus that's capable of causing a spectrum of illness that includes severe complications and death. Each person is different and each person experiencing this virus has a slightly different scenario. We've seen people with high fever and cough and respiratory illness and really not able to do much more than four or five days. Then we've seen people who have difficulty breathing, severe respiratory failure and need to be in intensive care unit for weeks. So I think there's really a spectrum. The neurologic features that we heard about in the NOWR yesterday are just the reminder of the many ways influenza can cause disease. Of course this new strain of influenza is causing some of the complex presentations as well, encephalitis, high fever and seizure. So I think, you know, it's very important we take this virus seriously.

Operator: Next question. Mike Stobbe, Associated Press.

Mike Stobbe: Hi. Thanks for taking the question. And I'll have a follow-up. First, Doctor, could you just discuss the expectations CDC has for how many cases you'll be seeing in the fall and speak to the importance of the vaccine, what kind of difference it could make and how many kids you're seeing. Yeah, go ahead.

Anne Schuchat: Thank you. Influenza is very difficult to predict. And a new strain like this 2009 H1N1 virus is even more complex. We are trying to make estimates based on what we saw in the spring, what we have seen in past pandemics and what we see in a typical year of influenza. Even with seasonal influenza, with strains year in and year out we see variation year on year. I can't give you an estimate how many people will be ill, what proportion of the population will have influenza illness or need hospitalization or die. What I can say, though, is that vaccination is one of the best ways to prevent influenza and its complications. That's why we vaccinate intensively for seasonal influenza and why we're working on having a vaccine available in the fall for this new virus. We know influenza vaccines are not 100% effective. So your second question is what kind of impact we might have with vaccinations. Vaccination is just one part of the interventions we have available to us. We have efforts that can be directed at the community and individuals, keeping people who are sick away from other people using anti-viral medicines for treatment, and of course social distancing efforts like occasionally school dismissals or mass gatherings cancellations. Those kind of interventions are used in different circumstances depending how bad things are and how much benefit you think they may offer. But vaccine is a very important part of the intervention tool kit. And the influenza vaccines tends to be more effective in healthy young people than they are in seniors. This particular H1N1 virus seems to be more of a challenge for healthy young people and for adults who aren't elderly or underlying conditions. So our expectations are that a vaccine against this would probably work in a similar fashion to the seasonal flu vaccines. Next question.

Operator: Next is from Maggie Fox from Reuters. Your line is open.

Maggie Fox: Hi, Dr. Schuchat. I'm sorry to ask you to do this because you say you don't like to say how many but the million number is getting kind of old at this point. We're trying to explain to people all around the world how many might truly be affected so we can get away from the count thing. Is there a better estimate how widespread this is likely to be, given that we have 500,000 deaths every year from seasonal flu which suggests many tens of millions are affected.

Anne Schuchat: For The United States for seasonal flu we have about 36,000 deaths and about 200,000 hospitalizations. And we think that millions and millions of people are affected. Probably 20 million or more people are infected every year with seasonal influenza viruses. What I can tell you that we know right now is that in communities where this particular virus has circulated, we saw community attack rates of 6% to 8%. But this virus didn't circulate everywhere this past spring. We had the 6% to 8% attack rate just during the spring months. So we think in a longer winter season, attack rates would probably reach higher levels than that, that we would see quite a bit more than that. Maybe more two or three times as high as that. So I think that when people are trying to really get their arms around just how bad this will be, what I like to say is that we need to be ready for it to be challenging. We have lots of ways that we can limit the impact that it has, but it's going to take us working together. We know that our emergency rooms are often crowded in the regular year, and particularly in the winter season they can be crowded. This particular virus might crowd the emergency department season more. So one of our goals is to work with the medical community and the population to help people know when you don't really need to go to the emergency department and when you do so we can free those up for the most relevant cases, the cases that really need management there. And so unfortunately with influenza we just can't put numbers down to this. I suspect years after next year we'll have a good idea exactly how large the impact was and how much we prevented through the efforts that we work.

Tom Skinner: Maggie, do you have a follow-up?

Maggie Fox: That was a nice answer, but I still think the millions numbers isn't, you know, over a million is not terribly informative. And I know we have 20 million in a regular flu season. Would it be misleading to say, you know, more than 10 million? More than 20 million?

Anne Schuchat: That we're expecting, you mean?

Maggie Fox: Yeah -- no.

Anne Schuchat: No, that wouldn't be misleading to say that.

Maggie Fox: That have been infected already.

