Tuesday, February 28, 2006

Taking stock, part II

We return to the task we set ourselves in Part I, surveying our ignorance about some important bird flu questions. Taking up where we left off, we ask what we know about what determines which species the virus infects. This is not an in-depth treatment. We just mention a few topics still being debated in each category. The extent of disagreement varies with topic.

Host range: This is being intensively studied. Paradoxically we may know less about it now than we thought we did ten years ago, as the complexity of the host range problem is being revealed by better scientific techniques. We originally thought that the determinant rested solely with the nature of the cell surface receptors in the host, with birds having one kind of receptor, humans another, and pigs having both. Pigs could thus act as a necessary "mixing vessel" where human and bird adapted viruses would exchange genetic information and produce a Frankenstein monster pandemic hybrid. We now know that the pig isn't necessary, as both the 1918 virus and the current crop of avian viruses seem to have jumped from birds directly to humans. Moreover the supposed division of cell surface receptors between humans and birds also isn't what we thought it was. The human respiratory tract has a lot of cells with the receptor we thought was characteristic of birds. (If you want to know more about this subject we treated it here in a series of four posts: here, here, here and here). Moreover the interaction between the receptor on the host cell and the HA protein on the virus that supposedly determines the specificity is quite subtle. Predicting and understanding the effects of a particular mutation is still not possible, although some relationships are known or can be inferred. It is also probably true that the ability to infect different hosts requires changes in other genes. A recent discovery that the presence of a ligand on the viru's NS1 protein that binds the PZD domain in host cells differentiates bird and human viruses raises a whole new set of possibilities. Obviously there is still a lot to learn and no guarantee we know the most important part as yet.

Becoming easily transmissible from person to person and virulence: Disease is not inherent in an organism itself but is from an interaction the between the virus, its host and the environment. We are now able to rapidly sequence viral isolates but the step from the genetic sequence to knowing its implication for disease is a big one. At the moment we don't know what makes one virus easily transmissible nor do we understand what makes one virus virulent and another likely to cause milder disease. The nasty and rapid symptoms and pathology of human H5N1 infection is still shrouded in mystery. The suspicion that "cytokine storms" -- uncontrolled inflammatory responses -- are responsible has scientific support but we remain at a loss as to the mechanism behind it. What is there about the virus that it is able to subvert the very machinery we use to defend ourselves for its own purposes and to our detriment? There is a also uncertainty about many details of the immune response, especially the cell-mediated response. The immune system is extremely complex, so our difficulty understanding its function in influenza shouldn't be a surprise, but many people assume we know all about it. We don't.

Vaccines and antivirals: We have yet to make a feasible experimental vaccine we are confident will protect people against this virus. Not only don't we yet know what the pandemic strain but existing strains have not made especially effective vaccines. For reasons still not clear the virus is not very immunogenic and efforts to date have not been able to produce potent vaccines. Nor do we have the production capacity to make much difference for years to come. For the near future vaccines do not seem to be the answer. Nor do we yet know how useful either of the two main classes of antivirals will be. Many strains of H5N1 are resistant to the older class of drugs (the adamantanes), and there is uncertainty about whether there is emerging resistance to the newer neuraminidase inhibitors like Tamiflu and Relenza. Whether Tamiflu resistant strains will be less virulent than sensitive ones, as some believe, or whether resistance will develop to any appreciable extent is still unknown. Finally, if the neuraminidase inhibitors are effective, there is now uncertainty what the proper dose regiment should be, both in daily dose and length of treatment.

How does influenza spread in human populations? Probably most surprising of all our areas of ignorance is that we are still not sure all the modes by which influenza virus spreads in human populations. The three main possibilities are via large droplets (from sneezing or coughing), which is a well established mode of spread and has a radius of about five feet; small droplet nuclei, tiny droplets that remain suspended for long periods in the air so the infecting radius is much larger; and fomites, or inanimate objects, like computer keyboards and door knobs. Handshakes, too, are still of uncertain importance. We know the virus will survive for long periods on hard surfaces but we don't know if this is an important mode of transmission compared to others. For example, there are some data the virus will only survive for minutes on human hands, so that if you touch a doorknob the amount of virus may diminish rapidly and even if you then touch your nose, eyes or mouth the amount of virus may not be sufficient in instances to infect you. We can be fairly confident, I think, that transmission via fomites happens sometimes. The question, however, is how often and how important is it in the scheme of things. A great deal of advice is being given out about how to avoid the flu, ranging from washing your hands to wearing a mask. In truth, while some of this advice is plausible and prudent, we have little idea how effective any of it is.

This has been a very cursory survey of our ignorance. There is a great deal more that could be said about all of these topics. And we will learn more, no doubt. I hope it won't be the hard way. Meanwhile, we will be forced to make our best guesses, given the uncertainties. People and nations will sometimes opt for different measures, influenced by valid considerations beyond the science (but no doubt invoking science as their rationale). That is inevitable and necessary.

All the while the virus is also learning the best way to accomplish its only task, making more copies of itself.

Part I, here.

Monday, February 27, 2006

Taking stock, part I

Highly Pathogenic Avian Influenza (HPAI) A/H5N1 has now spread to over 30 countries (by the time you read this the current count of 31 may well have increased so I'm not going to use a false precision). For a decade it has caused loss, fear and trouble in southeast asia and China, but suddenly, in the space of four months, it has burst out and is threatening to gain a permanent foothold among wild and domestic birds in Europe, Eurasia, the Indian sub-continent, the Middle East and Africa. Along with the bird infections have come sporadic human cases in southeast asia, China, Indonesia, Iraq, Turkey and perhaps elsewhere.

So it is time to pause and take stock, not so much of what we know but what we remain unsure of. There's a lot. Given the long interest in the influenza A virus and the new powerful methods of modern molecular biology, there is a surprising amount of basic stuff we don't know. This is not an indepth treatment but more like looking at wildflowers from horseback. We won't dismount to examine them closely and many will go unidentified. Because there's a lot to cover we'll do it in two parts. Part II tomorrow.

The setting: Influenza A is predominantly a bird disease. Birds can be infected by most of the many combinations of the 16 H subtypes and 9 N subtypes. Other animals become infected less frequently, but pigs, horses, cats, dogs, ferrets, marine mammals and of course humans are all capable of being hosts to one or another of the subtypes (H and N combinations) [terminological note: there are three types of influenza virus, A, B and C. The influenza A type has a possible 144 subtypes, the 16 H and 9 N combinations. Within each subtype, genetic variations are strains. This terminology is frequently abused and the use of strain for subtype is distressingly common.] Since the immune system "sees" the H and N proteins, our immunity is to these factors. Human influenza virus has been almost exclusively to H subtypes H1, H2 and H3. With the emergence a few years ago of documented infections with other H subtypes (H5, H7, H9) concern was raised about what would happen if one of these "new" (to humans) versions became easily transmissible from person to person, since there would be no immunological memory to protect us. If the virus were also virulent, meaning capable of causing serious disease, the resulting pandemic could be devastating. Just how devastating is provided by the historical event of the 1918 H1N1 pandemic.

When the first human cases of the H5N1 subtype (which was also extremely virulent for terrestrial poultry) were described, the alarm bells went off that this might be the early warning of a possible pandemic virus. Not only was H5N1 extremely virulent for poultry, but also for the human cases, with mortality over 30% (6 of 18 cases). Draconian measures of bird culling -- essentially attempting to kill all poultry in Hong Kong -- seemed to snuff out the threat at its origin. In the years that followed, human infections with H7 and H9 subtypes were also described but none had the virulence of H5N1. Then in 2003 H5N1 reappeared in Hong Kong and southeast asia. Thus began the outbreak which today seems to be spreading globally.

Here are some obvious questions. How is this bird virus spread from locality to locality? Are there effective ways to halt its spread among birds? What determines when an influenza A subtype will jump species boundaries and start infecting a new host, i.e., what determines host range? In particular, what determines if humans will become infected, and if infected be able to pass it easily from person to person? Why is H5N1 so virulent in people? How is influenza passed from person to person? How do we make a vaccine against it? What about antivirals? Will drug resistance emerge?

These are obviously significant questions but they don't exhaust the list. There are many others, I am sure, but it's more than enough to make the point I'm after. There remains a great deal about some important things we don't know.

