Friday, March 31, 2006

Ars gratia avis

In North Somerset (UK) bird flu is confronting art. Sort of.

Public art is a good thing. Good for the community, good for artists and it helps make our public spaces livable and enjoyable. So the North Somerset Council was considering erecting a 26 meter high glass spire, lit by fiber optic light from within. Sounds neat.

But that was before bird flu:
North Somerset councillor Bob Coleman believes the 26m high spire called Silica, which is destined for Weston's Big Lamp Corner, could become a roosting hotspot for birds infected with the HN51 virus.

At a full council meeting this week, Councillor Coleman said he feared birds using the artwork as a perch could spread the virus into the surrounding town centre cafes and restaurants.

He asked the council's executive member for strategic planning, Councillor John Crockford-Hawley, to scrap plans to build Silica this summer in the wake of a possible bird flu outbreak.

Councillor Crockford-Hawley said: "Silica has been specifically designed so there are no perches on it, so it will not attract birds." (The Weston Mercury)
Maybe not the most earth shattering effect of worries about bird flu, but in a way emblematic. Concern about the effects of this virus will appear in many surprising ways. Best to work through them now. These are ideal opportunities for people to learn something about avian influenza when they are not enveloped in crisis. The tendency to ridicule these concerns should be suppressed in favor of using them to useful purpose.

So it's good they are debating this in North Somerset, as trivial as the whole issue sounds at first. The more you know the less you fear.

Tasers killing more people

In the days before "bird flu every time, all the time," and about the time EM started, Amnesty International USA (AIUSA) released a report expressing concern about the increasing use of tasers in the US, documenting about 70 taser-associated deaths in people hit by this "non-lethal" weapon in North America. Many of the fatalities also were individuals under the influence of drugs or alcohol, so coroners tended to discount the role of the taser in the sudden deaths, although there was increasing concern that the tasers were combining with drugs or alcohol to cause the deaths. We blogged it a bunch of times after that (for example, here), reporting a variety of incidents where tasers were used on grandmothers and children, among others.

If you don't know what a taser is, it is a weapon used to incapacitate people by jolting them with 50,000 volts delivered by tiny darts trailing wires shot from a gun-like device. In 2004, AIUSA called on the police to limit their use to situations where a lesser use of force was not feasible and where the alternative would be use of a firearm. In a new report, just issued, AIUSA notes little has been done to control their use since the 2004 report.
With few exceptions, law enforcement agencies in the USA have not heeded Amnesty International’s call to suspend use of tasers pending further study. In fact, more agencies have moved to adopt tasers, arguing that they are safer than many other types of force. More than 7,000 law enforcement agencies in the US, out of a total of 18,000, now count tasers as part of their arsenal. Few place tasers solely on a level of "deadly force" and some have argued that placing tasers even considerably lower on the force scale may avoid situations escalating to the level of a deadly confrontation.

However, Amnesty International believes that the mounting death toll of people struck by tasers makes the need for a full, independent and rigorous inquiry, as well as restrictions on use, more urgent than ever. More than 150 people in the USA have now died after being struck by tasers since June 2001, 61 in 2005 alone. Furthermore, the patterns of concern highlighted in AI’s 2004 report continue to apply. Most of those who died were agitated and/or under the influence of drugs and most were also subjected to multiple or prolonged electro-shocks. Among taser related deaths in the past year, for example, 40 were shocked more than 3 times and one person as many as 19 times. (Amnesty International USA)
And the tempo of deaths is increasing. Only three were recorded in 2001, but 13 in 2002 and 17 in 2003. The number in 2004 jumped to 48 and by 2005 it was 61. Already in the first two months of 2006 there have been 10 deaths. Using press, autopsy and police and paramedic reports, AIUSA looked at 152 taser-related deaths and found they fit a pattern:
  • Most of those who died in custody were unarmed and were not posing a serious threat to police officers, members of the public, or themselves

  • Those who died were generally subjected to repeated or prolonged shocks

  • Use of the taser was often accompanied by the use of restraints and/or chemical incapacitant sprays

  • Many of those who died had underlying health problems, such as heart conditions or mental illness, or were under the influence of drugs
  • Most of those who died went into cardiac or respiratory arrest at the scene
Tasers have been used on prisoners, hospital patients, people already in restraints, the very young and the elderly (see the AIUSA for more case details). It is clear there are no consistent guidelines for the use of these potentially fatal weapons by law enforcement agencies in the US.

AIUSA is not of the view tasers should never be used (and neither are we):
Amnesty International acknowledges that there may be situations where use of tasers in dart firing mode may be a preferable alternative to deadly force in order to save lives. These situations might include instances where officers or bystanders face serious injury from a sharp edged instrument such as a knife or a broken bottle, or in an armed stand off. Tasers may be used in situations like these when less extreme measures have proved ineffective or without a promise of the intended result. However, police officers who deploy tasers should, according to the UN Principles, "exercise restraint in such use and act in proportion to the seriousness of the offense and the legitimate object to be achieved" and must "minimise damage and injury and respect and preserve human life". Accordingly, Amnesty International believes these weapons should never be considered a ‘low’ or ‘intermediate’ force option.

In practice, however, tasers are often used in situations where deadly force would never be justified. The taser continues to be used as a routine force tool, not as a last resort where the only other option would be use of a conventional firearm. Police departments in the USA continue to place tasers too low on their force scales, with some departments allowing tasers to be used when individuals refuse to comply with officers demands. Amnesty International remains concerned that tasers continue to be used in jails, where suspects are already in custody in a controlled environment. (Amnesty Report, cites omitted)
You may have trouble identifying with the victims of taser use, but on numerous occasions they have been used on "ordinary" citizens caught up in some kind of routine situation, such as a dispute at a Chuck E Cheese or a (naked) jogger. OK, so you don't jog naked. If you did, you also wouldn't be carrying a concealed weapon or threatening anyone with harm (unless you consider the fear of going to hell by some right wing fundamentalist who sees someone's genitals).

I'd rather be tasered than shot, but increasingly people are more likely to be tasered than controlled some other way. At some point we will need to come to terms with the fact that the label "non-lethal force" doesn't necessarily designate non-lethal force.

Thursday, March 30, 2006

Another vaccine trial, another disappointment

Another vaccine trial for H5N1. Another disappointment. The newly published vaccine trial, using a conventional vaccine prepared from a strain isolated in 2004 in Vietnam, only provided partial protection and that only at the highest doses (90 µg and 45 µg of protein antigen). The results just appeared in the New England Journal of Medicine and are available online gratis (thank you, NEJM; that's the way it should be done for H5N1 articles). Here is some explnation and a few of the dreary details.

When looking for a flu virus, what your immune system primarily "sees" are hemagglutinin and neuraminidase protein spikes on the outside of the virus (when the Flu Wiki is back up on its new servers you can read all about the virus there). Unfortunately your immune system has never seen one of the H5 subtype before, so it does not react right away to protect you. To help it along, we use a vaccine to show the immune system what the H5 protein looks like so that if it sees it during a natural infection it can react promptly. Something similar is done with the seasonal flu vaccines, which contain H3 subtype proteins. Although our bodies have seen H3 before (it is the prevalent flu virus since 1968), the H3 protein changes a little every year so it doesn't look exactly the same. It's like a person who changes clothes, sometimes wearing jeans, sometimes a suit. The immune system needs some help with the change, but more like a prompt than a whole new description. With H5, however, the clothes are so different (imagine a pirate or a bear costume) that the immune system doesn't recognize it at all until the infection is well underway. Hence the vaccine lesson for your immune system.

Conventional influenza vaccines are grown in fertilized chicken eggs and they grow in the amniotic sac of the developing chick. There is a problem with the Highly Pathogenic Avian Influenza H5N1 virus, however, as it is lethal to chickens, so some molecular surgery is first performed on the viral vaccine seed to eliminate the feature that causes the high pathogenicity (the polybasic amino acids at the cleavage site). Then the H5 and N1 genes of the Vietnam isolate are combined with other genes from a standard vaccine strain. When grown to high amounts ("high titer") in eggs, you have the relatively harmless persona of a standard vaccine virus wearing the clothes of H5N1.

The live virus is concentrated in a centrifuge and inactivated with formaldehyde (inactivated means it can no longer replicate). A series of purification steps then separates the viral antigen (the part you want the immune system to recognize) and it is put up in vials at different strengths. Strength here corresponds to how many micrograms (µg) of the antigen are in a single injection. The doses used were zero (placebo), 7.5, 15, 45 and 90 µg, administered twice in injections 28 days apart. For comparison, the amount of antigen in the usual seasonal flu vaccine is 15 µg, given once.

