Tuesday, January 31, 2006

Nature's terrorist now in Iraq

We have gone from no cases of bird flu in Iraq to a probable three, overnight. Two were the Uncle and niece first reported last week and the week before but denied by the Iraqis as bird flu even though clinically this was the obvious diagnosis. Now we learn a 54 year old woman was hospitalized almost two weeks ago as well with severe respiratory problems and remains under treatment. She comes from the same area as the other two fatal cases. (Reuters Alertnet)

The death of the uncle ten days after his niece suggests human to human transmission, although other explanations are possible. We don't know the dates of onset of the illnesses, whether there was contact or whether the uncle was exposed to diseased poultry.

None of this is a surprise. The village where these cases occurred is near the Turkish border and even closer to the Iranian border. It is remote but near a known focus of H5N1 poultry infection. Spread of H5N1 to Iran, Iraq, Azerbaijan and surrounding areas is a given. Already Turkish Cyprus has reported the infection in birds. Next step is the Greek side and then Greece itself. But Iraq is a special case, politically and epidemiologically because of the presence of 160,000 foreign occupying troops and constant warfare:
Battered by rampant violence and political instability, a new threat in Iraq was confirmed Monday - the first case of the deadly bird flu virus in the Middle East.

A 15-year-old Kurdish girl who died this month had the deadly H5N1 strain, Iraq and U.N. health officials said. The discovery prompted a large-scale slaughter of domestic birds in the northern area where the teen died as the World Health Organization formed an emergency team to try to contain the disease's spread.

"We regretfully announce that the first case of bird flu has appeared in Iraq," Iraqi Health Minister Abdel Mutalib Mohammed told reporters. "The results show infection with the deadly H5N1."

World Health Organization officials confirmed the finding, though it was not immediately clear how the girl, Shangen Abdul Qader, who died Jan. 17 in the northern Kurdish town of Raniya, contracted the disease.

The prospect of a bird flu outbreak in Iraq is alarming because the country is gripped by armed insurgency and lacks the resources of other governments in the region. Government institutions, however, are most effective in the Kurdish-run area of the north where the girl lived. (AP)
While Turkey was able to take vigorous measures to contain the disease, Iraq may not be in such a favorable position. As in Turkey, the disease first appeared in humans, not birds, suggesting either a change in its behavior or (more likely) that widespread disease in birds has gone undetected for some time.
The confirmation of the cause of the girl's death also suggests, officials said, that the disease may be spreading widely — and undetected — among birds in the countries of central Asia, which are poorly equipped to identify and report infections. Avian flu has never been reported in birds in Iraq.

As happened in Turkey earlier this month, the spread of the H5N1 strain of bird flu to a new part of the world became evident only through a human death. That is notable, and alarming to health officials, because bird flu rarely infects humans, and usually does so late in the course of an animal outbreak, after close contact with sick birds.

"We shouldn't be seeing human cases first, and this points to serious gaps in surveillance," a spokeswoman for the World Health Organization, Maria Cheng, said in Geneva. "But given the situation in Turkey, I don't think we'd be surprised to see isolated humans cases in surrounding areas."


[Juan Lubroth of the UN Food and Agriculture Organization], who is studying the spread of avian influenza, said that monitoring to detect the disease in animals was weak in much of the region and that governments needed to be more transparent — both in acknowledging outbreaks and in admitting when they lacked the capacity or money to detect the disease, which requires complicated laboratory testing.

For example, Dr. Rod Kennard, who is managing a year-old United Nations project to rebuild veterinary services in Iraq, said that the local government in Sulaimaniyah was monitoring commercial poultry flocks, "but they don't really have the ability to monitor what's going on in village flocks."

He said that "it is a really big question" whether a country in the throes of armed conflict could coordinate a response to a complicated problem like bird flu, although he noted that northern provinces were generally "not as troubled" as some of the areas in Central Iraq.


In October, there were large-scale deaths on commercial farms in northern Iraq, Dr. Kennard said. Birds were tested and "we were told it was negative," he said, "but we're not entirely sure how reliable that is."

In most countries with serious bird flu outbreaks, including Turkey, the military has provided the manpower required to contain them, going door-to-door to find chickens to cull. That is not an option in Iraq. (Elizabeth Rosenthal, New York Times)
The preliminary diagnosis of H5N1 was made by the U.S. Navy Medical Research Unit laboratory in Cairo, Egypt. There seems to be little room for doubt here.

Today, the US made its first acknowledgement of the situation, "offering help."
The United States has offered assistance to Iraqi authorities to help deal with the outbreak, while a World Health Organization team of epidemiologists and clinicians was expected to arrive later in the week to start tests.

"We are working with the government of Iraq and the World Health Organization to ensure that the necessary support for diagnosis and treatment of avian influenza is available as needed," U.S. Embassy spokeswoman Sylvia Blackwood said. (Newsday)
The US is already stopping support for rstoration of water, electricity and other infrastructure destroyed in the invasion. Will occupation authorities, who have made so many other errors, understand support for controlling this disease is a top priority?

Or is the switch from killing people to killing chickens just too big a leap?

Monday, January 30, 2006

Bird flu in Iraq: confirming the obvious

Once again we take no pleasure in being right (see here, here and here), especially as in this case being right was pretty much a no brainer. I guess that says that those who were wrong (WHO, CP the addle-brained ProMed Moderator who is an obsessive bird flu denier, the Iraqi "government", and the US occupying authorities by their silence) weren't using their brains at all or using them for a non-medical purpose.

Today we get the report of the perfectly obvious: the 14 year old little Iraqi girl who died last week (her age is sometimes given as 15 years old) and most probably her 50 year old uncle, succumbed to bird flu, the first human cases in the Middle East outside of Turkey. And after the denials, it isn't clear how many human cases there are now:
"We call on the World Health Organisation to send experts to confirm that Kurdistan is free of bird flu," said Imad Ahmed, deputy prime minister of Sulaimaniyah in Kurdish northern Iraq.

