Avian Influenza Update from the CDC

[Ace844]

Go to www.pandemicflu.gov --- everything I have stated is fact, and will make it's way to you soon. Our public health agency is taking great pains to educate ems, fire, and PD to this upcoming threat. I imagine other states will do so also.

Kindly refer yourself to my previous posts.....

ACE844

[GAmedic1506]

Here is where you and I differ. Regardless of whether or not I agree with you, regardless of whether or not I win, I think it is important to raise issues, have discussion, and then let people take from it what they will. I am not going to demand that you filter or arrange your ideas to meet my parameters, if i disagree with you, i will put it in the discussion notes, and let others decide who makes the better argument. You like to frame everything with a scientific study, which is not a bad thing, its just that i do not need scientific studies to back things that I know to be true. Obviously, if you have scientific data to refute anything that I claim, I would hope that you would use that as part of the discussion. So lets try to be better adults as we move forward, and not attack each other personally. There are some things that we will just have to agree to disagree on.

As far as this thread, it is a great topic, that everyone needs to get more education on. When I attended our Pandemic Summitt, I saw a fear in the PH official's eyes that I have never seen before. They are gravely concerned about this flu.

[Ace844]

(The Lancet Infectious Diseases

Volume 6 • Number 2 • February 2006

Copyright © 2006 Elsevier

Newsdesk

Oseltamivir resistance raises bird flu concerns

Helen Pilcher

--------------------------------------------------------------------------------

PII S1473-3099(06)70368-1)

Two Vietnamese patients infected with the H5N1 avian influenza strain developed resistance to the antiviral drug oseltamivir (Tamiflu) before their deaths. The finding raises concerns over the drug's use, and reinforces the need for better therapies to avert a global bird flu pandemic.

Menno de Jong (Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam) and colleagues analysed throat swabs taken from eight Vietnamese patients infected with the H5N1 strain of avian influenza. Viral isolates taken during and after the standard oseltamivir treatment regimen (two 75 mg doses per day for 5 days) were tested for a genetic mutation known to render influenza viruses resistant to oseltamivir.

The mutation was found in two patients. Both died, even though one received treatment speedily, within 24 hours of symptoms developing. Two other patients who did not carry the mutation also died. “With four patients surviving, the good news is that oseltamivir works in a proportion of patients”, says de Jong. “The bad news is that resistance to the drug may not be that rare.”

In one patient the development of resistance coincided with a dramatic worsening of symptoms, suggesting that resistance contributes directly to disease progression. “We need to minimise the development of resistance”, says de Jong.

One approach could be to increase the dosage. Higher doses may be better at stunting viral replication, so limiting the likelihood of oseltamivir-resistant mutations occurring. Another option may be to offer oseltamivir alongside other antiviral drugs. Zanamivir (Relenza), for example, is thought to be effective against oseltamivir-resistant influenza virus. However, the downside of zanamivir is that it is only available in inhaled form, and so does not offer the systemic protection thought necessary against avian flu.

But oseltamivir is still the main anti-influenza drug recommended by WHO, and many believe that there should be a supply in every medicine cabinet. This scenario is potentially dangerous, says Anne Moscona (Weill Medical College, Cornell University, New York, USA). Misuse of the oseltamivir could rob us of the drug's advantages by favouring the emergence of oseltamivir-resistant influenza virus.

With the continued global spread of avian flu among poultry and wild birds, concerns remain that the virus may trigger a human pandemic. But before this happens, the virus will have to change further—either by mutating or recombining with another virus—and become able to spread directly between people. But “it is impossible to say if this new virus would also become resistant to Tamiflu”, says de Jong. “We'll just have to wait and see.”

(Bird flu kills Thai youth amid new outbreaks Story List

July 27 @ 2006

By Darren Schuettler

BANGKOK (Reuters))

A 17-year-old Thai has died of the H5N1 bird flu virus, the country's first death this year as it battles fresh outbreaks of the disease, a senior health official said on Wednesday.

The young man died on Monday in the northern province of Pichit, where authorities have slaughtered hundreds of birds and restricted poultry movement in a bid to stamp out Thailand's first outbreak in eight months.

"The final lab test confirmed that he died of bird flu," Kamnuan Ungchusak, head of the Health Ministry's epidemiology bureau, told Reuters by telephone from the hospital where the youth died.

He is believed to have caught the virus while helping his father bury dead chickens last week.

The father showed no flu-like symptoms of the virus which has killed 15 Thais since it swept across parts of Asia in 2003. The last Thai victim, a five-year-old boy, died in December last year.

"We have quarantined the family and there is no report of a new case yet," Kamnuan said.

Not including this latest death, bird flu has killed 133 people worldwide since the virus re-emerged in Asia in 2003, the World Health Organization says.

At present, H5N1 remains essentially a disease of birds and is hard for people to catch.

But scientists fear the virus could mutate into a form that spreads easily among humans and trigger a pandemic in which millions could die.

