Tuesday, May 31, 2005

Bird flu entrenched in Indonesia

Indonesia hoped to be bird flu free, but the World Organization for Animal Health (OIE) doubts this is realistic and has declared the huge country an endemic area for avian influenza and at high risk for future outbreaks. Undeterred, Minister of Agriculture Anton Apriyantono said Indonesia won't lessen its efforts:
"This will instead encourage us to fight bird flu even harder, be it by enhancing bio-security or isolation," he said, adding that the ministry had not revised its target of being bird-flu free by 2007. (The Jakarta Post)
This latest blow comes on the heels of the discovery of H5N1 in pigs on Java island. The pigs were asymptomatic but harbored H5N1 virus, raising additional concern that they will act as a "mixing vessel" for human/bird virus reassortment.

New requirements to separate pig farms from poultry farms by a specified distance are probably too late. This genie is out of the bottle, and not just in Indonesia.

Higher education

What did you learn in school today?

Song by Tom Paxton


What did you learn in school today
Dear little boy of mine?
What did you learn in school today
Dear little boy of mine?
I learned our government must be strong
It's always right and never wrong
Our leaders are the finest men
That's why we elect them again and again
And that's what I learned in school today,
That's what I learned in school.

What did you learn in school today
Dear little boy of mine?
What did you learn in school today
Dear little boy of mine?
I learned that war is not so bad,
I learned about the great ones we have had,
We fought in Germany and in France,
And someday I might get my chance,
And that's what I learned in school today,
That's what I learned in school.

Last week the House adopted an amendment to the Defense authorization spending bill requiring the Secretary of Defense to submit a report of all colleges and universities not allowing easy access to military recruiters and ROTC programs (Chronicle for Higher Education). This comes after a federal appeals court decision in November allowing colleges to restrict military recruiting on campus. The Senate has also passed a spending bill and the two versions must now go to Conference to iron out differences.

The Bush administration is appealing the decision to the Supreme Court which has agreed to hear it in the next session (beginning next October).

I guess that means Schools of Medicine and Public Health, too. War is a public health issue. What's next? Forced acceptance of recruiters from the tobacco industry?

Monday, May 30, 2005

Memorial Day

We follow the lead of our fellow public health blogger, Jordan Barab at Confined Space:

Were it possible, we would also list the names of Iraqis killed in this senseless war.

Senseless loss of life is not confined to the battlefield. Jordan also has this :
In Memoriam

Some people don't accept that the loved ones they lost in workplace accidents should just end up as filler on a slow news day: In Memory Of Lance.

More tributes here.
Sigh . . .

The vaccine business

With the antiviral Tamiflu in short supply and a threatened pandemic from avian flu, attention has once again turned to vaccines. If there is a pandemic in the next few months with H5N1 flu there is insufficient time to manufacture a vaccine against it. But let's be optimistic and say the pandemic doesn't materialize. Even in a "normal" flu year, almost 40,000 Americans die of influenza, and in the absence of a policy of universal vaccination, this will happen again next year.

In the 1960s there were as many as 26 companies in the US flu vaccine business and even in 1992 there were 10 (Motley Fool). Last year the list was down to two, Chiron and Sanofi-Pasteur, so the contamination in the Chiron UK plant was a serious blow. Other big drug manufacturers had switched their investments to more profitable pharmaceuticals like impotence or cholesterol lowering drugs, items with extremely high profit margins and a requirement for constant use. Vaccines, where the demand is inconstant or unpredictable and use perhaps once in the patient's lifetime, were of less interest, not because they weren't profitable, but because they aren't obscenely profitable.

But contrary to what manufacturers claim, there is still plenty of reasonable profit in vaccine manufacture. Their arguments to the contrary are directed at wringing regulatory and legal concessions to make them even more profitable. Senator Joe Lieberman's (R. D.-CT) new "Bioshield II" Bill is an egregious example of buying Big Pharma's argument and giving away the store.

Evidence for the "reasonable" profitability of influenza vaccines comes from the new interest of drug comopanies in the area, even without the incredible concessions they are demanding. Taking advantage of the Chiron debacle, which cost the US half its flu vaccine supply last year, the UK's GlaxoSmithKline (GSK) has applied for FDA approval for its Fluavirix vaccine, already available in 75 countries, and ID Biomedical is conducting clinical trials for its Fluviral product for the 2006 - 2007 season (Motley Fool). Sanofi-Pasteur and MedImmune are already approved providers in the US, so the new additions would double the vaccine sources.

It is expected that Sanofi-Pasteur will be able to provide about 60 million doses this year, with Chiron another 30 million and MedImmune 3 million. MedImmune's FluMist is a nasal-spray vaccine, not an injectable. MedImmune expects to slash its price this year and will put on a full court press of "physician eduction" in the hopes of boosting its popularity. However it needs to be stored frozen and is so far not approved for the very young and the very old, the two biggest high risk groups. It is also a live virus vaccine, raising questions about side effects in immunocompromised people or immunocompromised contacts of those vaccinated (Motley Fool).

Even with GSK's entry into the market, it is unlikely we will have enough supply for a policy of universal vaccination in the US. But what is really needed is global universal vaccination. If the market doesn't work, we should be looking at non-market solutions, such as state or national vaccine institutes. A dozen vaccine institutes scattered around the world would be a major step forward in 21st Century public health.

Unfortunately this solution has the drawback of being too simple.

Vietnamese bird flu vaccine effort withdrawn

The story of the Vietnamese human bird flu vaccine is a curious one. Vietnam has suffered serious economic loss in the current outbreak of bird flu and also had 76 human cases and 37 deaths. Experimental vaccines are in trial in the US and Canada, but there is no timeline for any product to be available. Thus the Vietnamese decision to make their own vaccine made sense, at least from their standpoint. WHO claims, however, that Vietnam had assured them it would not do so, and now it is reported Vietnam has formally agreed not to pursue a vaccine on its own, but to use a prototype seed strain of the virus provided by WHO.
[WHO flu Chief Klaus] Stohr said his agency had been prepared to raise formal objections with the Health Ministry in Hanoi after the head of the vaccine development project told The Washington Post that Vietnam was determined to develop a vaccine on its own.

The comments by Prof. Nguyen Thu Van, including the disclosure of plans to hold human trials by August, contradicted guarantees from Vietnamese officials that they would call off the endeavor, WHO officials said.

WHO researchers expressed concerns that material used to produce the vaccine strain could be contaminated by other viruses and that a breach of security in the laboratory could allow a more dangerous version of the bird flu virus to escape. (Alan Sipress, WaPo)
Three issues seem to be involved. One is that an H5N1 vaccine, when administered to someone co-infected with an easily transmissible human influenza virus could result in a disastrous reassortment of genes that would produce a pandemic strain. The process for producing the vaccine was also considered risky by some at WHO. The virus would be grown in monkey kidney cells and thus become adapted to primates. While the vaccine was being produced, workers could become infected and an epidemic start this way. Finally, concerns were expressed about security in the labs, although exactly what kind of problem this presents is unclear.

Some of these arguments seem plausible. On the other hand, it is hard not to sympathize with a country with essentially no available supply of antiviral medication and a legitimate suspicion that in the face of a pandemic they will be left unable to afford vaccines made by international drug companies. Both sides of this curious episode make sense.

Meanwhile the Chinese are claiming to have their own vaccine. I don't see Klaus Stohr writing them angry letters. I wonder what the difference is.

Sunday, May 29, 2005

Poisons in the penitentiary

The top safety official of the Federal Bureau of Prisons, Steven Tussey, has resigned suddenly "to pursue some safety consulting work." Translation: he didn't jump. He was pushed.

The resignation, after just three years on the job, comes in the midst of a system-wide review of toxic contamination from seven prison computer recycling enterprises.
This spring, Leroy Smith, the safety manager at Atwater Federal Prison, a maximum-security institution located just outside of Merced, California, went public with documents that inmates using hammers for breaking computer terminals down to components parts for recycling are also spewing particles of heavy metals, such as lead, cadmium, barium and beryllium, over themselves and civilian prison staff. The factory at Atwater also provided an open food service in the contaminated work areas.

Now, safety officials at the Federal Correctional Institution at Elkton (Ohio) are raising similar red flags about their facility’s computer recycling operation. Filters coated with lead dust have been routinely been handled by untrained staff and improperly stored in open bins. Neither staff nor inmates were warned of dangers of direct exposure to the toxic dust that coated their hair, skin and clothing every day.


