A Journey Through The World of Pandemic Influenza

Part V: The Vaccine Puzzle

Part V of CIDRAP's series The Vaccine Puzzle, "What role for prepandemic vaccination?" has been posted, another excellent offering from Maryn McKenna (contributing writer).

I am a huge proponent of prepandemic vaccine stockpiling and deployment when the pandemic appears to be imminent. While not perfect, and it is never purported to be, it is, in my non-expert opinion, a critical piece of our ability to respond to a moderate to severe influenza pandemic.

Hopefully there will be time to answer some of the questions begging to be studied.

MRSA and a Minor Obsession Collide

MRSA (Methicillin-resistant Staphylococcus aureus) has been in the news a lot lately, and rightly so. To be honest I have been willfully ignoring the issue but Scott McPherson's blog on the subject "The MRSA march continues on keyboards and in class" set off a cascade of thought rambles.

My first thought was that the media is going to whip everyone into a frenzy of germ phobia. While being aware of germs is a good thing, assuming one acts appropriate to that knowledge, a phobia strength fear and obsession with them is not good.

I envision entire armies of concerned people running to the store to purchase case loads of all manner of antimicrobial products, of which there is an ever expanding dizzying array. When I envision these swarming hoards I don't know whether to jump up and down shouting at the top of my lungs STOP or throw up my arms in defeated resignation.

Almost immediately after I came to the PanFlu cyber community I stumbled across an article from what was then RedNova, now RedOrbit, about the hidden, but known, danger of the ubiquitous use of products that contain Triclosan.

The following article is quite long, and I have attempted to only snip the portions that I felt crucial to my point and my concern, but I earnestly ask that you read the article in its entirety, as I feel its vitally important to us all.

The Dawn of the Domestic Superbug

The huge popularity of antibacterial household cleaners is encouraging superbugs, allergies, immune-system failure and dangerous environmental pollution. It's time to stop cleaning ourselves to death BY PAT THOMAS

Superbugs don't just appear out of nowhere. They aren't invaders from Mars or the result of some mysterious process that science can't fathom. They're the consequence of human behaviour, and creating them is fairly easy. Expose bacteria to repeated doses of antibiotics, and they will genetically mutate into more robust and resistant strains. Keep repeating this process, and you will eventually produce a bacterium that no drug will kill. This is how 'superbugs' such as methicillin-resistant Staphylococcus aureus (MRSA) and other resistant strains of bacteria are created.

Indiscriminate use of antibiotics has received deserved criticism for provoking the rise of hospital superbugs. Less well publicised is the role that domestic antibacterial cleaners play in producing unique strains of resistant bacteria.

Today we use a variety of synthetic antibacterial chemicals, in particular quaternary ammonium compounds and the chlorophenol Triclosan, to keep the bugs at bay. Unlike soap and water, which work efficiently by physically loosening dirt and germs from surfaces and bodies and washing them down the drain, antibacterial chemicals are designed to kill. Worse, Dr Stuart Levy, director of the Center for Adaptation Genetics and Drug Resistance at Tufts University School of Medicine, Boston, and chairman of the Alliance for the Prudent Use of Antibiotics, says: 'What is being touted as an antibacterial in household products is really, clinically, an antibiotic.'

Over the past decade our enthusiasm for fighting germs at home has become unstoppable. Today we can buy antibacterial hand soaps, laundry and dish detergents, surface cleaners, toothpastes, mouthwashes and hand wipes. Antibacterial agents, known as biocides, can be impregnated into clothing, furniture, blankets, insoles, the plastic lining of refrigerators, food-storage containers, shower curtains, rubbish bags, bins, chopping boards and even high-chairs and toys.

Even so, five years ago the American Medical Association (AMA) issued a startling statement saying that antibacterial soaps were no more effective against germs than common soap. Manufacturers of toiletries and household cleaners, who had lobbied vociferously against the AMA taking any stand at all on this issue, greeted the statement with purple rage, defending their antibacterial products as both effective and desirable. They were, they claimed, simply giving consumers what they wanted - products to protect themselves and their families from the 'germs' that can cause disease.

Several recent studies suggest they do no such thing. Antibacterial hand soaps, for instance, may initially kill more bacteria and viruses on the skin than regular soaps. But within an hour or so after use, there is generally no difference in the number of microbes on the skin. Hardly surprising, given that the average adult touches approximately 300 different surfaces every 30 minutes. Similarly, while antibacterial surface cleaners may initially remove more organisms than soap and water, within 90 minutes or so there is generally no difference in the numbers of bacteria and viruses that have repopulated cleaned areas.

[snip]

Tucked away in the AMA statement was another even more telling concern: that antibacterial chemicals used in the home could be contributing to the ongoing threat posed by drug-resistant bacterial strains. This concern is based on rapidly accumulating evidence, much of it originating from Levy and his team at Tufts. 'There will always be people who say they don't care what's in the product,' Levy says. 'As long as it kills bacteria and other micro-organisms that's better for them and their families and they're going to buy it. But if you said on the label "this product contains an antibiotic", people might not be so quick to buy them.'

