H1N1 another Y2K?

This from Candace Corley of the Colorado Department of Public Health and Environment:

It would be wonderful if H1N1 was another Y2K, and I hope it is.

Regardless, the precautions we are recommending, are good life skills; get your immunizations, wash your hands, adult and pediatric first aid and psychological first aid.

What could be better?

Maybe H1N1 is just a good excuse to be more competent.

We should rename it Life Competency Training.

Pandemonium about pandemic?

You probably heard that today the World Health Organization raised the level of pandemic alert to full pandemic. No pandemonium is needed.

What is important to remember is that this is a geographic designation, acknowledging the widespread illness resulting from the H1N1 virus. It does not mean that the virus is causing more severe illness.

When I look back on my post from May 22, what is most remarkable is that our information and messages have not changed. The good news about that is the virus is still stable, which makes efforts to create an effective vaccine possible.

So what should we do now?

In public health, we need to use this time to prepare for the fall in case the virus re-emerges. We don't know if it will; we don't know if it will be more severe; we don't know if we will have a vaccine. Regardless, there are many things we can do in the meantime. We have immunization and stockpile people thinking ahead; communicators can prepare information, too.

Tomorrow, look for a post on what individuals can do to prepare for the fall, in case we see the return of H1N1 in a more severe form.

Antivirals no magic bullet

Excessive Use Of Antiviral Drugs Could Aid Deadly Flu According To Study

08 Jan 2009

Influenza's ability to resist the effects of cheap and popular antiviral agents in Asia and Russia should serve as a cautionary tale about U.S. plans to use the antiviral Tamiflu in the event of widespread avian flu infection in humans, scientists say.

Researchers analyzed almost 700 genome sequences of avian influenza strains to document where and when the virus developed resistance to a class of antiviral drugs called adamantanes and how far resistant strains spread. The analysis suggests that widespread antiviral drug use can accelerate the evolution of drug resistance in viruses, and that resistant strains can emerge and spread rapidly.

The results should serve as a warning to those who consider Tamiflu the next great antiviral medication, the researchers say. Stockpiling Tamiflu has become a standard part of many government, business and health organization plans to prepare for a long-feared pandemic flu outbreak, especially in the event that avian flu mutates enough to infect and be easily transmitted among humans.

"We can't necessarily say what we've seen in adamantanes is predictive of what will happen with Tamiflu. But in the larger dynamic, perhaps it serves as a cautionary tale," said Daniel Janies, senior author of the study and an associate professor of biomedical informatics at Ohio State University.

"Fighting infection is an arms race, and if we're not smart about how we use our arms and understand the evolutionary implications, then we will have ongoing and accelerating problems with drug-resistant microorganisms."

Resistance to adamantanes among strains of seasonal influenza spiked in Asia in 2002, and by 2006 the agents were considered virtually worthless worldwide as a treatment for the flu because more than 90 percent of the strains had developed a resistance to the drugs.

With that knowledge, Janies and colleagues analyzed hundreds of avian flu genomes isolated from avian, feline and human hosts between 1996 and 2007. They found that about one-third of those samples carried mutations enabling the virus strains to resist the effects of adamantane drugs.

The researchers also looked at resistance to oseltamivir-based agents (Tamiflu is the brand name for oseltamivir phosphate), but found that fewer than 1 percent of all of the samples were resistant to that class of drugs. Different classes of antivirals target influenza in different ways in the hosts' cells.

Janies and researchers from the University of Colorado and Kansas State University also designed a four-dimensional interactive map that traces the resistant avian flu lineages, showing over time where they originated and where they moved, mostly across Asia, but also to one European site in Belgium. The map is projected onto a virtual globe using Google Earth and can be downloaded at: http://supramap.osu.edu/supramap/files/h5n1_677.kmz.

The study is published online in the journal Infection, Genetics and Evolution.

So far, avian flu, the H5N1 strain of the influenza A virus, has been restricted to fewer than 400 human cases worldwide, but the virus's presence in birds has led to culling of large populations of infected species. Experts believe that to date, the avian flu can be transmitted to humans only from diseased birds. But the 63-percent death rate among the humans who had the virus has led to global concerns that if H5N1 were to become highly transmissible among humans, it could start an influenza pandemic.