How do you know if the vaccine works? We can't vaccinate people and then infect them with H5N1 to see if they are protected. Instead the researchers used some data from the 1997 Hong Kong outbreak suggesting antibody titers of 1:40 might be protective. This, then, was selected as the level at which the vaccine was considered to protect people when their blood was assayed for anti-H5 antigen. Current seasonal vaccines achieve efficacy rates of about 70% against circulating H3 strains. Thus the current vaccine does not protect everyone, yet it is still a relatively high proportion. But the new vaccine didn't make that benchmark for H5.

The results, in fact, confirmed what had been found in other trials (see here and here for some of our many other posts on vaccines). A little over half the 102 vaccinees who received the highest (90 µg) dose achieved titers of 1:40 or greater. At the 45 µg dose about 45% were protected, with 22% and 9% being the corresponding levels for the lower doses. Thus only about half the subjects achieved protection when given a vaccine dose twelve times what is currently used. Bear in mind that we have a very small production capacity, the result of years of disinterest by Big Pharma in products that weren't obscenely profitable, although they were still quite reasonably profitable. What this means practically is that this vaccine is not currently practically feasible as a way to protect the population. It might be used in a highly targeted sub-population, but even there might not be that effective.

Despite the high dose, side effects seemed to be minimal, mainly pain and tenderness at the injection site. However the ability of this smallish study to detect serious side effects was relatively modest. It had an 88% chance of picking up three or more serious events as long as the true rate of serious events was at least 5%. Five percent is a pretty high serious adverse event rate when you are vaccinating tens of millions of people. So the jury on the safety of this vaccine is still out. So far, however, we don't see warning flags, although our vision is far from perfect.

NIH's Dr. Tony Fauci acknowledged the disappointing outcome, even as he tried to put the best face on it:
''We have a vaccine we know can spur an immune response, albeit at very high doses. We're going in the right direction. The sobering news is we have a long way to go. So it's muted good news,'' said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which funded the study. (Chicago Tribune)
The lead researcher also put on a brave face, calling on a time worn cliché to take the heat for bad news:
"Every journey starts with a first step,'' said Dr. John Treanor, director of Rochester's Vaccine and Treatment Evaluation Unit and the overall leader of the project. ''We actually have a product. We're not there yet, but we're making progress."
The big question, of course, is whether we are traveling fast enough to get to where we need to before dark. Probably not.

Addendum: It's been pointed out to me that the NEJM article is just the published version of the earlier newspaper accounts (last August, I think). So this is not another disappointing vaccine trial result but the same one as earlier. My error. The paper has additional information, which is what I posted above.

Happy Blogiversary, Confined Space

Jeez. Jordan Barab's blog, Confined Space is three years old. It seems like just yesterday it was two years and 364 days.

Three years old. In the blogosphere that's Methusalah.

And a fantastic three years, too. Confined Space isn't just any blog. It's the pre-eminent health and safety blog in the world, which probably means in the Universe. Certainly in the Known Universe.

So congratulations, Jordan. You blazed the trail for us public health bloggers and we're still trying to catch up. I'm not always sure what keeps us blogging, but I know what keeps you blogging. You have a fire in your belly about worker health and safety. And we can see it burning brightly in every line you write at Confined Space.

Congratulations from all The Reveres at Effect Measure.

Wednesday, March 29, 2006

Flu Wiki pauses for breath

Just a note to say that The Flu Wiki, our sister site, will be down for 24 hours or so as we change servers. Places to sate your flu wiki thirst in the meantime are wiki partner DemFromCT's podcast interview over at theory.isthereason, providing a fascinating insight into the origins of Flu Wiki from one of the horse's mouths (but not a neigh-sayer). Dem also has a good rundown of recent flu story events at his blog The Next Hurrah.

Meanwhile, pogge (of pogge fame) and Melanie (Just a Bump in the Beltway) are working mightily to make the server switch.

The Flu Wiki isn't gone. It's finding better quarters appropriate to its higher profile and greater recognition. With your help and participation it will mutate and evolve. Paninformation.

Update, 3/31/06: Like you, we are waiting for Flu Wiki to "surface" on the internet. We believe the delay is caused by the time it's taking for the new IP address to propagate through the DNS servers in the system. We are as anxious as you are.

Fear itself

I am sorry to keep beating up on poor Marc Siegel but he keeps asking for it. Here is his latest from the Mercury News:
According to a significant study published in the prestigious British journal Nature recently, the H5N1 bird flu virus is at least two large mutations and two small mutations away from being the next human pandemic virus. This virus attaches deep in the lungs of birds but cannot adhere to the upper respiratory tract of humans. Since we can't transmit the virus to one another, it poses little immediate threat to us. (Mercury News)
I suggest he read the Nature paper before commenting on it (or he can read the Effect Measure post on it if reading the paper itself is too arduous). I would love it if he would explain the meaning of a "large mutation" and a "small mutation" and where in the article it says that we are two of each away from the next pandemic virus. I have just re-read it and it says no such thing. I would love it if he would explain where it says the virus attaches deep in the lungs of birds, since only human tissues were used in the study. I would love it if he would tell me where the paper says we can't transmit the virus to each other.

Ironically, Dr. Siegel goes on to say that fear causes the public to blur the distinction between birds and people, which he just did (to be fair, he confused them). And he goes on to explain why even if there were a pandemic, all is well:
Not only do we have vaccinations, antibiotics, anti-viral drugs, public information networks, steroids and heart treatments that were lacking in 1918 to treat victims of the flu; in addition, the growing worldwide immunity to H5N1 may lessen the outbreak in humans even if the dreaded mutation does occur.
The mortality from Acute Respiratory Distress Syndrome (ARDS) that H5N1 brings on is not much different today than it was in 1918, even in an intensive care unit (should there be a bed avaialble). There is no vaccine. Antibiotics don't work for the primary viral pneumonia that is currently killing bird flu patients. And steroids and heart treatments? A bit off topic, unless he is talking about the full dress critical care facilities that we will only providing to a privileged few since our capacity will be outstripped in a thrice. As for public information networks, it is just their information he was complaining about.

Then there is some gibberish about pigs ("a soup of viruses"). Try parsing the logic of this paragraph:
If H5N1 spreads in pigs (a soup of viruses) and exchanges genetic material with another human flu virus before passing to humans, the result is likely to be far less deadly. The swine flu fiasco of 1976 is an example of the damage that can be done by fear of a mutated virus that never quite lives up to 1918 expectations. About 1,000 cases of ascending paralysis occurred from a rushed vaccine given to more than 40 million people in response to a feared pandemic that never arrived.
Since this virus (and the 1918 one) passed directly from birds without an intermediate host, Siegel's allusion to the pig mixing vessel theory is a bit beside the point. But then it's followed with a logical non sequitur about the 1976 swine flu affair. And as I have pointed out to him before, the 1000 cases of Guillain-Barré syndrome (the ascending paralysis he alludes to) are not much different than what we would expect in a non vaccinated population of 40 million.

There is more:
In this country I have heard from more than one farmer and several poultry companies that the price of poultry has already dropped 50 percent in some places. Imagine what will happen if a bird in the United States gets H5N1 bird flu. Our fear is growing at such a rate that our own poultry industry, No. 1 in the world, is likely to be destroyed. We are already petrified by fear of mad cow disease, another case where a species barrier protects us.
A species barrier protects us from mad cow disease? Really! Since when? Reading this, it seems Siegel is almost in a panic about the effect of bird flu on the poultry industry.

As he would be the first to point out, sometimes fear clouds your judgement.

Update: Marc Siegel has posted a long reply to me in the Comments. I have responded there. Take a look.

Comment on comments: I have scrubbed the Comments thread of some of the more personal back and forth regarding another site (if I missed some, let me know by email). It was off-topic and not exactly what I would call a "community building" trend. I will be the first to admit this thread had a tendency to jump the tracks now and then and some commenters deplored this. I am not so bothered. The blogosphere can be a wild place (one of its charms for some of us) and word choice and style of argument are different than professional publications. But the level of rigor and respect for facts and truth shouldn't differ. Indeed I think they are higher because there is the possibility of many voices, not just one person's. I've learned from all who have contributed (even those whose views I disagree with).

The bird flu problem is an urgent concern for many people, as the frayed tempers and temper fraying remarks show too well. That many take it very seriously is not inappropriate, however, nor is it avoidable. It is one of the facts of the situation as it now stands. I won't call for temperance or tolerance or even complete civility all the time (not that it would do any good to call for it), but I can intervene when things are spiralling out of control, which is what I am doing now. The Reveres aren't changing their style or mode of expression, so don't fear if you like it and don't get your hopes up if you don't.

The Reveres want this to be a venue for argument -- forceful when necessary -- as well as dialog. There is too much we don't understand and too little time to pussy foot around with niceties. Marc Siegel's public contentions are fair game, as are anyone else's, including ours.

But now we've all had a bit of a blow off, time to move on and get back to work. Lots to do.