Research is now showing that a whole range of antibacterial chemicals used as disinfectants in household cleaners and as preservatives and active ingredients in personal care products are producing resistant strains of bacteria. There is evidence, for example, showing that 7 per cent of Listeria monocytogenes strains (which cause severe gastrointestinal symptoms such as diarrhoea), isolated from the environment and from food, are now resistant to quaternary ammonium compounds, commonly used in household cleaners. Strains of Pseudomonas aeruginosa, which cause skin and wound infections, have also exhibited resistance to these chemicals.

While the glare of the spotlight has focused on hospital- acquired MRSA, another type of the superbug - community-acquired MRSA (caMRSA) - is widely reported in the medical press in the US, Britain, Australia and Canada. This strain arises in people who have had no contact with the hospital environment and is principally resistant to penicillin-derived antibiotics, cephalosporins, carbapenems and monobactam (known collectively as beta-lactam antibiotics), but not, like the hospital-acquired variety, to multiple other types of antibiotics as well.

Studies from Japan suggest a strong link between caMRSA and the use of antibacterial cleaning solutions. When investigators there looked at the generational effects of exposure to the common antibacterial agent benzalkonium chloride (used in household cleaners and certain toiletries) in caMRSA strains, they found that as each new generation of bacteria evolved its resistance to the antibacterial grew stronger - as did its resistance to common antibiotics like methicillin and other beta-lactam antibiotics.

As resistance grows the minimum amount of antibacterial and antibiotic needed to kill bacteria also grows, in some cases dramatically. In another Japanese study, the concentration of the antibiotic oxacillin necessary to inhibit the growth of third- generation benzalkonium chloride-resistant caMRSA organisms was 32 times greater than first-generation resistant varieties.

[snip]

While a number of antibacterial chemicals used in the home can produce this cross-resistance to antibiotics, one in particular - Triclosan - towers above the rest. Although Triclosan (also known commercially as Microban) has been used in consumer products since 1967, it is only recently that scientists have discovered how it works. Most antibacterial agents have a non-specific action: that is, they kill bacteria in fairly general ways such as depriving them of oxygen or disrupting metabolic processes. This non-specific action was one of the things that differentiated them from antibiotics, which usually attack bacteria in very specific ways, often altering the genetic make-up of the organism to prevent it from reproducing. Until recently, Triclosan was classed as a non- specific antibacterial substance. But newer evidence reveals that, in common with many penicillin-derivative antibiotics, Triclosan produces a genetic change in bacteria such as Escherichia coli, Staphylococcus aureus (S. aureus) and Mycobacterium smegmatis, inhibiting an enzyme responsible for fatty acid synthesis and so preventing the organism from making a cell wall and replicating. This type of action means that Triclosan has more in common with antibiotics than antibacterials.

Resistance, both innate and acquired, to Triclosan is now well documented among several types of bacteria. Innate resistance among harmful bacteria, such as Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus pneumonia, would normally not casuse much concern. However, in environments where Triclosan is overused and putting bacterial populations under pressure, this innate resistance can be passed on to other strains of bacteria to make them immune to the effects of Triclosan as well (see box 'The bacterial community'). Levy and his colleagues have discovered three types of E. coli that have already evolved to become Triclosan-resistant. Variants of 5. aureus that are Triclosanresistant have also been reported in the medical literature.

In some cases Triclosan resistance also produces a cross- resistance to conventional antibiotics. For instance, Triclosan- resistant strains of E. coli are also resistant to the experimental antibiotic diazoborine. Triclosan-resistant strains of Mycobacterium smegmatis are also resistant to isoniazid - an antibiotic used against tuberculosis.

Triclosan is so much like a drug, in fact, that scientists are already working on ways to use it medicinally. Doctors are currently investigating the possibility of treating malaria with Triclosan. The parasite responsible for the transmission of malaria uses the same enzyme for fatty-acid synthesis as E. coli. Such innovations serve to reinforce the idea that Triclosan is simply an over- the counter antibiotic that has slipped through the regulators' net. Unmonitored and largely unregulated, the overuse of Triclosan in the home is likely to have the same devastating effect as overusing antibiotics in the hospital or clinic, producing increasingly resistant strains of bacteria that can't be killed and have the potential to make people very sick.

[snip]

For people who are truly ill, and who desperately need the curative potential of an effective antibiotic, it is a bleak picture indeed. And while it can be difficult for the average person to make the mental leap from household cleaner to incurable disease the link inevitably exists. 'Knowing antibiotics as well as we do, it just doesn't make sense to say that exposure to these chemicals won't result in resistant species,' says Levy. 'It's just a matter of time.'

In the home, Triclosan can profoundly disrupt the micro- environment, killing off all but the most resistant strains of bacteria. Washed down the drain, it threatens the wider environment and human health. Triclosan is one of the most frequently detected compounds in rivers, streams and other bodies of water. It is highly toxic to aquatic life, especially algae. High levels of Triclosan have been found in fish, and, via our waterways, the compound has found its way back into the human body. A recent Swedish study found Triclosan in the breast milk of 60 per cent of women surveyed. This is a worrying finding given that no human data exists to show that it is safe to ingest. Similarly, no studies have examined what happens when Triclosan combines with other chemicals in the body, though evidence of what happens when Triclosan combines with chemicals in the wider environment provides some clue.