Janies and colleagues obtained 676 whole genomes of influenza A/H5N1 available in Genbank, a public database of sequences supported by the National Institutes of Health, as of June 2007. They then used powerful supercomputers to analyze these genomes and their various mutations.

Adamantanes fight influenza by inhibiting the function of a protein called the membrane ion channel, or the M2 protein. According to the computational comparison of the avian flu genomes, upwards of one-third of the strains contained a key mutation that changed the M2 protein in a way that allowed the virus to escape the inhibiting effects of adamantanes. To evade adamantanes, mutations can occur at several positions on the protein, suggesting that influenza can evolve in many ways to resist the drug.

The researchers also were able to demonstrate that the resistance developed as a result of natural selection, because the avian flu virus strains experienced mutations that changed the M2 protein to evade the drug more often than one would expect by chance. Sometimes, dramatic changes to the genetic code occur when diverse strains of viruses shuffle whole genes among themselves in a process called reassortment. The analysis determined that any reassortment that occurred in the H5N1 strains studied did not lead to drug resistance.

The study also showed that the mutation-mediated cases of drug resistance didn't start in just one strain of avian flu. One resistant strain originated in China and spread through Southeast Asia, while another strain that was originally susceptible to adamantanes spread to Indonesia and then independently developed resistance in that country. The Google Earth map offers a vivid visualization of exactly where in the world these resistant lineages originated and where they are spreading.

At the height of their popularity in China and Russia, adamantanes were added to over-the-counter cold medicines and were also given to animals in some agricultural settings.
"We don't have hard data on how it was used or whether it was appropriately or inappropriately used, but in general, people are putting a lot of antimicrobials into the environment now," Janies said. "When people do that, they change the selective landscape. The virus would rather remain in its wild type form, but that one gets killed by the drug. So according to the survival of the fittest, a slightly modified virus can spread by escaping the effects of the drug."

Researchers believe that Tamiflu has not been used widely anywhere in the world except Japan, and no pattern of resistance similar to that seen for adamantanes has emerged. However, recent reports have suggested a spike of resistance to oseltamivir in strains of seasonal influenza have occurred in Northern Europe and Canada. In analyzing the avian flu genomes, the researchers looked for mutations that would show the virus's ability to resist the oseltamivir class of drugs to which Tamiflu belongs. These drugs fight flu by inhibiting the neuraminidase protein in the virus.

"Resistance to Tamiflu was not nearly as widespread as is resistance to adamantanes," Janies said. "But based on our results, we know resistance to Tamiflu can occur spontaneously in nature, we know it can occur in patients, and we know Tamiflu is widely used in Japan. We should continue to watch for resistance, and use this adamantane history as a warning."

A critical part of any genome comparison is assembling supercomputers that allow researchers to put complex data into context.


"Genomes are represented as raw, partially annotated strings of letters. Each genome on its own doesn't tell you much because all you see is a single state. What we need to see is change over time to find the evolutionary history. That requires computational power to match like regions of the genome, put the data into context and see the trajectory of the change," Janies said.

The result is called a phylogenetic tree that documents the shared mutations. Phylogenetics is the study of the evolutionary relationships among various biological species believed to have a common ancestor. In this analysis, the phylogenetic tree is projected into Google Earth and animated to show when mutations emerged and where drug-resistant avian flu strains are traveling.

Key to any ongoing tracking of antiviral drug resistance will be the broad availability of genomic data, Janies said. The technology exists to do the job, but worldwide cooperation in data sharing is still a work in progress."Not all viruses that are isolated are sequenced, and not all viral genomes that have been sequenced are shared," he said.With this publication, Janies and colleagues have done some sharing of their own, establishing a service for other researchers at http://supramap.osu.edu. "Anyone can go there, upload genomes, and our computers will calculate a tree for them and give them both the tree and that tree data mapped into the earth. We're rolling out our methods and making our supercomputer available for anyone in the world to do this kind of work," Janies said.

This research is supported by the U.S. Army Research Laboratory and the U.S. Army Research Office; the Hewlett Packard Corp.; the Ohio Supercomputer Center; and the Department of Biomedical Informatics and School of Biomedical Sciences within Ohio State's College of Medicine.