Geographic spread: It now seems that wild and migratory birds can be infected and that some at least can harbor the infection but not be too sick to travel long distances. Unlike the asian case where the virus was discovered by its high mortality in poultry, in Europe it is the wild bird populations that are showing the first signs of local infection. But how does this virus get around: local poultry movements (trading, smuggling, etc.)? wild bird migrations? longer distance movement of poultry via trains, as was recently suggested? some other way? Do wild birds give it to poultry or do poultry give it to wild birds? If spread is a combination of these factors, what is the predominant mode of spread and are there any critical points where we could intervene to stop or slow spread? Many people think they know the answers to one or more of these questions but they don't agree with each other. The spread to a commercial turkey farm in France last week is especially puzzling as allegedly there was no chance of contact with wild birds. There are underlying political and disciplinary issues involved, as well. (e.g., the bird conservancy scientists versus public health scientists). Related to this question is whether it is small backyard holdings or factory farms that are the true incubators, and perhaps origin, of the HPAI strains of H5N1. This has implications for the economy and for control measures. Everyone has an opinion.

Control of spread among birds: Several main methods are in use. Mass cullling over a large area. Quarantine combined with mass culling within an area. Selective culling. Vaccination of birds. It is an open question as to the effects of mass culling in slowing the spread but it obviously is unable to stop it. Even the attempt at total extermination on an island venue (Hong Kong) didn't do it. In my view the option that makes the most sense at this juncture is selective culling of flocks where there are infected birds as a way to prevent infected animals from getting into markets. But it is easy to think of the weakness of this method, too. Vaccination has the virtue of being able to protect the birds from dying, but there is substantial evidence it doesn't protect them from being infected, after which they remain infective but shed virus at a considerably lesser rate. Thus this is unlikely to stop the spread of disease and may make it more difficult to track it since the birds will not be obviously ill nor will we be able to detect past infection by looking for antibodies (since all the birds will have antibodies if vaccinated). That's the best case, and assumes the bird vaccines are effective and effectively administered. In a mass vaccination situation with quickly ramped up production and many untrained vaccinators, this is not a safe bet. The result could be ineffective protection, with the virus being trekked from farm to farm with the vaccinators. Thus we still don't know the best way to control this disease among poultry, even if it weren't a public health problem but "just" an economic one.

We'll finish our stock taking survey in Part II.

Sunday, February 26, 2006

Christian beheadings

Sunday is a good time to remind everyone about one of the essential characteristics of all religions. None has a monopoly on evil.

Take beheadings. Nasty. Abhorrent. Beyond the pale. Hard to understand how any civilized person would do it.

Unless you were French and you had a handy dandy machine so you wouldn't have to get your hands bloody. But that was a long time ago. 1939. Or Germany. 1949. Here we preferred to fry people with a few thousand volts while they were strapped into a chair. But that's another topic.

Back to beheadings. Not a specially Muslim practice. Christians liked it, too.

And, as it turns out, still do:
An enraged mob of Nigerian Christian youths has slaughtered dozens of Muslims in two days of rioting in the southern city of Onitsha.

Rioting broke out in the lawless trading town on the banks of the Niger River yesterday when members of the Igbo tribe launched revenge attacks in response to an earlier massacre of Christians in the north of the country.


Frank Nweke, a magazine editor who ran the gauntlet of the mob to escape Onitsha and made it to the bridge, said he had seen 15 more corpses lying in the streets of the city.

"Some of them had been beheaded, others had had their genitals removed. I saw one boy holding a severed head with blood dripping from it," he said. (The Courier News [Australia])
Just a reminder.

It's not about the bike

The G8 summit of world leaders in Gleneagles, Scotland last June was the scene of an incident the details of which are only now being made public. My Wiki partner Melanie from Just a Bump in the Beltway was alerted to this by one of her readers. You draw your own conclusions (excerpt from The Scotsman):
After a hard day's discussion with fellow world leaders, [President Bush] was looking for some relaxation. Instead, he ended up the subject of a police report in which the leader of the free world was described, in classic police language, as a "moving/falling object".

It was "about 1800 hours on Wednesday, 6 July, 2005" that a detachment of Strathclyde police constables, in "Level 2 public order dress [anti-riot gear]," formed a protective line at the gate at the hotel's rear entrance, in case demonstrators penetrated the biggest-ever security operation on Scottish soil.

The official police incident report states: "[The unit] was requested to cover the road junction on the Auchterarder to Braco Road as the President of the USA, George Bush, was cycling through." The report goes on: "[At] about 1800 hours the President approached the junction at speed on the bicycle. The road was damp at the time. As the President passed the junction at speed he raised his left arm from the handlebars to wave to the police officers present while shouting 'thanks, you guys, for coming'.

"As he did this he lost control of the cycle, falling to the ground, causing both himself and his bicycle to strike [the officer] on the lower legs. [The officer] fell to the ground, striking his head. The President continued along the ground for approximately five metres, causing himself a number of abrasions. The officers... then assisted both injured parties."

The injured officer, who was not named, was whisked to Perth Royal Infirmary. The report adds: "While en-route President Bush phoned [the officer], enquiring after his wellbeing and apologising for the accident."

At hospital, a doctor examined the constable and diagnosed damage to his ankle ligaments and issued him with crutches. The cause was officially recorded as: "Hit by moving/falling object."
It's not clear what the immediate cause of this accident was, although all accounts seem to agree it was Bush's fault. An error in judgement perhaps. Not that serious, really. It's not as if this lapse cost the lives of 2300 Americans, maimed or injured another 17,000 and killed a hundred thousand or more Iraqis, as well as being perhaps the single most serious foreign policy blunder in the history of the country.

That was a different lapse in judgement.

Flu Wiki makes the news

The Flu Wiki makes news. Malcolm Ritter, AP Science Writer, interviewed our publisher and wiki partner Melanie Mattson of Just a Bump in the Beltway, and wrote a great story about the site. Of the three founders, the Reveres, DemFromCT (The Next Hurrah, a Koufax Best New Blog finalist) and Melanie, the Reveres are the least involved on a day to day basis. We were joined early on by pogge (of pogge blog fame), our technical guru who deserves more praise than I can adequately give. Dem has policed and contributed to the Forum Discussions on a daily basis while still holding down his home base at The Next Hurrah and leading a busy life in the real world. Melanie has been the publisher par excellance in more ways I can count, tangible and intangible. And I have throughly enjoyed basking in their reflected glory.

And glory it is. The AP reporter went to a couple of very "establishment" flu experts who essentially gave FW their seal of approval. Remember, academics are like dogs (I know because I am one). We like to pee on things just to mark our territory, so we were pleased with their comments (there was of course the obligatory dribble on us, but we don't mind). Here is what they said:
And Flu Wiki, the Virginia resident [Melanie] said, is "probably the most complete authority in English on pandemic influenza on the Internet."

Even for a site with more than 1,200 pages of content, that's a bold claim. The field includes not only an official U.S. government site, http://www.pandemicflu.gov, but also others from the U.S. Centers for Disease Control and the World Health Organization. There are also plenty of bloggers who focus on flu.

But Flu Wiki also offers the wisdom of its expert contributors, Mattson said.

She can't identify them publicly, mostly because they fear losing federal money for giving opinions that clash with the Bush administration, she said. The disagreements aren't so much on the basic science of bird flu, but rather on what to do about it.

Flu Wiki, which averages up to 5,000 hits a day, impressed some flu experts who examined it recently at the request of The Associated Press.

Dr. Arnold S. Monto of the University of Michigan said he found the site's information reliable in general. Such sites can provide "a single place for people to go who want to get information which they may have to troll for in some of the official sites," he said.

Peter Cowen of North Carolina State University, moderator of a disease-monitoring Web site sponsored by the International Society for Infectious Diseases, said he had mixed feelings about Flu Wiki.

"In general they have a lot of good information," but some of the site's links lead to places with information of questionable value, Cowen said. Still, on balance, he said, "it looks pretty good." (AP via Newsday)
The "disease-monitoring Web site" Cowen is associated with is ProMed. Also lots of good information but on occasion some if-fy links. That's what you have to live with in a fast changing situation where the scope and pace of information from official channels are narrow and slow.

Anyway, Flu Wiki is now a community project, where the community is the whole world. Major portions have already been translated into French, Spanish and Turkish. A Norwegian version has just debuted (all are accessible from Flu Wiki's front page). We have had many dedicated posters contributing tirelessly to provide a huge body of content, links and stimulating discussion. If you haven't visited, now's the time. You'll have lots of company. We are now getting in excess of 5000 visits a day. You can find some of the Wiki's early history in posts I did here, here, here, here and here.

The Wiki is a collective effort. Anyone can contribute, even in minor ways like copy editing or supplying links. We have turned the keys to the car over to you. Drive responsibly and take us places we all need to go to get us ready for what might come.

Freethinker Sunday Sermonette: her-r-r-r-e's . . . Richard (NOT)

Sunday, time many relax in front of the tube. In the US we get to choose among such journalistic icons as Chris Matthews or his genital counterpart, MSNBC Geraldo-wannabe Rita Cosby (no link; my keyboard refused on grounds it didn't do pornography). But what if we lived in more enlightened climes?
Earlier this month, Britain's Channel 4 aired The Root of All Evil?, a two-part exploration of religious faith hosted and narrated by Richard Dawkins, the eminent Oxford ethologist and author who is one of the world's most outspoken proponents of the theory of evolution. He's also an aggressive critic of religion. The Root of All Evil? follows Dawkins as he travels to some of the world's religious centers—among them Jerusalem, Lourdes, and Colorado Springs—to observe services and to interview leaders and followers of various faiths.