For years manufacturers have reassured consumers that Triclosan breaks down quickly in the environment. Depending on where it is and what other chemicals it comes into contact with in the environment, some Triclosan does break down. The rest, however, can be converted into even more toxic compounds.

Although vehemently denied by the manufacturers for years, evidence published in 2003 demonstrated that sunlight converts Triclosan into 2,8-dichlorodibenzo-p-dioxin, which has been described as a 'mild' form of dioxin. Given that 2,3,7,8- tetrachlorodibenzodioxin (TCDD), best known as a highly toxic impurity in the herbicide Agent Orange, has the same toxic profile as most other dioxins, the concept of a 'mild' dioxin would appear to be more of a figment of the industry's collective imagination than a rigorous scientific classification.

Dioxins are hormone-disrupting chemicals that mimic the action of natural oestrogen. In the body, oestrogen levels are generally low and finely balanced. In excess, however, oestrogen is a recognised carcinogen. It accumulates in the environment and in the body and produces the kinds of excesses that, besides leading to cancer, are linked to reproductive and developmental problems and immune-system damage.

What is more, Triclosan in waterways can be altered further by repeated exposure to chlorine. If chlorineexposed Triclosan is then exposed to sunlight it turns into a much more toxic form of dioxin.

When all this made the headlines in 2003 it was shocking to the public but hardly news to the scientific community. Triclosan is not a natural substance, and so must be synthesised in the lab. This process produces a number of harmful by-chlorinated products, including up to nine different dioxins and dibenzofurans. A similar range of toxins can be released from Triclosan-impregnated products at the end of their lifecycle, during incineration, for instance.

This year, research carried out at Virginia Tech University in the US found that chlorine in tap water and the Triclosan in some soaps and other products such as toothpastes and mouthwashes can react together to create harmful chloroform gas that can be absorbed through the skin or inhaled. If inhaled in large quantities, chloroform gas can cause depression, liver problems and, in some cases, cancer. [see following snipped paper for further information on this]

Five years ago the AMA called for regulators in the US to expedite their review of products containing Triclosan and other antibacterials and determine the extent to which they might actually be contributing to the health threat created by excessive use of antibiotics. No such reviews have taken place.

Continues…

 

Posted on: Thursday, 14 June 2007, 06:08 CDT

Triclosan: Friend or Foe?

By Anonymous

In our increasingly germ-phobic culture, antibacterial products have rapidly gained in popularity. Always on the hunt for new ways to satisfy consumers, companies frequently retool their products, looking for the next best thing in personal hygiene. Triclosan, a heavily used antiseptic and antibiotic that was invented 35 years ago, is now under the microscope because it causes a troubling chemical reaction. Peter Vikesland and a team from the Virginia Polytechnic Institute and State University found in 2005 that chloroform- a chemical once used as an anesthetic but abandoned when found to be toxic-was formed when products with triclosan reacted with chlorinated water. Although toothpaste was not included in the study, many stores in China pulled toothpastes with triclosan from their stock.

Now, two years later, Vikesland and his team have followed up on their original research. The group tested 16 household products, some containing triclosan and some without. All products with triclosan were found to either directly produce chloroform or result in other chlorinated output. Chloroform can cause dizziness, fatigue, and headaches when breathed in and ingesting chloroform over long periods of time can cause liver or kidney damage. Chloroform is also suspected as a carcinogen.

Vikesland urges that "a full risk-benefit analysis of these products should be conducted" to gauge the level of potential harm from triclosan. In the meantime, Palo Alto, California, has banned all soaps with triclosan from city facilities. By contrast, Shane Snyder of the Southern Nevada Water Authority advises against a ban on soaps in the Las Vegas area. "I don't find the formation of chloroform surprising," Snyder says. "I think it will form under many scenarios in our daily lives."

Vikesland believes the issue warrants more study, but, "it's hard to predict exactly what's going to happen at an individual's tap."

-Environmental Science & Technology, 1 April. (M.E.P.)

 

I can only hope that I have given anyone who reads this post reason to reconsider using all of those antimicrobial products we are tempted to buy, especially in the face of a threat like MRSA.

Soap and water are just as effective in guarding your health, and that of your loved ones, than any product containing Triclosan, and alcohol gel hand sanitizer is a great portable and waterless solution for sanitation-on-the-go. These products are just as effective and don't harm the environment, nor will they create SuperBugs for us to have to deal with, all "upside" and no "downside".

 

Lastly, there is this issue…

 

PERSONAL HEALTH; How Germ-Phobia Can Lead to Illness

By JANE E. BRODY

Published: June 20, 2000

To listen to the manufacturers of an ever-growing list of germ-fighting products -- including antibacterial soaps and sprays, toothbrushes and toothpastes, pajamas and slippers, sheets and mattresses, potty chairs, high chairs, toys, sponges, cutting boards and even chopsticks and paper towels -- my family and I should have been riddled with disease all these many years.

My husband is allergic to antibacterial soaps, so we abandoned them 34 years ago. I do not have a dishwasher, so our dishes, glasses and utensils are not ''sterilized'' at high temperatures. I had no clothes dryer for 20 years and still don't use one for drying and ''sterilizing'' our clothes. We use sponges to wipe the kitchen counters and cloth towels to dry our hands. We ride the subways, often holding the poles that the ads tell us are crawling with billions of germs. And we do not use instant ''hand sanitizer.''