Janies' coauthors are Andrew Hill, Meredith Wilson and Robert Guralnick of the University of Colorado and Farhat Habib, a former Ohio State graduate student now at Kansas State University.

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

Article adapted by Medical News Today from original press release.----------------------------
Source: Daniel Janies Ohio State University
Article URL: http://www.medicalnewstoday.com/articles/134777.php

Very interesting..... bird flu, human-to-human transmission, and musings from others around "Flubogia"

There is an interesting thread posted on a pandemic flu-watching blog that I follow:

http://scienceblogs.com/effectmeasure/2008/04/bird_flu_staying_calm_about_pa.php

First interesting point: It refers to the recent release of information about human-to-human transmission of bird flu in China, just published in the British medical journal The Lancet. The case reported, which actually occurred in December, was a transmission from son to father.

So far, all of the human-to-human (H2H) transmission has been between family members, mostly family members with a genetic relationship rather than marital relationship (second interesting point!). That is leading some of the scientists to believe that there could be a genetic predisposition to infection with this H5N1 virus.

Another interesting aspect of this report was how the father was treated. He was vaccinated by transfusing him with blood from someone who had been vaccinated with a trial H5N1 vaccine. Wow. However, a noted health reporter, Helen Branswell (The Canadian Press), emphasizes that there is no way to be sure that the transfusion is what led to the father's recovery.

The follow-up postings meander from the report to Chinese motives, to authenticity of the information, to the pan flu threat (more "interesting points").

There are some conversations about being too melodramatic about pandemic flu. One person feels that all this pandemic flu stuff is another Y2K - nothing to worry about.

He says, "H5N1 is going nowhere fast, much to the chagrin of the fear mongering crowd. The situation has remained unchanged over the past 4 years and there is ZERO evidence that it's evolving into a human pandemic virus."

And, finally, a highly respected writer, Jody Lanard, reminds us how a message of "don't panic" is interpreted. From Dr. Lanard:

On telling people to stay calm:
Here is an excerpt from Appendix 5, "The Problem with Saying 'Don't Panic'," which I wrote as part of the draft background document for WHO's Outbreak Communication Guidelines in 2004:
Officials clearly have the fear or belief -- the mental model -- that panic is imminent. Instead of diagnosing, validating, and addressing the public's actual level of anxiety, officials repeatedly warn them not to panic.
To the public, "There is no need to panic" implies at least four things:
1. "The officials think or know that people are close to panicking. Things must be pretty bad." This increases public alarm.
2. "The officials think we're about to panic. How insulting." This decreases respect for officials.
3. "The officials are close to panicking themselves." This increases public alarm.
4. "Sometimes there must indeed be a need to panic."
Very hard lessons to teach officials.

Public health and "unintended consequences?"

Social distancing. Community resiliency.

These are two phrases that are used a lot by experts who analyze the potential impacts of a pandemic - an unfamiliar disease that is causing serious illness around the world.

A commentary in the February 6 issue of JAMA, the Journal of the American Medical Association, brings the conflicts to the surface again (JAMA, vol. 299, no. 5, pp 566-568, subscription required).

The state epidemiologist from Florida writes of the American respect for diversity, based on shared goals and aspirations. But, he says, recommendations for "social distancing" are "based on limited current scientific evidence and could have serious adverse unintended consequences for the social fabric of society..."

Dr. John Middaugh is concerned. This public health leader believes that public health is changing its longstanding, science-based recommendations for flu that focus on protecting the most vulnerable people with either vaccinations or antiviral medications.

The new messages from public health, he says, tell us that we each have the power and responsibility to prevent exposure to a pandemic flu virus and it will be up to us to take action to reduce the effects of a pandemic on everyone.

Hmmm, I can see what Dr. Middaugh is saying.

When the U.S. secretary of Health and Human Services visited Colorado, his main point seemed to be, "Don't count on us [the feds] for help."

Is that what all of public health is saying now?

That would really be a shame. It kind of takes the "public" out of "public health," doesn't it?

What do you think?

• If we encourage social distancing, do we risk weakening our commitment to community? Does social distancing = social disorder during a crisis?

• Will social distancing mean that we abandon those who would not survive a pandemic without the support of others -- the ill, the young, the old, the disabled?