Ahmed said 12 people had been quarantined after they fell ill with pneumonia, but could possibly be infected with the fatal H5N1 strain of bird flu which has killed at least 80 people worldwide since 2003.
Iraq's Kurdish provinces, which lie on the border with Turkey, are a major poultry producing region supplying chicken and eggs for much of the entire country. (AFP via ChannelNewsAsia)
So there you have it. The Fourth Horse of the Apolcalypse is cantering towards a war torn area with a destroyed civil infrastructure, overwhelmed medical facilities and 160,000 foreign occupiers poised to become global vectors.

What did you expect?

Disappointing, Rep. Meehan

Representative Marty Meehan is a moderately liberal Democrat from Lowell, Massachusetts, a working class town on the Merrimack River 45 minutes north of Boston (Massachusetts 5th Congressional District). He's not the greatest, a middle of the roader. If we could replace all Republicans and a good number of Democrats with Meehans we'd be better off, although he could use a little more backbone. OK. End of the nice stuff.

It turns out members of his staff were directed to rewrite his bio on Wikipedia. He's not the only one to do so, apparently, but he's the one I know about, courtesy an article in The Lowell Sun. So I'll use it as an opportunity to say that I think what Meehan did is reprehensible.

Wikipedia is a collaborative project that harvests the collective wisdom of the world's mind hive. It is remarkably accurate and up to date, but like newspapers and other media (Lowell Sun take note!) it sometimes has inaccuracies, sometimes accidental or out of ignorance on the part of the writer/reporter (Lowell Sun take note!) or out of ulterior or malevolent motives (Lowell Sun take note!), but usually out of carelessness (Lowell Sun take note!).

In this instance, Meehan's staffers went into his Wikipedia bio (whether it was good or not I can't say) and replaced it with his official bio, which was much longer but also deleted information the CongressThing thought unflattering.
Matt Vogel, Meehan's chief of staff, said he authorized an intern in July to replace existing Wikipedia content with a staff-written biography of the lawmaker.

The change deleted a reference to Meehan's campaign promise to surrender his seat after serving eight years, a pledge Meehan later eschewed. It also deleted a reference to the size of Meehan's campaign account, the largest of any House member at $4.8 million, according to the latest data available from the Federal Election Commission.

"Meehan first ran for Congress in 1992 on a platform of reform," the pre-edited entry said. "As part of that platform Meehan made a pledge to not serve more than four terms, a central part of his campaign. This breaking of the pledge has been a controversial issue in the 5th Congressional District of Massachusetts."

The new entry reads in part: "Meehan was elected to Congress in 1992 on a plan to eliminate the deficit. His fiscally responsible voting record since then has earned him praise from citizen watchdog groups. He was re-elected by a large margin in 2004." (The Lowell Sun)
It is fine for Meehan to correct incorrect information. It's more than fine. It's the thing to do. What is not the thing to do is delete factually correct information.
"To knowingly remove a truthful statement is just wrong," [Geoffrey Bowker, director of the Center for Science, Technology, and Society at Santa Clara University] added. "It's not the place of any special-interest group to tamper with the facts available to the public."
Maybe I feel so strongly about this because I am a founding editor of The Flu Wiki. There is an honor system there and on Wikipedia. Marty Meehan dishonored himself by violating that honor system.

Yes, he's a liberal Dem and it's good to have them in Congress. And yes, this isn't the worst crime. Unlike those of many of his Republican colleagues, it isn't even indictable.

But it still stinks.

Addendum: Micah Sifry has posted a much longer list of CongressThings that have similarly sanitized their bios. It's just that Meehan is the first to admit it. If you live in their districts, let them know you don't like it. As Micah notes, it appears there are many more Republicans than Democrats (probably because they had more stuff that "needed" editing out). At the top of the list is Richard Pombo (R.-Calif.) whom I will deal with in a post tomorrow.

Sunday, January 29, 2006

Another suspected case in Iraq

A week ago (here and here) we reported on the death of a 14 year old girl with symptoms and signs reminiscent of bird flu. She lived near the Turkish border and birds in her household had died shortly before. But tests by local doctors said she didn't have bird flu. WHO compliantly rolled over and accepted the suggestion she died of heart disease. Allegedly samples were sent to a reference laboratory for confirmation of the "negative" tests done locally, but so far I haven't seen any reports of the results.

Well if she died of heart disease, whatever caused it must be catching, because her 50 year old uncle has now died of a severe respiratory disease that again sounds a lot like bird flu, too.
Although tests made in Iraq on samples from the girl, who died on Jan. 17 near Sulaimaniyah, not far from the country's border with Turkey, were negative, both had suffered breathing difficulties, WHO spokeswoman Maria Cheng told Reuters.

"Given that both these people had severe respiratory problems and that it is near the border with Turkey, we need to check," she told Reuters.
Yeah, I'd say so. What about the dead birds?
So far there have been no confirmed cases amongst poultry in Iraq. However, some birds died recently in the area from which the girl and her uncle came, but it was not yet known whether the deaths were due to bird flu, Cheng said.

"Birds often die of many things," she said.

"It would not be surprising if it had spread from Turkey, but at the same time, we have no evidence yet that it has," Cheng added.
What do you want? The birds to rise from the dead and whack you over the head with a two-by-four?

So far we have heard nothing about this from the US occupation authorities. I guess news of human bird flu in the midst of 160,000 US troops might have a wee tendency to step on the Bush Administration's "don't worry, be happy" Iraq message.

It is rumored the State of the Union Address next Tuesday night will feature the President's solution to the health care crisis in the US.

How timely.

Freethinker Sunday Sermonette: show your ID, please

Sunday, but no rest for the wicked. The wingnuts who run the Utah Senate are at it again, this time approving a bill to make public school teachers tell their pupils evolution is of questionable validity.
Sen. Chris Buttars has tried to eliminate any possibility that his bill questioning the validity of evolution could allow for religious instruction in the classroom - and avoid the legal risks associated with such teaching.

But religion is the reason he proposed the bill and religion drove most of the debate Friday, as the full Senate gave its initial approval to SB96.

Comments on the Senate floor commending God's creation of man and condemning atheists for pushing their "religion," could potentially end up as evidence in court should the bill become law.