From the vantage point of the United States, the program is remarkable: You simply would never encounter such a brazen denunciation of religious faith on this country's airwaves, because the outcry from the religious right would be deafening. Dawkins's narration drips with contempt; as he goes about his rounds, it's as if he can hardly restrain himself from shouting, "I'm surrounded by IDIOTS!" The smoke coming out of his ears leaves a trail behind him wherever he goes. (via panopticist)
Alas, it's true. You can find nauseating religious drivel on every channel, including PBS, but a proudly atheist and rationist view? Hell, no.

So my Sunday is my own and I'm not wasting it in front of the TV or in church (my Fridays and Saturdays are similarly free for more productive work, as well; like watching re-runs of the Brady Bunch).

Unfortunately I don't get to watch Richard Dawkins either.

Saturday, February 25, 2006

Indonesia and questions about its virus

A curious news story in The Sydney Morning Herald quotes a Dr. Andrew Jeremijenko, as saying the Indonesia H5N1 virus that is killing humans is different than the one that is killing birds. The only evidence cited in the article is this:
He said there had been no human deaths in Turkey, Vietnam or Thailand after effective control programs were implemented. But in Indonesia there was poor communication between the departments of Health and Agriculture and the deaths kept on coming, with two suspected H5N1 deaths in the past week. (Sydney [Australia] Morning Herald)
This can either be read that deaths have continued because of failure to control the disease as efficiently in Indonesia as in southeast asia or that there is something different about the virus. Apparently Dr. Jeremijenko believes it is the latter. We would be interested to know why.

Dr. Jeremijenko is identified as an Australian expert who has worked in Indonesia, most recently "leading influenza surveillance studies for a US naval medical research group." He was indeed listed as an Indonesia region expert in the South East Asian Nations Infectious Diseases Outbreak Surveillance Network website, with his affiliation as USNAMRU-2 (US Naval Medical Research Unit No. 2), whose uncertain fate we discussed in an earlier post. It was slated to close on December 31 of last year and it appears this has happened. If anyone has information on this please email us or leave them in the Comments to this post. The US NAMRU infectious disease laboratory in Jakarta was the most advanced in the region and important in training Indonesian scientists in diagnostic techniques like identification of infection with the bird flu virus. Demanding (and possibly getting) its shutdown is an act of colossal stupidity by the Indonesian government, one for which we may all pay in lost warning time.

Meanwhile we would like to know Dr. Jeremijenko's reasoning and evidence that the human virus in Indonesia is different in character than the one circulating in the poultry population there.

Update (3:14 pm EST, 2/25/06): Thanks to an alert and assiduous Commenter we have the link to the interview from which the newspaper article was taken. Unfortunately it doesn't shed a great deal of light on the evidence. Here is the relevant portion:
PETER CAVE: Are you seeing mutations in the virus in Indonesia?

ANDREW JEREMIJENKO: Yes, that's a good question. We are seeing mutations in the human virus. We are not seeing that same mutation in the bird virus. And that's of great concern.

Basically, when you do an investigation of a bird flu case, you should try to find the virus from the human and match it up with the virus from the bird and find the cause.

Now, in Indonesia, the investigations have been sub-optimal, and they have not been able to match the human virus to the poultry virus, so we really do not know where that virus is coming from in most of these human cases.

PETER CAVE: Does it suggest it's going through an intermediary before it's infecting humans?

ANDREW JEREMIJENKO: It's a possibility that we can't rule out. I think they really need to do a lot more investigations. So far the closest match we have to the human virus is from a cat virus. So the cat could be an intermediate. We really don't know what's happening yet. They need to do more studies, they need to get better investigators on the ground to work out what is happening in Indonesia, and it needs to be done urgently.

PETER CAVE: Can Indonesia do this on its own?

ANDREW JEREMIJENKO: I think they need international assistance. So far the investigations have been unable to match the viruses. It is poor communication between the Department of Health and the Department of Agriculture. There are many reasons, but they don't seem to be able to match the viruses from the human case to the animal case, and that is putting the world at threat.
Another reader has sent along the Doctor's email so I will query him directly and update further if and when I get an answer.

Naked City comes to Arkansas (and the rural south)

There used to be (1958) a TV police drama set in New York called Naked City. Every episode ended: "There are eight million stories in the naked city. This has been one of them."

Well the city has moved to the country in the form of huge aggregations of chickens and in Arkansas alone the amount of manure produced by these poultry farms is equivalent to the waste of 8 million people.

Poultry? When we think of backyard poultry we think of China, southeast asia, Indonesia -- the places where bird flu has become endemic. But the US?
A person driving through the South might notice the chicken houses dotting the hills and flatlands. He might marvel at the larger ones, as long as a football field. He might react to their gagging stench for a moment, and then forget as he travels on. But those who live near the structures -- stuffed with as many as 25,000 chickens each -- combat the odor and health hazards daily.

"There's a horrible odor, a stench, and I have flies and rodents digging in, trying to get into my house," says Bernadine Edwards, whose 39-acre farm near Owensboro, Ky., is surrounded by 108 chicken houses within a two-mile radius. "It is unbelievable." (Suzi Parker in Grist Magazine via alternet)
The growers of these animals (and their hapless neighbors) are as much victim as exploiter. Many have invested their life savings and more, borrowing heavily from huge bird producers like Tyson, to scrape out a back breaking living in destitute rural areas where there is little work and less hope.
The companies provide local growers, who work under contract, with chicks, feed, medicine, and transportation. Growers take care of the rest, investing hundreds of thousands of dollars in construction, maintenance, and labor costs. When the company requires upgrades, the costs fall to the growers. The massive amounts of manure, too, are their responsibility. (In Arkansas alone, chicken farms produce an amount of waste each day equal to that produced by 8 million people.) Payment is results-oriented, based on measures like total weight gain of the flock. It's a system, says the United Food and Commercial Workers, that leaves 71 percent of growers earning below poverty-level wages.

If growers protest, companies can cancel their contracts, leaving farmers responsible for incurred debt, says Laura Klauke, director of contract agriculture reform at the North Carolina-based Rural Advancement Foundation International. And that debt can be substantial: since banks in the region will more readily loan money for poultry houses than other types of agriculture, Klauke says, some farmers put everything on the line, mortgaging their property to make a living this way.
This is both an environmental justice and a public health issue. The industry is not unionized, has developed very rapidly, and is largely unregulated. Many politicians are in the industry's back pocket:
Last year, Oklahoma Attorney General Drew Edmondson (D) filed suit against Tyson, Cargill, and several other poultry companies, seeking to stop water pollution caused in his state by soiled chicken litter dumped in Arkansas. Polluted runoff, also known as non-point source pollution, is the biggest remaining water pollution problem in the U.S., according to the EPA, which cites agriculture as the largest source of such pollution. Edmondson described the problem as "an economic development issue, an agricultural issue, and a quality-of-life issue." Not to be outdone, Arkansas Attorney General Mike Beebe (D) -- who is running for governor -- countered in November by suing the state of Oklahoma directly, asking the U.S. Supreme Court to prohibit Oklahoma from forcing his state's poultry farmers to adhere to the stricter standards. Both cases are still pending.
Shame on Mike Beebe. But of course he has no shame. What of the workers?
"In rural America, the poultry companies can get workers for a song, and the workers are so grateful to get the jobs," says Jackie Nowell of the United Food and Commercial Workers. These workers -- usually poor, and often African American or Hispanic -- "are exposed to feces [and] any disease the chicken has," Nowell says. "There are also horrible levels of dust and dander inside these houses."

Nowell adds that researchers in the region are currently exploring the possible crossover of various viruses from poultry to humans, like avian flu. "That's a real concern. These workers and people who live near these houses will be on ground zero of an outbreak."

Workers in poultry processing plants also face serious dangers from machinery, carpal tunnel syndrome, and health hazards such as contaminated microorganisms and dust. "There are huge health and safety violations in every plant," says Jennifer Rosenbaum, a lawyer with the Southern Poverty Law Center in Montgomery, Ala. In 2004, for example, the Occupational Safety and Health Administration issued citations to Tyson for alleged violations after an employee was asphyxiated when he inhaled hydrogen sulfide, a gas created by decaying organic matter. OSHA fined the company $436,000.