Anne Schuchat: That would be misleading. I'm sorry. That would be misleading. I don't think it's that high. The more than a million estimate was actually based on a modeling effort. And what we're trying to do is refine that model. So I hope in the weeks ahead we'll be able to share with you a little bit better figure of what we think has happened so far. we're actually working on this, have gotten some good feedback about some of the assumptions and the ranges, and we're trying to really make this model as strong as possible before we share it more publicly. so that's really -- I do think we'll be able to get you what you need in a couple weeks. I'm sorry. I misunderstood.

Tom Skinner: Next question, please.

Operator: Next is from Lisa Stark with ABC News. Your line is open.

Lisa Stark: Thanks so much for taking my question. I'm unfortunately going to talk about numbers too. You know, as you heard an AP story saying you have a worst-case scenario, if the vaccine doesn't work and other measures aren't successful there could be as much as 40% of Americans infected and several hundred thousand deaths. Can you comment on this worst-case scenario and what these numbers are that you're working on in that regard?

Anne Schuchat: We are planning for the most likely scenario and also for more severe scenarios. Worst-case scenarios we don't want to take us by surprise. With the pre-pandemic planning that we did the last several years we spent time focusing on pretty severe scenarios, like 1918, where the H5N1 virus that had 60% fatality with it would take off and be transmissible. So much of our framing has been focused on the very severe impact where 40% of the workforce might be absent because they're sick or staying home to care for a sick person. A more likely scenario, which is the kinds of patterns we saw in the spring in the most affected communities like New York City or Seattle, for instance, are seen in more general -- in many, many communities or really across the country. And that scenario is also, I think, challenging. You know, because I know that people read about this about New York City, Chicago, Seattle, and some of these areas, many children were sick. They were outbreaks in schools. Some of the schools were closed. Emergency departments were busier than they wanted to be. It was hard for people to get the care that they needed, and the information needs were very, very challenging. So planning for that more likely scenario where other communities discuss that disease transmission is a big focus for us and we think that we can limit somewhat the illnesses and severe complications of that kind of virus circulation with updated guidance, with partnership between the private and public sector, and of course with the efforts that we're making towards development of the vaccine. So those planning scenarios talked about, you know, talked about something like 40% of people missing work and how do we cope with that in society. But right now we're not expecting that high an absentee rate, but we are expecting challenges.

Tom Skinner: Lisa, do you have a follow-up?

Lisa Stark: But is it true that based on the pandemic of 1957 that, you know, if you had a worst-case scenario that you would have 40% of Americans who would have gotten the flu and maybe several hundred thousand who would die. Is that what you're thinking, could be, in fact, the worst-case scenario?

Anne Schuchat: I think we really need to get back and say worst-case scenario planning has a couple different assumptions in it. It talks about what proportion of people are ill, what proportion of people have very severe illness requiring hospitalization or leading to death, and what proportion of people are disturbed by the frequency of illness, need to stay home to care for others, or are impacted because their job is closed because the workforce can't remain open because of illness. So worst-case scenario is looking at the different sectors and see how extreme could things be. One of the values of worst-case scenario planning is it helps us think about continuity of operations. It helps people figure out is there anybody besides me at work who knows how to do the stuff that I do? Because what if I'm home ill or staying home with my child for a couple weeks, how will our workforce keep functioning? Who knows how to do my job? But worst-case scenario planning isn't the only important thing. It's very important we plan for what is quite likely. Based on what we saw in the spring and in the southern hemisphere, we think there's a lot of planning we need to do around what is likely. So this is a very important message. Things don't have to change for us to have a lot of work to do, for each parent and each person to be thinking about getting ready for how they're going to manage their child when they're ill, who can take care of my child if I can't stay home with them. Are are there others at work who can do what I do because I'm staying home with my child. How will I get information from school or the local health department about where to go or what I need to know. These are preparedness steps that everybody can take. And we think things don't have to change at all for it to be time for people to think ahead about being ready.

Tom Skinner: Next question, please.

Operator: The next question is from Tom Maugh of the Los Angeles Times. Your line is open.

Tom Maugh: Hi. The schools are going to be opening in the east at least within the next month well before any vaccines are going to be available. This suggests that this new flu is going to be pretty firmly entrenched in the population before vaccines come out. How much good are the vaccines going to do then?