Besides Atwater and Elkton, five other federal prisons have similar computer recycling plants: Ft. Dix (NJ), Lewisburg (PA), Marianna (FL), Texarkana (TX) and Tucson (AZ). The Federal Bureau of Prisons is part of the U.S. Department of Justice, headed by Attorney General and former White House Counsel, Alberto Gonzales.
Ah, yes, Torture Man, now head of one of the world's largest prison systems. Not unexpectedly, allegations of prisoner mistreatment are not a very high priority and the Attorney General's investigation is not exactly moving with alacrity. But the main thing has been accomplished. No one was held accountable.

Sunday Sermonette: Simon Says

Herein our weekly homily, extolling the virtues of freethinking:
I retain vivid memories of the astonishment and disbelief expressed by the architecture students to whom I taught urban land economics many years ago when I pointed to medieval cities as marvelously patterned systems that had mostly just "grown" in response to myriads of individual human decisions. To my students a pattern implied a planner in whose mint it had been conceived and by whose hand it had been implemented. The idea that a city could acquire its pattern as naturally as a snowflake was foreign to them They reacted to it as many Christian fundamentalists responded to Darwin: no design without a Designer!

Herbert Simon, The Sciences of the Artificial, 3rd ed., pp. 33 -34, 1996; quoted in P. Ball, Critical Mass, Farrar, Straus and Giroux, 2004, p. 154

Saturday, May 28, 2005

We all scream after ice cream (or at least one third of us do)

What's the most common cause of head pain (as in headache)? A recent Editorial in the British Medical Journal (an Open Access journal, which means anyone can read it for free and without a registration!) notes that lots of things can cause headache, including sex (what do you say, "not tonight, dear, it will give me a headache"?). But the most frequent cause (one third of a random sample) was ice cream ("brain freeze").
The pain begins a few seconds after the rapid ingestion of cold foods or beverages and peaks in 30-60 seconds. The pain is usually located in the midfrontal area, but can be unilateral in the temporal, frontal, or retro-orbital region. It is a stabbing or aching type of pain that recedes 10-20 seconds after its onset. Rarely, it persists for two to five minutes.
RO Smith, writing in the Handbook of Clinical Neurology (Vol. 5) in 1968, reported some courageous self-experimentation on the matter. When he applied crushed ice to one side of his palate he got head pain on that side, and if in the midline he got pain on both sides. But it only occurred in hot weather, never in the winter. Effects on blood vessels (first contracting and then widening) have been invoked to explain this. Migraines are also thought related to blood vessel effects in the head, although there is conflicting evidence whether people who get ice cream headaches are more or less likely to have migraines.

Ice cream headache is almost always transient and self-limiting. While sufferers rarely seek medical attention for the condition, there is a flourishing industry of folk remedies, at least judging from the Letters section of the BMJ.

This information is to show that we at Effect Measure understand there are other problems in the world besides bird flu. And because it's Saturday.

Friday blogrollin' (Saturday edition): Steve Gilliard

Many moons ago PSOtD inveigled us into using space every Friday to highlight another blog we like (community building and all that). This week it's not someone who needs any recognition, but an A-list blogger, Steve Gilliard (The News Blog).

I picked it because I liked this post which I got via James Wolcott. Here's a little bit (it's long), a response to another blogger, Big Media Matt, who was espousing the bullshit of the "hawkish" liberal:
Let me start by saying that I like Big Media Matt. He's a nice kid. But he's wrong, talking out of his ass actually.

Matt, if you are "hawkish", I think there are recruiting station in Boston Common, Times Square and off the Mall in DC. Any one will accept your enlistment. Because if you are going to support interventions, you need to get your ass in the Army and support it as an 11B. This is real life. You can sit on your ass and proclaim policy and not be taken seriously, or you can get a commission, lead a platoon for a couple of years and have real world experience. Because, otherwise, you are pretty much a chickenhawk suggesting poor people die for your ideas. And I think you're smarter and better than that.
The whole post is pretty good. Itself a bit too hawkish, maybe, but still pretty good. Worth a read, along with much else there.

Chinese bird flu vaccine redux?

Back in February we posted about the supposed Chinese vaccine breakthrough. We are again getting press releases and news conferences about Chinese bird flu vaccine, touted this time as "100% effective." As other commentators have noted (for example, John Woodall of ProMed here), no vaccine is 100% effective in those who receive it, but this claim may refer to the ability to raise antibodies and hence some protection in all of the bird species tested. Too little information has been released about these vaccines to make an informed judgment as to the significance of the claims of the Chinese government.

Meanwhile, take a glance at the earlier post for an interesting "back story" to the February announcement. The relationship of the currently announced vaccines and those from 3 months ago is not clear at this point. It is likely they are the same or very similar.

Friday, May 27, 2005

Migratory bird deaths in China: number increases

The number of migratory birds dead from H5N1 avian influenza in Qinghai Province in northwestern China has gone from a little less than 200 barheaded geese last week to over 500 birds of five different species a few days ago to more than 1000 in an announcement from the Agriculture ministry today (Reuters).
A strain of bird flu deadly to humans has killed more than 1,000 migratory birds in northwest China, an agriculture ministry official said on Friday, more than five times the number of birds initially reported dead.

Earlier this week, China sealed off nature reserves and rushed more than 3 million doses of bird flu vaccine to far-flung Qinghai province after migratory birds were found dead from the H5N1 strain.

"What we have been doing is preventing domestic fowl and people from having contact with wild migrant birds," Jia Youling, director general of the veterinary bureau of the Agriculture Ministry, told a news conference.

None of the 2.18 million domestic birds in the province had been found to be infected, he said. He dismissed rumours any humans had been infected.
Those rumors, that more than 120 people in Qinghai have died, continue to circulate on the internet (see post here).

China needs to allow independent scientific and public health observers into this area. Their own statements suggest they are doing what is indicated so there should be no risk to them from having the rest of the world see it. At the same time it is important to have specimens so that genetic sequencing can compare the virus that caused the bird deaths in Qinghai with those circulating elsewhere.

Bird flu is not a Chinese problem or a Vietnamese problem or a US problem. It is a global public health problem and should be approached that way. It is also time to get the Great Powers (including the US) to think that way.

Additional note: We have added a second Update to the previous post on this issue, suggesting a possible source for the blackout rumor in Qinghai.

Decisive inaction on bird flu

It's decided then. Definitely. They'll decide by the end of the summer. Maybe.

The US pandemic influenza plan, in the works for five years and in only in draft form since last August will be completed in final form "by the end of the summer."
Marcia Cross, the [the Government Accountability Office's] director for health care, told lawmakers that federal officials have yet to determine what role the federal government will take in purchasing supplies of vaccine against bird flu and other flu strains. The government has also not cemented which population groups would be priorities for emergency vaccination in the event of an outbreak or finalized plans for possible quarantines or travel restrictions.

The delay has left state health departments unable to properly plan for flu emergencies, she says. (Via WebMD)
No plan. How about a drug stockpile for an emergency? CDC Director Dr. Julie Gerberding explained the Administration's failure to establish an adequate stockpile of antiviral drugs this way:
Officials said they are moving to purchase more drugs for the stockpile but defended their decision not to engage in a massive buildup. While the drug can lessen disease severity if taken with 48 hours of the start of symptoms, no studies have shown that it improves patients' chances of surviving bird flu, Gerberding says.

"Making enormous purchases in stockpiling may be a premature decision," she says. "The studies simply haven't been done." (WebMD)
That's interesting. Because there is excellent data to show that antivirals like oseltamivir are effective if taken prophylactically. Doesn't preventing the disease improve your chances of surviving it? I guess one of us skipped that class in Epidemiology 101. Of course, maybe the evidence doesn't rise to the level of the protective effect of inspecting shoes at airports, but hey . . .

An experimental bird flu vaccine is undergoing safety and effectiveness testing at the National Institutes of Health. Early safety data are expected this summer, [NIAID Director Tony] Fauci says.
That's great. About time. Except . . . the vaccine they are safety testing doesn't contain an adjuvant, an additive which could extend the vaccine supply many fold. They're going to test adjuvanted vaccine at a later time. End of the summer maybe? Of what year?

The party's over. Time to call it a day.

Welcome to the party, Dr. Gerberding (Director, CDC). We were expecting you earlier.
Top health officials warned that the United States was ill-prepared to counter a pandemic which could come from a mutation of the bird flu H5N1 that has badly hit Asia. (Agence France Presse via Yahoo News)
And whose fault is that? Isn't preparing for the foreseeable YOUR job?
"Although we cannot be certain exactly when the next influenza pandemic will occur, we can be virtually certain that one will occur and that the resulting morbidity, mortality, and economic disruption will present extraordinary challenges to public health authorities around the world," [Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, warned the House of Representatives].
Well, Dr. Gerberding, maybe it won't be that bad, say, compared to the obesity epidemic you have spent so much time talking about:
Julie Gerberding, director of the US Centers for Disease Control and Prevention (CDC), said that even a "medium level pandemic" in the United States could result in 89,000-207,000 deaths and up to 734,000 people people being hospitalised.