Poultry companies "hire relatively low-income people, immigrants who have less of an understanding of rights and health issues," Rosenbaum says. Simply put, she says, the companies are hurting the South's small towns while they fatten their own wallets.
Now bird flu looms. It is a potential organizing tool for all concerned. It's good for organizing workers into badly need unions. It's a good issue for environmentalists who can point to a Naked City's worth of fecal effluent in Mike Beebe-head's state alone, feces that can carry H5N1 virus. It's a potent argument for neighbors who have had their land devalued and their lives made miserable by the stench of out of control poultry producers. And it should be a good reason for more public health professionals to sound the alarm that these disgraceful operations are health disasters waiting to happen.

On the other hand, if bird flu strikes this squalid industry, we are all going to get plucked. More than eight million stories. Sad stories.

Friday, February 24, 2006

Needed: new scientific norms for emergency times

The tale of bird flu virus hoarding by scientists goes on. We have noted it often here, here, here, here, here and here. Canadian Press's Helen Branswell was among the first to call attention to one of the sources, the desire of scientists and national efforts to garner credit for work they have done or resources they "own." Both the US (here and here) and the Chinese have been accused of not sharing bird flu virus isolates. Today Nicholas Zamiska has a follow-up story in the Wall Street Journal verifying most of Branswell's earlier reporting and adding some additional details.

There are at least two issues involved. One is the "normal" behavior of scientists who want as much credit as possible for their scientific accomplishments. I understand this completely. I have spent a great deal of my professional career in academia. Publications, not money, are the coin of the realm in our world, the keys to promotion, reputation, lab space, grant funding and much else. This serves a useful function for science, acting as an incentive for high quality publications and sharing of results with the world community of scientists. But it can also have the opposite effect, leading to polluting the literature with the "least publishable unit" (splitting up a body of work into as many publications as possible to build a resumé), hesitation about sharing samples, data and techniques until they have been maximally milked, embargoing of scientific work by journals seeking to make news -- and distressingly often, nasty authorship disputes. All of these seem to be involved in the stubborn refusal of the Chinese Ministry of Agriculture to share important viral isolates with WHO and the world scientific community. Various slights involving failure to acknowledge Chinese sources are cited, and apologies tendered for past misdeeds or mistakes. The Wall Street Journal article has some of the details and they ring true to these ears.

But there are also issues of national pride and the knowledge that viral isolates are an economic resource if they are used as seed for a vaccine. This, too, seems to have entangled itself in both the Chinese and US/CDC cases. In neither instance does it bring credit on the nations and scientists involved. In the context of an impending pandemic it is the worst possible outcome of an unlovely reality of academic science.

Viruses move across borders much more quickly than data, even though the latter are capable of moving with the speed of electrons. The speed bottle neck here is social and political. Neither the outmoded system of international relations nor the twentieth century mentality that governs senior academic researchers and journal editors works in this situation. In an emergency there must be some recognition that the usual criteria of personal and national credit are suspended. That might entail both a real and a perceived sacrifice in recognition, credit and perhaps economic benefit. Since that is a lot to ask of people and nations, we see the best antidote is worldwide censure of behavior that in other circumstances would be considered acceptable and usual but in this circumstance is reprehensible.

We should not tolerate withholding sequences, isolates or vital information until this emergency is over (and then we should re-evaluate previous norms). This is not just directed at the Chinese. It is also directed at many highly regarded western scientists in the US, Europe and elsewhere who have important scientific results they withhold pending publication in a peer reviewed journal. Journal editors are partially to blame and they should allow pre-publication announcements before formal appearance of papers. The best way to encourage a change of behavior now is punitive. Expose every instance and call the responsible scientists, journals or responsible national agencies to account.

Let's start with China's high ranking veterinarian in its Ministry of Agriculture, Dr. Jia Youling. It is time to provide all viral isolates to WHO for access in an international repository. Scientists using those or any isolates should credit the source. Failure to honor WHO's request should bring dishonor and international condemnation on Dr. Jia and China. The same is true for CDC. Release your viral sequence data and isolates in the same fashion. Your failure to do so brings shame on American science.

Who's next?

Between the lines of the WHO India update

WHO has issued a terse (200 word) update on the evolving situation in India. We'll have to read between the lines on this one:

WHO update: The Ministry of Health and Family Welfare in India has informed WHO that no human cases of H5N1 infection have been detected to date. Tests conducted on samples taken from persons under investigation and their close contacts have yielded no positive results as of today.

My translation: WHO will only say that the Indian government will not admit to any detection of cases or any positive tests.

WHO update:Testing has been undertaken at the National Institute of Virology in Pune and the National Institute of Communicable Diseases in Delhi
It was not clear if samples from a 27-year-old poultry worker from Gujarat State, said to have died of respiratory disease on 17 February, were among those tested.

My translation: WHO is suspicious some important specimens have not undergone appropriate testing.

WHO update: In India, as in all countries experiencing their first outbreaks of highly pathogenic H5N1 avian influenza, WHO strongly recommends that patient samples be sent to a WHO collaborating laboratory for diagnostic confirmation. Certainty about the status of human cases in a newly affected country is important for accurate risk assessment.

My translation: India should be sending the samples to a properly qualified WHO laboratory, not keeping them within their own laboratory system.

WHO update: In addition, analyses conducted by WHO-approved laboratories can yield information about the possible evolution of the virus and clues about how the virus may have arrived in the country. Genetic and antigenic studies of circulating viruses also help ensure that work on the development of a pandemic vaccine stays on track.

My translation: The reluctance of the Indian government to provide samples to WHO is obstructing a vital function and denying scientists possibly vital information.

WHO's consternation is plainly visible. So should the world community's.

Harvard poll on bird flu

A fascinating new poll (as reported by USA Today) shows that concern over bird flu has ramped up significantly in recent months. Over 1000 adults were polled by Bob Blendon's unit at the Harvard School of Public Health. A year ago an Ipsos poll showed only a third of Americans were concerned about bird flu. In this poll, done January 17 - 25, that proportion had risen to almost 60%. Events in Europe since have probably increased that number.

The internals of the poll are interesting. What is immediately evident is that if people act as they say they will in this poll there will be major economic consequences.
About 46% of respondents who eat chicken said they would stop eating it if bird flu hits the U.S. poultry industry.

If human outbreaks occurred, 75% said they would reduce or avoid travel, 71% said they would skip public events and 68% said they would stay home and keep their children at home while the outbreak lasted.
Judging from responses to this poll, however, the suspicion of widespread hoarding of the antiviral Tamflu is not true. Less than 2% had even talked to a doctor about the drug and fewer had succeeded in getting a prescription. In the event of an outbreak, 68% said they would try to get the drug. Makes sense.

As of the third week in January, only a quarter of the respondents thought US poultry would be affected and only 14% thought the disease would affect humans in the US. Again, that number might increase now that one European country after another is reporting bird infections.

Finally, there is an interesting racial difference. 70% of African Americans expressed concern compared to 54% of whites. I take this as an expression of increased vulnerability.

CDC issued a statement saying that the results show Americans are keeping informed but not panicking. I hope health officials take note and keep us informed. Because the best way to avoid panic is to have an informed public. And the best way to cause panic is to make people think you are keeping things from them.

CDC, DHS and state health departments: got that?

Thursday, February 23, 2006

The luck of the Irish

With dead birds showing up all over the EU, at least if you live in the Republic of Ireland, there's good news:
Experts on avian flu tonight insisted sufficient measures had been put in place to combat the threat of the deadly H5N1 strain of the virus.

After considering a series of contingency measures with the Avian Influenza Expert Advisory Group, Agriculture Minister Mary Coughlan said it was too soon to begin the compulsory housing of poultry.


. . . Mrs Coughlan has insisted Ireland has plans in place to combat the virus. (Ireland On Line)
OK. There have been a few glitches:
Following reports which suggested the Department of Agriculture hotline for reporting suspected bird flu cases was not manned at weekends or after 9pm during the week, the minister said the service would be enhanced.

Ms Coughlan confirmed that a new low-call number was being provided with immediate effect – 1890 252 283.
Don't worry. They've got it fixed:
She said anyone who wanted to report dead birds could contact this number 24 hours a day, 7 days a week.

The minister noted the helpline would sit alongside the existing Head Office reporting number 01 6072000 for animal disease incidences.

And she said An Garda Siochana, the Health Services Executive and local authorities were being reminded that calls from members of the public about dead birds should be redirected to the helpline.

Mrs Coughlan also revealed details of the collection and testing of dead birds by Agriculture officials.

She said it was designed to act as a surveillance/early warning system.
Here's the bad news:
The bewildered response of officialdom to the reported finding of a dead swan in Co Waterford does not inspire confidence in Ireland’s preparedness to cope with the threat of bird flu.

As the first meeting of the national emergency management committee takes place today, it defies credulity that the finder of the dead bird on the foreshore at Cheekpoint in Waterford Harbour, where other swans were swimming at the time, had to make no fewer than 10 phone calls before he finally succeeded in contacting an official who said the body would be collected.