As infants, our sons crawled around the streets and parks of New York, putting whatever they happened to find into their mouths, which is how babies test their interest in all manner of objects.

Yet, to my knowledge, none of us has ever acquired an ''environmental'' infection or even spread microorganisms from one person to another. In fact, we have been remarkably healthy for more than three decades, despite what the manufacturers tell us: that everything from our hands to our counters to our supposedly clean laundry is crawling with potentially pathogenic bacteria that their products can wipe out.

But can they? And if they can, at what price does this superhygienic environment come? People frightened by a microbial world that harbors superbugs they believe are out to get them may be adopting an approach that actually fosters rather than suppresses serious infections.

[snip]

Another potential problem of creating a superhygienic environment is misdevelopment of the immune system in children that persists throughout life. The developing immune system may need to be primed to function properly.

During their first year of life, babies need to be exposed to germs to foster the production of T-helper 1 cells, which make antibodies to dangerous microorganisms. If the baby's environment is too clean, the production of T-helper 1 cells is not adequately stimulated and the immune system instead overproduces T-helper 2 cells, which create antibodies to allergens and could result in lifelong allergies or asthma, a recent study in Italy showed.

 

 

The Pandemic Vaccine Puzzle Part IV

CIDRAP's Part IV of their series The Pandemic Vaccine Puzzle "The Promise and Problems of Adjuvants", Maryn McKenna contributing writer, has now been posted.

In the interest of full disclosure I will admit that the concept of adjuvants used on the general population scares the you know what out of me.

[snip]

While adjuvants hold the greatest promise for dose-sparing, they also provoke trepidation because they are by definition immune-system activators. While many have been tested over the years, few have entered the market, because they proved too reactogenic to be acceptable to consumers or safe. Only one set of adjuvants, aluminum salts or alum (aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate), is licensed in the United States. Aluminum adjuvants and MF59, an oil-in-water emulsion that contains squalene (an oil found in some fish oils), are licensed in Europe (see Bibliography: Petrovsky 2007).

 

Now, I am fully appreciative that nothing is 100% safe 100% of the time, and an extraordinary threat can, and often does, warrant an extraordinary risk, but there is risk and then there is risk.

I am going to "snip" some of SusanC's Adjuvant series she posted on FluWiki as well as link the four diaries. Should your curiosity of this very important issue be piqued please do read through each of them.

Adjuvants, Autoimmunity, and Vaccine Safety in a Pandemic I (SusanC)

[snip]

The thing is, excessive response to the degree that is damaging instead of beneficial, specifically the induction of autoimmune reactions, is a lot less common in the elderly than the rest of the population.  In other words, one way to NOT have a particular adverse consequence be pegged with your product is to AVOID the kind of people who are most likely to have such adverse consequences in the first place.  Pick the group that is most unlikely to have problems, particularly since in this instance they are elderly and have all sorts of other health challenges such that it would be easy to say "there were no reports of vaccine-related serious adverse events after the first, second, or third immunization", to quote that first study by Minutello et al 1999.  Make sense?

To cut a long story short, the vaccine Fluad, an inactivated subunit influenza vaccine adjuvanted with MF59, was duly licensed in Italy, and by the quirks of EU regulations, in the EU, for use in the elderly.  And it has been used by now for thousands millions of people with apparently good safety profile.  It has even been used, I'm told, from time to time off-label in younger people when they ran short of the regular seasonal flu vaccine.

You might say, so what's the problem?  The problem is, in the meantime, scientists are finding stacks of evidence in animals that such kinds of oil adjuvants including squalene or MF59 were causing distinctive patterns of autoimmune responses and induction of lupus autoantibodies - antibodies that target the hosts' own cells, believing them to be foreign, thus causing inflammation, tissue destruction, and disease - antibodies that are involved in a host of autoimmune diseases, the most important one being systemic lupus erythematosis or SLE, a very nasty, often fatal, disease which typically appears in young females, black more commonly than Caucasians, and hardly ever happen to men except very occasionally in elderly ones.

 

Adjuvants, Autoimmunity, and Vaccine Safety in a Pandemic II (SusanC)

[snip]

III. Animal models
Here I will not repeat what I have already written about before in part  I of this diary, but will add some very recent references to show both the reactogenicity of squalene and similar adjuvants, and their continued use, indeed efficacy, in inducing autoimmune conditions for experimental purposes.

2000 Carlson The Endogenous Adjuvant Squalene Can Induce a Chronic T-Cell-Mediated Arthritis in Rats

2001 Holmdahl Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis.

2002 Holm The arthritogenic adjuvant squalene does not accumulate in joints, but gives rise to pathogenic cells in both draining and non-draining lymph nodes

2003 Satoh Induction of lupus autoantibodies by adjuvants

2004 Adjuvant oil induces waves of arthritogenic lymph node cells prior to arthritis onset

2004 Kuroda Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine

2006 Kuroda Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice

 

Adjuvants, Autoimmunity, and Vaccine Safety in a Pandemic III (SusanC)

[snip]

FLUAD

Fluad is the licensed MF59-adjuvanted vaccine for seasonal flu.  First some basic facts:

• This vaccine was first licensed in 1997 in Italy.
• In 2000 it was licensed in the rest of the EU via a European Mutual Recognition Approval mechanism, ie it did not have to go through more regulatory barriers in other countries once it was approved in Italy.
• It is licensed for those aged 65 and over only.
• The company claims variously that between 22 to 30 million doses of the vaccine have been 'distributed'.  That's not the same as the number of doses given, nor the number of people who have received it.  Still, suffice it to say that it's been given to millions by now.