Figuring out Tamiflu

The one antiviral people hope will work in H5N1 prophylaxis (and marginally for early treatment) is oseltamivir (Tamiflu). Yet there is much uncertainty about how to use it and its efficacy for this virus. Helen Branswell reports on a meeting this week in Geneva where available clinical reporting on its use in H5N1 infections will be picked over and wrung out for as much information as possible. There are no clinical trials of the drug in H5N1.
"Clearly we need more information on how the drugs work in the actual prevention and treatment of avian influenza," said Dr. John Treanor, author of a number of scientific papers on neuraminidase inhibitors, and a professor at the University of Rochester, N.Y.

"We've extrapolated everything from what has been done with conventional flu. And it's very likely, or at least possible, that the response to treatment with H5 would be different in several different ways."
Tamiflu is not the only drug of its class. Zanamivir (Relenza) also works through the same mechanism, but has to be administered by inhalation because its active form is not absorbed. Tamiflu, by contrast, is actually a "pro-drug" that is converted to active form after absorption. Tamiflu can therefore be given orally, an advantage which has made it considerably more popular. Some believe that Relenza may have been overlooked in the process:
"To me, a really big question is: What about Relenza? And I really hope that gets talked about a lot," said Dr. Anne Moscona, an infectious diseases specialist at Weill Medical College at Cornell University in New York.


[A] number of experts, including Moscona, believe its potential has been under-explored.

For one thing, they suggest the drug's design makes it less vulnerable to the emergence of resistant viruses. To date there have been no reported cases of resistance to zanamivir, whereas oseltamivir resistance has been seen in low numbers both with human flu strains and in cases of H5N1 infection.
I am not sure what the evidence is for a lesser propensity to resistance in Relenza. But while it works by the same mechanism as Tamiflu, the occasional examples of H5N1 reported resistant to Tamiflu were still sensitive to Relenza, so at least resistance to one is not perfectly correlated with resistance to the other.

Then there are the older M2 blockers, the adamantanes. There is variable resistance to these drugs in different H5N1 lineages, so they may be useful in some places or some circumstances. Resistance to this class of drugs develops more readily, however, and it is not clear to what extent the Geneva meeting will discuss these drugs.

In fact it isn't clear exactly what will be on the table in the Geneva meeting. The discussion is clearly important for clinicians. But these drugs are not going to stop a pandemic that is underway. Nothing will do that. It is important to be clear about that.

Unfortunately WHO is not always as clear as it could be on this count. Maybe it is time they said so unambiguously.

Tuesday, March 28, 2006

"Tastes like chicken"

It is achieving the status of a mantra. The Wikipedia tells us mantras are constantly repeated poems or phrases "used as spiritual conduits, words or vibrations that instill one-pointed concentration in the devotee. Other purposes have included religious ceremonies to accumulate wealth, avoid danger, or eliminate enemies."

This is pretty abstract. It's always good to have an example:
With bird flu spreading to wild or domestic birds in 17 new countries since the beginning of last month, the United Nations health agency again stressed today that humans are not at risk of acquiring the deadly infection through food when poultry products are safely handled and properly cooked.

“The main health risk currently is to people who are in close contact with infected poultry, such as families with backyard flocks and poultry workers in wet markets or live animal markets,” the World Health Organization (WHO) said in a news release.

“Globally, the evidence demonstrates that there is no risk of infection when birds and eggs are well-cooked, as this kills the virus. Poultry products are important sources of protein throughout the world,” it added. (UN)
This mantra has the advantage of being literally true. Influenza virus is inactivated by heat high enough to "properly cook" food. And that's most cooking processes.

However. . . except in restaurants, the food doesn't come to you cooked, it comes to you raw. In order to cook it properly someone has to handle uncooked poultry and if it's infected that's a potential source of contagion. That's what the little phrase "safely handled" means in the mantra. Since proper cooking is much more common than safe handling, it can't be taken for granted this is sufficient guidance.

The real meaning of the mantra is in the little added after thought (" 'Poultry products are important sources of protein throughout the world,' it added."), which I believe is the real point of the statement. The fear of bird flu is sending poultry demand plummeting and with it an important source of protein. So this is a public health balancing act.

I sympathize with WHO's quandry. At the moment their rhetorical solution probably works and nets out positively. But if the time comes that the virus is more readily "catchable," they are going to have to send out a modified message, possibly that it's OK to eat properly cooked poultry but too dangerous to cook it. That will be another quandry.

But we're not there yet. For now, "It tastes like chicken" can still safely apply to the real thing. Say that over and over again.

Some things you can't blame on H5N1

Influenza A/H5N1 (bird flu) has shown itself more resourceful than the humans trying to stave it off. In the last seven weeks alone it has enlarged its geographic range to infect birds in 29 new countries (Jia-Rui Chong in the LA Times). It is thumbing its viral nose at the Draconian control measure of slaughtering its poultry hosts by the millions. It is now in the wild bird population, so any hope of containing it is lost. Even vaccination of poultry, once a last resort, can no longer stop its spread. And while this seems to be the new line of defense advocated by the same people who said culling was the route to take, vaccination has problems of its own.

Vaccination is a logistical nightmare since we are talking about globally distributed poultry numbers in the billions. It also has the potential to allow birds to be healthy but still infective and traipsing from farm to farm by low paid inexperienced vaccinators also may spread the disease. And of course, there's the obvious: vaccinating the wild bird population isn't possible.
"We cannot contain this thing anymore. Nature is in control," said Robert G. Webster, a virologist at St. Jude Children's Research Hospital in Memphis, Tenn., who has been studying the virus since it emerged in 1997. (LA Times)
The speed with which this virus has jumped its Asian origins has confounded and startled most everyone. Authorities in North America are now resigned to its appearance here, although when and where is unknown. Most speculation centers on Alaska where there is overlap with Asian flyways (birds fly north - south, not east west). But we should remember that birds can get around in many ways. They can be smuggled in via the rare bird trade, or even conceivably blown by storms clear across the Atlantic, one of the proferred explanations for the appearance of West Nile virus on the east coast of the US in 1999.

The remaining issue is whether the virus will find new hosts. It seems to have made the jump to some mammals relatively easily, although is not (yet) very contagious in these new hosts. Cats, dogs, martens and mink have been naturally infected and a number of other animals (mice, ferrets) have been infected in the laboratory. And of course, humans.

The H5N1 of today is not the H5N1 that made its first appearance in 1997 in Hong Kong. It has evolved genetically, exists in multiple forms and continues to change. What all this means is uncertain, but uncertainty in this instance is far from comforting:
"Something generally disturbing is going on at the moment," [WHO's David] Nabarro said. "It's certainly in the bird world, and it's pushing up against the human world in a serious way."

For most of its existence, H5N1 stewed in Southeast Asia.


The outbreak of the virus in Europe and Africa is traced to the discovery last spring of thousands of dead migratory birds at Qinghai Lake in remote western China. The lake is a crucial stopover for many birds that ultimately mix with others that migrate through Europe, Africa and Asia.

Webster suspects that the virus mutated as it circulated among the birds at Qinghai Lake, allowing it to infect wild birds more easily and hitch a ride with them on their long travels.

The genetic fingerprints of the Qinghai strain have shown up in Russia, the Middle East, Europe and Africa.

"Each morning I sit down at the computer … there's another country, another outbreak or another human case," said Nancy J. Cox, chief of the influenza branch at the U.S. Centers for Disease Control and Prevention.

"It keeps us breathless," she said.
Breathless is perhaps an unfortunate but all too appropriate turn of phrase. But maybe we will have a human vaccine developed in time (I would say, don't hold your breath, but . . . ). Unfortunately, most countries on this globe, including the US, wouldn't have the public health infrastructure to administer it in a timely fashion, so many people would go unvaccinated even in that most optimistic of outcomes.

But that's not the virus's doing. That's ours.

Monday, March 27, 2006

Bird brains in Indonesia

Indonesia is struggling (half heartedly some say) to control a bird flu outbreak that started last July and has now made them number two in the overall list of cases and fatalities amongst people. The country is the fourth most populous one in the world, has a vast population living close to poultry, and has shown itself unable to investigate the many human cases that have appeared, some clustered. Many of us think that it is in the simmering Indonesian bird flu pot that things will boil over.

Now we hear that Indonesia won't sign a bird flu financial assistance agreement offerred by Australia ($10 million Australian) because Australia granted temporary visas to 42 political asylum seekers from Indonesia's Papua province.
"The postponement is triggered by Australian government's move to grant temporary visas for 42 Papuans," said Lalu Mara Satria Wangsa, a senior staff with the Coordinating Ministry for People's Welfare.

Coordinating Minister for People's Welfare Aburizal Bakrie was slated to sign the 10 million Australian dollars assistance agreement with Australian Ambassador Bill Farmer earlier in the day.