Buttars' bill would require teachers to say that scientists are not in agreement about theories explaining the "origins of life or the origins or present state of the human race" and that the state doesn't endorse any such theory. (Salt Lake Tribune)
Interestingly, four Republicans, including the Senate Majority Leader, joined all the Democrats on the losing end of a 17 - 12 vote. Welcome to the coven of secularists and atheists.

Not that this has anyting to do with religion, as the upright Senator Buttars swears, his hand on an imaginary stack of bibles:
"I challenge anyone to say that somewhere in those lines that I'm trying to promote religious philosophies," Buttars said. "My bill from the get-go never included anything about intelligent design, creationism or any faith-based philosophy."
I'll take that challenge. Senator Buttars, you are trying to promote a religious philosophy.

I guess no one told this neanderthal that lying is considered a sin by most religions. Although now that I think about it, there has been a lot of cheating, stealing, killing and lying in the name of most religions, too.

Maybe Senator Buttars is just being observant.

Quick vaccine cycle follow-up

As promised, I have now had a chance to read the paper by Rao et al. that has just appeared online in the Journal of Virology (Feb. 2006, pp. 1959 - 1964; thanks to Selise for .pdf). It describes the new quick cycle bird flu vaccine from the University of Pittsburgh group reported on the wireservices. After some back and forth on my part given the vagueness of the descriptions, it turns out my original impression was correct. This is what is usually called a DNA vaccine using a common cold virus as a vector.

Here are some of the details and explanations. The usual seasonal flu as well as the current experimental NIH H5N1 vaccines are inactivated flu viruses that carry the surface proteins of the H5N1 virus but the inner proteins of a more benign virus. They are grown in eggs, inactivated and then injected in two doses into arm muscles. The immune system "sees" the viral surface protein and makes protective antibodies against it. In the trials so far it took a lot of viral protein to produce a response (twelve times the usual amount found in the seasonal flu vaccine) and attempts to boost this with additives have been relatively disappointing. Given these numbers, there wouldn't be enough production capacity to satisfy demand globally for a long time, if ever. Egg supply would also be a problem. And to top it off, it takes 6 to 8 months to make the vaccine once a candidate pandemic strain has shown itself. We could go through several pandemic waves before a vaccine was ready.

So quicker, more efficient ways to produce a vaccine have been under intensive investigation. One appraoch would be to grow the vaccine in cell cultures rather than chicken eggs. This could produce capacity and reduce production cycles. And another has been to use DNA vaccines, which is what the Pittsburgh work is about.

Many of you know that the genetic material in the flu virus is RNA, not the DNA of human cells. But either one codes for proteins, so the tactic is to get the DNA of the viral surface protein (or some other component of the virus) into a human cell and let the cell make just that protein (not the whole virus), thus eliciting (it is hoped) the kind of immunity one gets from the inactivated virus. DNA can be made much faster and cheaper than growing viruses. But there are a couple of technical obstacles. The first is the matter of getting the DNA into the cell in the first place. Not such an easy task it turns out.

You might try to physically shoot it into the cell, and this is the basis of one approach being employed by PowerMed, Ltd. in the UK. They coat tiny particles with the DNA genes and shoot it into the skin with a superfast injector device (no needles). There are many immune cells in the skin and PowerMed claims good results. But they don't have FDA approval as yet and it sounds like there is still development work to do. You could also try to inject "naked" DNA (in a plasmid loop) into the skin, and this approach is being used for some other infectious diseases.

But the most efficient carrier of genetic material into a cell remains a virus, which needs to get at the cell's genetic machinery so it can make new copies of itself. So there has been a lot of work using viruses as vectors to get DNA into human cells, not just for vaccines but for gene therapy (correcting genetic defects). A number of different viruses have been used for this purpose (baculovirus, vaccinia virus, Adeno Associated Virus) but adenovirus type 5 has been one of the more successful, and it is this that the Pittsburgh group used as a vector (or vehicle) for DNA segments that code for the HA surface protein (the H5 part of H5N1).

The AD5 virus was modified so that it didn't cause disease and in fact couldn't replicate or be integrated into human genes. It also has a finite lifetime, as the body makes antibodies also to AD5, neutralizing it after a relatively short time. It is during this period that the body's immune response must go into action. It was not at all obvious this would work, although a human trial with AD5 incorporating an H1N1 gene was shown to be safe and to elicit a good immune response (see van Kampen et al.)

The Pittsburgh group followed the same approach, splicing into AD5 segments of the HA surface protein from two different H5N1 viruses, one a Vietnam isolate from 2004, the other a Hong Kong isolate from 1997. They obtained genetic sequences from CDC for either the whole HA proteins or two subsections of it, the HA1 segment (the far end of the protein which elicits an antibody response), and the HA2 (closer in) segment, important for entry and then uncoating of the virus within the cell. Thus they put in an adenovirus vector DNA sequences from either of two H5N1 HA proteins, each either full length or in pieces (HA1 or HA2), six combinations in all. They report that from the day the sequence information arrived to the day the vector AD5s were made was just 36 days, thus demonstrating this could be accomplished on a very short cycle.

They then injected the AD5 modified viruses into mice on day 0 and again on day 14 (a booster shot). Antibody response to the full length HAs was quite rapid and the authors believe it might be possible to get by without the booster for full length HA. In addition, there was also some cross-strain immunity, i.e., in the full length versions there was the strongest response to the strain from which the HA sequence was taken but also a measurable response to the other strain as well (i.e., the Vietnamese versus the Hong Kong strains). Response after boosting was also good for the HA1 versions, but not the HA2s, perhaps not surprising because the immune system recognizes HA through parts of the protein that are at the HA1 end.

Also of interest was the fact that another arm of the immune system, cell mediated immunity, was also stimulated. The exact function of cell-mediated immunity in prtoecting against influenza is still being worked out, but this response usually precedes the antibody response by several days and is initially relatively non-specific. Interestingly, HA2 also participated in cell mediated immunity and there was evidence of strain cross-reactivity as well.

Finally the Pittsburgh group demonstrated that the animals were truly protected against challenges with amounts of flu virus rapidly 100% lethal to unvaccinated animals. While some of the vaccinated animals did fall ill, all recovered.