Presumably, samples have been sent to Britain for laboratory tests?

This bizarre scenario gives the lie to Government claims that Ireland is geared to cope with an outbreak of avian flu. It also suggests that Agriculture Minister Mary Coughlan is grasping at straws by stating we could escape altogether because of the migratory pattern of wild birds. (Irish Examiner)
Here's more of the bird finders story:
Realising the danger, the finder first contacted the gardaí but they were unaware what procedure should be followed.

Astonishingly, the Health Service Executive told the finder not to worry because bird flu had not yet reached Ireland. He was informed that all relevant officials were at a meeting but would be available at 9 o’clock yesterday morning.

Adding that no information had been received from any Government department about bird flu, the HSE source suggested the local vet should be contacted. But it also transpired the vet had no information about contingency plans.

Finally, after being passed from Billy to Jack, an official at the Department of Agriculture said the dead swan would be collected. This appalling chronicle bodes ill if avian flu ever arrives here.
There's two sides to every story, but frankly, the bad news side has the ring of truth and the official "we've got it under control" side has the ring of bullshit.

Maybe the Irish are counting on their proverbial luck. Because they don't seem to have much else going for them.

Dumb and dumber in the Middle East

The Palestinians and the Israelis may be pretty exercised over who is occupying whose territory and the Israelis may be building a wall they think will separate themselves from the Palestinians, but the bird flu virus could care less. Egypt to the west, Turkey and Iraq to the northeast and Saudi Arabia to the east all have infected birds. Now people in Gaza are saying their birds and chickens are dying. The Palestinian Agriculture Ministry doesn't have the ability to test for H5N1 so yesterday they handed over chicken and turkey carcasses to the Israeli military for testing in Israel (AP via Haaretz).
"It is in Israel's interest to ensure that agricultural standards in Gaza are maintained," Madar told the Post as he prepared to transport the samples to Israel's veterinary service laboratories in Beit Dagan.

If these diseases are confirmed, the situation could have fierce repercussions in terms of finance and health, Israeli security officials were quoted as saying.

On Wednesday morning, Madar was notified that 12 to 13 dead wild fowl were found in Khan Younis in southern Gaza, not far from borders between Gaza and Egypt, where bird flu cases were reported for the first time on Feb. 17. (Xinhua)
The Israelis may rue the day they purposely destroyed the Palestinian civil infrastructure, including its health services (and continue to do so by withholding money they got by taxing Palestinians). And they will surely rue the day they bankrupted themselves and crippled their own infrastructure along with it by waging perpetual war, just as the US and its perpetual war has seriously weakened its own civil society.

Until now, however, there has been cooperation between Israel and Palestine on public health matters, particularly on bird flu. But that is about to stop:
Security officials warned that once the Islamic Resistance Movement (Hamas) establishes a new Palestinian government, the possibility of maintaining such close coordination and contacts will be in doubt.

"If Israel's policy is to refrain from speaking with Hamas, then once the new Palestinian government is installed and new ministers take their posts, all contacts will be stopped," a security official said.
The virus is indifferent to this stupidity. From its point of view a Muslim or Christian Palestinian looks exactly the same as a Jewish Israeli. Same human cells. Same respiratory tract. Same immune systems. Same genetic machinery it can commandeer to make more copies of itself. It doesn't ask what superstition addles the brain of its new host. Superstition can't hurt this virus.

Let me ask: who's smartest, a Palestinian, an Israeli or this little virus?

The expected

Austria is recording the first EU cases of bird flu in chickens. Until now the seven EU countries affected have found the virus in wild birds. The Austrian chickens are not on a commercial poultry operation but in an animal refuge and are being characterized as "an isolated case" by the Austrian Health Ministry. The source of infection is supposedly a lost swan brought to the Noah's Ark animal pound in Graz earlier in the month. Three ducks also died there from the virus. There are 200 dogs and 300 cats at Noah's Ark in a separate building. While Austria has an emergency plan, instituted after wild swans were discovered February 14, the swan came to the refuge four days before these measures were put into effect. This is another example of the difficulty of containing a disease that is infectious before symptoms are manifest. Hungary, Bosnia, Croatia and Malaysia are also reporting more infected birds.

But the nastiest stories today are coming from India, where the disease is continuing to spread. The nasty part is the allegation that one or more major poultry producers there covered-up a mass die off of their birds almost a month ago, paying locals to bury dead chickens. No notifications were made to authorities, required, even if, as the companies now claim, they thought the birds died of Newcastle Disease, not bird flu. India's egg producer trade association is still denying bird flu is in India. But according to the Agriculture Ministry there is no ambiguity in the test results. The disease is H5N1, not Newcastle Disease. (TV Padma via SciDev.Net)

The probable cover-up is just the kind of event that we would expect. As authorities start to quarantine whole villages and areas, as India is doing in some places, the natural consequence will be to conceal the presence of the disease. Efforts should be put into getting ready for what will happen next, not shutting the chicken coop after the birds have scuttled.

Wednesday, February 22, 2006

Oklahoma has flu (but not bird flu)

Oklahoma has an influenza problem. It's not bird flu. It's just "ordinary" flu and this isn't a particularly bad flu season.

But for Oklahoma it's bad enough:
Flu season has made its way to northeast Oklahoma, often forcing hospitals to capacity.

Ched Wetz, vice president of Corporate Services at Muskogee Regional Medical Center, said MRMC has had to transfer some patients to Tulsa hospitals.


Optimal capacity at MRMC varies from 225 to 240, and full-time staff size is approximately 1,100, Wetz said.

All hospitals in the Muskogee area are experiencing high occupancy, Wetz said, but cooperate with each other to make sure patients receive care.

“There are also situations where we receive patients from hospitals in cities like Tahlequah, Eufaula, Stigler and Wagoner,” he said. “MRMC is a part of a larger macro system of health care providers.” (Muskogee Phoenix)
The Oklahoma Department of Health knows a pandemic will be a much bigger problem (excuse the understatement):
A pandemic influenza event most likely will overwhelm our health care system. It is essential that each county and region develop a local pandemic influenza management plan congruent to the state plan that includes strategies for patient triage, respiratory infection control, and alternate medical care facilities. (Oklahoma Pandemic Flu Plan, Fact Sheet [.pdf])
Yes, essential. Have they done it yet?

Science fantasy for hire

In a news article in the current issue of Environmental Science and Technology Paul Thacker writes about a document he found buried in a document repository related to EPA's recent review of the risks of perfluorooctanoic acid (PFOA). We have written about this a number of times here (and here), but the "marketing letter" Thacker discovered puts a spotlight on the shadowy world of hired gun consulting companies whose task is to muddy the waters sufficiently that the regulatory wheels grind to a halt. Those of us in the business know this goes on all the time, but it is still startling to see the strategy spelled out in black and white.

From Thacker's story:
Tucked away inside the U.S. EPA’s docket on PFOA, a chemical manufactured by DuPont, is a 5-page letter written in April 2003 by the Weinberg Group, an international scientific consulting firm based in Washington, D.C. The letter is addressed to DuPont’s vice president of special initiatives, Jane Brooks, and lays out a proposal for how the Weinberg Group can help the company deal with a growing regulatory and legal crisis over PFOA (perfluorooctanoic acid). PFOA is a common building block of the perfluorocarbon family of chemicals, which are renowned for their water and stain resistance. PFOA is the compound used to make Teflon and was once used in other products such as Scotchgard, Stainmaster, and Gore-Tex.


“The constant theme which permeates our recommendations on the issues faced by DuPont is that DUPONT MUST SHAPE THE DEBATE AT ALL LEVELS,” states the letter (emphasis in original). For 23 years, the letter continues, the Weinberg Group “has helped numerous companies manage issues allegedly related to environmental exposures. Beginning with Agent Orange in 1983, we have successfully guided clients through myriad regulatory, litigation and public relations challenges posed by those whose agenda is to grossly over regulate, extract settlements from, or otherwise damage the chemical manufacturing industry.” (EST)
Dupont confirmed to Thacker that they had hired Weinberg but wouldn't say for what purpose.
Passages from the letter describe how the firm will develop a defense strategy based on science. “[W]e will harness, focus and involve the scientific and intellectual capital of our company with one goal in mind—creating the outcome our client desires.” Another sentence reads, “This would include facilitating the publication of papers and articles dispelling the alleged nexus between PFOA and teratogenicity as well as other claimed harm.”
In other passages Weinberg describes how they will engage as consultants scientists they feel might be useful to PFOA's opponents:
For example, the Weinberg letter lists a series of proposed tasks designed to limit liability, including the recruitment of scientific experts on PFOA “so as to develop a premium expert panel and concurrently conflict out experts from consulting with plaintiffs.” Experts who worked for DuPont through the Weinberg Group would have been unable to testify for plaintiffs.