According to Gerberding, between 15 percent and 35 percent of the US population would be affected by a flu pandemic and the cost to the US economy would be between 71 billion and 166 billion dollars.
Oh. Never mind.

Thursday, May 26, 2005

Qinghai, as of now

New Scientist is providing a bit of additional information on the Qinghai (China) reports of many people dying of an unidentified cause in the same area as the recent die-off from bird flu of migratory birds. Not much more information, but a little.

The reports come from an online Chinese language news service, Boxun (Abundant News), where correspondents may freely post information. (Here is the link for Chinese readers. Further information solicited and appreciated). Postings there on May 25 reported 121 people in 18 villages have died of bird flu, with approximately 1300 people having been "isolated."
The media reports are said to have come from nine correspondents in Qinhai, who report that people connected to the cases have been forbidden to talk to outsiders. Boxun cautions that the reports cannot be independently verified, but says it hopes by drawing attention to them they can be further investigated.

The reports say that sick people in the border region between Qinghai and the neighbouring, impoverished province of Gansu had visited the nature reserve where the birds were found. But they also report that there have been large scale outbreaks of unexplained deaths among livestock in the area.
China has a spotty record for open reporting, the most notorious example being their cover-up of the SARS epidemic in 2003. However it is widely believed Chinese authorities recognized this was a damaging policy and have generally been given good marks since then. Given this history and the remoteness of Qinghai province in northwest China there remains some legitimate skepticism about official denials. If the reports are true, it is a serious evidence a major pandemic is solidly underway. At this point, however, we do not know if these reports are true in their entirety, partially true but distorted in some way, or completely false.

This is another example of how a history of lying is ultimately self-defeating. If there is indeed an outbreak there it will become known in short order and it is useless to cover it up. We anxiously await better information.

Update, 11:23 pm, 5/26/05: Snowy Owl of the CurEvents board has kindly provided us a translation from the Chinese of the boxun site linked above. Thanks to Mikala who did the translation and Snowy Owl who sent it on. It is in the Comments to this post (comment number 3). You will have to draw your own conclusions from it.

Update, 2:35 pm, 5/27/05: From China Daily (reporting press conference held by Jia Youling, director general of the Veterinary Bureau of the Ministry of Agriculture):
Qinghai Province, has been sealed off right after death of some migratory birds was found. He said there had been no precedent in the world to prevent and control avian influenza among migratory birds, and China's measures are all aimed at preventing the virus from spreading to domestic animals and human beings.

Up to May 26, more than 1,000 migratory birds including bar-headed geese and great black-headed gulls were killed by bird flu virus in northwest China's Qinghai Province. No tourists and irrelevant persons had been allowed to get into the habitats of migratory birds and the infected areas since the outbreak, he said.
"Sealing off the province" might be the source of the "blackout" rumors and also the suspicion something dire was happening there. We will keep watching developments.

China's "isolated" bird flu outbreak

The statement by China's Ministry of Agriculture that the Qinghai bird flu in migrating geese "has so far proven to be an isolated case" can't even be taken at face value.

You've got over 500 dead bird of five different species on a flyway that extends from New Zealand to Siberia, and every one of the infected migratory birds just decides to plop down on the same quarter square kilometer island to die?

We note that China also practices vaccination, which allows birds to be infected but not sicken. Vaccinated birds shed significantly less virus but may still be infectious. So the notion that the problem was isolated and is over with is not very credible. I'm trying to say it nicely.

Meanwhile there are cryptic and unconfirmed reports suggesting there might be human deaths from an unknown cause in Qinghai. Chinese authorities in the provincial capital of Xining (via XinhuaNet) are denying any human infection or unexplained deaths from pneumonia:
XINING, May 26 (Xinhuanet) -- No human infection of avian flu or unexplained pneumonia case has been detected in northwest China's Qinghai Province and health departments are going all out to prevent a possible outbreak of bird flu, according to a local health official.

Emergency measures have been taken by the provincial health authorities after Ministry of Agriculture investigators confirmed on Saturday that migratory birds found dead in Quanji Township of Gangca County had been killed by the deadly H5N1 strain of the bird flu virus, said Ai Keyuan, an official with the provincial health bureau.

Health departments in the provincial capital Xining and at least four prefectures have been mobilized. They have stepped up infectious disease control and prevention by closely monitoring and screening all pneumonia and flu-like cases among human beings,fowls and livestock, Ai told Xinhua in an interview Wednesday.

Ai said hospitals in Gangca County, where the avian flu cases were reported, have opened up a separate outpatient department forfeverish patients alone. "The county's health department, meanwhile, is assisting the provincial disease control and prevention center in medical observations of people who had had close contacts with the birds," he added.

Ai said his department is also helping local animal husbandry departments to sterilize the infected areas and properly dispose of birds' droppings.

"All hospitals have been told to set up a task force and put aside medication and facilities for the treatment of any avian flucases that might be detected," he said.

Qinghai Province took emergency measures by closing off some scenic spots to prevent people and poultry from contacting wild birds. Quarantine measures have also been adopted.

The Ministry of Agriculture has told the public not to get too nervous but said monitoring for the epidemic and the early-warningsystem should be enhanced.
I don't find this report especially reassuring. It says there are dead birds in Qinghai and that no one should panic because they have stopped the spread in birds. At the same time it says hospitals have set up special fever clinics and that "[q]uarantine measures have been adopted." It doesn't say if these measures relate to people or birds. It denies unexplained deaths "from pneumonia." It is impossible to know from this if it covers all unexplained deaths from all causes as well.

It is too soon to jump to conclusions about what is happening here. The suggestion there has been a news blackout is worrisome. China is especially sensitive about such charges because of the SARS episode so I think this is unlikely, but we just don't know at the moment. We will keep our eye on this.

"Frist Family" Values

All Bill Frist wanted was to let President Bush's horror show judges have their "day in court," as it were. Well a "day in court" is exactly what John Smelik is going to get in Texas, against the for-profit Humana Hospital Corporation, alleging they negligently and fraudulently caused the premature death of his wife from kidney failure:
A case that could allow you to sue your HMO is going to court. A woman died from a health problem she knew nothing about, and her husband is now suing her insurance company blaming it for her death.

"She was soft," John Smelik said of his wife Joan. "She was gentle, and she was kind."

"She was an understanding kind of person," Smelik said. "She put up with me for 47 years."

Smelik loved his wife Joan so much he refused to leave her side after rushing her to the emergency room four years ago. He said without warning, her kidneys were failing.

Joan Smelik spent 19 days in the hospital.

"We said, 'Honey, we'll see you in the morning, and we love you,'" John Smelik said. Those were their last words to each other because Joan's kidneys shut down. (WOAI)
Neither John nor Joan were aware there was anything wrong with her kidneys, although the hospital had notified Humana (the insurer) of the fact many months before. So far, just another sad story of a health care system not working. So what else is new?

This. It is a case about suing your HMO, an issue in the 2000 Presidential campaign (you remember that one don't you?). Humana is not just an HMO. It is a for-profit HMO. For-profit health care, like HCA (Hospital Corporation of America), the Bill Frist family business. The same HCA that got tagged for defrauding Medicaid, Medicare, and Tricare (the federal program that covers the military and their families) for over $600 million dollars and wound up paying penalties reaching $1.7 billion. (You can read about it in a wonderful book about whistle-blowers and the Federal False Claims Act, Giant Killers by Henry Scammell, Atlantic Monthly Press, 2004.)

We got wind of this story from reader Kimberly Soenen (hat tip, contact info at end of post), who also supplied a background refresher. When George W. was Governor of Texas he refused to sign the Texas HMO Act which gave enrollees the right to sue their HMOs. Instead he allowed it to become law without his signature and then took credit for it in a debate with Al Gore. Then in a landmark legal case before the Supreme Court about whether patients could sue their HMO's, President Bush sent the Attorney General to argue the Texas HMO Act was pre-empted by federal law, prompting the Supremes to toss it back to Congress to enact a Patient's Bill of Rights. And guess who in Congress notified the press he had no interest in trying to get a federal Patients Bill of Rights passed?

Bill Frist.