All in all this is a promising proof of principle for a new approach to an H5N1 vaccine. It builds on other work and is parallel to several other efforts to do the same thing. Perhaps the most important signal here is that there is a great deal of interesting work being done on new vaccine technology. We note this work has been going on for some time and didn't need Bill Frist to hand Big Pharma the Christmas gift of liability immunity. But that's another subject.

Still, there is a long way to go. It has to be shown that such a vaccine is both safe and effective in humans. Protecting mice is relatively easy. Protecting humans is another matter. There may be a lot of natural immunity to adenovirus 5 that could interfere with the efficacy of the vaccine, which might require a move to another serotype or vector. Not an insurmountable problem but one that takes time. The safety issue isn't trivial when hundreds of millions or even billions might be vaccinated in a pandemic setting. A risk of death of only one in a million, while very favorable in the risk-risk trade-off calculus, might be a significant psychological barrier if in the first weeks of a mass immunization campaign the public sees several dozen deaths related to vaccination. Finally there is the problem of scaling up to produce adequate amounts of vaccine. This will be easier for this kind of vaccine than an inactivated whole virus one, but won't be trivial.

Let's hope we are closer and have enough time to get to where we need to go.

Saturday, January 28, 2006

Quick vaccine cycle?

It sounds like big news, and perhaps it is. Perhaps. A group at the University of Pittsburgh Medical Center has announced that it has produced a bird flu vaccine in just 36 days from start to finish. This compares with the six months or more needed for conventional egg-based vaccines. Moreover it protected mice and chickens 100% in challenges tests with H5N1 (Reuters).

The feat was accomplished by taking genetic sequence information for the hemagglutinin (HA) gene of an H5N1, making a DNA sequence to match it and splicing the DNA into an adenovirus, a causes upper respiratory tract infections ("colds") in humans. Adenovirus is a DNA virus (as opposed to influenza which is an RNA virus), but its genetic information still encodes for proteins, and in this case it was able to make the designated portion of the influenza HA protein when injected in animals, i.e., the animals were infected by a non-disease causing modified adenovirus which then produced in them the HA protein fragment (at least that's how the newswire accounts read [See addendum below]). Thus this is a live virus vaccine, but it contains no live influenza virus. The influenza protein induced both antibodies and an immune cell response (cell mediated immunity). This apparently protected the animals from a viral challenge that was sufficient to kill unvaccinated animals.

This team's efforts are not unique. A reliable source told me that several other groups are working on variations of this theme and that it isn't so hard to protect mice (and he implied others had done it without announcing it). But protecting mice is one thing, protecting humans another. So the proof of the pudding will be successful human trials. The LA Times reported that the Pittsburgh team is working with the FDA to begin human trials soon, perhaps within a month.

So the news is hopeful but perhaps not as exciting as appeared at first blush. Perhaps.

[NB: The paper is supposed to be published online in the February 15 issue of Journal of Virology but as of this writing (late night 1/27/06) had not yet appeared on their site, so I am working off of wire service reports.]

Addendum: I found the abstract here but I can't get the Full Text yet as my proxy server seems to delete cookies automatically. The Abstract says the adenovirus is replication incompetent, which must mean like they are using it in cell culture to produce the HA protein. I will add to or correct this if and when I find out more. Anyone who has managed to get the article before I do is welcome to weigh in.

To kind readers who have offered us the .pdf: Thanks to one of your number (hat tip, Selise) I now have a copy of the vaccine paper and hope to read it tonight (I have been on the road almost constantly and am a bit tired, so I'm not sure I'll manage). Will report back once I have had a chance to digest it. It sounds like my first reading of the wireservices was more or less correct, however. They made the adenovirus into a vector to get the sequence into human cells where it the cells manufacture the HA or portions thereof.

Weight loss to go

The FDA won't let you buy the emergency contraceptive "Plan B" (the "morning after" pill) over the counter (OTC) because they aren't confident it won't be bought and used by underage girls, for whom no safety information was available, but they have no problem putting a weight-loss medication (Xenical) out there, even though its efficacy hasn't been shown.
Xenical acts by keeping about 25 percent of the fat a person consumes from being absorbed; this fat is passed from the body in stools that can be loose or oily. Other side effects include the inability to absorb fat-soluble vitamins such as D, E, K and beta carotene. (MedicineNet)
Studies have shown the drug does cause modest (5 to 6 lbs) weight loss in obese people, but the weight is put back on when the pill is stopped. GlaxoSmithKline recommends users take multivitamins to prevent deficiencies of fat soluble vitamins. Unfortunately the studies also show that only about half took the multivitamin advice.

Putting an (at best) marginally effective medication like this OTC encourages the idea that you can "take a pill" to solve a problem that is a matter of better nutrition and more exercise. But these things are secondary to the main point of selling this dog of a drug over the counter, bucks for GSK (and Roche, who makes the drug).

It's a good thing the FDA is so concerned about the possible health consequences of OTC drugs on adolescent girls, who of course have no potential for abusing a drug that might make them shit their guts out. That would be almost as much of a turn off as trying to lose weight by vomiting after eating.

This also solves another problem with not having the Plan B emergency contraception available OTC. When a woman becomes pregnant, she will have a way to control her weight.

Friday, January 27, 2006

Not betting against the spread

While Turkish Cypriot officials anxiously await tests on dead poultry to see whether they have died of H5N1, a WHO team is headed to Azerbaijan to see what the bird flu situation is there. No outbreaks have been reported there as yet, and the visit is ostensibly to help officials plan prevention activities and look around the capital Baku and several regions. But Turkey suspects there is a problem with its neighbors and I am sure WHO does too.

Thailand has the same suspicions about its neighbors, especially the closed society of Myanmar (aka Burma). The border between the two countries is studded with refugee camps and migrant communities, so local officials and NGOs are getting ready for a possible outbreak by organizing a workshop (Thai News Agency via Xinhuanet).
The workshop, co-organized by the provincial public health office and three international agencies -- the International Organization for Migration (IOM), the United Nations' Childrens Fund (UNICEF) and the World Health Organization (WHO) -- will take place in Tak and is expected to attract over 70 delegates from the provincial government, international organizations, UN agencies and non-government organizations ( NGOs) as well as embassies, theNews Agency disclosed.