First let's look at the safety profile.  Yes, there is a series of clinical trials for subjects over 65, and the results generally show that the vaccine provides better immune response and protection.  The vaccine tends to cause more local reactions but generally these are considered mild and transient.

As always, the devil is in the detail.  Let me just show one example.  This particular paper appears at first look to include a very large patient sample, which should give us a sense of comfort, right?

Podda, The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine, Vaccine. 2001 Mar 21;19(17-19):2673-80.

from the abstract:

Data from a clinical database of over 10 000 elderly subjects immunised with this adjuvanted vaccine (Fluad®, Chiron Vaccines, Siena, Italy) demonstrate that, although common postimmunisation reactions are more frequent in recipients of the adjuvanted vaccine, this vaccine is well tolerated, also after re-immunisation in subsequent influenza seasons.

How exactly was the safety profile determined? 

All adverse events and specific post-immunisation reactions were recorded during the first 7 days, as well as the adverse events requiring physician consultation during days 7 through 28 post-immunisation.

COMMENTS:

I think we can agree that if we are worried about autoimmune disorders, they may not manifest within this timeframe.

These disorders do not tend to have severe acute onset, but as generalized non-specific symptoms such as 'aching all over', which are so common in the elderly it is very likely they would not seek medical advice for them.

Whether one seeks physician consultation is also often dependent on socio-economic status as well, and the elderly is hardly the group that can afford to spend money except when absolutely necessary.

 

 

Well, you get the idea… it isn't straight forward or easy. But here is Diary #4 just for thoroughness' sake: Adjuvants, Autoimmunity, and Vaccine Safety in a Pandemic IV (SusanC)

It behooves us to educate ourselves on these issues, no one is going to spoon feed us the myriad technicalities, or break it into easily digested "sound bites".

 

SZ

H5N1: A Reminder of the Threat

Will the threat from H5N1 ever go away? Not until we either solve the problems with our influenza vaccine or we suffer a PanFlu event from it.

H5N1 is getting further and further entrenched in our wild water fowl, and has shown up in other wild birds as well. As long as it is in our wild water fowl it will continue to show up in our domestic poultry flocks on occasion.

No one knows with certainty that H5N1 will ever cause a human pandemic. Strong arguments have been made that since it hasn't yet it never will. People who say that are just as foolish as those who say that it will with equal certainty. Although it is my opinion that the ones who are certain it will are closer to the truth than those who say it won't.

After reading FM's blog entry today, A Predilection For The Young, I was once again reminded of my continual failure to understand how anyone can just blow off the threat as if it doesn't exist except in the heart and minds of the few Flu Obsessed. If you haven't yet read this seminal piece from one of our preeminent PanFlu bloggers please do so, and share it with as many people as you can place it in front of. Although what he writes is emotionally disturbing, at least it was for me, it is of vital importance that what he says is understood, and taken with the seriousness that it deserves.

SZ

Update #1: The 111th Case in Indonesia

Today the machine translations of the Indonesian press (thanks to the hard working folks at FluWiki) report that the father of this little three year old has refused hospital treatment and removed him from their care.

According to one of the machine translated articles the child was sent with medication (Tamiflu), instructions for care, and he is being checked on once a day by local health care personnel.

So, it really does appear that we have had a mild case of H5N1. Egypt has seen several, but not this mild.

The world needs viral samples from this child, as well as a serious effort to attempt to pinpoint his route of infection.

 

A Special Thank You

I want to say a very special Thank You to Crawford Kilian of crofsblogs/H5N1, Mike Coston (FLA_MEDIC: my cyber twin and Dear Friend) of AvianfluDiary , and Scot McPherson of Scott McPherson's Web Presence for their kind words and Welcome Back to active blogging.

 

It's good to be back!

 

SZ

Part III: The Vaccine Puzzle

Part III of CIDRAP's series The Vaccine Puzzle is now available, "H5N1 poses major immunologic challenges" by Maryn McKenna

Living in what is often described as a "developed" country, with a modern health care system, which is, by some measures, one of the best available, I am spoiled. If I want an immunization I just have to pick up the telephone and request whichever one I want from my family physician.

The public has a right, and a need, to know the problems that will be faced in the manufacturing and distribution of a pandemic strain influenza vaccine. While those of us who occupy ourselves with PanFlu issues are painfully aware of all of the issues raised in part 3 of the series the general public has no idea. They will assume, right up to the last moment, that all they will have to do is pick up their phone and make that appointment (or go to their normal immunization venue).

Plain English: It takes a lot of work and time to get the "stuff" that will then need to be "grown". Then the "stuff" doesn't "grow" well. And last but not least, it takes a lot of the "stuff" to do any good. End result: You and I will not be able to call up, or queue up, to get that magic vaccine we will so desperately want.