Anne Schuchat: That's a very important question. We do think that schools reopening will lead to increases in illness in some places. Of will it be in every school? I really don't know. I don't think it's too likely that every single school is going to have problems. What we saw in the spring was patchwork. Some communities had a lot of disease and others didn't see any really. I think that schools will be reopening at different times over the next several weeks. And we want them all to be ready, but we also know that influenza is so unpredictable. It can just skip communities altogether and it can really affect some communities quite hard. So what we're trying to do, working with the department of education and working with the state and local governments as well, is to strengthen our ability to manage. You know, it's -- we're going to be updating school guidance, but it's very important for people to know that the local and state levels really are in charge of the school programs in their communities. What we're doing now is looking across the spectrum of what happens in schools, how do we keep kids healthy and learning and sick children home and away from other students. How do we make sure that we have provisions around school lunches and around the various supervision and education functions that occur in our schools. So we're really -- there's a lot that we can do even before we have a vaccine available, for instance, to make sure that kids are healthy and learning. And that's really where the government is focused right now.

Tom Skinner: Do you have any follow-up?

Tom Maugh: No.

Tom Skinner: Okay. Next question.

Operator: The next is from Donald McNeil, New York Times. Your line is open.

Don McNeil: Thank you. So, are you specifically bluntly recommending that summer camps stop handing out prophylactic Tamiflu to their campers? Are you doing anything to stop them? Are you calling summer camp associations or pharmacies and asking them to stop or cut off?

Anne Schuchat: I don't think that's a good idea, the prophylactics to all campers. What I can say is we have guidance about anti-viral medicines and the best ways for them to be used. We've been working closely with the camp associations and with the health departments who work locally with their camps, and we really want the public to know that anti-viral medicines are important. They're part of our armamentarium. I think another important thing to say is we have the resistance to Tamiflu in the new virus. I believe now there are about five cases that have been reported that are Tamiflu resistant. That's a very small number compared to the very large number of cases we're seeing around the world. But we have seen with other influenza viruses them taking off with a low level of resistance to virtually all strains being resistant. We think it's important to be careful about how the medicines are used but there are circumstances where preventive use of anti-virals is still important in people who have severe medical problems, who have been in very close contact with someone with influenza. So I think our efforts are really trying to make sure people know the right way to use the medicines, the role that they play and the risk of resistance that's out there that we don't want to get any worse.

Tom Skinner: Next question.

Operator: The next is from Joanne Silberner. Your line is open. From NPR.

Joanne Silberner: Thanks. And I hate to plague you with numbers but got to do it. Follow-up on the 40% of Americans over the next two years. That number, that's the number who may be affected in terms of they themselves are ill or people around them are ill and they're caretakers? And the second question is earlier you said the attack rate in communities was 6% to 8% with this flu. How does that compare to seasonal flu?

Anne Schuchat: Okay. The 40% figure that I gave was not about illness. what I was trying to say was our planning assumptions for a severe pandemic were that at a certain period up to 40% of the workforce might be affected and not able to work either because they were ill or because they needed to stay home to care for an ill family member. So a lot of that is the ill family member, not the worker themselves. The second question that you asked -- I'm just forgetting what it was. I'm sorry.

Joanne Silberner: How does the 6% to 8% attack rate compare with seasonal flu?

Anne Schuchat: It's difficult to compare that. One reason that it's difficult is that 6% to 8% attack rate occurs in the May to June period when there was zero cases of seasonal influenza. To some some extent we were seeing a lot of transmission when the circumstances weren't that great for transmission. During seasonal influenza, the winter months, we might see rates of 10% to 15% of people developing influenza-like illness. And so what we saw in that sort of three to four-week period with the 6% to 8% was probably just a glimpse of what might happen over the longer winter season when transmission circumstances like temperature are different. So it's really an apples and oranges comparison.

Tom Skinner: Next question?

Operator: The next is from David Brown, Washington Post. Your line is open.

David Brown: Yes. Thank you very much. Two unrelated questions. One is, has CDC done any modeling in which they have taken the clinical characteristics, to the extent they're known of this virus, attack rate, case fatality rate and said, okay, if it peaks in let's say mid-October and there's essentially no vaccine protection, what is likely to be the effects on the population in terms of number of cases that are severe enough to be hospitalized and the number of deaths? So that's my first question. My second question is, can you talk a little bit about camps and the military academies. How many camps? Which military academies? What the attack rate is there. Whether you've been studying them closely to try to get a better sense what the epidemiology is. So a few details about these recent outbreaks.

Anne Schuchat: The first question about whether we're modeling to try to estimate the impact in October and so forth, we are working on that. I don't have numbers today to be able to share. But that's the type of effort that we're making. There's a lot of modeling that's going on around the world and around the U.S. with academics, investigators and the number of institutions. They have been meeting with us to plug our data into some of these modeling efforts. What I believe is that we will see a range of estimates to come from these. It's very clear when one is doing these modeling efforts that there's some information that is pretty hard and fast and there's others that's really expert opinion or best guess. And some of the most important factors may be ones that we really don't have hard estimates to plug in. But I think these are really important efforts and they'll help us really put some limits around the range of possibilities. But I think we do have to be -- you know, it's very difficult to be comfortable with uncertainty. And I don't know the reporters today want much to be much more crisp in my predictions. But I think there's models are only going to be precise -- these models will not be precise. We think it's important to step back from a focus on a single number and sometimes even a range around the number is much less precise than we need. I don't think that influenza and its behavior in population lends itself very well to these kinds of models.