The outbreak in Pichit, one of seven high-risk Thai provinces where surveillance was stepped up this month, was confirmed by the Agriculture Ministry on Tuesday, but the source of the infection was not known.

The U.N. Food and Agriculture Organization (FAO) called for an "intense investigation" of the outbreak. It said Thailand had done a good job in fighting the virus so far, but it may need to fine-tune its surveillance.

"Clearly they have pushed this thing down to the level of almost non-existence, but either it's been reintroduced or it has persisted and at such a low level it did not cause any significant blips," Laurence Gleeson, a senior FAO official in Bangkok, told Reuters.

Thailand was slow to respond to bird flu when it first began ravaging poultry flocks in late 2003, badly damaging what was the world's fourth largest chicken export industry.

Critics accused the government of trying to cover up this latest outbreak, a charge denied by Livestock Department officials who said they had informed the public as soon as tests confirmed the presence of H5N1.

Gleeson said the FAO, which has stressed the need for rapid and transparent reporting of outbreaks, had no complaints about Thailand's reporting procedures. (Additional reporting by Nopporn Wong-Anan)

(The Lancet Infectious Diseases

Volume 6 • Number 5 • May 2006

Copyright © 2006 Elsevier

Newsdesk

Human-to-human spread of H5N1—location may matter

Jane Bradbury

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PII S1473-3099(06)70450-9)

The H5N1 avian influenza virus attaches predominantly to cells deep within the human respiratory tract, report two research teams. Although both senior researchers— Thijs Kuiken (Erasmus Medical Center, Rotterdam, Netherlands) and Yoshihiro Kawaoka (University of Wisconsin-Madison, Madison, WI, USA)—stress that many factors affect human-to-human transmission of H5N1, the absence of attachment in the upper respiratory tract might, they suggest, contribute to the current inefficiency of this process.

More than 100 people have been infected by H5N1 but this highly pathogenic virus has rarely, if ever, passed between people. Indeed, given its widespread occurrence within bird flocks, relatively few people have caught H5N1 from birds. Could it be, therefore, that only people who get bird flu have receptors on their cells for H5N1? Flu viruses attach to sialosaccharides on their host cells through haemagglutinin. In human flu viruses, this protein spike recognises sialic acid linked to galactose by an ɑ2,6 linkage; avian flu haemagglutinin recognises ɑ2,3-linked sialosaccharides.

To investigate whether human cells lack H5N1 receptors, Kawaoka's team stained material from the human respi ratory tract with lectins specific for these two linkages. They found that cells in the upper respiratory tract contain receptors for human flu viruses but only cells deep in the lungs express avian virus receptors. This receptor distribution, which the researchers confirmed by examining the binding of avian and human flu viruses, provides a partial explanation for H5N1's poor human-to-human transmission, says Kawaoka. “Because H5N1 viruses don't grow in the upper portion of the respiratory tract, they cannot be readily transmitted by coughing and sneezing.”

Kuiken and his team also investigated H5N1 virus attachment to the human respiratory tract. “We wanted to understand why H5N1 causes pneumonia”, explains Kuiken, “and like Kawaoka, we found that this virus attaches to alveolar type II pneumocytes and to non-ciliated cuboidal epithelial cells in the terminal bronchioles”. The attachment to type II pneumocytes, says Kuiken, provides new insights into the pathogenesis of H5N1 because these cells normally repair damaged lung tissue. But, he cautions, “our results only suggest, rather than prove, an explanation for the poor spread of H5N1 between people”.

“These two papers help to define the receptor distribution within the human respiratory tract for avian viruses like H5N1”, comments flu expert Frederick Hayden (University of Virginia, Charlottesville, VA, USA), “and they fit well with the clinical observation that H5N1 can cause severe primary viral pneumonia. But the idea that this receptor distribution explains poor person-to-person transmission is only speculation.” And, although mutations in the H5N1 haemagglutinin that change its binding pattern to human cells might take H5N1 a step closer to causing a human pandemic, other adaptations will also be required, conclude Hayden, Kuiken, and Kawaoka.

[Just Plain Ruff]

What the heck is a pandemic summit? GA Enlighten us on that. Was it all about the flu or other things? I'm curious

Also, didn't they also say Bird flu a couple of years ago was going to turn into a pandemic? This sounds strangely familiar.

[Ace844]

High immune response seen with novel H5N1 avian influenza vaccine Story List

July 27, 2006

LONDON (Agence de Presse Medicale for Reuters Health) - A new H5N1 avian influenza vaccine may be filed with regulatory agencies in the coming months after study results showed the vaccine elicited a high immune response even at the lowest dose of antigen tested, vaccine-maker GlaxoSmithKline said Wednesday.

Early analysis of a clinical trial with 400 healthy volunteers showed that the vaccine elicited a strong seroprotective immune response in more than 80% of subjects who received 3.8 micrograms of antigen. "This level of seroprotection meets or exceeds target criteria set by regulatory agencies for registration of influenza vaccines," the company added in a statement.