The visa decision, Wangsa said, "really hurts the Indonesian people." (Xinhua)
Australia is hurting the Indonesian people because Indonesia won't take $10 million dollars in badly needed aid over a visa dispute? If this is the government in control in a bird flu hotspot, the world is in a lot of trouble.

Taking a chance on Iran

The Bush administration's preoccupation with Iran has puzzled many observers familiar with that country's lack of a real nuclear bomb capacity.

Now comes this report to explain the real "back story."

Punish the lawbreakers

There was a NYT story Sunday about the House's immigration bill -- the one that makes ordinary, hardworking people criminals because they weren't born on the couple of square feet where you were born. Now I know a lot of people will say that the fact that they work hard, they pay taxes (for which they get nothing in return) and are exploited by US businesses who don't want to obey the law of supply and demand to pay higher wages to "real" Americans is irrelevant. What's relevant is that they are breaking the law.
The legislative battle has pitted Republican against Republican, with conservatives deriding guest worker programs as an amnesty for lawbreakers . . . .


In December, the Republican-controlled House defied Mr. Bush's call for a temporary worker program. Instead, the House passed a tough border security bill that would, among other things, make it a federal crime to live in this country illegally, turning the millions of illegal immigrants here into felons, ineligible to win any legal status. (Currently, living in this country without authorization is a violation of civil immigration law, not criminal law.) (NYT)
I suppose it's a fair point. Respect for the law has to mean something. Stop! I know what you're thinking. Revere's going to rant about George Bush's lawbreaking with the NSA wiretaps. Wrong (anyway that's already a criminal violotion, as I understand it). You're wrong. I'm going to rant about something else.

According to a new report from US Public Interest Research Group:
Nationally, 62 percent of all major industrial and municipal facilities discharged more pollution into U.S. waterways than their permits allow at least once during the 18-month period studied.

The average facility discharged pollution in excess of its permit limit by more than 275 percent, or almost four times the legal limit.

Nationally, 436 major facilities exceeded their Clean Water Act permits for at least half of the monthly reporting periods between July 1, 2003 and December 31, 2004. Thirty-five facilities exceeded their Clean Water Act permits during every reporting period.

The 3,700 major facilities exceeding their permit limits reported more than 29,000 exceedances of their Clean Water Act permit limits. This means that many facilities exceeded their permits more than once and for more than one pollutant.

The ten U.S. states with the most exceedances of Clean Water Act permit limits during this time period are Ohio, Texas, New York, Pennsylvania, Louisiana, Tennessee, Indiana, West Virginia, Massachusetts, and Illinois.

The ten U.S. states with the highest percentages of major facilities exceeding their Clean Water Act permit limits at least once are West Virginia, Rhode Island, Connecticut, New York, Iowa, Ohio, New Hampshire, Utah, the District of Columbia, and Maine. (US PIRG via Common Dreams)
If you want to take those who break civil laws and turn them into felons, why start with hard working people whose only crime is being poor and not speaking English? Here is a whole shithouse full of civil lawbreakers poisoning our rivers and streams. Let's prosecute the corporate officers and responsible officials as felons.

Given the choices, which one do you think would make the average person better off?

Sunday, March 26, 2006

No frills status summary

For my own purposes I made a quick status summary of where we are in the H5N1 story. This is a no frills account.

As of today 41 countries have reported H5N1 in birds and 9 of these countries in humans (I have added Egypt to WHO's official tally of eight. Four or five dozen bird species and 9 mammals (including humans) have been found naturally infected and a handful more have been infected experimentally. Among the mammals are pigs, cats and dogs, all animals that live closely with humans in many parts of the world.

Thus almost a quarter of the countries with bird infections also have human infections. This is a conservative estimate as many countries with reported bird infections have limited ability to detect human cases. So far none of the seven western European countries with infected birds have reported human cases, although mammalian infections have been reported in Germany and Austria (cats, marten). Human cases have been reported as far westward as Turkey and Iraq. Vietnam has reported the most cases and deaths (93/42, 2003 - present), with Indonesia rapidly coming up in second place (29/22, all since July, 2005).

The virus has crossed species barriers in birds (approximately five dozen species now infected) and in mammals (9 species). It has not been looked for in many other species, so we do not know the full extent of its host range. It has retained its lethality in most species where it has been detected. The age distribution of viral infections continues to show a marked shift to younger age groups compared to the usual seasonal flu age distribution. It is differentiating genetically and continuing to evolve, although the meaning of this in terms of public health is unknown.

Cambodia, China and Indonesia have reported additional human cases in the last few days, so the virus continues to propagate in birds and humans. The official WHO total count as of March 24 is 186 cases of whom 105 have died (56%). The WHO official tally is an undercount and only includes cases where laboratory confirmation has been obtained from a WHO reference laboratory or equivalent.

A year ago this virus seemed bottled up in Asia and Southeast Asia. In July it suddenly became visible in Indonesia, with cases in humans, birds, cats and swine. Since then we have seen a steadily accelerating geographic spread of the disease in birds with sporadic cases in other species, including humans, in other areas. Small clusters of human cases have also been seen, although spread beyond secondary cases is not known to occur at this time.

Clearly there is a lot going on with this virus, only some of which we know and less we understand. It is obviously time to be taking prudent measures to plan for a possible pandemic at some time in the near future. The best time to do this is when we can do it calmly, rationally and efficiently.

If it doesn't happen, that will be great. Anyone who says it couldn't happen or that we needn't be concerned about it yet because it has only killed birds and a handful of people is unbelievably irresponsible. I will name names: Marc Siegel and Peter Doshi.

Freethinker Sunday Sermonette: Bang the drum slowly

Three peace activists were freed from captivity in Iraq this week, but the good news was tempered by the knowledge that one of their number, Quaker peace activist Tom Fox, was not among them. He was murdered by his captors. An unknown group calling itself the Swords of Righteousness Brigades claimed responsibility (CNN).

The Fellowship of Reconciliation, an interfaith peace organization, issued a statement about Tom Fox's death:
The Fellowship of Reconciliation grieves with the family, friends, and colleagues of Tom Fox, Quaker peace activist, who was recently killed by his captors in Iraq. But we will not turn our grief into hate.

Tom’s death was not an easy one, as he had apparently been tortured by those who kidnapped him, along with three colleagues from the Iraq Christian Peacemaker Team, on November 26, 2005. The kidnappers, a group previously unknown, twice before threatened the execution of their captives if their demands were not met. This time they carried out the threat.

Tom is one of thousands of casualties of the tragic and violent fiasco in Iraq. His life was neither more important, nor less important, than any other single life needlessly lost. Indeed, it was Tom’s commitment to humanize the dehumanized, to stand with the invisible and voiceless.

We knew Tom. He was dear to us. That brings him to the foreground now. But, as Tom himself taught us, so very many whom we did not know have also died in this conflict. The human mind cannot quite grasp the reality of so many individuals: the scope of our hearts is therefore often small. But Tom cared about the depersonalized and discarded, and for their cause, he has sacrificed his life

Tom was deeply affected by the madness and futility of the war in which he had willingly immersed himself. On August 30, 2005, dispirited by a sectarian bombing, he posted to his blog, "Is there something in life that will fill this vacuum and prevent this sad wearing away of the heart?" But by the end of the entry he had reaffirmed the profound conviction that had brought him into danger in the first place. "The only something in my life I can hold onto," he declared, "is to do what little I can to bring about the creation of the Peaceable Realm of God."
We respect, although we don't share, FOR's and Tom Fox's religious motivations. He died another victim of hate, misunderstanding and cruelty. Tom Fox is not alone, in Iraq or elsewhere. It seems appropriate to also take time to remember another peace activist victim, Rachel Corrie on the third anniversary of her murder.

This is the third time we are posting about the death of Rachel Corrie (see here and here), and I expect we will have occasion to do it again. For those who don't know her story, she was a member of the International Solidarity Movement (ISM), working against an illegal Israeli occupation thorough non-violent protest. Three years ago last week, on March 16, 2003, she stood alone in the path of a giant Caterpillar bulldozer being used by the Israeli Defense Forces to destroy the house of a Palestinian doctor. Here is the eyewitness account of Tom Dale (via The Uncapitalist Journal):
The bulldozer drove toward Rachel slowly, gathering earth in its scoop as it went. She knelt there, she did not move. The bulldozer reached her and she began to stand up, climbing onto the mound of earth. She appeared to be looking into the cockpit. The bulldozer continued to push Rachel, so she slipped down the mound of earth, turning as she went. Her faced showed she was panicking and it was clear she was in danger of being overwhelmed.

All the activists were screaming at the bulldozer to stop and gesturing to the crew about Rachel's presence. We were in clear view as Rachel had been, they continued. They pushed Rachel, first beneath the scoop, then beneath the blade, then continued till her body was beneath the cockpit. They waited over her for a few seconds, before reversing. They reversed with the blade pressed down, so it scraped over her body a second time. Every second I believed they would stop but they never did.