The second question was about the military camps. I don't know whether we have active investigations going on. That's something I can check on. But I'm not aware we're assisting -- I'm certain that -- I know there are a number of reports we heard, but I don't have the information about whether we're actually helping with some of the investigation.

Tom Skinner: Next question?

Operator: The next is from Stephen Smith, The Boston Globe. Your line is open.

Stephen Smith: Hi, Dr. Schuchat. Thanks for taking the call. I was hoping to get a better sense when you were talking about the summer camps and prophylactic use of Tamiflu what your sense was into how widespread that is, whether -- and additionally whether you have sent any investigators out to investigate clusters of illness at summer camps and, if so, in what parts of the country.

Anne Schuchat: You know, summer camp situations are quite different than schools. One thing I want to say is that we have been in touch through the states and local health departments about the camp situation. We have had heard reports on prophylactics, and on further probing we did not find that to be the main response -- the common response. We didn't find that to be typical or what everybody was doing. I know there have been media reports about individual camps who have taken that route, but that wasn't the typical response we've heard of.

A thing about summer camps that's quite different than school scenarios, is they're a lot shorter. They're usually one- or two-week experiences and you have a high turnover. So the circumstances for investigation are often not that stable. We did a number of field investigations with schools in the spring to try to understand the population, what was going on and what interventions were working. But the way things are usually quite short-lived in the camps, I don't believe we've actually sent teams out. The health department is really the front line of public health out there are actively working with camps in their jurisdictions to make sure good information is available and that they're able to help provide guidance. so I don't believe we've been, you know, in a field on the camp situation.And it is not a fixed population that is managed over the months. It's a shorter-term population.

Tom Skinner: Next question?

Operator: The next is from Steve Sternberg, USA Today. Your line is open.

Steve Sternberg: Hi. Thank you very much. I'm wondering how much is known about resistance in the Novel H1N1 virus. There were cases in Asia and Europe, as I recall. Do we know anything more about them and whether -- are there any cases in the U.S. now?

Anne Schuchat: At this point what we're aware of is five cases have been reported either by the WHO or by the countries. One of these five cases was detected in Hong Kong, but it was an American who was traveling there from San Francisco. And the assumption was that the person probably acquired the infection in San Francisco. An investigation was done in California around that to understand whether there are influenza viruses circulating in that area that are resistant. Large specimens were tested and no other resistance was bad. It could be that are Tamiflu resistant circulating in the U.S., but so far the only one report that we have is of a traveler from here who went to Hong Kong and was tested in Hong Kong. You know, this is something that should not surprise us if we see more and more of this. This is, you know, influenza viruses mutate frequently and any viral resistance could be acquired easily. Most of the cases that were detected so far, most of them occurred in people who were taking anti-viral Tamiflu because they had been in close contact with somebody who had the disease. The good news is none of them spread it to anybody else. Some of the investigation involved testing their contacts and they didn't see any evidence of spread or, you know, passing that along. But I think it won't surprise us if we see resistance emerge as a bigger problem in the fall or in the years ahead. As I mentioned with the other two influenza viruses, this has been a problem. The seasonal H1N1 viruses right now are virtually all resistant to Tamiflu.

Tom Skinner: Next question.

Operator: The next is from Jon Cohen, Science Magazine. Your line is open.

Jon Cohen: Hi. Thank you for taking my call. I think there's a lot of confusion about clinical trials. Two days ago five trials did not have adjuvant. They said there would be tests with adjuvant. The companies have spoken of doing clinical trials with adjuvant. The government has purchased it with a separate ingredient that can be mixed and matched. What is the plan for doing clinical trials with adjuvant?

Anne Schuchat: They are planned. They're a set of -- there are several different ways that the trials get summarized. The NIH or National Institute of Allergies and Infectious Diseases is coordinating a set of studies with their vaccine, treatment and evaluation units around The United States. And those are a set of trials that I believe that are listed on their website. The manufacturers will be doing trials in collaboration with the FDA. And of course there are trials being done in other countries on behalf of those other countries vaccine planning efforts. The U.S. has purchased adjuvant as well as antigens and we are expecting to see results from trials of how well adjuvant works in terms of changing the immune response to a given antigen. I don't actually have the details of how many trials with adjuvant and the timelines for the trials but there are definitely plans to look at the behavior of this -- of the vaccine when it is adjuvanted.