Organizers hope that the meeting will help to identify key elements of an avian flu preparedness plan in an attempt to protect refugees and migrants living in crowded camps and communities in close proximity to their livestock, along Tak province's border with neighboring Myanmar, according to the News Agency.
Speaking of closed societies, the Japanese newspaper Sankei Shimbun is reporting at least one human case in the North Korean capital of Pyongyang last month. The capital is also said to be the site of poultry infections. The North Koreans are denying it (naturally), but one of the many defects of a closed society is that no one believes you whether you, whatever the truth of the matter.

Don't forget the newly reported deaths in China and Indonesia. The realization has finally sunk in that bird flu is on the way, extending its reach inexorably. Some places don't know they have it or haven't admitted its presence. Still others know its coming, and probably pretty soon.

Meanwhile the virus is changing, adapting to its many new environments and going about the only business it has in this world, making copies of itself. It doesn't care what it has to do in the process. Since we are the only species we know of with any kind of foresight or ability to plan, you'd think we would be adapting, too.

Maybe we're not as smart as a virus.

Prescription for Big Pharma written by Dr. Abramoff

The Medicare Prescription Drug Act is now taking its proud place in the Bush Administration Incompetence Hall of Fame along with the War in Iraq, FEMA and other exhibits. So it's time to find the artist who crafted it so lovingly.

A letter from Democratic House Leader Pelosi to Republican House Speaker Hastert tells us it was the work of "Dr. Feelgood" Jack Abramoff. Here's an excerpt:
The Medicare Prescription Drug Act, which has caused so much confusion and havoc since January 1, was a product of a corrupt legislative process. Whenthe bill passed, we knew that Democratic members had been denied opportunities to offer amendments and that the vote had been held open for hours in the dead of night to twist arms. Afterwards, we learned that crucial cost estimates were illegally withheld from Democratic members; that the key Administration official responsible for writing the bill was simultaneously negotiating a high-paying job representing drug and insurance companies; and that the Republican chairman responsible for steering the legislation through Congress subsequently accepted a lucrative job in the pharmaceutical industry. We further learned about a Republican member who had alleged that a bribe had been offered him on the House floor.

Recently, with the indictments of Tom DeLay and Jack Abramoff, new questions have arisen about the role of the Alexander Strategy Group in this dishonest process. We know from lobby disclosure forms that the largest single client of the Alexander Strategy Group was the pharmaceutical industry, which paid the small firm over $2.5 million, including nearly $1 million in 2003 when the prescription drug law was being written. We also know from these records that the primary lobbyist for the drug industry at Alexander Strategy Group was Tony Rudy, who previously worked for both Mr. DeLay and Mr. Abramoff and who is identified as "Staffer A" in Mr. Abramoff's indictment. And we know from multiple accounts in the news media that the Alexander Strategy Group has been deeply implicated in the scandals now sweeping through Washington.


The Medicare Prescription Drug Act symbolizes all that has gone wrong in Congress. The bill's monstrous complexity frustrates nearly everyone, and its high drug prices enrich the pharmaceutical industry at the expense of seniors and taxpayers. The primary beneficiaries of the legislation have become the special interests that gave millions to Republicans in Congress, not the millions of seniors and persons with disabilities that the legislation was supposed to help. We have an obligation to the public - and especially to the seniors of America - to find out how the legislative process went astray and to hold those responsible to account.
These are the allegations (use the link for many more details, documented by 44 footnotes). Do I believe them? You bet.

And spare me the "just another Bush bashing post" crap. Yes, it's Bush bashing. He deserves it and so do his Republican buddies.

Thursday, January 26, 2006

Another China sharing post (sigh)

I guess I should make a standard template post that WHO is again complaining China is not sharing viral samples from their poultry outbreaks with the international community. Because that's what WHO officials said again this week.
Negotiations continue between the World Health Organization and China over requests for the Chinese to share samples of H5N1 bird flu. International experts complain that China has not cooperated fully in the fight against the virus, and they fear this could hamper the global effort to prevent a pandemic.

For months, the World Health Organization has expressed frustration over China's failure to hand over tissue samples from animals that died of the H5N1 virus in the country in recent months. (chosun.com [Korea])
Bits and pieces have been shared, to be sure, and the Chinese Ministry of Health seems to be more forthcoming with the human isolates than the Ministry of Agriculture has been with the animal isolates (see posts here, here, here and here). The genetic sequences are not enough, as for the most part our knowledge is not sufficient to predict important biological properties like virulence, host range and transmissibility from this information alone.

The reasons for China's attitude seem to be a combination of national pride and desire to control a resource (the viral isolate) that might be useful to make a vaccine. But as WHO points out, these motives are misplaced:
Speaking in Beijing last month, Shigeru Omi, the WHO's top official for the Asia Pacific region, said it is essential that nations cooperate in the effort to develop vaccines and other prevention measures. He reminded the Chinese that they also have gained from the system of international cooperation.

"WHO provided [the] seed virus to all the manufacturers, international level manufacturers. This seed virus was derived from Vietnam," he said. "China received it. China benefited from this international collaboration."
Other nations with a bird flu problem have been forthcoming, with Vietnam, Indonesia and Thailand freely sharing actual isolates. Only China has been recalcitrant, their claims to have cooperated by hosting conferences and sharing other information notwithstanding.
"It is to China's advantage to have these specimens considered, because if China is not handing over specimens or is not sharing their specimens, other countries could do it [not share information]," said [University of Michigan epidemiologist Arnold] Monto. "This could be dangerous in the long run to China because, with birds flying from place to place, with chickens being shipped from place to place, there's no telling where important virus variants may originate."
No international laws require China to supply these isolates, so the only recourse is continued dialog and "negotiation." Time for all concerned -- the Chinese, any researchers who use the isolates, WHO, other nations -- to act scrupulously and generously with credit and recognition to all concerned.