“They’re offering to get rid of inconvenient witnesses for the other side,” says [Dr. David Ozonoff of Boston University]. He adds that he has received similar requests in the past from lawyers asking him to consult on cases. “I wouldn’t have to testify,” he says, “but I knew right away what they were doing was trying to conflict me out of a case.”
There apparently is no compunction about raising outrageous trial balloon arguments, either:
Ozonoff, who sat on EPA’s Science Advisory Board review panel for PFOA, points to a passage in the memo that details how to identify the likely health benefits of the chemical “by analyzing existing data, and/or constructing a study to establish” that PFOA is safe and “offers real health benefits.” The next sentence mentions the oxygen-carrying capacity of blood and the prevention of coronary artery disease.

“That blew me away,” says Ozonoff, adding that data on PFOA seem to show an effect on lipid metabolism; this raises concerns that the chemical may actually increase the risk of cardiovascular disease. “This [proposal] is a ‘manufacturing doubt’ strategy. If you say, ‘Gee, this might cause heart disease,’ then they’ll come back with another story that says it’s good for your heart.” Constructing this sort of narrative, he says, sets a research agenda that any independent scientist wandering into the field must address.
When confronted with this, Weinberg's President, Mr. Matthew Weinberg, didn't push the point. Instead he dismissed it as "marketing":
Thacker: Did you find any, has there been any, um, anything published in the peer-reviewed literature that would lead one to believe that?

Weinberg: I have no...I am not an expert on PFOA and I couldn’t tell you what’s been published or what hasn’t been.

Q: Okay. Alright. I just wanted to give you a chance....Do you have anything else to say?

A: I guess I have a question for you. I don’t understand what you see in that document that’s worthy of a conversation between us.

Q: Well, it was very interesting, is when I showed this passage, that passage, particularly to David Ozonoff. I don’t know if you know who he is.

A: I’ve heard the name, but I can’t place him.

Q: Um, he’s at BU. He was on the SAB panel for PFOA and he, uh, called that particular passage sort of, uh, “fantasy thinking.”

A: Okay. Uh, uh, I would...would suggest strongly that the letter you are looking at appears to have been a marketing document.

Q: Okay.

A: I do not think that it is a document that in any way, shape, or form, makes claims, nor is it intended to represent a specific point of view. It is a marketing document telling them things we maybe think...are possible. But I believe it clearly states...you just read me a part that says “study and analysis are needed.” I don’t believe the document purports to say that that’s been done.

Q: Okay.

A: It may have been done. It may have been done by others. I don’t believe this document makes this claim that we had done that work at this point or that we were ever going to do that work.
In other words, fantasy thinking. I am not aware that this piece of scientific weirdness ever made it into the argument, probably because it couldn't pass the laugh test, much less the smell test.

You can find a .pdf of the Weinberg document here. The Thacker article too, is fascinating. And the well respected journal where it appears is published by the American Chemical Society, whose members, I am sure, are not happy about the commercial perversion of their science. Good for them.

Tuesday, February 21, 2006

WHO update on H5N1 mutations

WHO has an update with their view of the genetic status of the H5N1 virus. Given the "two mutations to a pandemic" statement by Nabarro followed by the furious backpedal, it's not surprising. The WHO statement is interesting, mainly informative -- and very carefully worded. Can't complain about that.

Here's the opening:
Several recent media reports have included speculations about the significance of mutations in H5N1 avian influenza viruses. Some reports have suggested that the likelihood of another pandemic may have increased as a result of changes in the virus.

Since 1997, when the first human infections with the H5N1 avian influenza virus were documented, the virus has undergone a number of changes.

These changes have affected patterns of virus transmission and spread among domestic and wild birds. They have not, however, had any discernible impact on the disease in humans, including its modes of transmission. Human infections remain a rare event. The virus does not spread easily from birds to humans or readily from person to person.
Here's my translation:
The virus is mutating and the mutations have affected its biological behavior but not at this point affected its transmission from human to human. The statement is silent on whether mutations have affected transmission from bird to human
WHO goes on to say (correctly) we know too little about the relationship between the genetic sequences and the biology to be able to know what properties it needs to acquire to become a full-fledged pandemic strain. We do see genetic changes that have affected its behavior in animals however.
In animals, some recent evolutionary changes in the H5N1 virus appear to have made control efforts more difficult and further international spread of the virus in birds more likely. Such changes are fully understandable, particularly in view of the exceptionally large number of birds that have been infected with the H5N1 virus and the frequent interactions between infected free-ranging poultry and wild waterfowl.

Studies have shown that H5N1 viruses from the current outbreaks, when compared with viruses from 1997 and 2003, have become progressively more lethal in experimentally infected chickens and mice, and are also hardier, surviving several days longer in the environment. Other studies have shown that the virus is not yet fully adapted to poultry and is continuing to evolve.

Domestic ducks have acquired an ability to resist the disease caused by some strains, and are now capable of excreting large quantities of highly pathogenic virus without showing the warning signs of illness. In endemic countries, this altered role of domestic ducks is now thought to contribute to perpetuation of the transmission cycle. Research conducted in South-east Asia has recently shown that multiple distinct lineages of H5N1 virus have become established in poultry in different geographical regions, indicating the long-term endemicity of the virus in parts of Asia. That research also detected highly pathogenic H5N1 virus in apparently healthy migratory birds.

In birds, one important recent finding has been the remarkable similarity of viruses from recent outbreaks to those isolated from migratory birds that began dying at the Qinghai Lake nature reserve in central China in late April 2005. Evidence is mounting that this event, which resulted in the deaths of more than 6,000 wild birds, signalled an important change in the way the virus interacts with its natural reservoir host.
WHO goes on to say that the genetic changes seen in these birds have become fixed in the circulating virus, something they say has not (yet) happened in mutations in a single human isolate in Turkey, which they characterize as "transient." The relative stability of the mutation seen since the Qinghai outbreak may signal adaptation to wild migratory birds, and its geographically widespread occurrence may be evidence of spread via bird flyways. This carries with it the probability the virus will be reintroduced into cleared areas when birds return on their migration cycles. WHO does not believe any human cases have so far been "associated with" exposure to wild birds versus domesticated poultry.

Finally comes the money section:
Some mutations have been detected in human viruses isolated in 2005 and, most recently, in one virus isolated from a fatal case in the January 2006 outbreak in Turkey. Although these mutations were found at the receptor-binding site and involved the substitution of more mammalian-like amino acids, the effect of these changes on transmissibility of the virus, either from birds to humans or from one person to another, is not fully understood. Moreover, recent studies show that these mutations were transient and did not become fixed in the circulating viruses.

Scientists do not presently know which specific mutations are needed to make the H5N1 virus easily and sustainably transmissible among humans. For example, it is not known whether the absence of a specific receptor in humans for this purely avian virus is responsible for the present lack of efficient human-to-human transmission. For this reason, virological evidence of mutational changes must be assessed together with epidemiological information about transmission patterns actually occurring in human populations. This necessity further underscores the importance of close surveillance and thorough investigation during every outbreak involving human cases.
I can't disagree with any of this. In my view, it states accurately and precisely what we do and don't know (mainly what we don't know). Unfortunately the effect is somewhat spoiled by the last paragraph:
Assessments of the outbreak in Turkey, conducted by WHO investigative teams, have produced no convincing evidence that mutations have altered the epidemiology of the disease in humans, which was similar to the pattern consistently seen in affected parts of Asia. There is no evidence, at present, from any outbreak site that the virus has increased its ability to spread easily from one person to another.
The first sentence doesn't say there is no evidence that the epidemiology is altered, only that if there is evidence it is not convincing. Since we don't know what it takes to convince WHO (I have previously suggested a whack on the head with a two-by-four might be needed to get their attention), this is neither comforting nor informative. Is there some "non convincing" evidence? If so, what is it? And if the last sentence is completely accurate -- no evidence whatsoever, anywhere -- then why the qualification? Saying there is no evidence of any kind is different than saying there no convincing evidence, or that there is scant evidence, or there is some evidence but it hasn't risen to a level of concern, or some evidence WHO is arguing about amongst themselves but not ready to discuss publicly, or . . . what?

One of the two sentences in that paragraph is wrong. I'd be willing to lay odds it's the last one.

Maybe it won't be so bad

On the weekend a nasty storm knocked out power to a quarter of a million homes and businesses in the Northeast US and temperatures dropped even as wind gusts above 70 miles an hour hit some areas. In New Hampshire 40,000 homes were without electricity, 7000 in Vermont, 1800 in Massachusetts. In upstate New York 328,000 customers were without power on Friday and 160,000 still on Saturday.

