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H5N1 Flu Pandemic Watch

Note: if you are new to H5N1 flu info you may want to start at the Background section below.

July 14^th 2008 Update

A new article in Nature, The Long War Against Flu, is a very worthwhile read.

"That the H5N1 strain of bird flu has not yet caused a pandemic is no cause for complacency. Preparations for the inevitable must be redoubled to mitigate the potential devastation."

We suggest that you give the whole thing a read (it's not very long).

May 25^th 2006 Update

Over the past year, there have been sporadic cases of human H5H1 influenza in many places throughout Europe, Africa, and Asia. One country that has had many flu-watchers perpetually on edge is Indonesia -- it is often described as a simmering pot that might boil over at any time. Over the past month, there has been the largest cluster of human H5N1 infection to date: 8 people, only 1 of whom has survived. There is evidence that this time the virus has been transmitted human-to-human-to-human. Unfortunately, the WHO seems to be putting politics above science and is continuing to keep the virus sequences private, while making vague public statements about how the virus does not show "significant" mutations. Many of us would like to have the sequences available for other scientists to examine before we can take any comfort in the WHO's comments.

H5N1 may never become a human pandemic. But there is every chance that it will. We continue to urge you to review our Resources section below and formulate your own personal, family, and community preparedness plans.

January 13^th 2006 Update

In the past several weeks human H5N1 flu infections have been popping up all over Turkey. The symptoms include bleeding in the throat. The is much discussion as to whether this flu is being transmitted bird-to-human (B2H) or human-to-human (H2H). Part of that answer lies in the genetic sequences in the H5N1 strain. The Effect Measure blog had a nice summary today; here are the good bits:

The news dribbling out about the sequencing of the Turkish isolates is not encouraging but also not surprising. As I noted several days ago, the proposition that the hemagglutinin protein of the isolates is "very close" to the avian sequences is not very informative because extremely small changes can cause important changes in host range, as studies by Stevens et al. on the 1918 HA show. That paper described studies with glycan arrays (see previous post) that looked at the binding of various viral HAs to various linkages of sialic acid, the cellular receptor. Sialic acid is linked in two forms, one characteristic of bird intestinal cells, one characteristic of human lower respiratory tract cells, although we now know that humans have avian-type linkages in sialic acid in their upper respiratory tract. Most avian viruses bind well to the avian receptor, human viruses to the human linked receptor, but the HA protein from a case from New York's second wave in the 1918 pandemic showed some affinity for both humans and birds.

I haven't seen the sequences for the Turkish cases, but news reports suggest this kind of adaptation to humans is what is being seen in some of the Turkish isolates.

[Snip]

The sequencing also shows that there are many genetic variants out there, sometimes infecting the same individual. Again, this is to be expected. This virus replicates into billions of copies in an infected person and it is lack of fidelity in this replication which is one source of the genetic variation upon which selective pressures act.

This mutation has been seen before in isolates from Hong Kong in 2003 and Vietnam in 2005 (Branswell, CTV). The Turkish sequences also bear similarity to the Chinese Qinghai viruses responsible for a mass kill of migratory birds there. For some technical details, see post by Henry Niman of Recombinomics which he has kindly reprinted in the comments of a recent post here. Many experts believe Turkey's location along north-south bird flyways has made it especially prone to infection of its poultry stock. Opponents of this notion point to the lack of documented outbreaks at intermediate points along the flyways. However we neither know the pattern of viral shedding along flyways nor can we be sure that outbreaks have not occurred undetected in many of the remote areas concerned.

There is some good news in the sequencing. Apparently the virus is sensitive to both classes of antivirals (amantadine/rimantadine and oseltamivir (Tamiflu)/zanamivir (Relenza). (Branswell, CTV). But all in all, the Turkish picture is one of continued progression geographically and genetically. It is not time to panic, because it is never time to panic. But making appropriate preparations in your area might be prudent.

October 9^th 2005 Update

The Effect Measure blog had a nice summary today, so we reproduce it here:

Pandemic Flu Awareness Week officially ends today. We'd like to say we planned the timing of all this, but in fact it was conceived over a month ago by the three blogger partners-in-crime who started the Flu Wiki (DemFromCT of The Next Hurrah, Melanie Mattson of Just a Bump in the Beltway and The Reveres of Effect Measure. Then there was still little MSM attention to bird flu. Obviously this has all changed (late, but better late than never). The new attention has had the added effect of bringing many people to The Flu Wiki, which now averages almost 3000 visits a day.

So where are we? DemFromCT has an excellent wrap up of This Week in Bird Flu at DailyKos. Here's my overall take on it from the perspective of a practicing epidemiologist with 40 years in medicine and public health. I'll try to make it as succinct as I can (no easy task for me, as you know).

* The threat of a serious influenza pandemic with a large global and national death toll globally is real, but of uncertain magnitude and timing.