Because if a pandemic rolls down the tracks at all of us, national pride, authorship and licensing won't mean much.

Are you loathsome tonight?

You might be. Check the list of the 50 Most Loathsome People in America in 2005. If you're there, you'd be at number 4. You can find it at The Buffalo Beast (hat tip John Sintauer at The Daily Irrelevant). I might quibble with the order of a few but they are all sadly hilarious (you'll see that's not a contradiction when you read them).

To whet your appetite, here are a few of my favorites (but they're all good).
41. Charles Krauthammer

Charges: Considered an intellectual authority among neocons, Krauthammer, like his colleagues George Will and Tony Blankley, really only presents a passable facsimile of gravitas, substituting vocabulary for intelligence, mischaracterization for argument, and intolerable haughtiness for authority. The fact that this wanton fascist’s opinions are not only considered fit for mainstream consumption, but among the cream of the conservative crop, is a maddening indictment of both the media and conservative movement.

Exhibit A: Posed a hypothetical scenario involving 9/11 ‘architect’ Kalid Sheikh Mohammed to advocate legalizing torture, when the actual Kalid Sheikh Mohammed was actually tortured without any such legislation.

Sentence: Lockheed-designed bionic exoskeleton he receives from Dick Cheney in exchange for opposing stem cell research goes berserk, ignoring Krauthammer’s excited protestations as it uses its powerful titanium arms to pulverize his loved ones and donate his life savings to Hamas.

31. Rita Cosby

Charges: Unholy pastiche of fearmongering and celebrity ringworm with the brain of a moth, the integrity of a tapeworm, and the appearance and larynx of a sugar-addicted, glass-eating drag queen.

Exhibit A: Her banter with Joe Scarborough kills children.

Sentence: Kicked in the nuts.

28. Joe Lieberman

Charges: Technically there are 55 Republicans in the Senate, but that’s not counting their favorite shill Joe Lieberman. He’s a Democrat because…well…he’s from Connecticut. And he’s Jewish. But Lieberman has spent his time since “losing” to Bush/Cheney in 2000 spooning the White House and attempting to inoculate their increasingly insane policies from legitimate criticism. Resembles Tex Avery cartoon character Droopy Dog in voice, demeanor, and spinelessness.

Exhibit A: “Freedom of religion doesn’t mean freedom from religion.” Apparently, it also doesn’t mean freedom from asinine revisionism.

Sentence: Made into Oval Office footstool.

17. William A. Donohue

Charges: If Jesus Christ were alive today, Catholic League president Bill Donohue would regularly call him a faggot in casual conversation. Purports to somehow defend Christianity by attacking nearly everybody on the planet in a perpetual frenzy of hateful, red-faced rage. As far as Donohue is concerned, the main focus of Catholicism is to stamp out homosexuality and Hollywood Jews who “like anal sex.”

Exhibit A: When a liberal blogger posted an “O’Reilly Factor” parody transcript wherein Donohue launches a campaign against responding to sneezes by saying “gesundheit” instead of “God bless you,” many failed to get the joke, because, well, it’s just plain realistic.

Sentence: Actually judged by true Christian god.
I've got to stop. I want to put them all up. But that wouldn't be fair (use), would it. So go read it for yourself.

And weep. And laugh.

Wednesday, January 25, 2006

Slimeball: I'm not playing

I'm going to weigh in on the Chris Matthews upset because, well, I'm upset. I had the misfortune to have actually heard "live" one of the incriminating segments on the faux journalist's MSNBC infotainment slot last Friday, and it was something. My jaw went south. It was billed as a new "Friday feature" with Matthew's MSNBC "colleagues," Tucker Carlson, Rita Cosby and Joe Scarborough, all three representing the right end of the right end of political views. I guess Fox was so full of crap there wasn't room for more so they shoveled some of it over to MSNBC. Conspicuously absent from Matthew's "colleagues" was the only MSNBC primetime voice of sanity, Keith Olberman, but if you watch Olberman you run the risk of being slimed by his usual quick segue into Rita Cosby's show, even a minute's glimpse of which will make you want take a shower (and not with her, either; with the biggest bottle of disinfectant you can find).

I recently gave a talk where I asked the audience how many people listened to Chris Matthew's show, Hardball (allegedly hardnosed political reporting but really soft porn Bush sycophancy). No one raised their hand in a room of about 50 public health professionals. This is encouraging, so it is with some trepidation I am even calling attention to this brownosing narcissist who claims to be a reporter. But I will, because the case against him and his ilk--and a call to let his sponsors know--is now on the web and experiencing phenomenal traffic. You might as well see what the fun is about and join in. It has all the quotes, history and ways you can express your opinions about the state of cable news "journalism."

The idea that main stream media are "liberal" is one of the greatest propaganda coups the rightwing has managed to pull off, and Matthews is exhibit number one in a whole museum's worth of exhibits.

Here's the site, An Open Letter to Chris Matthews. Enjoy.

Your mother wouldn't be proud

There are some jobs your mother probably wouldn't be proud of, like "My son, the international arms merchant," or "My son the tobacco lobbyist." Here's another one to add to the list. Working for these folks, Life Partners, Inc.

Life Partners, Inc. offers terminally ill people enough money to live comfortably in their last days in exchange for their life insurance policies. It's a business and I guess you could make an argument they are doing a service to people without anyone to leave their money to. And they are running a risk. Not a big one, but a risk nonetheless. Like maybe you might live too long because they'll find a cure for your disease.

This is now the substance of a contract dispute coming before the New Jersey Superior Court. Here's the story, courtesy columnist Monica Yant Kinney in The Philidelphia Inquirier.

In 1994 a woman in her early thirties was diagnosed with AIDS, then essentially a death sentence.
She began treatment, but wasn't optimistic. Back then, it seemed as if everyone who had AIDS died quickly.

Single, self-employed and with little savings, Smith was intrigued by an ad offering to buy her life insurance.

The terminally ill person gets money to live comfortably until the end - and then, the company makes a killing.

"It's ghoulish, but all insurance is a bit ghoulish," says Goldfein, who oversaw "tons" of deals like Smith's in the early 1990s. "AIDS was a sure thing."