I ran for an ambulance, she was gasping and her face was covered in blood from a gash cutting her face from lip to cheek. She was showing signs of brain hemorrhaging. She died in the ambulance a few minutes later of massive internal injuries. She was a brilliant, bright and amazing person, immensely brave and committed. She is gone and I cannot believe it.
Those of you who get The Nation (and if you don't, you should) can read about the suppression of the New York staging of a successful play based on her journals and letters, My Name is Rachel Corrie. I guess some things are too dangerous for New York theater goers to see.

Both Tom Fox and Rachel Corrie were victims of a cruel violence that dares to parade righteously in the name of religion. Tom Fox was a person of deep faith, upon which he acted. Rachel Corrie was a person of committed politics, upon which she acted. They were killed by religious zealots of opposite sides, materially aided and abetted by states and politicians who also bear responsibility for their murders.

Neither Tom Fox nor Rachel Corrie were killed by God's Will or by the Forces of Evil. They were killed by other people. I am sure neither expected to die, any more than soldiers expect to die in battle. They died without trying to kill others. They died without defending themselves with guns or laser guided bombs. They died opposing violence but not being part of a violent system.

The Reveres pause this Sunday to pay them tribute. Bang the drum, slowly. Play the pipes lowly.

Koufax Award voting for Best Expert Blog ends tonight!

The voting for Best Expert Blog in the lefty blogsphere ends tonight (Sunday), and Effect Measure was honored to be a finalist. Competition was stiff and we have done respectably (and more). You can still vote for us (but only if you haven't already!) by going here and scrolling down to the bottom of the comments and leaving a new one with the words "Effect Measure" in it (and anything else nice you care to say).

The Koufax Awards are all about building the lefty blog community, so it's just for fun. The competition are wonderful blogs and bloggers and try to take some time to look at them all. To all who voted (no matter for whom), thanks for your support. Blogging is tougher than it looks and more rewarding than it out to be. The readers of this blog are a spectacular group. I love your comments even when I hate your comments. You're smart, funny, snarky, contrary, wrong (when you disagree with me, which you do often) and dead on (when you agree).

If only I could agree with myself I'd be right more often. But maybe not.

Saturday, March 25, 2006

Doctors without Hospitals

We have all heard of Doctors Without Borders/Médecins Sans Frontières, the medical humanitarian group that has fought hard and courageously to deliver "emergency aid to people affected by armed conflict, epidemics, natural or man-made disasters, or exclusion from health care in more than 70 countries."

But have you heard of Doctors without Hospitals? You can not only hear of them but see them this afternoon (March 25) in New Orleans:
On March 25, 2006, at 2 p.m. several hundred doctors, residents, medical students, nurses, hospital employees, patients, community members, and political activists will rally together outside Charity Hospital in New Orleans, Louisiana to protest the closure of this esteemed public hospital. Considered the oldest continuously running public hospital in the country, Charity has cared for hundreds of thousands of members of the New Orleans community for two centuries.

These New Orleans residents are now largely without access to healthcare and forced to rely entirely on understaffed emergency rooms for basic health needs, such as monthly prescriptions and routine medical complaints. This shift has caused a healthcare catastrophe in the New Orleans metropolitan area and will be the focus of this rally, along with a discussion of the future of Charity Hospital and the fate of this city's uninsured.
Doctors without Hospitals. In the richest nation on earth. President Bush? Dr. Frist? Speaker Hastert? Will you be there? Are you "there" for any of us without a fat wallet or a crucifix on our voter registrations?

Lying, incompetent, mean spirited and selfish screw-ups

The Bush administration is fond of saying we are fighting terrorists in Iraq so we won't have to fight them here at home. Apparently there are a lot more things they don't feel they will have to fight here at home, either. Like disease. Or this (from Jordan Barab's blog, Confined Space):
There are 3,400 high-priority chemical facilities in this country where a worst-case release of toxic chemicals could sicken or kill more than 1,000 people, and 272 sites that could affect more than 50,000 people. Yet despite reports from government agencies and independent journalists since 9/11 that chemical plant security is seriously flawed, the Bush administration has refused to address the issue.
Better not to get involved:
The Bush administration called Tuesday for federal regulation of security at chemical plants, but would largely let the industry decide how stiff the protections should be and leave inspections to private auditors. (San Francisco Chronicle)
And just to make sure no else meddles with the industry's plans to keep us all safe from their chemicals, Homeland Security Secretary Michael Chertoff wants to pre-empt the states from doing it:
But he said the government would not set minimum standards for chemical companies to follow, allowing the industry to tailor its own "so we can go about the objective of raising our security in a way that doesn't destroy the businesses we're trying to protect."
Here is Jordan's typically astute analysis at Confined Space:
1. Industry opposes any government regulation.

2. States that have given up hope of federal action begin to issue their own regulations.

3. Industry, suddenly facing the prospect of being forced to comply with multiple different state regulations, turns around and advocates for a weak federal regulation that pre-empts the states.

This debate has been going on since shortly after 9/11, initially with legislation introduced by former New Jersey Senator Jon Corzine that would have forced the chemical industry to implement, where possible, inherently safer technologies (e.g. substituting safer chemicals, storing smaller amounts of hazardous chemicals, etc.), along with increased traditional security measures. The American Chemistry Council (formerly the Chemical Manufacturers Association) and their clients in Congress managed to kill Corzine's bill and instead suggested an approach that focusses almost entirely on traditional security (guns and fences), and relies on compliance with voluntary guidelines -- developed by the American Chemistry Council. (Confined Space)
This has also been the pattern of the Bush administration on all things related to national security: incompetence yoked to ideology led around by the nose by big money industries. We see it daily in Iraq. After Hurricane Katrina. Every day in the gutting of health and environmental protection by Congress. And the list goes on.

None of us are safer. All of us have been made more threatened by these lying, incompetent, mean spirited and selfish screw-ups.

Friday, March 24, 2006

Bush slashes into CDC bone and muscle

We reported on this before (here and here), but now we now have more details in an analysis by the Campaign for Public Health (CPH), a CDC advocacy group that includes as senior advisors four former CDC Directors (William Foege, William Roper, David Satcher and Jeffrey Koplan) and a former Secretary of HHS (Louis Sullivan). Many were Republican appointees.

Under President George ("Keep Us Safe") Bush's budget request, CDC is going to take a big hit. CPH makes clear the cuts are deep and go to core CDC functions. The extent of the damage is concealed on paper where CDC appears flatlined, but there is a huge chunk in the budget earmarked specifically for bioterrorism and bird flu and a huge chunk of that goes to develop vaccines and purchase antivirals.
"Once these items are excluded, it becomes clear the administration's proposal drastically cuts the CDC," the organization said.

[CDC Director Dr. Julie] Gerberding acknowledged the budget cut during an appearance at a forum on government investment in research and development.

"That's correct," she said. "Obviously, it creates a challenge. We do what every family does when their budget is short. They have to really priortize and make sure that the investments they're making are accomplishing the most they can."

She added that the CDC was "working hard to be more effective with less, but I'm not going to pretend that it's not a challenge." (Atlanta Journal Constitution)
According to CPH (and its advisors would know), the current fiscal year is the first time in 25 years CDC's operational budget has been slashed. It was done by our "Promise them anything but give them Jack Abramoff" Republican congress.
The further cut anticipated by Bush's proposed federal budget for next year would mean "core programs at the CDC will be cut by more than 8 percent in just two years," the organization sai
Core programs at CDC include research on infectious and environmental diseases, health promotion, and studies on public health and occupational safety and health concerns.

At Tuesday's forum, Gerberding said the country "simply cannot sustain this lack of investment in effective [disease] prevention sciences."
So you read about it here. You might also have read it in the Atlanta Journal Constitution. But think how many more people would read about it if the CDC Director, Dr. Gerberding, would stand up and say, "I'm mad as hell and I'm not going to take it anymore."

It might have miraculous effects, like restoring her reputation among her public health colleagues. Sure, Bush would fire her. So what? She would go out in a blaze of glory. And it's not like she's going to be living in a Kelvinator box on the street.

(h/t crofsblog)

The papers in Science and Nature

The newswires have been buzzing about the papers just outin Science and Nature concerning the location of H5N1 attachment in the human respiratory system. Most stories jump to the punchline: what it might mean for human susceptibility and transmissibility. That part, however, is interpretation and speculation. Let's look to see what these papers actually say.

The central issue is the question of host range (or host specificity), that is, what makes one influenza virus primarily a bird virus and another one a human virus? This also bears on the ease of bird to human transmission and possibly human to human transmission, although the latter is where the speculation rather than the scientific results enter. First a bit of background. If you want even more, we did a four part series not so long ago that lays the science out in even more detail here, here, here and here. I'll crib a little from them to save time (after all, I'm just plagiarizing myself).