[NB: If you are interested in further information or the court opinion regarding Smelik v. Humana, you may contact Kimberly Soenen at kimberly.soenen@rcn.com]

Wednesday, May 25, 2005

Historic special issue on avian flu in Nature

In an extraordinary special issue, the world's top scientific journal, Nature, again sounds an urgent warning regarding the threat of a pandemic from avian influenza.
Trouble is brewing in the East. A highly pathogenic strain of avian influenza is endemic in southeast Asia. Many millions of chickens have been culled, but there is a persistent reservoir in domesticated ducks and wild birds. The H5N1 virus isn't going to go away. And each time it emerges, people can be infected.


This week, Nature devotes its News Feature and Commentary pages to a detailed consideration of the risks posed by avian flu, and how well we are prepared to deal with it. In the pages that follow, our reporters examine nations' capacity to produce a vaccine against a pandemic strain, and the adequacy of global stockpiles of antiviral drugs. They do not paint an encouraging picture.

Repeated warnings about the international community's failure to respond to the pandemic threat have fallen on deaf ears. So in our opening News Feature, we use the benefit of fictional hindsight to throw the issues into starker relief, describing a future pandemic through the weblog of a journalist in the thick of things. This is fiction, but not fantasy — the storyline was drawn up in consultation with those who could soon be dealing with the situation for real.
The fictional weblog is highly realistic, absolutely convincing and for those reasons very frightening. An extended Commentary section has pieces from noted authorities (Robert Webster, Michael Osterholm, David Ho among others) and those in authority (Tony Fauci). Full texts are free online for most articles, including avian flu articles from other Nature publications journals and past articles (index here). Direct links are also up on Connotea, courtesy Declan Butler, Nature Senior reporter. This is a treasure trove of information I have only had a short time to skim. I will be digesting it over the next several days but thought it important to alert everyone.

Nature is doing nothing less than trying to jump start action on avian flu. That a private publication should find it necessary to take this on is a sad commentary on the dereliction of duty from local, national and international public health authorities.

Kudos to Nature. A groundbreaking and possibly historic publishing event. If it succeeds.

New rules at WHO--for some

The idea of national sovereignty goes back to the Peace of Westphalia, ending the Thirty Years War in 1648. Globalization and other factors have weakened the nation-state system and the threat of emerging infectious disease with pandemic potential has highlighted further the difficulties of allowing each country to determine its own public health course when what happens in one can threaten its neighbors and even entire regions or the global community. But WHO's original International Health Regulations (IHR) still assumed the Westphalian system, making the agency's ability to require its member states to cooperate difficult or impossible. The IHR have remained essentially intact in that form since 1951. In its last incarnation (1981) the IHR"required" WHO notification of cholera, plague, yellow fever, smallpox, relapsing fever and typhus, but today only the first three remain as diseases requiring immediate notification. And notification was essentially the only substantive requirement.

Now, WHO through its governing body the World Health Assembly, has revamped the IHR (.pdf) in ways that challenge its Westphalian foundations--but not by a lot. It is requiring member nations to notify WHO immediately of the presence within their borders of any of four diseases: bird flu, Severe Acute Respiratory Syndrome (SARS), smallpox and polio. In addition, countries must put in place the capacity for routine preventive measures and monitoring, including specific public health actions at ports, airports and border crossings. If countries don't comply, the WHA voted to establish a standing committee of external independent health experts to advise WHO on actions such as recommending travel and commerce restrictions to affected areas, a clear departure from the notion of pure Westphalian sovereignty. WHO took such actions to a limited extent in the SARS episode and this experience is now being formalized in the new IHR.

Member states have two years to establish these requirements in their own laws and regulations, after which they will automatically be bound by them--except, if they decide to opt out or express reservations. And guess who was the first to do that?
The United States, which welcomed the new rules, was the first country to announce its plans to file a reservation - saying that when it came to US armed forces, it would comply with the rules unless they compromise national security. (AP via Jamaican Observer)
Let me see if I understand this. If a deadly disease (say, for the sake of argument bird flu) breaks out in the military, the US isn't bound to notify any other country or its own people? Because of national security? I guess I don't get what "national security" means. I thought it had something to do with keeping us safe.

TBI: "signature wound"

I suppose it is good news that more soldiers from the Iraq debacle are surviving. But there is a flip side. Traumatic Brain Injury (TBI).
"Traumatic brain injury is the signature wound of this war," said Lt. Col. Rocco Armonda, an attending neurosurgeon at the National Naval Medical Center in Bethesda, Md. [In the first year of the war Armonda and his colleagues] performed 270 brain surgeries, 60 of which were for penetrating wounds. "In previous conflicts, most of these people would have died," Armonda said.

In the following year, Armonda said, neurosurgeons doubled the number of craniectomies, in which part of the skull is removed to accommodate brain swelling. According to the New England Journal of Medicine, mortality from brain injuries in the Vietnam War was 75 percent or greater, with 12 to 14 percent of all combat casualties having a brain injury. In the Iraq and Afghanistan conflicts, traumatic brain injury accounted for 22 percent or higher of the injuries - a larger proportion of casualties than it has in other recent U.S. wars. (Newsday)
Many of the TBI symptoms are cognitive: memory and attention problems, inability to speak clearly or carry out certain kinds of thinking tasks, headaches, thought disorders, forgetting words. Some have personality changes. Others have disinhibition, irritability, anxiety and depression. Sometimes the symptoms get better. Often they don't.

It is not just penetrating wounds but concussions from proximity to strong explosions.
Doctors at Walter Reed Army Medical Center in Washington, D.C., are assessing all injured troops returning from Iraq. As many as 60 percent have brain injuries, the [New England Journal] reported. Some are mild. Most are moderate to severe. "There is a good chance that they will be living with symptoms for a long time," [Dr. Susan Oakie] said [writing in the journal].
Sixty percent of injured soldiers [see clarification below] with Traumatic Brain Injury. With kevlar vests and helmets. What if you were an Iraqi civilian?

Clarification, 1:57 pm, 5/25/05: I have gone back to check the figures in the NEJM paper, as I was bothered by the 60% figure in the Newsday quote, above. The 60% figure does appear there (actually it is 59%) but refers specifically to admitted patients exposed to a blast (as from an IED). The best data I can find on the proportion of injuries due to blast suggests it is about 50%. Thus the proportion of all injuries with TBI would seem to be 30%, still a horrendous figure. We apologize for the lack of clarity here, for which we take responsibility.

Tuesday, May 24, 2005

New York City (almost) gets it

It's nice to see somebody in authority in public health gets it, even if it's a local health department, in this case New York City's.
Infectious-disease experts at the Health Department have been meeting every two weeks to prepare a strategy for protecting the city against diseases such as the Asian bird flu, or H5N1, which many scientists believe is just one crucial mutation away from turning into a monster malady.

The written blueprint, which officials expect to complete before the next flu season starts in late fall, spells out how the agency will tackle potentially controversial measures.

The issues addressed include how to handle quarantines, test virus samples for new strains, cope with overcrowded hospitals and ration lifesaving vaccines and other treatments. (NY Daily News)
At the moment, the only generally available therapeutic agent is the antiviral, Tamiflu (although an inhaled antiviral, Relenza, should be available to a lesser extent). But the US has only purchased enough for about 1% of the population, while the UK, France and New Zealand have ordered enough for 20% of their populations, Canada 17%. London officials have also independently bought 100,000 doses for use with essential personnel (fire, police, transit workers). This is a sensible plan and one New York and other cities should adopt immediately. Health care workers and nurses should be included. By targeting essential personnel there would be enough Tamiflu to go around, but only if plans and distributions are done now. Neither New York nor any other American city has yet to take this step.

The Daily News article suggests that New York's hesitancy is related to not moving ahead of, and hence upstaging, their federal counterparts, upon whom they might depend in a crisis. Wake up, New York. In a crisis the federal authorities will be even more useless than they are now, since demands will be coming from everywhere. They are paralyzed now. What makes you think they will awake from their coma in time to do you any good?

War now number one cause of hunger

To paraphrase Mark Twian, everybody talks about War, but no one ever does anything about it. So it has now become the number one cause of world hunger, beating out weather and natural disasters, according to the UN's Food and Agriculture Organization. In a report presented at a food security meeting Monday, FAO pointed to a dramatic increase in food emergencies in the period of the nineties compared to the period of the late eighties. Most of the countries with a third or more of their populations under nourished were in states of armed conflict in that period.
"Armed conflicts are now the leading cause of world hunger with the effects of HIV/AIDs and climate change not far behind," the FAO said in a statement.

It added war "contributes to the spread of HIV/AIDS through displacement, rape or commercial sex."