Tom Skinner: Next question?

Operator: The next is from Kate Ryan, WTOP radio. Your line is open.

Kate Ryan: Hi. Thank you. I'd like to kind of backtrack a little bit on the concern about school populations. And you mentioned earlier for seasonal flu recommendations going from encouraging parents to have their children vaccinated to recommending -- a flat-out recommendation. What's the difference, and do you see a time when schools should be advised to say, if you don't have your immunization, if you don't get these kids vaccinated we're not going to let you in?

Anne Schuchat: The comment I was making about the recommendations were for the seasonal flu vaccine. So I want to make sure everybody is aware of that as I go forward. So my next few sentences will relate to seasonal flu vaccine recommendations. The advisory committee for immunization review practices looks into the question of whether vaccinations should be broadly recommended for school-aged children. And it was a multiyear process. They reviewed data on the burden of disease, the direct and indirect benefits of vaccines, the feasibility and problematic concerns, the cost-effectiveness, vaccine behavior, how well the vaccines were tolerated in terms of their safety profile, short and long term. They looked at all factors. And when they voted on recommendations for school-aged children, one of the critical factors that was discussed was that this wasn't something that could happen overnight, that it might take a while to be able to implement vaccination of school-aged children because the logistics are complex and because we don't really have a very, very strong school infrastructure or public health infrastructure for school associated immunization. So what they recommend was a multiyear process that would encourage vaccination of school-aged children where feasible but the recommendations wouldn't be fully implemented until the 2009 season. So we're butting up against that 2009 season for full implementation. And the idea was the last couple years the state and locals were going to be able to start planning how this might work. Of course it has gotten a little complicated this year because the same public health infrastructure is also coping with the new H1N1 virus and working on whether plans will be in place to be able to offer vaccine to school-aged children against that virus, as well as the seasonal flu viruses.

So the second part of your question was about mandates. Mandates for immunization for school entry are a state and local matter. The immunized states, every state mandates use of certain vaccines for school entry, such as measles vaccine. Influenza hasn't typically been a vaccine that has been on that same kind of listing. Measles, of course, is a disease that we have eliminated in The United States. Much of the tremendous control that we've had with measles has been through high immunization coverage, as well as high second dose coverage, which is where the school entry requirements came through. so at this point I am not anticipating mandated influenza vaccine for school-aged children. But whatever happens, that will be a state and local matter.

Tom Skinner: Time for a couple more questions.

Operator: The next is from Rehema Ellis, NBC News. Your line is open.

Rehema Ellis: Thank you very much for taking my call. My question is about vaccine production. Can you speak more directly to exactly how the trials are going and when do you expect the vaccine will be able, and will it be available for every one of the populations you are recommending should get the vaccine?

Anne Schuchat: The clinical trials of vaccine require pilot lots to be produced. So you basically use relatively small amounts of vaccines in order to carry out a clinical trial. And right now in Australia they have already launched a clinical trial and the NIH is about to launch several trials next week, I believe. So the clinical trials will be happening over the next several weeks to months, and that will be providing helpful information right away about how people react within the days after they receive vaccines and later on about their immune responses to the vaccine. Production is also going forward right now. The U.S. has procured vaccines from five companies, and those companies are all taking the steps to make large amounts of vaccine available. They are producing antigen in bulk and at a certain point in the next couple months, decisions will be made about filling and finishing that antigen into actual vaccine that can be given, putting it into vials or put it in open syringes. It's expected that the decision will be made about how much antigen should go into the vials in the months ahead. At this point, the U.S. government has procured large amounts of vaccine but we haven't yet made recommendations on what populations ought to be offered vaccine.

A key step in that process will be next week when the Advisory Committee for Immunization Practices meets and looks through information about the disease burden and the vaccine, expected impact, and the logistics and the risk benefit kind of circumstances, and they will make recommendations on which populations ought to be targeted for vaccination. At this point the planning and investments that the U.S. government made suggests to us that we are likely to have plenty of vaccine for the groups that are targeted. Of course it is always risky to say that because influenza vaccine manufacturing is not always as predictable as you would like. And sometimes we have surprises. But at this point we're expecting there to be a reasonably large numbers of doses available and the middle of October is the point that we're looking at in terms of our planning, that we hope to be able to launch a vaccine program, assuming several factors in terms of safe and effective vaccine is available and no big change in the antigen properties, we're planning the middle of October timeline. The exact number of doses that we'll have, whether everything will be ready to go, those are things that we really have to be prepared for some surprises around.