The influenza (or any) virus needs to get inside a host cell in order to make new copies of itself. Reproducing is essentially its only task in life. We know that viruses and other pathogens don't usually infect all animals (they have a specific host range) and within an animal, usually infect only specific tissues. So cells from different animals and different tissues must somehow look different to the virus. How does a virus "recognize" the right cell?

The first view the virus gets of the cell is a surface covered by a dense canopy of sugars linked to cell surface proteins. This outer fur-like sugar surface is called the glycocalyx and plays an important biological role, including cell-cell recognition and communication, interacting with and binding of cells to the material that glues cells together (the extracellular matrix), altering or modulating the response of immune cells and proteins, and, most important for our purpose, protecting against or determining sensitivity to pathogens like the flu virus. The influenza virus has learned to recognize one of these projecting sugars and uses it to grab onto the cell and initiate the process of getting inside it.

The particular sugar we are interested in is called sialic acid. It often rests at the tips of a sugar chain in turn attached to proteins that are part of the cell surface (see the earlier posts for pictures and a lot more explanation). How the sialic acid is attached to the other sugars in the chain is the key to what the papers are about. For our purposes there are two ways this attachment can be done, designated either an α-2, 3 or an α-2, 6 linkage. These denote two different ways to attach the sialic acid tip to another sugar, galactose, which is next in line in the sugar chain. Other sugars and configurations further in may also be important but the papers at issue consider only the Sialic Acid α-2, 3 or α-2, 6 Galactose linkages (often written NeuAc α-2, 3 Gal or NeuAc α-2, 6 Gal because another name for sialic acid is neuraminic acid; the two papers use the designations SAα-2, 3Gal and SAα-2, 6Gal). This all may seem somewhat esoteric, but it turns out that avian viruses like to bind to sialic acid linked α-2, 3 while human viruses like the ones linked α-2, 6.

The story used to be fairly simple. Birds had cells with SAα-2, 3Gal visible and available for binding to the virus in their intestines and influenza in birds is primarily an intestinal infection. Human beings have SAα-2, 6Gal in their respiratory tract and the viral subtypes that looked for that linkage were the ones that infected humans. Alas, like everything else related to influenza, the story is more complicated. For one thing it was discovered several years ago that humans also have SAα-2, 3Gal on some of their cells. But which cells? That's where these papers come in.

In 2004 Matrosovich and colleagues used a tissue culture system derived from the human respiratory tract to try to figure out which cells had α-2, 3 and which ones had α-2, 6 (Proc. Nat. Acad. Sci. 101:4620 - 4624. 2004). Their conclusion was that the avian virus infected ciliated cells of the respiratory tract while the human viruses infected the non-ciliated ones. The ciliated cells are higher up and in the upper, mid and a bit of the lower respiratory tract, decreasing in density as you go deeper. There are non-ciliated cells throughout, too, but deep in the lungs, especially in the areas where the gas exchange is taking place (the alveoli) the cells are non-ciliated. The number of α-2, 6 cells in humans seemed to be higher, but there were significant numbers of α-2, 3 throughout as well. This was a bit of a puzzle. Why didn't the avian virus infect humans more easily?After all, there were sufficient numbers of α-2, 3 cells in humans, too. Moreover, in human influenza infections, ciliated cells throughout the upper respiratory tract are infected. The story was unclear.

Matrosovich didn't use an intact human respiratory tract but a tissue culture model of one, that is, one that had the same kinds of cells as the respiratory tract but not organized into actual respiratory tract tissue. The two new papers were designed to answer the question of exactly which cells in the intact human respiratory tract the H5N1 virus preferentially bound.

The Dutch group didn't bother with determining α-2, 3 or α-2, 6 characteristics but instead incubated inactivated virus with a label on it with archived formaldehyde preserved tissue sections and then looked to see what part of the lung and which cells bound the virus. The results were that H5N1 mainly bound to a type of cell in the deepest part of the lung where gas exchange takes place (see the earlier posts for an explanation of lung structure). The cell is called a type II pneumocyte and it secretes a protein that helps the lung stay expanded by decreasing its surface tension. Secretory cells make abundant protein, which may be an advantage to the virus because it hijacks the cell's protein making machinery to make copies of itself. The virus also bound to wandering immune system cells called pulmonary alveolar macrophages, which play an important part in fighting pathogens and other garbage in the delicate tissues of the deep lung where gas exchange is the main order of business.

The Japanese group (Nature) did look for α-2, 3 cells and found them in the same place that the Dutch group saw viral binding: deep in the lungs in the type II pneumocytes. Additionally they showed that avian viruses bound to those human cells, as would be expected because they had α-2, 3 sialic acid linkages. Cells higher in the human respiratory tract (nose, throat, bronchial tubes that lead down into the lung) had abundant α-2, 6 linkages. Human viruses tended to bind to and infect cells higher in the respiratory tract, although some type II pneumocytes also had α-2, 6 linkages.

These findings show virus infecting non-ciliated cells just as in Matrosovich's study, but don't mention ciliated ones. So the story isn't complete. Nor does it explain a number of things, for example, if there are α-2, 3 and α-2, 6 studded cells throughout the human respiratory tract, why do the avian viruses seem only to prefer the ones down deep and the α-2, 6 viruses the ones further up? There are quantitative differences in the density of these cells but the details aren't known at the moment and other factors besides the sialic acid linkage might be involved. The finding that H5N1 (an avian α-2, 3 virus) destroys the deep part of the lung has been found clinically and is an explanation for the remarkably virulent nature of this disease. Orange over at the excellent bird flu site The Coming Influenza Pandemic? has resurrected several earlier stories identifying type II pneumocytes as the site of the primary lesion in fatal cases of bird flu, so this isn't a completely new finding.

Finally we come to the question of what it means. My answer may be disappointing. At this point we don't know. The investigators speculate (in the news stories more than the papers themselves) that the reason bird flu is not as "catchable" as ordinary flu is that its residence deep in the lungs makes its transmission more difficult. There is no mucus in the gas exchange units so coughing and sneezing is less likely to create a virus-containing aerosol. Or so it would seem. In truth, however, we don't know the main routes of transmission. Gas from the alveoli (the deep air sacs) is certainly expelled on exhalation, likely contains virus, and once outside the humidified environs of the respiratory tract would rapidly dessicate (dry up) and could form droplet micronuclei. The assumption that virus deep in the lungs is less transmissible might be correct but it has not been shown. Other factors might be involved. Neither paper tested the transmissibility question, which remains pure speculation (although not implausible). The Japanese paper also points out that if the virus were to develop the ability to dock with α-2, 6 cells, either in addition to or instead of α-2, 3, we could have a nasty actor on our hands. One isolate from Hong Kong in 2003 seems to have this ambidextrous character, although most H5N1s do not.

That's my initial read of these two fascinating papers. They are a step forward but leave much to be discovered. Contrary to the more optimistic interpretations, it is too early to conclude that H5N1 is not likely to be easily transmissible from person to person soley on account of its location deep in the lungs. The papers do not show this nor do they conclude this.

This is exciting science, but also urgent science. Much, much more to learn.

Thursday, March 23, 2006

Unhelpful commentary

Debate, skepticism and different perspectives are usually a good thing. So I'm not going to complain too much about another piece of Commentary from Harvard graduate student Peter Doshi in this week's Christian Science Monitor, even though I think it is completely wrong-headed. I know people who think that about me, too. But it is wrong headed.

First, what did he say? He starts with what I consider a straw man argument. The media, aided by politicians out to gain advantage, are spreading unwarranted fear about bird flu which is distorting priorities and creating public anxiety. Doshi had an earlier piece in the British Medical Journal implying that the CDC estimates for flu-related deaths are grossly inflated. There was a good response from one of NIH's best flu epidemiologists, Dr. Lone Simonsen, whose specialty is understanding and interpreting flu statistics. Doshi just didn't understand the system or the basis for the estimates. Moreover if one really counted non-respiatory flu-associated deaths the figure could easily be a gross underestimate.

Doshi also rehashes Dr. Peter Palese's reservations about H5N1 again. I have discussed Peter Palese's views here before. I know Peter, like him a lot, and respect his authority as a ldeading flu virologist. But the data he cites in the Shortridge paper of 1992 contains nothing specifically on H5N1 and there are reasons to believe the H5 data summarized may not be accurate because of the condition of the samples and the method used at that time. The highest seroprevalence reported for H5 in that paper is 7% and for most areas it is 0%. This is not evidence of widespread immunity. I will concede that I myself have been of the opinion that there has probably been a lot of mild and inapparent infection with this virus, but seroprevalence data now coming out seems to indicate otherwise and I now believe I was wrong (see the entry at The Flu Wiki and this from ProMed). This means that the case fatality is not as underestimated as we have assumed. That's bad. It also means that Doshi's comparisons with the 1968 pandemic are not particularly appropriate. 1968 was an unusually mild pandemic, as Doshi knows.