Here's another take on the JAMA commentary:

http://scienceblogs.com/effectmeasure/2008/02/toughening_a_community_for_a_p.php

Oh, and P.S.
Dr. Middaugh also talks about fear-mongering around seasonal flu and flu vaccination campaigns. Is he right that flu shot campaigns are really our government's approach to increasing the demand for vaccine so vaccine manufacturers will expand production? And, he says, "The campaign to increase use of influenza vaccination for seasonal influenza adds to the fear of this disease and fuels separation and isolation." Yikes. What does this mean for public health?

The scientist who cried "WOLF"?

What do you think, have they snowed us on pandemic flu?

The New York Times has an article today called "A Pandemic That Wasn't but Might Be." You can read the whole thing at http://www.nytimes.com/2008/01/22/science/22flu.html?ref=science .

There are some who are beginning to step back from the ominous predictions about the coming pandemic.

But, while 2007 saw a decline in the numbers infected with bird flu, it's still with us, and it's still deadly.

One doc has been saying that he doesn't think H5 viruses will cause a pandemic, but he quickly adds that another subtype of the influenza virus very well could set off an international outbreak of a lethal flu.

In other reports, scientists are arguing about the stability of the virus that causes bird flu.

• If it is stable, it is less likely to change into a form that is more human-friendly.
• If it is not stable, it could change into what many fear would be the scourge of the 21st century - a new virus causes serious illness and that is easily transmitted from person to person.

Denial seems to be part of the human condition. No one wants to believe that a pandemic could turn life as we know it upside down. I wonder what will be written in the history books someday.

What do you think?

Are conditions ripe for a pandemic?

Vote today above!

Seasonal flu, bird flu, pandemic flu…. What’s the difference?

Here's something from a Georgia health department that very clearly explains the types of flu that make the news these days:

Seasonal, avian (bird) flu, and pandemic flu have gotten a lot of attention, and understanding the differences can be difficult.

Seasonal flu happens every year. In the U.S., it hospitalizes 114,000 and kills 36,000 annually. Most people who get it feel awful for a while and recover. There are many flu viruses, and there is an annual vaccine which contains the three strains experts believe to be the biggest threat each year.

Avian flu affects mostly birds. There are several avian flu viruses. Wild birds carry avian flu, seldom get sick from it, and even more rarely die from it. However, domestic birds, such as chickens, do not have immunity against some avian flu viruses, so they can get sick and die.

The H5N1 virus is a deadly strain of avian flu. H5N1 has been found in birds in Asia, Africa, and Europe. Millions of chickens have been destroyed to try to control spread of the virus. Human cases have been identified in Asia, the Middle East and Africa. So far, it has not been identified in the western hemisphere. Since 2003, about 300 people worldwide have been known to get H5N1, and about half have died. Nearly everyone who has gotten ill has caught H5N1 from infected poultry.

Experts think the H5N1 virus could cause a worldwide outbreak of flu in people, called a pandemic. To do that, the virus must mutate to spread easily from person to person. No one knows when or if H5N1 (or another virus) will become capable of causing a pandemic. There is no pandemic flu anywhere now, but it makes sense to prepare for it.

The 20th century saw three significant flu pandemics. The 1918-1919 Spanish Flu was the biggest and many millions of people died, including 675,000 Americans, and millions more were ill. Milder pandemics happened in 1957-1958 (“Asian Flu”) and 1968-1969 (“Hong Kong Flu”).

If a flu pandemic like the 1918-1919 Spanish Flu were to happen today, it would be devastating. Lots of people would be sick, and millions could die. We can all do things now to prepare, which you will learn about through this series. In the meantime, visit http://www.pandemicflu.gov/ to learn more.

--Rhiannon Brewer is the public relations and information specialist for the Northeast Health District in Georgia and can be reached at rcbrewer@dhr.state.ga.us.

To Tamiflu or Not to Tamiflu?

Several newspapers around Colorado made mention of yesterday’s report from the Trust for America’s Health in which Colorado received a rating of 9 out of 10 on pandemic preparedness.

Good news, right? For those of us in public health preparedness, it is always nice to hear some good news about our efforts. But it really doesn’t tell the whole story, like most evaluations of this sort.