The public is not being informed of these issues, instead, they are being spoon fed pap. All the wonderful progress we have made and how many billions of dosages of vaccine will be available if, and when, a pandemic should strike. Oh, but wait, that is if the pandemic is nice enough to hold off until 2010 (or later)… but that's the fine print and we don't want to call too much attention to that now do we.

Ms. McKenna was kind enough to post a comment on my post that referenced part II of this series saying that when complete the seven part series will be combined into a White Paper. I was thrilled to read that because this series is not only excellent, it is easily understood, even by those who are not already familiar with the issues. As such, it will make a perfect piece for the media to utilize if, and when, they decide that truth should replace pap.

Thank You CIDRAP and Ms. McKenna.

 

SZ

Vulnerable Populations in Emergency Situations

One thing that Hurricane Katrina so glaringly demonstrated to authorities was disaster response, as well as the ability to meet the unique challenges of a disaster, are not consistent across all population segments and demographics.

CHHS Organizes First Conference on Vulnerable Populations in Emergency Situations

The University of Maryland Center for Health and Homeland Security (CHHS), in partnership with the McCormick Tribune Foundation, has organized the first national conference on vulnerable populations in emergency situations to be held Nov. 5-7 in Washington, D.C.  

The needs of vulnerable populations-the poor, the isolated, the elderly, the disabled, children, immigrants, and refugees-during emergency situations was made especially evident in the aftermath of Hurricanes Katrina and Rita in 2005.

This "invitation only" event will include academic and health care experts, as well as first responders, who are knowledgeable about inner cities, elderly, homeless, and immigrants. Participants will evaluate the nation's emergency preparedness and what needs to be done to better serve vulnerable populations in future emergency situations.

The conference will result in the first national action plan on this subject for federal, state, and local officials, as well as first responders and health care workers.

The issues that will be examined at the conference include: communicating with vulnerable populations during a mass disaster; ensuring the effective delivery of necessary provisions, including medical assistance to communities; considerations of the disabled, the elderly, and other special needs individuals during a disaster; the involvement of residents in the emergency planning process; transportation and evacuation procedures for vulnerable populations during a disaster; and funding and leadership role recommendations.

[snip]

Michael Greenberger, JD, a professor at the University of Maryland School of Law and director of CHHS, has been especially interested in this subject since the hurricanes of 2005.

"Despite the availability of school buses and other available modes of transportation during Hurricane Katrina, and despite a local evacuation plan that dictated that everyone should have been out of New Orleans when the levees broke, over 100,000 mostly poor and otherwise disadvantaged citizens were left behind, to wait out the storm in the Superdome and Convention Center. These facilities had inadequate supplies and were without law and order," Greenberger said.

"The poor, the elderly, the disabled, the homeless, and non-English speakers were, and have continued to be, wholly ignored in federal, state, and local emergency planning efforts pre-dating and post-dating Katrina," Greenberger added. "Despite thousands of pages of governmental `lessons learned' after Katrina, little attention has been paid to preparing vulnerable populations for catastrophic emergencies, even though the prospect of a pandemic influenza, for example, is staring the country in the face."

Full Article…

 

And this: [Credit Wulfgang]

Thousands would face food, water shortages in flu outbreak, report says

By DAVE HELLING

The Kansas City Star

Tens of thousands of Kansas Citians [sic] could face critical food and water shortages in a pandemic flu outbreak, a new report says.

The reason? They're too poor to stockpile supplies for a flu crisis.

"I've been talking about this for three years — how are we going to feed people?" Kansas City Health Department director Rex Archer on Wednesday told the City Council's Finance and Audit Committee.

Archer met with the committee to discuss a new study by the city auditor's office, part of a national examination of pandemic preparedness. It found government officials were trying to prepare for a flu outbreak that could make hundreds of thousands of residents sick. But the audit says potential flu patients aren't making the same effort: "Local citizen preparedness is not at the level it should be."

Public-health guidelines say families should have a two-week supply of food and water for an emergency. In Kansas City, the report estimates, between 10 percent and 15 percent of families now have a three-day supply of food and water.

However, more than 80,000 Jackson County residents live in poverty and may not be able to stockpile essential supplies, the study said.

Also, the report found, almost every child in Kansas City ate a free or reduced-price school lunch — food that would not be available if schools close in a flu pandemic.

"The people impacted the most … are the lowest income," said Councilwoman Deb Hermann.

She said efforts to train local health officials to help in an emergency won't solve the problem.

And if flu strikes, the report's authors say, residents won't be able to completely rely on government to bail them out.

"Government will be impacted, too," said Sharon Kinsgbury of the auditor's office, noting many social and health workers would get sick.

Archer said his office has talked with churches and other community groups about stockpiling food, water and medicine, and that most are willing to cooperate.

In a pandemic, though, it won't be enough.

"You could have one-third to one-half the entire population sick, and you can't get food in here," he told the Finance and Audit Committee.

To reach Dave Helling, call 816-234-4656 or send e-mail to dhelling@kcstar.com.

 

We are at the point where all of our agencies and organizations are, or minimally, should be, putting the final touches and polishes on their respective pandemic plans. As these two articles demonstrate the Vulnerable Populations have been left out and are just now being remembered, by a few anyway.