If you live in the midwest or northeast of the US you expect this kind of thing periodically. So do the electric companies, who send out their linemen to repair lines downed by wind, ice or snow. Usually power is back in a day or two, in bad cases three. People will hang on the first night, but on the second they'll often get themselves to a state run shelter. That's winter in the northern US.

Now imagine a general 30% to 40% absenteeism that has delayed maintenance on the trucks, caused spare part shortages from slow or sluggish supply lines, caused many roads to go unplowed because of a shortage of plow operators out sick and now one out of three linemen not showing up to restore power. The two day outage goes to three, four five days. In some rural areas maybe a week or ten days. No electricity for a week. No refrigerator. Maybe no power to run the pump for your well. Your cell and cordless phones not working. Of course no TV or radio unless you have a supply of batteries. No lights. Maybe no heat or stove or toaster. That's just your home. The same will be true of businesses not able to function.

Maybe it won't be that bad. Absenteeism only 5% or 10%. If there are a lot of people are out sick for a few weeks at a time, maybe there won't be any winter storms. If there are storms, maybe your utility has it all figured out already. If there are prolonged outages, maybe your community has adequate shelter and the hospitals and other vital supports have back-up power. If there are serious power problems, maybe that will be the only problem from a lot of serous flu.


Monday, February 20, 2006

What, them worry?

I don't get what's up with WHO. Today the Wall Street Journal reported an interview with WHO's Indonesian spokesperson that recent concerns expressed by Indonesian health officials are no big deal. The Indonesians have pointed to the increasing number of clusters and believe the speed with which the virus is killing patients is becoming faster. WHO disputes the latter, saying the average length of illness was 8 days in 2005 and 10 days in 2006. Presumably this refers to Indonesian only cases, although the news report did not specify and suspicion of WHO news spinning is now so high many will believe they have manipulated this figure by including cases outside Indonesia as well.

Which is the point, I guess. WHO's current position is that the clusters may just represent common exposures to poultry and the rising number of cases is just observation bias, that is, greater awareness on the part of the health care system and doctors. Yes, these are reasonable explanations. But there are others as well, so why push the most conservative when in fact WHO doesn't really know the explanation? Better just to keep their mouths shut.
"Should we be more worried? Not at this stage," Sari P. Setiogi, a spokeswoman for the WHO in Jakarta, said in an interview, adding that as health-care workers in the field become more aware of the disease, the number of reported cases may rise. (Wall Street Journal)
So we can answer the question, "when is it time to be more worried?" this way. When WHO says it's time to get more worried, it's really time to be terrified.

Wedding party in Iraq

The Iraqi Ministry of Health now is testing 25 people (12 in the north and 13 in the south) as suspected cases of bird flu.
"We're testing blood samples from 25 locals from the Missan and Sulaimaniyah governorates because they've been showing symptoms very similar to those of bird flu," said Ibtissam Azize, a spokesman for the bird flu programme at the health ministry.

The blood samples are being analysed in local government laboratories and results are expected before 21 February. Ten samples have also been sent for simultaneous testing to a World Health Organisation (WHO) laboratory in Cairo, while the remaining 15 are to be transported by the end of the week. (Reuters Alertnet)
Two bird flu deaths in the Kurdish north have been confirmed by WHO and 14 more have been confirmed negative by the reference lab in Cairo. A half million chickens and ducks have been slaughtered in an effort to stem the infestation, although this seems fruitless. The government is promising to compensate the farmers for their losses. With what? The government is broke, and worse, powerless (literally and figuratively).
Nearly 500 people are now working on the campaign against bird flu in Iraq, including doctors in hospitals where suspected cases are being treated, according to Ministry of Health officials. "We were not expecting a crisis like this one, and we'll have to dislocate budgets from other sectors for the prevention campaigns because it's an emergency situation," Azize explained.
Not expecting something like this? They should have been. Disease is War's constant and loving companion. And there are 160,000 foreign occupiers to help them celebrate their betrothal.

What did we buy for $33 billion -- and why?

Milton Leitenberg, a researcher at the University of Maryland, knows biological weapons. He wrote a book about them, Assessing the Biological Weapons and Bioterrorism Threat, which you can download from the US Army War College website. And here's what he had to say in the LA Times this week:
The United States has spent at least $33 billion since 2002 to combat the threat of biological terrorism. The trouble is, the risk that terrorists will use biological agents is being systematically and deliberately exaggerated. And the U.S. government has been using most of its money to prepare for the wrong contingency.

A pandemic flu outbreak of the kind the world witnessed in 1918-19 could kill hundreds of millions of people. The only lethal biological attack in the United States — the anthrax mailings — killed five. But the annual budget for combating bioterror is more than $7 billion, while Congress just passed a $3.8-billion emergency package to prepare for a flu outbreak. (LA Times)
Indeed an entire bioterrorism industry has grown up around a threat whose probability and magnitude we can guess only dimly but which would have difficulty equalling even a mild influenza pandemic in lives lost. Among the chief fear bioterrorism mongerers are the principal agents for Big Pharma in the Congress, among them Senators Bill ( Dr. Quackenbush) Frist, Senate Majority Leader, and Joe Lieberman, alleged Democrat of Connecticut. Here is Leitenberg's read:
Last year, for example, Senate Majority Leader Bill Frist described bioterrorism as "the greatest existential threat we have in the world today." But how could he justify such a claim? Is bioterrorism a greater existential threat than global climate change, global poverty levels, wars and conflicts, nuclear proliferation, ocean-quality deterioration, deforestation, desertification, depletion of freshwater aquifers or the balancing of population growth and food production? Is it likely to kill more people than the more mundane scourges of AIDS, tuberculosis, malaria, measles and cholera, which kill more than 11 million people each year?


At a conference in Tokyo this week, bioterrorism experts called for new programs to counter the possibility that terrorists could genetically engineer new pathogens. Yet three of the leading scientists in the field have said there is no likelihood at this time that a terrorist group could perform such a feat.


There is no military or strategic justification for imputing to real-world terrorist groups capabilities that they do not possess. Yet no risk analysis was conducted before the $33 billion was spent.
But if terrorists don't have the skill, knowledge or facilities to perform these complicated experiments, they don't really need them. Because the $33 billion has bought that expertise in the form of "biodefense" laboratories whose main goal is to defend ourselves against non-existent weapons (for example, by designing detectors, vaccines or antivirals against them) in ways that require those same laboratories to first make the agents. Suddenly the weapon that was impossible for a terrorist to make and which didn't exist has come into being. Now all a terrorist needs to do get his hands on them. This is a lot easier than the science of creating them and not impossible, as the 2001 anthrax attacks illustrate. Most people believe that weapon came from within the biodefense world itself.

So the situation is worse than Leitenberg makes out. Not only has the money been misspent and priorities distorted, but the spending has the potential for making us less safe than if the money had been simply flushed down the sewer.

Heck of a job, George.

Sunday, February 19, 2006

Flawed reasoning in India

The Indian government -- who seems to have learned nothing from the experience of others about the way you talk to the public about bird flu -- has told everyone not to worry. In the wake of the discovery of the disease in poultry in two regions of the country, a number of people were placed under observation as a precaution with the diagnosis of "rule out avian influenza." Blood samples from 30 people with flu-like symptoms in Nandurbar district (western Maharashtra state) were sent for testing (it isn't stated where the tests will be performed or by whom). Now one of them has died. But don't worry.

Today, in advance of reliable test results, the government said "that earlier fears of the country’s first human victim were unfounded, after 'preliminary' tests on a dead farmer showed he was not affected." (MSNBC) According to AFP,
"Ramesh Sonar died in general hospital in Surat (in western Gujarat state) on 17th February. The death has been reported as (due to) bacterial infection," senior health ministry official Vineet Chawdhry told a press conference in New Delhi.

Officials had earlier said that the man was a poultry farmer, but Chawdhry said the man had not handled poultry.

"Those reports must have been speculative. He did not have history of handling poultry." (AFP)
So a 27 year old poultry farmer dies of a disease like bird flu in a region where there is an outbreak, and bird flu is ruled out because, (a) he had a bacterial infection, and (b) he didn't have a history of handling birds. The problem with this "reasoning" should be obvious. Secondary bacterial infection is a common complication of influenza (his death occurred 10 days after onset, so this wasn't a fulminant viral pneumonia) and a history of handling poultry may have been missed or he may have contracted the disease from the environment (feces or raw poultry being prepared for a meal) or from another person, not from a bird. If we are going to be vigilant about detecting early signs of human to human spread, we can't use contact with poultry in our case definition.

I'm fully expecting this will turn out not to be avian influenza (the odds are against it -- although one of these days we'll probably get a nasty surprise). But the reasoning is deeply flawed and smacks of false reassurance.

Bad idea.