The question is not whether the virus as it currently is constituted is a pandemic threat but whether it will become one. There are many reasons to think this can happen and happen soon. When and i it does, there will be no time to prepare, so waiting to do so is not prudent, although that is what Doshi is advocating. As we have emphasized here many times, and will do again, the way to prepare for an influenza pandemic is to strengthen a community's social service and public health infrastructure. Concentrating on vaccines and antivirals is not a useful way to prepare because if there is no pandemic (we should be so lucky) it would be wasted and the use of either requires an infrastructure to distribute them. Instead the task before us is one of community mobilization but requires a proper appreciation for the nature of the threat.

Doshi's view is very unhelpful in that regard, but not because he objects to scaring people as a tactic. I consider it a bad tactic,too. It is unhelpful because it doesn't do what it should: provide people with a sane appreciation of the risk so they can start to develop the kinds of relationships, structures and orientations that will respond to widespread community illness by encouraging and allowing neighbor to help neighbor.

Homework time again

Among the many vexing issues we will face if a pandemic materializes is what to do about schools -- daycare, elementary, highschools, colleges. Previous data from Boston's Children's Hospital indicated school age children might be the drivers of seasonal influenza epidemics. Their syndromic surveillance system saw the outbreak signal in that age group about a month ahead of the general population. Other data had suggested that closing schools might have ameliorated flu risks in communities where it had been tried. But now computer modelers have entered the fray with a prediction that school closing wouldn't work after all.

The paper has only been given orally at a meeting so I have only seen news reports, but it sounds like what is called agent-based modeling where individual computer "agents" are given attributes of the general population (age, sex, how many contacts they have a day and with whom, how far they travel, where they work or go to school, etc.) and other relationships governing the rate at which the disease is transmitted is put on top of that. Then scenarios are run many times and some idea of the probability of various outcomes is determined. It takes a lot of computing power and it is hard to know whether it produces results that are at all accurate. It still depends on a lot of assumptions. But it is a useful technique to get a feel for the range of things that might happen and to detect unusual or counter-intuitive possibilities.

This week the result of one of these computer simulations was presented at the International Conference on Emerging Infectious Diseases in Atlanta. Here is what the Emory University researchers found:
Using statistics and computer models, U.S. researchers simulated an influenza outbreak in a small urban community of several thousand people, where people made contact in a variety of places where disease could be transmitted, including schools, homes, day care centers, work places and long-term care facilities.

The results suggested that closing schools might simply send children to other places where they could encounter a virus.

"When we assume school closing, it doesn't mean the children are sent home. They will meet at the movies or other places in the community," said Michael Haber, the study's author and a professor in the Emory University Department of Biostatistics. "Children who are not ill may become sick outside the school."

Much more likely to help slow the spread of bird flu and other viruses is home confinement of anyone who is ill or exposed. The study found that under certain circumstances, infection rates could be reduced up to 52 percent and death rates up to 60 percent by home confinement. (Reuters)
This is not a counterintuitive result. It says that if you close the schools you better be sure the kids don't just congregate elsewhere, especially mixing with a random assortment of adults not related to them and it points up the extremely difficult nature of the school problem. If "social distancing" (a euphemism for artificially making it difficult for people to be near each other) is going to be a prominent tactic during a pandemic, school closings will be one application. Federal and state officials are already discussing plans for this. And they should. But schools serve purposes besides education: childcare for working parents, nutrition via school lunches for poor children, ways to disseminate information to parents and much more. If you close them you also have to make provisions for the consequences, as the modeling suggests. Closing wouldn't be for a day or a week, but probably for weeks or a month or more. The consequences would ripple throughout the community. There is not good time for a pandemic, but this is an especially bad time in the US. The tax cut craze at home and the export of hundreds of billions abroad for the Iraq War has left us defenseless. If irony weren't already dead . . . .

So what to do about schools? Parent Teacher groups and local school officials should designate a committee to start meeting on a regular basis to review developments, hold public meetings of the school community and consult with other agencies and voluntary organizations. There are a number of immediate problems to solve. Who is going to make the decision to close and on what basis? When a closure occurs, what will be the various consequences? Taking them one at a time and dividing the labor, what are some ways we can think of ahead of time to work around those consequences?

No one has the answer to these tough questions. But thinking them through ahead of time may come up with some good approaches and may avoid some disastrous mistakes made in a moment of panic or disarray. The more advance work that can be done in a calm atmosphere the better everyone will react in case action is needed. If a pandemic occurs, all of these problems will get solved because they will have to be solved. But they might be solved badly or destructively. An investment in foresight can pay huge dividends later.

Once again. Homework time.

Wednesday, March 22, 2006

Egypt, Azerbaijan and the task ahead

Egypt and Azerbaijan are both reporting more human cases of bird flu. First, Egypt. There are now a total of four cases, one fatal, all with histories of contact with sick poultry. Three more people are suspect cases and under observation. Poultry infection is now widespread in the country, affecting 18 of 26 provinces. While Egypt lies along migratory bird flyways, it is likely that spread in the country is from the movement of poultry or people contaminated with poultry products.

The situation in Azerbaijan is similar, although a relatively large cluster of four related people is cause for some concern (apologies to Henry Niman for using his trademarked phrase). WHO issued an update today, saying that as of ten days ago 7 of 11 cases were confirmed as H5N1, five fatal. WHO anticipates an official Azerbaijan government statement "shortly." Six of the seven cases are in Daikyand settlement (800 homes) in Salyan province in the southeast.
A 17-year-old girl died on 23 Feb 2006. Her first cousin, a 20-year-old woman, died on 3 Mar. The 16-year-old brother of this woman died on 10 Mar. A 17-year-old girl, a close friend of the family, died on 8 Mar. All 4 of these cases lived together or near each other. The source of their infection is presently under investigation.

The additional 2 cases in Salyan involve a 10-year-old boy, who has recovered, and a 15-year-old girl, who is hospitalized in critical condition.

The 7th case occurred in a 21-year-old woman from the western rayon of Tarter. She died on 9 Mar 2006.
thus we have six cases in the same province, four of them related or in contact with each other. The dates of onset are not given, only dates of death, so it is not possible from this information to judge whether person-to-person transmission is plausible.

The WHO update speculates on a possible scenario for these infections in Salyansk, citing "some evidence" of a swan die-off some weeks ago where the carcasses were left unburied.
In this community, the defeathering of birds is a task usually undertaken by adolescent girls and young women. The WHO team is today investigating whether this practice may have been the source of infection in Daikyand, where the majority of cases have occurred in females between the ages of 15 and 20 years. Interviews with surviving family members have failed to uncover a history of direct exposure to dead or diseased poultry for several of the cases.
The update mentions two additional suspect cases in an adjacent province, but Mosnews is reporting that WHO now has 14 suspect cases under investigation. The suspect cases may be the product of an ongoing house to house surveillance effort for influenza like illness (ILI) being done by local medical teams. A US Naval Medical Research Unit (NAMRU3) is providing laboratory support.

What does this all mean? Influenza A/H5N1 continues to infect poultry over a widespread area of the globe. In nine countries where poultry infection exists there have also been human cases (China, Vietnam, Cambodia, Thailand, Indonesia, Turkey, Iraq, Egypt, Azerbaijan). Thus this virus in its various forms is capable of crossing bird and mammalian species barriers. It is also changing genetically. So far its clinical forms have been strikingly virulent.

Many uncertainties remain because we don't understand the biology of this virus well enough to make accurate predictions. At this point, however, the H5N1 subtype is the top candidate for the next serious pandemic influenza virus. Not a day passes that this doesn't become more likely.

None of the news is reassuring. None. It is time to take a deep breath, roll up our sleeves and calmly but with serous purpose methodically and systematically set about the task of getting ready for a period of widespread community illness that will tax our resources, our patience and our ingenuity. Every community has done it before and we can do it this time. While we prepare to look after ourselves and our families, we will all fare much better if we also put significant effort into how we can help each other. You might as easily be the one who needs help as the one able to give it. And that received help might be the difference between you or a loved one's life or death.

The best outcome will be if this pandemic never materializes. This is possible, although seeming less likely by the day. The advantage of strengthening community relationships and structures that foster mutual aid in prepration is that it will not be wasted. We get better, stronger, more resilient communities for whatever happens.

There is still time to fill the sandbags and get our treasures up off the floor. We can help each other. Let's get busy.

UK's warship just keeps on killing

Old soldiers never die, they just fade away, the old saying goes, but a veteran of the UK's Falkland conflict, the ship Sir Geraint, will go on killing even after death. No gentle fade for this asbestos-laden toxic scrap heap.