According to this organization, Colorado’s primary shortcoming is in its decision not to stockpile antiviral medications for pandemic flu. While we are glad to hear that they think we have made great strides in the other nine areas, we didn’t get to tell you why Colorado is not buying huge quantities of antivirals.

During a news conference yesterday, the Trust for America’s Health representatives made a really important point. I’m paraphrasing, but the message was, “Antivirals are just one tool in the whole toolbox for pandemic response.”

I wanted to cheer – but I just breathed a sigh of relief. We have felt misunderstood by the Trust folks ever since they started their annual report on preparedness five years ago because their indicators seemed rather arbitrary and superficial. So, it was nice to hear that they agree with us on the antiviral issue, in spite of ranking Colorado as “deficient” in this area.

Why hasn’t Colorado (and six other states) jumped on board with antiviral stockpiling?

You need to know some background to understand the big picture, so here’s the top 10 reasons why Colorado is not stockpiling antiviral medications such as Tamiflu:

10. The federal government only pays 25 percent of the cost of the antiviral stockpile. That means that state governments are expected to come up with nearly $350 million (collectively)!

9. Since we don’t know what a pandemic virus will actually be, we also don’t know what antiviral medications will work best!

8. Since we don’t know what a pandemic virus will actually be, we also don’t know if antiviral medication will be the best approach to preventing the spread of disease. Right now, the research is leaning toward what we call “social distancing” as the most useful control mechanism – also known as a “non-pharmaceutical intervention.” Social distancing can be the simple act of staying home when you are sick – or it can be the more complex process of closing schools and canceling events.

7. There have been reports of serious side effects from Tamiflu, currently the most effective antiviral for bird flu virus that has spread in other parts of the world in recent years.

6. Antiviral medications, just like the medicines you have at home, have a limited shelf life. Right now, Tamiflu is only useful for five years. What happens in five years – do the states cough up another $350 million?

5. States are not allowed to rotate the stock of medicines. That means that the antivirals stay on a shelf in a locked facility until and/or if there is a pandemic. They can’t be used for any other purpose. Colorado had been negotiating with a big health care provider to host the storage site and rotate the stockpile, so the medication would not expire all at once and be thrown away, but the federal government would not permit this arrangement.

4. Disposal of mass quantities of antiviral medications could be a problem. There are ecotoxicologists (that was a new one for me, too) who predict that wild birds will develop drug-resistant strains of influenza if they are exposed to antiviral medication waste by-products in our water sources. And, it is possible that up to 80 percent of the active chemicals in Tamiflu remain in our wastewater, due to the amount that is excreted by the human body and the way that the chemicals breakdown after disposal.

3. As noted in the Trust for America’s Health report, the Strategic National Stockpile has only 6,000 courses of treatment for children (pediatric antiviral suspension). The federal government has not set any target for stockpiling pediatric antivirals even though children and adolescents are known to often be disproportionately affected by contagious respiratory illnesses.[1]

2. Also noted in the TFAH report are three barriers to stockpiling antivirals at the state level: (i) not all states have the fiscal resources to pony up 75 percent of the costs; (ii) antivirals are all states’ priority for pandemic response; and (iii) states have concerns about storage, rotation, and shelf-life extension strategies.[2]

1. And finally, as Dr. Ned Calonge (NOT Colange), the state’s chief medical officer, said to the media yesterday when the report was released, “We're really talking about using precious state resources to pay for a drug of really uncertain benefit that would be used to address an event of uncertain timing and uncertain severity.”

Here are three newspapers with the Associated Press article:
http://www.rockymountainnews.com/news/2007/dec/19/colorado-scores-high-in-report-on-public-health/
http://www.denverpost.com/search/ci_7752620
http://www.gjsentinel.com/search/content/gen/ap/CO_Pandemic_Readiness_Colorado.html

See the full report at http://healthyamericans.org/reports/bioterror07/.

So what do you think?

Did Colorado and the remaining six states make the wrong choice?

To Tamiflu or not to Tamiflu? That is the question for our survey this week.

Endnotes:
[1] Trust for America’s Health, “Ready or Not? Protecting the Public’s Health from Diseases, Disasters, and Bioterrorism,” December 2007, page 23.

[2] Trust for America’s Health, “Ready or Not? Protecting the Public’s Health from Diseases, Disasters, and Bioterrorism,” December 2007, page 26.