* Even in the worst plausible case, we're not all going to die if it happens. Not even most of us will die. Probably the majority of people (but possibly a bare majority) will be unaffected or affected little by the virus. But very many people will get quite sick and many of them will experience a protracted period of recovery lasting weeks or longer. A significant number will die in a relatively short period of time. This happens in any influenza outbreak but will be much worse if a pandemic strain emerges.

* Because of an anticipated high rate of absenteeism (perhaps 30% or more), many things we take on faith as "just working" won't work as well or at all. For example, if there is a major snow storm and power is lost to a wide area, it may make take considerably longer to restore if the trucks haven't been maintained, the number of linemen is much reduced, the roads aren't cleared and the inventory of repair supplies is interrupted by transportation failures. The reductions in each sector can add to each other and cause a much larger effect than would be anticipated from any one separately.

Or not. As difficult as many of these issues are, they can be substantially ameliorated by advance planning.

For example, pharmacies and supermarkets typically use "just in time inventory" systems, meaning they have in stock only a quantity sufficient for short term demandThey depend on frequent deliveries to keep supplies current. If deliveries are interrupted, as they were in Katrina, many people who depend on life sustaining medicines like insulin or blood pressure medication will be in trouble. The just-in-time system is now a deeply ingrained practice and can't be reversed. But interrupted supplies are not very important for most of what pharmacies carry. Who cares if the deodorant or the viagra doesn't come in? What we need is a short list of half a dozen or a dozen high-use critical medications (insulin, blood pressure meds, some antibiotics, etc.) and an emergency source that pharmacies, hospitals and patients can access. This is a task for state and local health authorities. The National Guard can be used for transportation and logistics and community centers or other facilities used as access points. The same can be done with food staples. You won't still have your Cheezits. But you will have milk. I'm not going to spell it all out here, because you get the idea. All it takes is some forethought and planning.

Which hasn't been done, for the most part. This is a problem of community mobilization. Leadership is needed, so if your "leaders" are missing in action, step up and lead yourself. If we sit down rationally and calmly BEFORE [it] hits the fan we will be able to get through it rationally and calmly. It will still be painful, but less painful and more easily endured. Share what you know and what you learn with others. The Flu Wiki is designed for that.

Background (August 2005)

An extraordinary event is happening right now in Southeast Asia that has the potential to affect humanity in ways thought banished years ago. Scientists are closely monitoring what looks like the birth of a super strain of one of man's oldest and most persistent nemesis, the influenza virus. This new strain has the potential to kill hundreds of millions given the right conditions. According to the World Health Organization and the US Centers for Disease Control and Prevention, the required conditions are now in place. We stand on the verge of a once in a 100-year influenza pandemic that is an event quite different from our routine seasonal flu. Pandemic flu spreads like wildfire through the human race leaving death, chaos, and civil disorder in its wake.

It is certain that we will have another influenza pandemic, and probably soon. What is not known is whether the pandemic will be of the major variety resembling the 1918 flu, or a minor one more like the 1958 flu pandemic. My advice is to prepare for the worst and hope for the best.

The above quote is from a monograph written recently by Grattan Woodson, MD, FACP, a doctor in Decatur, Georgia, USA. His motivation? "I wrote it both to inform [my patients] about this health threat and to provide them with some practical guidance on how they can survive the pandemic." This paper is the single best resource we have found on this subject. If you only read one thing about the coming flu pandemic make it this. (Download available below in the Resources section below.

We have been following the news of H5N1 avian flu in Asia since January, and have come to the conclusion that there is a good chance that H5N1 will blow up into a full-fledged world-wide pandemic. Soon. As in winter 2005/6, perhaps. We are not alone in this thought. I won't go into all the details here since you can delve into the sites listed in the Resources section below if you care to, but I do breifly outline why we are concerned below.

It may be that this pandemic will be a minor one such as 1958's Asian Flu Pandemic, just a worse-than-usual flu season. It may be that it won't happen this season and that governments around the world will realize what they should be doing to prepare and spend the next year doing it. But it may well be that this will be major pandemic event like the 1918 Spanish Flu.

The 1918 Spanish Flu came on very fast and was quite deadly. Fast, as in weeks from first case to everywhere. Many, many people were very sick, many people died. The next flu pandemic could easily be as bad, or even worse. A much greater percentage of the world's population now live in urban areas where a virus can spread quickly, and there are lots more people everywhere now than in 1918.

Our much-improved medical technology really can't help us with a pandemic flu virus. There are not nearly enough hospital beds for so many ill patients; flu often kills with respiratory symptoms, including secondary infections such as pneumonia, that would require being on a ventilator in a hospital. There are only a handful of antiviral medications available and they appear to have limited effectiveness on H5N1. Our flu vaccine is still produced using 1940's technology: virus is killed (and perhaps genetically modified to make is less virulent) and the virus is inoculated into fertile chicken eggs; the whole process takes at least 6 months; H5N1 is evolving very rapidly and there are several fairly different strains on loose in Asia. In the last few months there have been some attempts by governments to provide incentives for drug companies to increase their manufacturing capacity and to develop new vaccine technologies, but the fruition of these efforts is years away. We likely do not have years.