And so, in 1994, Smith sold her $150,000 life insurance policy to Life Partners Inc. of Waco, Texas, for $90,000. As part of the contract, Life Partners set aside $5,510.64 to pay the premiums for Smith's health- and life-insurance policies, which were linked and could not be separated.

By investing in her fate, Life Partners assumed responsibility for the premiums as long as she lived.
"Purchaser," the contract read, "agrees to make any necessary contributions to the escrow fund to pay future premiums in the event that escrowed funds are exhausted and Seller shall have no further liability for payment of premiums on the policy." (Philadelphia Inquirer)
This looked like a pretty good deal for Life Partners because they would make $60,000 on a $90,000 investment. And indeed it would have been a good deal if new drugs for AIDS hadn't come along. Because Ms. Smith (not her real name) is still alive and has just turned 50. Life Partners has already ponied up $100,000 in insurance premiums in the interim.
Stung by the costly miscalculation, the publicly traded company (www.lphi.net) is balking at paying Smith's combined health- and life-insurance premiums.

A stranger claiming to represent angry investors has twice called Smith at home to ask her how she was feeling.

All of it has her lawyers wondering whether Life Partners is trying to hasten Smith's death with all the stress about whether she's going to lose her health insurance.

"They were in a risky business, hoping for a massive windfall," notes Ronda Goldfein, executive director of the AIDS Law Project in Philadelphia.

"And when they don't get it, they slowly torture her and eat away at her peace of mind," she said.
It's not as if Life Partners is a company in trouble. Far from it. They paid investors dividends that average 16%.

Ms. Smith's life insurance is now $26,000 a year, higher than her yearly income. She couldn't possibly afford it, and now the company says it wants out.
Life Partners' president and General Counsel, Scott Peden, declined comment about the lawsuit - which he said he believes is the first of its kind in the company's 15-year history of helping "thousands of terminally ill patients."

Life Partners wants the case dismissed. In e-mails between the lawyers, Peden said Life Partners paid Smith's bills as an act of goodwill, not obligation.

"We didn't buy her health insurance. There's no value there, it doesn't benefit us," Peden told me in a brief phone interview Friday.

"I wish I could get somebody to make my house payment for me, but that's not going to happen."
To which Ms. Kinney, the columnist, sensibly replies:
Well, it could happen. If, say, a company hoping to make some money agreed to do it in a contract.
Good point. Really, really good point.

Early warning or false hope?

WHO is again encouraging Asian countries, where most of the human cases of bird flu have occurred, to tighten up their ability to detect and report cases quickly.
"The window of opportunity for containment is very narrow, meaning rapid containment measures must be carried out at least two to three weeks after detection of a potential pandemic event," Omi said in a speech to the WHO's Executive Board.

"However up to now, only half of the reports for human H5N1 cases meet this target. Some reports have been received as late as one or two months after disease onset," he added.


The WHO says that if a pandemic strain of the virus emerges, it may be possible to halt human-to-human spread, but only if "fire blanket" measures including distribution of antivirals and restrictions on movement of people are taken quickly. (Reuters)
There is no doubt prompt reporting might be important as a way to gain preparation time, but it is hard to credit WHO's public stance that doing so might allow smothering and outbreak at its inception with a "fireblanket" of antivirals if the virus gains the facility to move easily from human to human. About a year ago two research groups (in the Ferguson in the UK and Longini in the US) reported computer model results suggesting that under extremely optimistic assumptions this might be possible. Not only are the requirements indicated by the model stringent and unlikely, but the models themselves have many built-in assumptions that have never been validated. Thus the predictions of either of the models may be wide of the mark in any direction.

Recently we had two examples of ways this won't work. Turkey is held up as a case where we now have prompt reporting of human cases. But in the last two weeks we had cases of a traveler and a journalist who had returned from Turkey to their home countries but became ill either in transit or on arrival. At this point it is said neither had become sick from H5N1. But authorities in both countries (Belgium and France) understood clearly either or both could have been bird flu cases, and if the disease were passing easily from person to person this scenario would be even more likely.

My guess is that WHO knows this and is holding out the hope that a pandemic could be stopped in this fashion as an inducement to member nations to improve their surveillance and reporting capabilities. I truly hope that is their motivation, because if they really think they have the remotest chance of stopping H5N1 once it has adapted to humans, they are badly mistaken and are likely to make bad policy decisions.

Good surveillance and reporting can sound the alarm weeks earlier, giving precious time for the rest of the world to get ready to mitigate the consequences. But it won't stop an inflluenza pandemic from happening.

Tuesday, January 24, 2006

More Halliburton negligence regarding US troops

When you're being shot at, roadside bombed and scared shitless, maybe bad water is not at the top of your list of worries. But if you are Dick Cheney's Halliburton KBR subsidiary and it's your job, your responsibility and the very thing you are being paid to do and instead you supply contaminated water to US service personnel--well, you supply the rest of this sentence.
Water supplied to a U.S. base in Iraq was contaminated and the contractor in charge, Halliburton, failed to tell troops and civilians at the facility, according to internal documents from the company and interviews with former Halliburton officials.

Although the allegations came from Halliburton's own water quality experts, the company once headed by Vice President Dick Cheney denied there was a contamination problem at Camp Junction City, in Ramadi.

"We exposed a base camp population (military and civilian) to a water source that was not treated," said a July 15, 2005, memo by William Granger, the official for Halliburton's KBR subsidiary who was in charge of water quality in Iraq and Kuwait.

"The level of contamination was roughly 2x the normal contamination of untreated water from the Euphrates River," Granger wrote in one of several documents. (AP via Yahoo News)
Bottled water was used for most drinking, but the allegedy contaminated water was used for everything else, and, as public health professionals know, probably for drinking too. That's always what happens with dual water supplies.

But Halliburton and the military say not to worry. Despite numerous reports of diarrhea and stomach cramps, the water was safe to drink, they say. But it doesn't say what the evidence is, and the concern here is that having a sewage outlet less than 2 miles upstream of the intake was a health hazard. Even strong chlorination of the water wouldn't have made it safe under those conditions because parasites like Giardia and Cryptosporidium have cyst forms resistant to chlorine. Nor would parasites show up with the usual water quality tests (which were abnormal, to boot).
[Water expert Ben] Carter said he resigned in early April after Halliburton officials did not take any action to inform the camp population.