"The impact... is not limited to the conflict area. It diverts resources from national development programmes and weakens government capacity, indirectly affecting the provision of services to the whole population," the FAO said. (via Reuters Health)
Of course you might say we are doing something about both war and the weather: we are making both worse.

Monday, May 23, 2005

Lack of bird flu action a national scandal

China is taking vigorous measures to contain H5N1 infection allegedly brought to the country via migrating wildfowl, apparently bar-headed (or spot-headed) geese, possibly from India (see coverage by Recombinomics here, here and here). 178 dead geese were found on bird island in Qinghai Lake in remote Western China. The lake is China's largest saltwater lake and the quarter-square kilometer island, said to be home to more than 100,000 birds, is a tourist attraction, especially for birders. It has now been closed and farms near migration routes have been ordered to vaccinate their birds.

Agence France Presse (AFP) also reports a much wider provincial vaccination campaign underway:
China has ordered the immediate vaccination of three million birds among other emergency measures to stop the spread of bird flu after discovering the H5N1 virus had killed some migratory birds, state media said yesterday.


Poultry in farms around the affected area had been mostly vaccinated by Saturday, Xinhua said.

The dead birds were found on the edges of Lake Qinghai, where the presence of migratory birds is a tourist attraction.

The area has been sealed off for more than 10 days, with police stationed there around the clock to prevent tourists from entering, the Beijing News said.


Veterinary institutions across China were also asked to determine the species and territory of migratory birds in their regions and to take precautionary measures.

The agriculture ministry has asked local governments to prohibit people from entering the habitats of migratory birds and to prevent contact between migratory birds and poultry, Xinhua said.
Confusion remains about the source of the migrating birds, with news reports quoting Chinese authorities as suspecting southeast asia but adding that the virus is not the same as the one currently circulating there. China last reported H5N1 infection in birds last July. The H5N1 virus is not always highly pathogenic for geese, although it apparently is in this case. A previous outbreak in China in 1996 also was deadly for geese.

The Chinese authorities are clearly taking this outbreak seriously, but it is hard to see how they will be able to prevent the spread if migrating birds are indeed the source, as there are major migratory flyways across this vast country. Once H5N1 infection in birds becomes an Asian panzootic we will be in yet another segment of an extremely worrisome trajectory for global public health.

Meanwhile, deaths from bird flu continue to be reported from Vietnam, the latest a 46 year old man from an area 40 km west of Hanoi. Two other cases are hospitalized.

All national health authorities are now on notice that pandemic planning should be highest priority. If this were intelligence regarding a possible terrorist action we would be on Red Alert. Yet there is still no visible action from the US CDC or most state health authorities. This must now be counted a national scandal.

Doubt production: a growth industry

In an important article in this month''s (June 2005) Scientific American, epidemiologist David Michaels of George Washington University School of Public Health lays out the enemy's battle plan in their assault on health and safety regulations. Its title, "Doubt is their Product," is taken from a 1969 memo from an executive of the Brown and Williamson Tobacco Company (now owned by RJ Reynolds): "Doubt is our product since it is the best means of competing with the 'body of fact' that exists in the mind of the general public." We posted on one aspect of this recently here regarding regulation of benzene. But this article has much more, depressingly more [disclaimer; I know the author].

Consider the beryllium standard. Michaels had previously been assistant secretary of energy for environment, health and safety at the Department of Energy in the Clinton Administration. On his appointment the standard for beryllium exposure, a lightweight metal used in the production of nuclear warheads that is extremely toxic, had not changed since 1949. It was responsible for causing many cases of a serious scarring of the lungs called chronic beryllium disease (CBD) which affected not only workers machining the metal but also those working nearby and even residents living around the factory. By the time of Michaels' appointment it had become abundantly clear that the old standard was woefully inadequate. The process of promulgating a new standard in the 1990s was met by a counter attack by Brush Wellman, the leading producer of the metal, who hired Exponent, a California consulting company to do a series of reviews which suggested skin exposure was a factor (not just inhalation) and that size, surface area and number of metal particles might be important factors in CBD. More research was needed, they concluded.

After due consideration, the Clinton DOE decided there was enough information to issue a rule and the exposure standard for DOE facilities was lowered by a factor of 10. But it applied only to DOE workers. Those in the private sector still worked under the old standard, ten times higher. When OSHA tried to follow DOE's lead in 1998, it became enmired in procedure. By 2002, the Bush DOE had decided more research was indeed needed. That is the current situation.

As Michaels makes clear, this is not an isolated example. He cites the fact that of almost 3000 large volume chemicals (one million pounds or more annually), OSHA has enforceable exposure limits for less than 500. In the past 10 years has issued new standards for only two. All others come under "voluntary" standards set before 1971. They have been untouched by new science. The standard setting process has become so muscle bound and cumbersome and the political will so weak that it is almost impossible to set new standards.

Part of the reason is that the business of "manufacturing scientific uncertainty" has become a growth industry. Michaels gives numerous chilling examples involving drugs and notes the effect of the Supreme Court Daubert decision in preventing legitimate scientists from testifying in tort cases on behalf of deserving plaintiffs (see earlier post here). He recounts briefly some much publicized manipulation of scientific advisory committees by the Bush Administration and also alerts us to another ominous industry weapon, the Data Quality Act. This was snuck into law via a midnight rider on a 2001 appropriations bill and passed without hearings or debate. The DQA sounds great. It authorizes the development of guidelines for "ensuring and maximizing the quality, objectivity, utility, and integrity of information." What it means in practice is that industry can easily slow or halt regulations by challenges of any scientific data used to support a regulation. The challenges then trigger cumbersome and lengthy procedures. It has been used to attack climate change assessments, WHO dietary guidelines and even NIH advice that we limit our salt consumption.

I haven't done full justice to this fascinating but also disheartening, even frightening, article. Scientific American is available on newstands or digitally for $5 here.

Sunday, May 22, 2005

Activists dismiss bird flu fears

The distrust of WHO from its lack of transparency and obeisance to member states (some of dubious virtue) has borne the expected bitter fruit. Yesterday Satya Sivaraman of the People's Health Movement dismissed fears of an influenza pandemic, charging it was the product of a climate of "panic."
Sivaraman is attending the World Health Assembly, meeting in Geneva until May 25, where one of the items on the agenda is a draft revision of the WHO International Health Regulations aimed at heightening security against the international spread of disease, essentially in response to the SARS and bird flu outbreaks.

While he believes that revising the regulations is a good idea, he fears that the reaction to these diseases is closely linked to ”American paranoia about biological terrorism.”

Since the early 1990s, he said, the United States has been trying to convince the world that biological terrorism is possible, but ”nobody was listening to them.”

But then, with the outbreak of anthrax, followed by SARS and the chicken flu, they have finally succeeded in ”creating this mood.”

One of the implications of this situation is a restriction of the movement of people, he said. ”Talk with any doctor in Europe, and they will tell you that tuberculosis is back in Europe because of migrants, that HIV is spreading because of migrants. This is all linked between migrants and diseases.”
I understand these views. The US government has cynically manipulated fears of "global terrorism" and used them for political purposes, while European governments have raised disease fears to cope with domestic backlash over foreign workers and immigrants.

However, this time the situation is genuinely dangerous. Pandemic influenza, especially with a virus with the characteristics of H5N1, is a genuine threat, no more so than to the world's poorest countries. They will not be the beneficiaries of any last minute vaccines or anti-viral stockpiles and most have no medical care system to speak of. They will suffer grievously, and as usual, disproprotionately.

In actual fact, the US and many other nations have done relatively little with regard to preparing their own populations for a pandemic, nor has it become part of an anti-immigrant or xenophobic campaign, maybe because it doesn't particularly lend itself to such uses. So this is not a concern instigated by WHO and the US but one that arose in spite of their timidity.

So while The People's Health Movement's suspicions are understandable, in the end I am not sympathetic. There comes a time when critical thinking needs to be exercised in place of off-the-shelf reactions. This is the time.

Sunday Sermonette: Ingersoll on religious diversity

Herein are usual Sunday homily. This time from the famous 19th century Republican speechwriter (and free-thinker) Robert Green Ingersoll (1833-1899):
“Few nations have been so poor as to have but one god. Gods were made so easily, and the raw material cost so little, that generally the god market was fairly glutted, and heaven crammed with these phantoms.” (From The Gods)

Saturday, May 21, 2005

Friday blogrollin' (Saturday edition): Bird flu sites revisited

Judging form the increased traffic on this site, interest in bird flu has ramped up considerably in the last week after WHO began to sound a more insistent and urgent alarm about the developing situation in southeast asia (and here). The last time we updated our list of sites that provide bird flu information was all the way back on January 12 of this year. Time for another look.