"Efficacy results at these levels of antigen dosage have also not been reported for any other H5N1 vaccine in development to date, including those using other adjuvants such as alum," Glaxo continued.

J. P Garnier, GlaxoSmithKline's Chief Executive Officer, said: "These excellent clinical trial results represent a significant breakthrough in the development of our pandemic flu vaccine. This is the first time such a low dose of H5N1 antigen has been able to stimulate this level of strong immune response.

"There is still a lot more work to be done with this programme, but this validation of our approach provides us with the confidence to continue developing the vaccine, including assessment of its ability to offer cross-protection to variants of the H5N1 strain.

"All being well, we expect to make regulatory filings for the vaccine in the coming months," Garnier said.

The study was conducted in Belgium and involved adults between 18 and 60 years old who were vaccinated twice during the course of the trial. Four different levels of antigen dose were tested; 3.8 micrograms was the lowest dose assessed.

[AZCEP]

This is another case of policy makers being caught in the moment.

"Bird flu" was supposed to be the next big threat, right behind smallpox, bioterror, West Nile virus, and WMD's. Makes you think that maybe they are spending too much time watching CNN for their own good. They see a story about something, then inflate the dangers to unrealistic levels.

How many flu patients did you see this last year? Were any of them "Bird flu"? I didn't think so.

Wash your hands, cover your cough, eat some chicken soup. The "Bird flu" is not a significant danger yet. The yet is important, because it can become one, but until it happens we all need to relax just a bit. Walking around looking for this one bug, blinds us to the possibilities of other bugs that are more of a problem.

[Ace844]

(Avian influenza transition to pandemic virus may be complex process

August 1 @ 2006

NEW YORK (Reuters Health))

A simple exchange of genes between the H5N1 avian influenza virus and a human influenza virus appears to be insufficient to cause efficient person-to-person transmissibility that could lead to a pandemic outbreak, scientists report in the early online edition of the Proceedings of the National Academy of Science.

Nevertheless, "these findings do not mean that the H5N1 avian influenza virus cannot become a pandemic strain," Dr. Julie Gerberding, director of the US Centers for Disease Control and Prevention (CDC) in Atlanta, warned at a media briefing. "It just means that such a transition will be more complicated than a simple one-to-one genetic transfer."

"We cannot become complacent about pandemic preparedness," she emphasized.

Dr. Gerberding explained that there are three requirements necessary for a pandemic virus to develop: The virus must have a new surface protein to which humans have no immunity; it must be able to cause infection and disease; and it must be able to move easily from one person to another.

"Two of those three conditions have been met," she continued, as evidenced by the facts that 231 humans have been infected with the H5N1 virus since 1997, of whom 133 have died. "The missing component is efficient transmissibility."

To better understand the molecular and biologic requirements for H5N1 viruses to confer efficient transmissibility among humans, Dr. Jacqueline M. Katz, from the CDC and an international team of scientists, developed an animal model of disease using the ferret, which is similar to humans in its susceptibility to influenza.

They used data from the 1957 and 1968 influenza pandemics, which were caused by a virus that had suddenly become more transmissible by combining genes from avian and human viruses.

Influenza is spread primarily through droplets expelled when infected persons cough or sneeze. Dr. Katz and her colleagues therefore developed a "specialized caging system" designed to study transmission between ferrets in close contact with each other, but could only transmit the infection through respiratory droplets. They also used "reverse genetics to make hybrid viruses containing genes from both," she said.

The reassortant viruses contained a surface glycoprotein gene of an H5N1 avian viral strain that had infected a human in 1997, and an internal gene from the H3N2 virus, the most common strain that circulates from season to season in humans.

Some of the strains were viable and could replicate after infecting a ferret. However, they were not efficiently transmitted and were less virulent than the original avian strain.

When nasal secretions from an infected ferret were transferred to healthy ferrets, "the virus did not acquire any additional capacity to transmit efficiently," Dr. Katz said. "That told us we have a good research tool to assess ongoing genetic changes that H5N1 may acquire that would enhance its ability to transmit efficiently."

However, she stressed that these results are only relevant to the specific viruses used in the study and cannot be generalized.

The team now plans to repeat their experiments using more recent avian and human influenza strains to generate reassortant virus in the lab, and assess their transmissibility.

They will also take another approach with the ferret model, "to look at viruses in the field that are naturally acquiring genetic changes over time," Dr. Katz noted, "and see if they develop an enhanced ability to transmit from animal to animal."

"That way, we should be able to identify critical changes that enhance this essential property of a pandemic strain," she added.

In conclusion, Dr. Gerberding commented, "We know that the H5N1 virus continues to undergo microevolution, through a series of subtle genetic changes." As a result, "the virus is constantly evolving" in ways that are not predictable

"So there is a lot of work to do to prepare for a future pandemic," she stressed, which history shows is inevitable, whether or not it involves the H5N1 virus. "Every community in every part of the world needs to be as prepared as possible."

Proc Natl Acad Sci USA 2006.