Nothing is easy when it comes to preparing ourselves and our communities for a moderate to severe influenza pandemic. I am well aware of that distressing fact, but there is absolutely no excuse for officials failing to account for what makes up a large segment of our population. This is also the segment that is in the greatest need of being made aware that governmental and private assistance organizations will not be there when they are going to be most needed.

As I have recently posted elsewhere: History has lessons for us, we just have to avail ourselves of them. Here's hoping we don't avail ourselves too late.

 

SZ

Indonesia’s 111th Human Infection

A three year old little boy has been officially reported as Indonesia's 111^th case today.

This from the Manila Times is typical of the statements coming out on him:

Toddler Confirmed as Bird Flu Victim

JAKARTA: A 3-year-old boy hospitalized in Jakarta has been confirmed as the
111th human bird-flu case in Indonesia, the nation worst hit by the virus, a health ministry official said Monday.

"Two tests were both positive so the boy is now the 111th confirmed bird-flu case," said Suharda Ningrum from the ministry's bird-flu information center.

Eighty-nine of the 111 cases in Indonesia have been fatal.

Ningrum said that the boy from Tanggerang, a satellite city just west of the capital, first showed symptoms usually associated with bird flu on October 22 but was only admitted to hospital on Saturday.

"The boy is still being treated there and reports showed that his condition was good," Ningrum said, without elaborating.

She said that the boy had been in contact with chickens, which later died suddenly. Contact with infected birds is the usual way that humans contract the virus.

Two other children from Tanggerang have died of bird flu this month.

Continues…

 

According to the articles that are reporting this case the child fell ill on Monday the 22^nd and was admitted to hospital on Saturday the 27^th. Additionally, the child is listed as being in "good condition".

Historically a delay of this length between symptom onset and hospitalization does not generally end happily.

Interestingly, on an intellectual level, there are hints in the machine translations of the Indonesian articles that the boy's symptoms are being described as "mild". I sat and wondered all day if the child's parents didn't administer Tamiflu independent of any doctor's care. That would certainly account for the "good condition" even with delayed treatment, as well as (perhaps) the mild presentation of symptoms.

It has been well documented in the press that pre-staged dosages of Tamiflu have been handed out to residents in H5N1 hotspots and the area that this child is from would qualify as a "hot spot" with the recent deaths of two other children from the same area. It also doesn't make sense that the child would have been tested for H5N1 with only "mild" symptoms, although being tested twice seems to be the norm, testing the first time is what is unusual here if "good condition" and "mild" are to be taken at face value.

Why is this important? Because one of the things the Flu Obsessed are on the lookout for is a drop in virulence, as it is likely (but not quite guaranteed) we will see this when (and if) H5N1 manages to become a pandemic strain. And, honestly, the Eternal Optimist in me can't help but hope that a PanFlu strain of H5N1 will only cause "mild illness". If it is only causing this minor degree of virulence in one so young then it is critical that the world's leading researchers get their hands on the viral samples and find out what the genetic variants are.

In the mean time, I will watch this case with great interest, and of course, hope for the best possible outcome, a healthy, happy three year old little boy returned to his loving family with smiles all around.

PS: Indonesia: Cough up those samples!

 

SZ

 

 

Influenza Research

When I came to the issue of pandemic influenza I knew what amounted to nothing at all. My first year (2005) was spent doing little more than learning as much as I could. One of the first things that I learned was that I was not the only flu ignorant person, which given the pride I take in "knowing stuff" I found comforting. However, that comfort soon evaporated when I learned that even our "experts" suffered a shocking dearth of knowledge.

Not knowing something is one thing, admitting that you don't know it is something else, and given human nature, extremely difficult for most to do.

There is so much we don't know about the influenza virus, research lost out to the more lucrative and illustrious human diseases as cancer, AIDS/HIV, Ebola, Malaria, and Dengue. These diseases were more lucrative and illustrious because solving their puzzle, and finding their solutions, would make such a difference to the lives of so many who lived under their threat and here-and-now consequences.

That all changed in 2003 and by 2005 significant money began to flow. Along with the money our few virologists who had expertise in influenza began to enjoy a certain celebrity status. Suddenly influenza research was not some back country hinterland of infectious disease, but critical and pressing.

Much of what we have learned in these few intervening years has been just what we don't know, or what we thought we knew was wrong. As in much of science, each new piece of information leads to innumerable other questions clamoring to be explored and answered.

Today's news offered a piece that highlights the scramble to learn and one of our viral luminaries.

Flu lab set to open

By David Wahlberg
608-252-6125

dwahlberg@madison.com

Ten inch walls made with crack-resistant concrete. Outlets sealed with silicone.

Sensors for broken windows. Infrared surveillance beams. Redundant air handling systems. A back-up generator.

UW-Madison's $12.5 million Institute for Influenza Viral Research, nearing completion at University Research Park, will have a collection of safety and security features the university hasn't seen before.

Many people will be watching the work of the institute, to be directed by virologist Yoshihiro Kawaoka.

The observers include health officials, who want a better understanding of the bird flu virus that is threatening a global flu epidemic. They include scientists, who are competing with Kawaoka to make discoveries about bird flu and other flu viruses.

They also include critics, who have charged Kawaoka with circumventing safety rules.