Tom Skinner: All right. We'll take one last question.

Operator: Marilyn Serafini, National Journal. Your line is open.

Marilyn Serafini: Hi. Thanks so much. I have a question about the vaccine. But I guess the first question -- well, the first part of the question is, is there any evidence at this point that the virus is changing?

Anne Schuchat: We're looking closely at the strains circulating in the southern hemisphere and here and in terms of the vaccine or immunologic properties of the virus, we don't see changes. We look for antigenic changes. That would mean the vaccines we're developing will not be great fits for this particular virus. But so far the virus hasn't changed in those ways. The only change we have seen is that the five cases we've learned about that have the resistance mutation. But that's not a kind of change that would affect the vaccine fit. You had a second part?

Marilyn Serafini: Do you have any expectations that the virus -- what would it take for the virus -- if changes in the virus to make the vaccine not efficient and also how do we look at the people who have had -- have already had H1N1 over the summer or believe they did, because not everyone knows for sure because they weren't specifically test but we assume they did, and how do we handle those people going forward? We know that, you know, there will be limitations to the amount of vaccine that's available up front. And if that is the case, do we know what kind of resistance these people already may have and will there be enough information available to them and to the public health system that perhaps they won't need the vaccine?

Anne Schuchat: The question of what will it take for the virus to change, influenza viruses can mutate relatively easily. And sometimes those changes result in major changes in their antigenic properties. We aren't expecting that to happen between now and when vaccine is veil but it could happen. It's one of the things we're looking at carefully with the virologic testing. The second question is about what kind of impact it would have for vaccination recommendations, if you have already had a flu-like virus that you think was the H1N1 virus. At this point I believe that's the kind of issue that the advisory committee for immunization practices may cover as they come up with recommendations. It's very important to say that most people who have respiratory illnesses don't find out exactly what caused it. Even most people with influenza don't know exactly which type of influenza caused their illness. So it's very difficult to differentiate what my fever and cough were due to on an individual basis. It may just be not possible to say whether the illness that you had in the past several months was truly caused by this new virus. So I believe that the ACIP will be addressing those kinds of questions as they make recommendations, and we hope those will be practical ones that will be helpful to both the clinicians and the people out there looking for vaccine.

Tom Skinner: Okay. We're going to conclude our briefing. Thank you, Rose, and thanks to all who dialed in. And we'll be sure to keep you all informed of future media briefings that we're having. Thank you very much.

END

[Sally Furniss]

Re: PLoS Med. What Is the Optimal Therapy for Patients with H5N1 Influenza?

Best Clinical Management For H5N1 Infection Debated



The best ways of managing patients with H5N1 infection (avian influenza) are debated by experts in this week's open access journal PLoS Medicine.

Higher than recommended doses of the antiviral drug oseltamivir Tamiflu should be used to fight H5N1 influenza, argues Nicholas White (Mahidol University, Bangkok, Thailand). In contrast to the current WHO guidelines recommending that oseltamivir be given at a dose of 75 mg twice daily for five days, Dr. White argues that higher doses should be given for H5N1 infection to avoid any possibility of under-dosing those patients with unusual pharmacokinetics and more resistant organisms. This will come at the expense of increased toxicity, he says, but is necessary given the mortality burden of H5N1 infection and the fact that H5N1 replicates more rapidly than seasonal influenza viruses, reaches much greater viral burdens than do other human influenza viruses, and resistance develops swiftly.

Robert Webster and Elena Govorkova from St. Jude Children's Research Hospital in Memphis, USA, writing in response to Nicholas White's article, disagree. They argue that we must instead consider a multidrug approach to managing patients with H5N1, an approach that is supported by animal data and "can guard against the emergence of resistant strains." Tim Uyeki from the Centers for Disease Control and Prevention in Atlanta, USA, emphasizes theneed for more data to help inform clinical management of patients with H5N1 infections. In the absence of these data, he argues, we need a multipronged strategy: pharmacological strategies including combination antiviral treatment, anti-inflammatory agents, and immunotherapy, and non-pharmacological strategies such as the standardization of optimal ventilator and fluid management, especially for acute respiratory distress syndrome, and management of other complications.

In a 2007 article in PLoS Medicine (PLoS Med 4(5): e119), Holger J. Sch?nemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases. The authors discussed how they developed such a "rapid advice" guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days.

Funding: NJW is a Wellcome Trust Principal Fellow. RGW and EAG are funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200700005C; and by the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in the decision to publish or preparation of the manuscript. TMU received no specific funding.