It wasn't supposed to happen this way. Its dismantling in Pakistan is proceeding in violation of an international agreement banning trade of hazardous wastes to developing countries. But Tony Blair's government turned a blind eye (and the Pakistani government could care less):
The ship was allowed to sail despite suspicions that it may be sent to a scrapyard on the subcontinent. Critics say the shipyard workers are poorly protected against asbestos and other harmful substances.
When the Ministry of Defence sold Sir Geraint to Babcock Support Services, in January last year, it secured a promise that it would not be sent for scrapping in the subcontinent.

Babcock included the same clause when it sold the vessel to Regency Projects, which buys ships and sells them to breakers overseas.

Late last year, when the ship, which had been renamed Sir G, prepared to leave British waters, the Environment Agency, responsible for monitoring where ships are scrapped, suspected it could be destined for the subcontinent.

It allowed Sir G to sail after receiving assurances that it would not be dismantled.

However, when the ship reached Pakistan it was sold to Bismilla Maritime Breakers and the dismantling began. (The Telegraph)
In typical British fashion, it was all put down to an unfortunate misunderstanding. Nobody's fault. It won't happen again. The UK Ministry of Defense and the Environment Agency are regretful but blameless.

I'm sure the Pakistani laborers who endanger themselves for crap wages will understand. I'm not sure about their surviving wives, parents and children, though.

Tuesday, March 21, 2006

Effect Measure a Koufax Award finalist!

We are pleased to report that (the) Revere(s) is/are Koufax Award finalists in the Best Expert Blog category. We're glad to have made it this far in the company of so many terrific expert blogs. Voting has been open for less than twelve hours and already Pharyngula is running away with it. Shit, even we voted for PZ, so why shouldn't everyone else.

However . . . if you should choose to vote for EM as a tip of the hat we would be pleased (who wouldn't?). This category -- like many of the others -- is a pile of apples and oranges (with a banana or pomegranate thrown in). As good as Pharyngula is (and make no mistake, PZ is really good) his site is nothing like EM or Bitch, PhD or firedoglake or any of the others in the same category. We know we won't win and we don't really care (OK, we'd like to win but not that much; it's not like getting your kid into the right Manhattan pre-school or anything like that). The Koufax Awards celebrate the richness and diversity of the left end of the blogosphere and is a wonderful service that our colleagues at Wabanaki do for all of us. If you get a chance, drop a couple of shekels onto their PayPal button to subsidize what they've done. The Reveres did it (under our own names, of course) and we hope some of you will too.

Here's how you vote. Just go to the category thread (here is the one for Best Expert that EM is in) and leave a comment with your vote. Simple. Just one vote per category, please. Play fair.

BTW, here are some of our choices (arbitrary since these are all terrific blogs in every category):

Best Blog (non-pro): Majikthise
Best Blog Community: MyDD
Best Blog (pro/sponsor):AmericaBlog
Best Group Blog: AmericaBlog
Best Writing: James Wolcott
Best Single Issue: Confined Space

To all who voted for us to get into the finals, many thanks. Anonymous blogs carry few rewards, so your kind comments over the year of daily blogging are more appreciated than you can possibly know.

No more business as usual for flu data

It appears the clamor over failure to share flu data is starting to bear fruit. Nick Zamiska is reporting in the Wall Street Journal that WHO is seriously discussing the mertis of opening their password protected flu sequence database to more scientists. Good, but not good enough. It needs to be made public. WHO is also about to ask its member states (n = 192) to pledge they will share virus data. Again, public accessibility is not yet explicitly on the table. It needs to be.

First, credit where credit is due. A public call for openness by a noted Italian flu researcher, Dr. Ilaria Capua, followed by an Editorial in Nature, one of the world's leading scientific journals, then an editorial in the New York Times and importantly, investigative news articles by excellent journalists like Zamiska, Helen Branswell of Canadian Press, Dennis Normile in the journal Science and Nature's Declan Butler (who was among the first to discuss the problem of failure to share sequences by CDC [here and here] six months ago) has helped shake some of this loose. (A few of our posts as background here, here and here). A handful of journalists with real expertise are making a difference. Our hat is off to them.

WHO could do more.
WHO officials have said they would like to make the information public but have emphasized that many countries would balk at sharing data with them if the agency didn't agree to keep it private.

The database contains some 2,300 genetic sequences of the H5N1 virus, around one-third of the world's known sequences. The WHO hasn't elaborated on details of the database.
WHO could elaborate, at least to the point of telling us which countries are balking at sharing data. Zamiska's story suggests many are involved:
According to a person familiar with the database's contents, most of the sequences hidden from public view are from sick birds in Indonesia, China and Vietnam. The database also contains sequences from Cambodia, Hong Kong, Malaysia, Mongolia, Russia, South Korea, Thailand, Turkey and the United Kingdom, this person said.
Butler's story in Nature in September reported CDC was also not as forthcoming as it should be. And the Chinese Ministry of Agriculture has been a sore point with WHO when it comes to sharing isolates. Dislodging the data from these other countries could have a salutary effect on China at a critical time. They are reported to be on the verge of turning over a large number of viral isolates (not just the sequences).

Now is the time to put on the pressure to set a standard we should require from the world scientific community. We can no longer afford the old academic privileges for avian influenza data. No more business as usual.

How not to prepare for a pandemic

Last week The Boston Globe carried an Op Ed piece ("Preparing for Pandemic") by Mr. Manuel Cortazal, identified as the managing editor of the American Journal of Infection Control. He is neither a doctor nor an infection control nurse. But he is a loose cannon.

Like a lot of pieces of this nature it starts out reasonably enough, pointing out that bird flu is appearing in countries like Nigeria and India whose public health system is not equipped to recognize, much less cope with, a genetic change in the virus that would allow easy transmissibility between people.

He then moves on to reprise the Bush administration strategy, which he characterizes as having three components: preparedness in the form of local response plans; surveillance for advance warning; and response and containment, again left to local authorities. Cortazal views these elements against Bush's sorry performance in the Katrina disaster. Preparedness was on paper and not real. Surveillance means nothing without capacity for response. And the ability to respond is sorely lacking in almost all jurisdictions as a result of neglect and budget cuts: "The federal government cannot assume that local authorities will be able to manage relief activities in response to a pandemic."

To this point Cortazal is pretty much on target. But then comes the punchline and this Op Ed rapidly runs off the rails:
The president's plan pays scant attention to quarantine measures, which many experts believe were the key to the containment of SARS. Also, it is weighted heavily toward vaccines and antiviral medications. Yet, national stockpiles are woefully inadequate and won't reach desirable levels until 2008. Owing to the glaring lack of vaccines and antiviral medications, quarantine may be the most effective response to an outbreak.
Cortazal apparently doesn't know the difference between isolation and quarantine (the former is the segregation of the sick, the latter the segregation of the well who might become sick), or if he does, doesn't realize that quarantine as a way to prevent the spread of influenza is considered fruitless by most experts in the field. He also doesn't understand the difference in the epidemiology of SARS and influenza, nor recognize that even in SARS the influence of quarantine is doubtful. Nor that its burden will fall preferentially on the least powerful while those with means and status will have little difficulty evading its provisions. He compounds his dreadful judgment by advancing its obvious consequences:
Officials responding to a pandemic outbreak will have to deal not with mass evacuation but with keeping citizens in place. State and local authorities have no experience in coping with the complexity of restricting the movement of entire metropolitan areas, which, ironically, is the opposite challenge that Gulf Coast emergency managers had faced.

It may come as a surprise to many that the federal government does not have broad police power to impose quarantines, a responsibility constitutionally vested in the states. The disarray among local, state, and federal agencies in the wake of Katrina vividly demonstrated the constraints on cooperation and coordination following a catastrophic event. If a regional outbreak, for want of cooperation among government agencies, were to spiral out of control, the deadly virus could spread nationwide.
The very idea that influenza could be regionally contained in the US is as stunningly naive scientifically as it is dangerous socially. It would, as he implies, also require adjustments to what is considered constitutionally valid, something this Administration has no compunction doing under the cover of public fear.
The unnerving prospects that await us, should an outbreak occur, call for unified leadership that recognizes the limits of state and local preparedness and the need for employing quarantine measures. Rather than delegating planning and response to myriad local health departments, the nation's governors and the president must urgently agree on plans to quarantine affected areas and prepare for the multitude of people who will need healthcare.
Cortazal's suggestion brings us inescapably back to Bush's quickly dropped suggestion that he might use the military to enforce quarantines in the event of a pandemic. It went over badly then and it should go over badly now. It won't work but will do much harm to those already stressed, powerless and overburdened.

This stuff is dumb and dangerous. The Association for Professionals in Infection Control and Epidemiology, the professional association of hospital infection control nurses that publishes this journal, should keep this guy on a shorter leash.