We'll start here (Effect Measure). This is a general public health site edited by epidemiologists, but the importance of avian influenza as a major developing story in public health has claimed a disproportionate amount of attention (see left side bar where bird flu links are listed). We try to cover much else as well (idiosyncratically, things that interest the handful of editors who call themselves Revere), but bird flu has tended to be Topic A. This is not only because of its importance per se but because it is a lens with which to look at the status of public health organization, policy and leadership more generally. We not only filter the news but provide (opinionated but informed) commentary.

Another key site, with a somewhat different flavor, is Henry Niman's Recombinomics. This is the website of Niman's biotech company whose "product" is the ability to predict genetic changes brought about by recombination. Niman is controversial in some quarters, but his Commentary on avian influenza has been spot on for the most part and far in advance of WHO and CDC's. These agencies are now saying openly what Niman has been saying for many months. His Commentary tends to be somewhat cryptic and technical in nature, but for those with adequate backgrounds it is very informative and for those not so well prepared there is still much that can be gleaned. You are not properly up to speed if you are not checking this site regularly.

Similarly, the University of Minnesota's Center for Infectious Disease Research and Policy (CIDRAP) is an essential source for accurate and readable information about emerging infectious diseases, bioterrorism and avian flu. They have also been keeping a more up-to-date unofficial case and case fatality count than WHO. Highly recommended.

The Coming Influenza Pandemic is a filter site that does a daily round-up, usually with a brief description or one or two sentence commentary on links, including Effect Measure, Recombinomics and CIDRAP as well as others of interest. Worth a daily check.

Somewhat similar is Pathogen Alert. Not quite as complete but always worth a look.

A new site that has just started up is Avian flu - What We Need to Know. It is run by economics graduate students at George Mason University. At this point it seems to be primarily a filter site, collecting news links about avian flu. We'll have to see how it develops. Welcome to the bird flu blogosphere.

The bird flu agent at News Now does a pretty good job of scarfing up news stories on bird flu. I also use an RSS reader (since I am on a Mac it is NetNewsWire) to look at a variety of sources, primarily Moreover Public Health News.

ProMed Mail is an alert service used by many public health professionals. It tends to be a bit late in its reports and often has rather timid commentary.

CDC's Avian Flu site is usually a day late and a dollar short, but background information conveniently arrayed.

There are also a couple of non-public health blogs that have a particular interest in bird flu and are worth checking on their own merits, which are considerable. One is Melanie Mattson's Just a Bump in the Beltway and the other is The Next Hurrah, where DemfromCT has developed both an interest and expertise in the subject.

There are also discussion groups devoted to the subject that deserve mention. The one we see most often is CurEvents.com. We are not members so we can't tell you how to get to the bird flu thread but there are a number of very knowledgeable and well informed people who post there. Our only complaint is that they take my posts and repost them in their entirety there. This is great because the more people who have access to information the better, but their posting method both obliterates the distinction between what we have written and what we have blockquoted and also has no links. Thus we are improperly credited with things we didn't write and the actual writer doesn't receive the proper credit. If they read this, perhaps they could remedy this unfortunate situation and also post here in the Comments how our readers can join their discussion threads.

We've probably missed a couple of good sources here, so don't hesitate to let us all know via Comments.
Update: Here is something we left out but shouldn't have. There is a new "social bookmarking" service out of Nature publishing especially for folks interested in science. There is a special tag, AvianFlu, for people interested in sharing links on this subject. Here is a description from one of the users:
Re: "Friday blogrollin' (Saturday editition): Bird flu sites revisited," perhaps you might give a mention of Connotea AvianFlu tag. Here is posted what are judged key news articles, plus significant scientific papers, important reports, powerpoints of recent talks, and other material that I and others come across when researching and reporting. The tag also has it's own RSS feed, which people can add to their readers. Contributors to Connotea, who share via tags, are mainly working scientists, editors, or reporters.

Northern virus genetics scarce

A brief report in The Scientist says that CDC researchers will publish findings on genetic changes in H5N1's HA binding site within weeks.
But the new 2005 gene sequences are taken from only a handful of isolates. WHO says scientists have had technical problems in trying to derive isolates from the hundreds of serum samples collected in over the past few months in Vietnam.

"CDC has only one isolate and sequence for H5N1 from North Vietnam cases reported in 2005," said Ruben O'Donis CDC's Chief of the Molecular Genetics Section Influenza Branch in an email to The Scientist.
This is consistent with other information that there have been unexpected difficulties in isolating and growing H5N1 virus from the north of Vietnam. It is not clear what the reason is for this.

The genetic sequence data is important information in assessing the likelihood of a genetic shift that might be evidence of pandemic potential. But it is only one kind of information. It is also unfortunately just as likely we will know a pandemic is underway when we start seeing obvious human-to-human spread in many areas in a short span of time.

Friday, May 20, 2005

Warning: idiots loose in Pennsylvania

Thanks to a reader (hat tip, James) we became aware of the most bizarre biodefense nonsense yet. The Pennsylvania pandemic flu plan is a state secret (very annoying registration required):
Pennsylvania officials say their decision is necessary to keep terrorists from gathering sensitive information with which to harm the public.


But Pennsylvania officials say their pandemic plan includes sensitive details - such as phone numbers and vaccination storage sites - that could devastate response efforts if the information got into the wrong hands.

"We are walking on a knife's edge," said Adrian R. King Jr., director of the Pennsylvania Emergency Management Agency. "We want to act in good faith to give information. At the same time, we have an obligation for operational security."
Let's be clear about this. Mr. King and anyone else who had anything to do with this are idiots. And incompetent. And dangerous. If there is an influenza pandemic, the response will be local because the disease will be happening in many localities at once, not like a disaster or an attack where federal or state authorities can send outside help. Every "outside" location will also be "inside" some other locality. Response to a pandemic requires cooperation and coordination from a wide set of actors: hospitals, clinics, emergency medical techs, pharmacies, nurses, doctors, public health authorities and many, many more. In Pennsylvania only 25 copies of the plan are available and are closely guarded. What happens if most of those people become ill? If there are antivirals available, who will get them? If there is some vaccine, who will get it? If there are a limited number of critical care beds or respirators, how will they be rationed? These and many others are public questions and require public debate. And buy in. And advance planning.

I won't go on and on about this. It is just too, too stupid. This is one of the most moronic things I have heard in a long time. Even in a time where moronic things are becoming commonplace, this is beyond belief. These guys only have a couple of neurons firing and they are using one to breathe and another to drink coffee. If there is a flu pandemic, the one they use to breathe may not do them much good if their lungs are stuffed with a hemorrhagic pneumonic infiltrate. That just leaves coffee drinking.

Nurses down the drain

If there is an influenza pandemic, one of the critical shortages will be hospital beds. Not just the physical beds. As has been often noted, beds don't take care of patients. Nurses take care of patients. So the critical shortage will be staffed beds.

In the US many nurses and nurses aides are resident aliens. Later this year the US is expected to lift restrictions on recruiting foreign health workers to ease the nursing shortage here. With a ten fold pay differential, this is an opportunity for many of these workers. But an Editorial in The Philippine Star reminds us of exactly what this means for the Philippines. Besides the loss of an expected 25,000 nurses and other health workers, there is also the lost investment in their education in Philippine nursing schools. It is a loss The Philippines cannot easily afford:
Already the nation is feeling the loss of a growing number of doctors, nurses and other health workers who are lured by much higher pay overseas. Many rural communities lack even a single physician. In some villages, residents depend only on occasional visits from government workers for basic health care such as dental services and cataract treatments. For serious illnesses, residents rely on herbal medicine and prayers.
Influenza pandemics are global. The Philippines will suffer grievously along with everyone else. But their native daughters and sons will be tending American patients. There is something wrong about this.

Thursday, May 19, 2005

WHO's chilling warning

CIDRAP has a superb rundown on the warning sounded at WHO's World Health Assembly in Geneva. Citing the "WHO Inter-country Consultation: Influenza A/H5N1 in Humans in Asia, Manila, May 6th-7th, 2005" (.pdf) CIDRAP sets out WHO's reasons for believing H5N1 is poised to become a pandemic threat:
The report cites several differences between epidemiologic features of human cases this year in northern Vietnam and those in southern Vietnam this year and overall last year:
  • Northern Vietnam has had eight case clusters this year, versus only two in the south.
  • Case clusters in northern Vietnam this year have lasted longer than did clusters last year.
  • The average age of infected people in northern Vietnam rose from 17 to about 31 years between 2004 and 2005, but it stayed about the same in southern Vietnam (15 to 18 years).
  • The case-fatality rate has dropped to 34% this year in the north but is 83% in the south.
In addition, the report says the recent discovery of three asymptomatic cases in Vietnam suggests that milder infections are occurring. A few asymptomatic cases also were found in Japan and Thailand in the past year, and others were discovered in Hong Kong after the H5N1 outbreak in 1997.