Critics objected three years ago to Kawaoka 's research at UW-Madison involving the deadly 1918 flu virus, saying his safety measures were not strict enough.

This September, they revealed that the university halted his work on components of the Ebola virus last year after the National Institutes of Health said the studies must be done in a lab more secure than any on campus.

Without proper precautions, the critics say, such viruses can escape.

"It's a very significant and a very real risk," said Edward Hammond, of the Austin, Texas-based Sunshine Project, which released documents about the Ebola work. "They handle viruses that could kill tens of millions of people. "

Jan Klein, UW-Madison's biological safety officer, said Kawaoka and other researchers at the university take adequate measures to manage the risks.

Kawaoka said his detractors didn't understand the extent of the precautions he used for the 1918 flu virus research. After shifting the work to a higher-security lab in Canada, he started doing some of it again in Madison this year after the U.S. Centers for Disease Control and Prevention approved it.

He said the guidelines regarding the Ebola research, which he hasn't resumed in Madison, are open to interpretation. Klein said the university may appeal the NIH's ruling about the Ebola work.

Kawaoka, a prominent and prolific flu researcher, was being wooed to the University of Pittsburgh until UW-Madison promised him the new institute. The 28,000-square-foot facility on Science Drive, to be finished next month, will enable him to expand his studies, he said.

Kawaoka plans to study several kinds of flu viruses in the institute -- including H5N1, the bird flu virus circulating in Asia, and a reconstructed version of the 1918 flu virus, which killed some 50 million people when it spread worldwide.

"Space has been a limiting factor for our research," Kawaoka said of the School of Veterinary Medicine lab he has been using. "Now we'll be able to do multiple experiments at the same time. We want to show people that the work we do is safe. "

BSL3-Ag

The institute contains lab space classified as Biosafety Level 3-Agriculture, a standard higher than any other lab at the university. BSL3-Ag is near the top of the federal government's four-level scale for labs involving infectious agents.

Only a few BSL-4 labs, in which workers don space suits with self-contained breathing devices, exist nationwide.

Several labs at UW-Madison, including some of Kawaoka's lab space in the veterinary school, are BSL-3. In those labs, researchers wear gloves and masks and work under cabinets, and the air is specially filtered.

The BSL-3 Ag designation carries additional requirements, such as extra air handling systems, showers upon leaving the lab -- and in the case of bird flu research, no contact with birds for several days.

Additional features also will ensure safety, said James Corkery, president of ACS. The Madison construction management company is overseeing the remodeling of a former office building, last used by Epic Systems, to create the institute.

Corkery said the steel airlock door used to enter the BSL-3 Ag lab is welded to its frame, like in a submarine.

He said petri dishes, animal cages and other lab equipment will be washed and run through autoclaves, sterilizing machines that use heat and pressure to kill germs. Liquid waste will be cooked in a separate system at 250 degrees Fahrenheit for an hour before flowing into the sewer system.

"Nothing can live after that," Corkery said, pointing to steam tanks surrounded by stainless steel pipes in the institute's basement.

The $12.5 million cost -- up from the $9 million cited when the university announced plans for the institute last year -- is being shared, roughly equally, by UW-Madison and the Wisconsin Alumni Research Foundation, the university 's tech-transfer agency.

Only one other BSL-3 Ag lab exists in Madison, at the National Wildlife Health Center off Schroeder Road.

CDC inspection

Though Kawaoka said he is eager to move his 18-person lab group into the institute and hire more researchers, the shift may not happen for months.

In order for him to use the H5N1 virus or the 1918 virus in the new building, the CDC must first inspect the lab and grant approval. The agency may visit in late November.

When Kawaoka applied for similar approval at his existing lab, it took a year, he said.

CDC permission to use the new space "could take weeks, months or even one year," he said. "I don't expect it to be done within this year. "

Much of the research in the institute will involve animals. Rooms are available for rodents, ferrets, poultry and monkeys.

Initially, Kawaoka said, he'll continue three research areas: studying how and why the H5N1 virus, the 1918 virus and other flu viruses are virulent, improving techniques for making flu vaccines and screening compounds that could lead to new antiviral drugs against flu.

Though bird flu has dropped off the national news radar, Kawaoka said its threat of causing a pandemic continues. The virus has killed 204 of the 332 people known to be infected since 2003, mostly in Asia, including 31 deaths in Indonesia this year.

A single genetic change could make the virus capable of spreading easily among people, Kawaoka said. If that happens, experts say the virus could be more dangerous than the 1918 flu.

H5N1 "is still spreading," Kawaoka said. "It's becoming more human-like."

Another lab in Madison continues to be closely involved in surveillance for bird flu and regular flu. The Wisconsin Laboratory of Hygiene, part of UW-Madison, is one of three labs in the country to use a new kind of test to evaluate regular flu samples for resistance to certain antiviral drugs. The testing began last year and will continue this flu season. The state lab has worked with 130 hospital and clinical labs throughout the state to prepare a flu pandemic checklist. Erik Reisdorf, a microbiologist at the lab, has traveled to India and Thailand to train scientists to use new molecular techniques to test samples for H5N1, the bird flu virus, and other types of flu. 

  --David Wahlberg

One of my favorite sayings is "We live, we learn, we move forward".

SZ