Competing Interests: NJW is the co-chairman of the World Health Organization antimalarial treatment guidelines committee. RGW reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals and receiving consulting fees from GlaxoSmithKline. EAG reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals.

Citation:
"What Is the Optimal Therapy for Patients with H5N1 Influenza?"
White NJ, Webster RG, Govorkova EA, Uyeki TM (2009)
PLoS Med 6(6): e1000091.

Source
PLoS Medicine

http://www.medicalnewstoday.com/articles/155052.php

[Commonground]

Tamiflu resistance in pandemic influenza - historical compilation of news

Vietnam: Tamiflu is still the drug treatment of influenza A/H1N1 effective

This is confirmed by a Department Director Department of Management, the Ministry of Health - Mr. Truong Quoc Cuong - in writing the number 875 was issued today, 27 / 7.

According to Department of Pharmacy Management, said the report by the World Health (WHO), the world, only with Denmark, Hong Kong, Japan found the resistance to the drug Tamiflu. Meanwhile, in Vietnam, according to a report by the Institute of infections and tropical Country, it is still no clinical evidence specific for influenza A/H1N1 virus shows drug resistance to Tamiflu.

However, in some cases certain, the treatment with Tamiflu can do a longer immunity and treatment of the virus except for the body.
So far, WHO and the medicines management Europe (EMEA), the management of food and medicines USA (FDA) has not notified a change is the use of Tamiflu (Oseltamivir) in the exposed control therapy for patients with influenza A/H1N1.

Therefore, Department of Management, the Ministry of Health requesting the function, the treatment, the hospital treating influenza A/H1N1 patients need extensive propaganda, dissemination of more effective Results of Tamiflu (Oseltamivir) in treatment of patients with influenza A/H1N1.

Department of Management recommended all information related to this is not propaganda for the people not get the confirmation of state management on health.

In addition, the treatment and people were influenza A/H1N1 must be strictly the instructions of the BS using Tamilu to avoid the situation occurring drug resistance is not necessary.

[Commonground]

Tamiflu resistance in pandemic influenza - historical compilation of news

Vietnam: Patients had serious complication

28/07/2009 09:49
* 2 patients foreigners suspected drug Tamiflu resistance

Influenza virus has increased in power?

Yesterday afternoon 27 / 7, the doctor Tran Tinh Hien - PGDBV TPHCM Tropical Diseases, said, hospitals are treating 80 patients for influenza A/H1N1 infection, including 8 of the foreigners. However, the most anxious to have you here appear in patients with severe complication. It is a male patient who has hospital treatment during the 9 days from now infected and influenza A/H1N1 complication severe pneumonia.

At first patients treated about 3 days then the fever, but after that the fever and accompanied by pneumonia. BV has determined this is the complication of severe A/H1N1 infected by the first BV Tropical Diseases recorded.

In addition, BV Tropical Diseases TPHCM also recorded the suspect drug Tamiflu resistance when 2 foreign patients treated to 9th but still positive for H1N1. Specifically, a patient indicated TPHCM treatment was 14 days but not from making BV Tropical Diseases had to redirect treatment. "Normally a patient treated for 3-4 days for negative results when the treatment time lasts more than 1 week are positive to have found the time to clean the virus slowly," Dr. Tran Tinh Hien confirmed.

Recognition of the NNVN that Ch Tropical Diseases has received treatment for a pregnant woman in first 5 months were influenza A/H1N1. Thai effects are manifestations of cough, fever BV to be tested this month and 4 days for positive results for influenza A/H1N1. There is additive pregnancy active treatment and no assessment of affect pregnancy. Before this poor place, Dr. Tran Tinh Hien salary, up to Vietnam may have died because of influenza A/H1N1.

3 more schools gotten flu

Also in yesterday, a student High School Building (on page Nơ Long, Binh Thanh District) has been officially identified with positive influenza A/H1N1. Initial investigation showed that, before the disease, students have to drink coffee and chat in the Internet service area shore scratch Language Dang Van. Then out of the rain and cold having fever, then the test at the Pham Ngoc Thach BV for the positive results for influenza A/H1N1.

Up to yesterday afternoon, girlfriend of students also have manifestations of high fever and was conducted in isolation, test flu. Am now 27 / 7, the high school construction was red alarm, prohibits all students to school, and implement isolation now 32 students in class with this patient. At the health sector has the 5 students of the high body temperature. BGH by the school, before detection of the disease, the school has 900 students are studying. In addition, parents and brother of the patient is also being conducted in testing.