The report says the longer duration of recent clusters may signal a growing number of ways in which people contract the virus, including exposure to sick birds, environmental infection, lengthy exposure to asymptomatic birds that are shedding virus, and person-to-person transmission.


"Investigators were not able to prove that human-to-human transmission had occurred. However, they expressed concerns, which were shared by local clinicians, that the pattern of disease appeared to have changed in a manner consistent with this possibility," the assessment states.
A number of recommendations are made, including the following:
  • WHO should convene its Pandemic Task Force to meet regularly, assess the data, and determine the risk for pandemic flu.
  • All nations should move as quickly as possible to complete "practical operational pandemic preparedness plans."
  • WHO should explore "all possible mechanisms" to make H5N1 vaccine available to the Asian countries affected before a pandemic. It should bring together technical experts, countries, manufacturers and possible donors to find ways to boost global H5N1 vaccine production.
  • Coordination of animal and human surveillance and viral information must be improved from the ground level to the national and international level, and data must be exchanged quickly.
  • The WHO should complete a handbook on how to investigate possible H5N1 clusters.
  • The WHO should explore building a stockpile of antiviral drugs that could be used to respond to early signs of a potential pandemic.
  • Countries needing funding and agencies that may provide funding must coordinate their efforts to avoid redundancy and eliminate gaps
The WHO report concludes in chilling fashion:
"Evolution of a pandemic strain of virus may be preceded by numerous small steps, none of which is sufficient to signal clearly that a pandemic is about to start. This poses a difficult public health dilemma. If public health authorities move too soon, then unnecessary and costly actions may be taken. However, if action is delayed until there is unmistakable evidence that the virus has become sufficiently transmissible among people to allow a pandemic to develop, then it most likely will be too late to implement effective . . . responses."

Preparedness is now "damage control"?

Indonesia, an impoverished country with a rudimentary public health system (2002 allocation 0.72% of gross domestic product) has bird flu in poultry and now likely in humans (via Dow Jones Newswires, no link). After pigs were discovered infected with H5N1 on Java island, blood samples from 63 local poultry workers found at least one with evidence of prior infection (antibodies to the virus in his blood). Confirmation of the result is underway, but it is likely there has been much unrecognized infection here and elsewhere.

That is also the message at WHO's annual governance gathering, the World Health Assembly now meeting in Geneva.
Officials in Thailand believe they will not be able to a detect a pandemic virus until it has reached its fourth line of victims, Kumnuan Ungchusak, head of the epidemiology at the Thai health ministry, told the meeting.

"If we detect it at that point, it would be easy to control, but it if we miss it it could be bad," he said. (Dow Jones Newswire)
WHO is now openly admitting that everyone is unprepared.
Health chiefs today warned of major doubts about their ability to detect and tackle a more virulent and deadly strain of the influenza virus before it spreads globally causing millions of deaths.

The warnings came at a meeting to discuss preparations for a looming pandemic, organised on the sidelines of the World Health Organisation's annual assembly in Geneva.

"We are working on pandemic preparedness on borrowed time," the WHO's top influenza official, Klaus Stohr, told the meeting, reiterating that conservative estimates indicated that up to 7.4 million people might die.

"The objective of pandemic preparedness can only be damage control. There will be death and destruction."

"National pandemic response plans are the key," he said.
National pandemic response plan? What's that? In the US we have a Draft Pandemic Influenza Preparedness and Response Plan from last August. It is very general and state health departments have said not very helpful. Moreover CDC has done little to ramp up public concern about the matter, something that is a prerequisite to kick-starting state and local health authorities besieged by urgent competing demands for shrinking funds. Clearly scaring the public is not much of a concern for an Administration that regularly scares them as a matter of policy.

What about a stock of antivirals, the only therapeutic option at the moment? The Wall Street Journal reports the obvious:
Amid growing fears that an outbreak of avian flu could spark the next flu pandemic, wealth has become more of a factor than need in determining who will get an essential drug.

Richer countries facing little immediate avian-flu danger have moved in recent months to stockpile large amounts of the drug, called Tamiflu. The poorer Asian nations at the epicenter of the threat -- the key staging area for fighting the current outbreak and possibly forestalling the pandemic -- have only small-scale donations of the drug at present and scant resources for ordering large amounts.
WHO recommends enough antiviral (Tamiflu) for one quarter of the population. But the drug is expensive ($39 to treat flu if recognized within 48 hours, the only time the drug is effective for treatment) or about $160 for a 6 week course of prophylaxis. Vietnam, the country with the highest case count and millions of infected birds, has 84 million people but only 2000 treatments. Cambodia's population of 14 million has only 300 courses of treatment, mostly donated.

Roche, the only manufacturer of Tamiflu, has an unknown inventory of the drug and most of that has been ordered by developed countries. The drug has a long production cycle -- 12 months -- and thus the newly increased demand can't be met instantly. However Roche, who reportedly doubled its production this year even without advance orders, has also devised a bulk method to facilitate stockpiling:
Roche has already taken unusual steps to try and increase the drug's availability. For instance, it adopted what it calls a "bucket chemistry approach," offering Tamiflu's active ingredient, a white powder known as oseltamavir, in 15-pound barrels and at half the price of the capsule form. The powder can be dissolved in water and consumed. Tests have shown that this form confers the same protection as the capsule and can be stored longer. A small portion of the bucket form has been ordered.
Sweden has ordered enough for half a million and tens of millions more doses have been ordered by Norway, Canada, Australia, New Zealand, Finland and France. The US has only ordered 2.3 million and may increase that to 6 million (enough for only 2% of our population). The UK is more ambitious with plans a $385 million for a quarter of its population. London wants 100,000 for its police fire and transport workers. WHO is trying to establish a "mobile stockpile" of 120,000.

Some public health authorities believe that a pandemic can be substantially slowed (but probably not stopped) by rushing Tamiflu to an initial outbreak and saturating the surrounding area. Whether this would work or not is unknown and some doubt it (see for example Henry Niman at Recombinomics). Even if effective, since the initial frontlines are likely to be in country's with few resources, the Tamiflu would have to be donated by the developed world:
Ensuring that Tamiflu gets to the front lines of an outbreak is so crucial to containing it that some public-health officials recommend that richer nations donate part of whatever stocks of Tamiflu they accumulate to the countries most affected by avian flu.

"Now that we can do something about it, we shouldn't be sitting on our haunches," said John Oxford, a British virologist whose research showed that Tamiflu was effective against the avian-flu strain. He suggests that wealthier countries set aside 10% or so of their Tamiflu stocks for use in Asian countries.
I think this is unlikely. Countries like the US are going to be scrambling desperately with their own "damage control" necessitated by a lack of due diligence. This was all foreseeable. Why we are in this fix now--and as far as I can see still not getting it in gear--is an example of dereliction of duty, incompetence and hardly what we would expect from a President that conned half the country into thinking he was "keeping them safe." In fact he has put them in mortal danger.

Wednesday, May 18, 2005

Another bird flu case in Vietnam

Bird flu cases continue to appear in Vietnam. AFter an apparent lull of almost a month, two new cases have been reported. We recently noted the case of the 52 year old man from Vinh Phuc province. Now comes news of a 58 year old from Thanh Hoa province, admitted to the Institute hospital in Hanoi last Friday with "typical symptoms of bird flu infection" according to his doctor (via XinhuaNet). No exposure information was given. Both men are reported in stable condition.

AFP says the patients' homes have been quarantined and the families are being monitored (via CIDRAP). CIDRAP's unofficial case and fatality count for Vietnam, mid-December 2004 to present, now stands at 43 cases with 16 fatalities (37% case fatality).

Big Pharma: right answers for wrong questions

Some people might consider the title of Richard Smith's article in PLoS Medicine [full text], "Medical journals are an extension of the marketing arm of pharmaceutical companies," provocative. I think people who follow this just think it's obvious.

Smith was editor of the British Medical Journal for 25 years. He is not talking about the ads that big drug companies run in major medical journals like BMJ but rather the scientific articles they fund and sponsor.