Our best hope, therefore, is for each of us to inform and prepare ourselves as best we can. Fortunately, the internet is allowing many scientists and knowledgeable laypersons (and, yes, some wacko nut jobs, too!) to share and pool their knowledge of what is happening with H5N1 right now in the world. We urge you to take the time now to peruse the resources below and perhaps begin to form your own family preparedness plan. We all will be taking our chances with H5N1 flu, but, as Louis Pasteur pointed out: Chance Favors the Prepared Mind.

Reasons For Our Concern

• Statistically, we are due for a flu pandemic
• The last three pandemic human flu virii had avian flu components
• Avain flu type H5N1 is presently endemic in much of Asia
• Over 150 million chickens and ducks have died or been culled (killed) worldwide due to H5N1
• Humans have no natural immunity to H5N1
• H5N1 since late 2004 has definitely infected and killed humans in Vietnam, Cambodia, Thailand, Indonesia, and more
• H5N1 in 2005 has most likely infected and killed humans in China (unconfirmed reports imply China may even have "culled" several villages)
• A few months ago over 6,000 migratory birds of 5 species were killed by H5N1 at Quinghai Lake in China
• Quinghai lake is at the crossroads of several major migratory bird flyways
• All 12 of the sequenced Quinghai Lake H5N1 virii had a mutation (PB2 E627K) rarely found in bird flu but always found in mamallian flu
• The genetic sequencing that has been done on H5N1 shows that it is rapidly changing
• There were two distinct strains of human H5N1 in Vietnam, one much more deadly that the other
• The migrating birds have been spreading H5N1 bird deaths all over asia, europe, and the middle east

Should H5N1 hit a magic combination of genetic material the renders it easily transmitted human to human, there will be no stopping it.

Resources

the_coming_influenza_pandemic_11pt_ver_5oct2005.pdf
Right-click the link above and Save As to download this 635K PDF file. It is a 27-page monograph written by a doctor in Georgia USA for his patients. This new version replaces the first one Dr. Woodson wrote in the summer -- "The content is virtually the same except I have removed some of the older tables and written a new portion addressing the containment of the spread of infection within the household." The first few sections deal with topics related to the influenza virus, with special attention on the 1918 Spanish Flu, which was the last major pandemic. What happened then is the best source of information on what could happen now. Given the predictable effect a major pandemic will have on society and essential services, several prudent suggestions are provided for you to consider taking before the pandemic sets in. Sections include: "Practical Pre-Pandemic Preparations for Individuals", "Symptoms of Influenza", "Supportive Treatment of Influenza", and "Advanced Home Treatment Considerations for Health Professionals". If you only read one thing about the coming flu pandemic please make it this.

Henry Niman is virologist with a particular interest in how virus evolve via recombination, which is the swapping of genetic information within specific genes. (Viruses also evolve using a method known as reassortment, which is the swapping of genetic information between genes from different viruses. This occurs when an animal is "dual infected" with two or more viruses at the same time.) Niman posts his views on the news at recombinomics.com in his "What's New" section. He generally posts several times a day and is not shy in expressing his opinion (which is, BTW, that H5N1 entered the final Pandemic Phase 6, increased and sustained transmission in general population, back in June -- the problem remains the lack of confirmation of human cases in China and inadequate information about cases in Vietnam.)

The are several good blogs that cover the flu news: Avian Flu - What we need to know, Crofsblogs' H5N1, and The Coming Influenza Pandemic? are ones we visit often.

In addition to the blogs, there are also discussion forums in which folks share their views, fears, and questions about the coming pandemic. CurEvents is a good one with an active Flu Clinic. There are several "sticky" threads at the top where you can find some folks' preparation lists as well as the infamous and utterly amazing, long, detailed, thought-provoking, and downright frightening H5N1: My Town - A Projected Epidemic by CanadaSue.

Another good forum is the SARS, Bird Flu and Other Contagious Diseases board at agonist.org. Dr. Niman posts here frequently.

A good evolving resource is the Flu Wiki (fluwikie.com). The purpose of the Flu Wiki is to help local communities prepare for and perhaps cope with a possible influenza pandemic. This is a task previously ceded to local, state and national governmental public health agencies. No one, in any health department or government agency, knows all the things needed to cope with an influenza pandemic. But it is likely someone knows something about some aspect of each of them and if we can pool and share our knowledge we can advance preparation for and the ability to cope with events. For those unfamiliar with this topic, or just getting started, the amount of material presented (and the site itself) may seem daunting. Click on "Where To Start" and heed to advice therein.

Effect Measure is a forum for progressive public health discussion and argument as well as a source of public health information from around the web that interests the Editor(s), which includes H5N1. The Editors of Effect Measure are senior public health scientists and practitioners. Their names would be immediately recognizable to many in the public health community. They prefer to keep their online and public lives separate to allow maximum freedom of expression. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things. Don't miss the comments, they are consistently good. Fair warning, Revere's political posture is very left-of-center and his religious views are, well, anti-religion. If these postures would bother you and hinder you from gleaning the flu info he has to offer, then by all means give this site a miss.