Vaccine breakthrough du jour

Yet another story about a "new" vaccine technology that shortens the production time to "weeks." This one also uses a viral vector (baculovirus, not adenovirus) to produce a designated HA protein in cell culture.
The protein is produced by first extracting the genes responsible for the production of hemagglutinin from the influenza virus and inserting them into a baculovirus. Specific host cells are then infected with the baculovirus and produce recombinant hemagglutinin (rHA). Phase II clinical trials show that rHA-based vaccines produced using this system are safe, elicit immunity equal to or greater than egg-based vaccines, and are 100% effective in the prevention of cell culture confirmed influenza.

Wang and his colleagues report the successful production of rHA from 4 strains of influenza that scientists believe to be likely the cause of the next pandemic (H5, H7, H9, and H2) at a level where manufacturing costs are expected to be equal to or less than that of traditional egg-based vaccines. (TerraDaily)
The researchers claim that starting with the prepared baculovirus a closely matched vaccine can be "massively produced" within 2 weeks. Sound pretty good. But like other recent "breakthroughs" this one has a long way to go before the "break" is "through." Even producing a vaccine as good as egg-based ones isn't that good, because the egg-based H5N1 lacked potency. This vaccine hasn't been tested for safety or efficacy. They haven't scaled it up in a commercial production facility. Not to mention that most places have neither the public health infrastructure nor the means to obtain, distribute and administer such a vaccine. We can include the US in that category.

It's good that many people are working on new vaccine technologies. And they didn't need Dr. Frist's Free Pass to do it, either. But there's still an awful long way to go. Too bad we didn't start much earlier. We could have. This isn't brand new technology.

Freethinker Sunday Sermonette: did I mention you were adopted?

Sundays, time to read the comics. This week there was a story in the LA Times that was so bizarre, it only needed . . . well, I'm not sure what it needed. It's about Mormonism.

Here's a little background on the Church of the Latter Day Saints from the Times article by William Lobdell (warning: this is not satire):
According to the Church of Jesus Christ of Latter-day Saints, an angel named Moroni led Joseph Smith in 1827 to a divine set of golden plates buried in a hillside near his New York home.

God provided the 22-year-old Smith with a pair of glasses and seer stones that allowed him to translate the "Reformed Egyptian" writings on the golden plates into the "Book of Mormon: Another Testament of Jesus Christ."

Mormons believe these scriptures restored the church to God's original vision and left the rest of Christianity in a state of apostasy.

The book's narrative focuses on a tribe of Jews who sailed from Jerusalem to the New World in 600 BC and split into two main warring factions.

The God-fearing Nephites were "pure" (the word was officially changed from "white" in 1981) and "delightsome." The idol-worshiping Lamanites received the "curse of blackness," turning their skin dark.

According to the Book of Mormon, by 385 AD the dark-skinned Lamanites had wiped out other Hebrews. The Mormon church called the victors "the principal ancestors of the American Indians." If the Lamanites returned to the church, their skin could once again become white. (LA Times)
Sort of like believing there is someone up in the sky that controls everyone's destinies and if you don't do what He says he'll burn you to a crisp. Or that he had a Son who died for your sins (even though you weren't even born yet; how did he know you were going to shop lift that candy when you were 6?). Or that . . . you get the idea.

If, by itself, this isn't bizarre enough, consider the success of this story in proselytizing amongst Native Americans and Pacific Islanders. About a third of LDS's worldwide membership of 12 million now includes indigenous peoples of the New World who have been told they are descendants of ancient Hebrews and soon their day will come in the bosom of the LDS Church.

Unfortunately, DNA evidence about the actual origins of the converted seems to be pretty conclusive they aren't from Palestine. The indigenous peoples of North and South America are from Asia. This has royally pissed off some former Hebrews:
From the time he was a child in Peru, the Mormon Church instilled in Jose A. Loayza the conviction that he and millions of other Native Americans were descended from a lost tribe of Israel that reached the New World more than 2,000 years ago.

"We were taught all the blessings of that Hebrew lineage belonged to us and that we were special people," said Loayza, now a Salt Lake City attorney. "It not only made me feel special, but it gave me a sense of transcendental identity, an identity with God."

A few years ago, Loayza said, his faith was shaken and his identity stripped away by DNA evidence showing that the ancestors of American natives came from Asia, not the Middle East.

"I've gone through stages," he said. "Absolutely denial. Utter amazement and surprise. Anger and bitterness."
Never mind. If you really are needing to believe ridiculous stories, there's no shortage being peddled by Islam, Judaism, Christianity, Zoroastrianism and the rest. Take your pick.

Meanwhile, Mormons are trying to figure out what to do with the inconvenient DNA evidence. In an otherwise fine article, we find this puzzling analogy:
For Mormons, the lack of discernible Hebrew blood in Native Americans is no minor collision between faith and science. It burrows into the historical foundations of the Book of Mormon, a 175-year-old transcription that the church regards as literal and without error.

For those outside the faith, the depth of the church's dilemma can be explained this way: Imagine if DNA evidence revealed that the Pilgrims didn't sail from Europe to escape religious persecution but rather were part of a migration from Iceland — and that U.S. history books were wrong.
Huh? Why would I care if the original European settlers came from Iceland or Spain or Italy? And I don't have to imagine how I'd feel if US history books were wrong. Little I was taught from those books 50 years ago was factually correct.

Anyway, it's Sunday. Read the article in the LA Times. It's much better than the funnies.

Saturday, February 18, 2006

The waiting game

If the pochard duck in Lyon, France is confirmed to have died from H5N1 (and most believe this will happen), we will have the virus in birds in the seventh EU nation in the last two weeks, a remarkable spread. The disease is now reported from Europe's east to its west and from north to south. The UK is bracing for what seems an inevitable discovery soon. Meanwhile, reports from the Nandurbar district of Maharashtra in India remind us that this virus is flying everywhere.

When and if birds in North and South America become infected is still an open question as the exact mode of predominant spread is still a matter of contention. It is clear migratory birds can carry the disease and most believe they can spread it over long distances. But there remain certain inconsistencies and unknowns here, and it is also quite clear that poultry movements and trade are also a major means for spreading the virus.

Public health people, however, are now anxiously waiting for the other shoe to drop. If Europe starts to see human cases, we would be in a qualitatively different phase, no longer able to maintain it is the peculiarly close relationship with poultry in China, southeast asia, Indonesia and Turkey that has made these localities the site of human outbreaks.

The waiting game begins in earnest.

Tell 'em what you know

Peter Sandman appeared at a meeting in Minneapolis this week and said to public health officials what needed to be said. Stop being so panicked about panicking people. Appropriate fear can be a motivator. Lying to people about things they really should be afraid of is a good way to lose credibility while simultaneously not giving the people they serve vital information, even if that information is scary.
"There's no way to get people to take precautions without frightening them," Sandman said.

What is likely to lead to panic is giving false reassurance, he said. "When you mislead people, when you overreassure people, they feel abandoned—because they are," he said. That's what happened in the United States during the flu pandemic of 1918 and during the SARS (severe acute respiratory syndrome) outbreak in China in 2003, he added.

"People panicked because the government was telling them there was no SARS," he said.

"People are much better able to handle a crisis when they are told the truth" and "treated as adults." (via CIDRAP news)
This is not a license to alarm people falsely or carelessly, for then when the dire event doesn't materialize, confidence is also lost. Public health scientists sometimes do this when they aren't careful or precise. As an example, Sandman notes that to say the question about a pandemic is not if, but when, obscures the fact that what remains uncertain is the severity of the pandemic. A 1918-style event still remains an if, not a when.

Perhaps the only place I part company from his advice, and then only slightly, is his belief that while people love certainty, they are always better served by frank admissions of uncertainty. "Uncertainty" is itself an uncertain concept, interpreted by different people in different ways. There are many types and varieties of uncertainty and it isn't always easy or possible to specify exactly what you mean or even what you are uncertain about. Some kinds of uncertainty are extremely unsettling.

But we both agree it is always best to tell people what you know as soon as you know it, keeping people briefed on what you know at frequent intervals, and when uncertain you should be "visibly, vividly, confidently uncertain." It's like sitting on a plane delayed on the tarmac for hours at time. Nothing is more infuriating than not knowing what's going on, even if it's to have the pilot say that you are being held on the ground by the control tower although he doesn't yet know the reason. That's a kind of uncertainty people can understand. As soon as the reason is revealed it should be announced and if no information is forthcoming, continued frequent updates should announce that, too.

It's a minor quibble. His main point is right on the money. The Department of Public Health is not the Department of Public Reassurance. Over the years I have seen countless examples of public health officials imagining in abject terror the consequences of releasing information they are sure will cause panic, only to find that people accept it with an appropriate degree of concern. What really sets them off is if they find out you knew it long ago and didn't tell them.

The result is not panic. It's rage.