The same day, Ho Chi Minh City Department of Health has confirmed an additional 1 student private high schools Germany Hong (Tan Binh) influenza A/H1N1 infection. It is the student Tran Thanh Tr., 14 years old. After receiving this information, although not more recognition of influenza A/H1N1 infection, but any school BGH Germany Hong decision temporarily close the school. The Department of Health Daklak province on 27 / 7 also confirm 1 students attending private school in Thai Binh (Tan Binh District, HCMC) positive for HPAI H1N1. Students develop this disease after 2 days of his TPHCM l?nh flu but then has the disease. At the Thai Binh has 200 boarding students and is temporarily closed (before the students of this disease) to students free to leave.

Recognition of NNVN that to the 27 / 7 has 8 students, 1 teacher and 1 staff RMIT University Vietnam (Q.7) positive for influenza A/H1N1. This is ch?m flu from 22 / 7 the Department of Health TPHCM not timely blockade, but to prevent the school temporarily closed for students free home. Ch?m flu at separate high schools private boarding Nguyen Khuyen (Tan Binh) had 10 students have influenza A/H1N1 and secondary schools in The Times Ngo (Q.9) also had 10 more children positive influenza A/H1N1 , raising the total to more than 90 infected children.

Institute of Hygiene epidemiological Central 27 / 7 has been officially confirmed case of death of a patient named T. live in Ky Tien, Ky Anh district, Ha Tinh province non influenza A/H1N1 and influenza A/H5N1.

Anh T. many epidemiological factors, clinical symptoms similar to influenza by influenza A/H1N1 and A/H5N1 tests but official results were negative.

[HenryN]

Re: Third case of Tamiflu-resistant swine flu in Japan

WHO mulls ways of using antivirals in flu fight
(AFP) ? 3 hours ago
GENEVA ? The World Health Organisation said Tuesday that it will consult experts on the way anti-viral drugs such as Tamiflu are used to tackle the swine flu pandemic, and possible drug resistance.
"In the coming days we're having technical consultations by teleconference regarding antivirals," said spokeswoman Aphaluck Bhatiasevi.
"But as of now WHO's recommendations for use of antivirals has not changed," she added.
"They will be looking at specifics related to antiviral resistance and use of oseltamivir. WHO's recommendation for use of oseltamivir is for treatment," she underlined.
Oseltamivir is the active ingredient of Tamiflu, one of two drugs the WHO recommends to treat influenza A(H1N1).
Different countries have gradually evolved different approaches on the use of Tamiflu -- normally a prescription drug -- and some have been distributing it more widely to fearful populations than others.
But some doctors have expressed fears that excessive use, especially for preventive purposes or to tackle mild symptoms, could lead to the development of wider drug resistance and reduce the effectiveness of Tamiflu.
Health officials in Canada recently identified a case of drug resistance, adding to cases in Denmark, Hong Kong and Japan.
Roche, the manufacturers of Tamiflu, has said it expects a 0.5 percent rate of case resistance based on clinical trials.

http://www.google.com/hostednews/afp/article/ALeqM5i4PkYvVctDRLbXKxVKgQpCD7tysg

[HenryN]

Re: Third case of Tamiflu-resistant swine flu in Japan

Rwilmer, do you have more info concerning this case than what is posted here? If so, could you post it? Thanks

oldman

The evidence is circumstantial, but Japan is the world's biggest user of Tamiflu, and this is the third reported case from Japan of a patient who developed resistance while on prophylatic Tamiflu. These patients are the most likely candidates for the discovery of H274Y because they are at risk due to contact and are being monitored, so when they develop symptoms while taking Tamiflu, they are tested and the resistant strain is isolated and sequenced.
The chance that this is not another example of H274Y is close to zero.

[HenryN]

Re: Third case of Tamiflu-resistant swine flu in Japan

Is it completely false to say that taking Tamiflu could be a causal factor in the development of Tamiflu-resistant strains? Or is it possible there is some truth to it?

Those who think "random mutations" are a major driver of antigenic drift think that the virus makes copy errors at a high frequency, and these errors include H274Y, which is selected in patients taking prophylatic Tamiflu. However, this mechanism doesn't explain why all resisatnce has been H274Y and not N294S, another resistance mutation that has been identified previously in N1.

The "random mutations' also do noy explain the emergence and spread of H274Y in H1N1 seasonal flu, because not anly was all H1N1 resisatnce due to H274Y, but there was no resistance detected in H3N2, even in counttries where the vast majority of influenza A was H3N2.

The resistance is most easily explained by recombination and the Tamiflu treatment just allows the minor population, which has already has acquired H274Y, to be identified.