For better or for worse, the randomized clinical trial has become the Gold Standard for evidence-based medicine.
A large trial published in a major journal has the journal's stamp of approval (unlike the advertising), will be distributed around the world, and may well receive global media coverage, particularly if promoted simultaneously by press releases from both the journal and the expensive public-relations firm hired by the pharmaceutical company that sponsored the trial. For a drug company, a favourable trial is worth thousands of pages of advertising, which is why a company will sometimes spend upwards of a million dollars on reprints of the trial for worldwide distribution. The doctors receiving the reprints may not read them, but they will be impressed by the name of the journal from which they come. The quality of the journal will bless the quality of the drug.
Those same reprints are a major source of income for the journals and the principal reason they refuse to go Open Access (free and unhindered access to contents), despite the fact that many of the articles are taxpayer funded and the goal should be to provide important medical and scientific information to the world-wide community of doctors and scientists.

Moreover, Smith points out that a 1994 study of 56 clinical trials funded by manufacturers for non-steroidal anti-inflammatories for arthritis by Rochon et al. found none that published unfavorable results, i.e., "[e]very trial showed the company's drug to be as good as or better than the comparison treatment."
By 2003 it was possible to do a systematic review of 30 studies comparing the outcomes of studies funded by the pharmaceutical industry with those of studies funded from other sources. Some 16 of the studies looked at clinical trials or meta-analyses, and 13 had outcomes favourable to the sponsoring companies. Overall, studies funded by a company were four times more likely to have results favourable to the company than studies funded from other sources. In the case of the five studies that looked at economic evaluations, the results were favourable to the sponsoring company in every case.

The evidence is strong that companies are getting the results they want, and this is especially worrisome because between two-thirds and three-quarters of the trials published in the major journals—Annals of Internal Medicine, JAMA, Lancet, and New England Journal of Medicine—are funded by the industry. For the BMJ, it's only one-third—partly, perhaps, because the journal has less influence than the others in North America, which is responsible for half of all the revenue of drug companies, and partly because the journal publishes more cluster-randomised trials (which are usually not drug trials). [cites omitted]
The drug companies achieve their results in two ways. First, by using "asking the right question" to enhance the chances of getting the "right" answer. If the question is properly "framed" a study can pass peer review and even be of "high quality." Here is Smith's partial list of some of the strategems for "asking the right question":
Examples of Methods for Pharmaceutical Companies to Get the Results They Want from Clinical Trials
  • Conduct a trial of your drug against a treatment known to be inferior.
  • Trial your drugs against too low a dose of a competitor drug.
  • Conduct a trial of your drug against too high a dose of a competitor drug (making your drug seem less toxic).
  • Conduct trials that are too small to show differences from competitor drugs.
  • Use multiple endpoints in the trial and select for publication those that give favourable results.
  • Do multicentre trials and select for publication results from centres that are favourable.
  • Conduct subgroup analyses and select for publication those that are favourable.
  • Present results that are most likely to impress—for example, reduction in relative rather than absolute risk.
Second, drug companies succeed in using the medical journals for marketing by publishing essentially the same results in many places. This can be done in various ways, for example, by presenting partial outcomes of multicenter trials in different combinations at different times in different journals.

Smith does not believe that more skeptical peer review or "registries" of clinical trials will solve the problem. His prescription is novel:
Firstly, we need more public funding of trials, particularly of large head-to-head trials of all the treatments available for treating a condition. Secondly, journals should perhaps stop publishing trials. Instead, the protocols and results should be made available on regulated Web sites. Only such a radical step, I think, will stop journals from being beholden to companies. Instead of publishing trials, journals could concentrate on critically describing them.
Sounds right to me. The drug companies should take two of their own trials and call the journal in the morning.

Tuesday, May 17, 2005

Smallpox, new and improved?

The man who thought he had rid the world of smallpox, Dr. D. A. Henderson, isn't too keen on allowing scientists to conduct experiments to genetically modify the virus. He wants all existing stocks destroyed. Unfortunately, his government and some of his US colleagues don't agree. They are asking WHO's World Health Assembly (its governing body) to allow experiments to proceed.
Researchers have already been given the go-ahead by a technical committee of the World Health Organisation, which accepts the argument that the research could bring new vaccines and treatments for smallpox closer. This week the debate will pass for a final decision to the floor of the full assembly of the WHO, whose representatives from 192 member states begin a 10-day annual meeting in Geneva today. (From The Guardian)
All smallpox stocks were to be destroyed by 1999, but this didn't happen, primarily because both the US and Russia "dragged their feet":
The WHO then set up the Variola (smallpox) Advisory Committee to give the WHO scientific advice on what should and should not be permitted. The committee, known as VAC, has gradually shifted the position away from destruction. At its last meeting, in November, the committee recommended that US proposals for further experimentation on the live virus, including genetic modification, should be allowed.
Not everone agrees. The Sunshine Project and The Third World Network are vigorously campaigning against genetic modification of the virus. They point out that the VAC is three fourths composed of scientists from the US, Europe and Russia. These countries have sufficient public health infrastructure so that if smallpox were to reappear they could vaccinate their populations. Moreover, smallpox vaccine is a live-virus vaccine made from cowpox virus and cannot be safely used in the huge HIV positive population of the developing world.

There is also the danger that working on the virus at multiple sites around the world will provide opportunity for development of weapons:
"The problem is that we have got a lot of people with a lot more talent working in biological laboratories around the world and a lot of them are very well-trained and the potential for mischief here is much greater," [Henderson] said.
And of course there is the potential for an unintentional release. It is worth remembering that the last person to die of smallpox was a photographer who worked upstairs from a laboratory that was working with the smallpox virus in Birmingham, England. The date of her death? September 11, 1978.

Epidemiology of constipation (one in seven)

Now for something different. Have you ever wondered just how common constipation really was? Probably not. It takes an epidemiologist to wonder about things like that. The Oxford scientists over at Bandolier took up this non-urgent question recently in "strangers to the lavatory" (yes, really the subtitle of their post on the prevalence of constipation).

Constipation is common. Meaning what? Since this is a family blog (of course it would have to be a very dysfunctional family) I'll forego the definitions. They are not appetizing. After reviewing ten reports published between 1964 and 2000, the curious folks at Bandolier concluded the overall prevalence (proportion of adults with constipation at a particular time) was about 15%, or one in seven. Women were about twice as likely to be constipated as men. Prevalence is lower with higher education and income, probably a diet factor. The older you are the more likely you are to be constipated.

It is a sobering thought that when you get on a bus or subway car with fifty people on it, on average seven of them will be constipated.

Monday, May 16, 2005

Time for Plan B

In December 2003 a Food and Drug Administration advisory panel voted 23-4 to recommend that Barr Pharmaceuticals Inc.'s Plan B contraceptive (the "morning after pill") be made available without prescription (over the counter). Then came a memo to the FDA from Bush appointee Dr. David Hager, a well known evangelical Christian OB-GYN on the panel. In May 2004 the FDA ruled against its own advisory committee, saying the drug had not been shown safe in young girls. Reuters reports that Senators Clinton and Murray are asking for an investigation as to whether Hager's advice was based on science or his religious beliefs.
The Washington Post reported on Thursday that Hager gave reporters conflicting accounts about who asked for the memo, at one point saying the request was from an FDA staff member and another time saying it came from outside the agency.

"Due to confidentiality, I am not at liberty to say who encouraged that this opinion be written," Hager said in an e-mail to Reuters.

An FDA spokeswoman said Hager sent the letter "as a private citizen" and that the agency does not ask for "minority opinions" from advisory committees. She said she could not release the letter, but that it might become public in response to a Freedom of Information Act request.
Hager is a spokesman for the Christian Medical Association and co-wrote a book that emphasizes the healing power of Jesus and prayer. But it turns out that Hager's co-author, his ex-wife Linda Carruth Davis, is disgusted by hypocrisy of his frequent proclamations of devotion to family values. In a lengthy report in The Nation by Ayelish McGarvey, she says he not only committed adultery but frequently engaged in non-consensual anal intercourse during their 32 year marriage and eventually she could not tolerate it.
According to Davis, Hager's public moralizing on sexual matters clashed with his deplorable treatment of her during their marriage. Davis alleges that between 1995 and their divorce in 2002, Hager repeatedly sodomized her without her consent. Several sources on and off the record confirmed that she had told them it was the sexual and emotional abuse within their marriage that eventually forced her out. "I probably wouldn't have objected so much, or felt it was so abusive if he had just wanted normal [vaginal] sex all the time," she explained to me. "But it was the painful, invasive, totally nonconsensual nature of the [anal] sex that was so horrible."
For the record, Davis remains a committed conservative and is still deeply religious. Her story has been corroborated by a number of friends and acquaintances in whom she confided during her marriage.

She at least, had a Plan B. That is more than Hager, the Bush Adminstration and the lapdogs at the FDA are affording women in this country.