The water expert said he told company officials at the base that they would have to notify the military. "They told me it was none of my concern and to keep my mouth shut," he said.

On at least one occasion, Carter said, he spoke to the chief military surgeon at the base, asking him whether he was aware of stomach problems afflicting people. He said the surgeon told him he would look into it.
We don't know if he did or didn't, although the implication is that nothing happened and no one was told about the problem.

But of course it's not about clean water, or electricity or clean food or security for Iraqis or Americans. It's about Freedom for the Iraqi People. And with so many reasons to be shitting your guts out, who is to say it's just from Halliburton's dirty water?

Excuse me while I interrupt

I thought I'd stick my nose, uninvited, into another conversation. Over at Scienceblogs there is a small forth and back between nosenada's Kevin Vranes and Aetiology's Tara Smith regarding the "crying wolf" syndrome and bird flu. I'll say at the outset my sentiments are completely with Tara, but the topic is important, so we will revisit it (see here, here and here) briefly. This is also an encouragement for all to head over to the new scienceblogs one stop shopping address where some of the blogosphere's premier science bloggers have set up new shingles. Aetiology is also up for a Koufax Best New Blog Award. For me it's a toss up between Aetiology and The Next Hurrah, the terrific political blog where my Flu Wiki colleague DemFromCT holds forth. The Wampum folks have wisely held off voting so we can actually take the time to peruse the nominees, so I'll do that before committing myself further.

Anyway, back to the topic at hand. It was precipitated by a post on Aetiology bemoaning a particularly ignorant piece at Huffington Post on why bird flu was just another BushCo scaremongering tactic. Written by Bill Robinson, who by the looks of his background and the content of his post wouldn't know a virus from a worm (I'm talking biological species here). It was a really dumb post and Tara was right to take him down.

Kevin still has a problem, though. It is the old "scarce resources" problem, competing needs, etc. Why bird flu, he asks, and not climate change or obesity or many other human and environmental needs?
But compounding the "many supplicants" problem for the infectious disease community is that this community is beset with a recent history of crying wolf. That's fine for a scientist who has no problem with the constant "corrections in understanding" inherent to science, but this kind of record drives a policymaker crazy. Policymaking is a system of taking in expert information from many quarters and coming up with the most tractable solution, which primarily must be politically tenable, if not practically and scientifically tenable (in that order).
Kevin's bio indicates he has a PhD in geophysics and has worked as a Senate staffer. Which explains some of his perspective. As a scientist he had to struggle with choices in a complicated environment where everyone wants something and they all have convincing arguments. Fair enough. This can give rise to genuine dilemmas.

But bird flu isn't one of them. Scientists are pretty much agreed about the possible magnitude of the threat although wary of making exact predictions. But this isn't one of the extremely low probability high consequence problems any more. For most who follow this situation closely, this is a borderline low to medium probability high consequence event. And that is a public policy emergency.

Kevin avers that there have been infectious disease false alarms in the recent past, and he cites West Nile and SARS. Neither were false alarms. West Nile, validating our fears, has become endemic throughout the US and is now one of the most serious vectorborne encephalititides. It has behaved just as predicted. SARS was considered a possible pandemic disease, true. It is fortunate it didn't turn out that way. But it very easily could have and constant vigiliance is required to prevent it actually becoming so. I don't think anything done in response to SARS was at all inappropriate, and if Kevin thinks so, he should say what it was. It did cost a lot of money, but that money was in lost revenue, not expenditures. Nor did policy makers do much about it. So there weren't major policy decisions at stake.

Kevin also seems to (mistakenly) think that there is an influential "infectious disease commnity" responsible for sounding the alarm. For the record, I am a chronic disease epidemiologist. My specialty is cancer. But like many of my public health colleagues I am extremely worried about the effects of a serious influenza pandemic because the consequences of a possible 30% to 40% absenteeism would ripple throughout society in very damaging ways if we don't plan for them. And because of this I am a strong advocate of thinking through the consequences in advance and preparing for them with effective workarounds. You can't do that if you don't think about them ahead of time. And you won't bother to do that unless you move it up the priority scale.

The approach we have advocated (and the one that is behind The Flu Wiki) is to strengthen the public health and social services infrastructure so that our society can be sufficiently resilient to withstand the shock of a pandemic with minimal damage. Any investments made to that end are multi-use and will pay off in many ways. We need to work on tools that allow neighbor to help neighbor. Trying to solve the pandemic problem by throwing money at vaccines and antivirals alone is both fruitless and barren with respect to the other important needs Kevin points to. But the policy makers with their hands on the levers of power aren't interested. they would rather spend money than mobilize the community.

So finally, I'd like to take a gratuitous swipe at today's policy makers. Kevin's version is of rational people beseiged by conflicting and competing demands. What's a poor CongressThing to do? But of course that's not how the system works -- or at least that's not how it's working. Whether we address or don't address bird flu versus energy, say, isn't about crying wolf or fear mongering or even choices. Sometimes it's about money. Sometimes it's about bribes. Sometimes it's about mistaken notions or helping a constituent. Sometimes it's hard to know what it's about.

But it certainly isn't a game played by the rules of logic's predicate calculus.

Monday, January 23, 2006

Wash hands after using

Here's something to consider as you sit at your keyboard reading this. From the Swedish publication PCs for Everyone a short piece entitled, Ny undersökning visar: Ditt tangentbord är skitigare än en toalettring, which loosely translated means: New Research shows your keyboard is shittier than a toilet seat.

The kind folks at PC För Alla tell us a lab they hired showed 33,000 bacteria per square centimeter on their keyboards, 265 times more than on a toilet seat. I read the article and I didn't think the writing was that shitty, but hey, my Swedish isn't that good. The bacteria were accompanied by 3100 fungi. The dirtiest keys were the return and spacebar.

Of course I don't know any data that says you can get disease from bacteria, fungi or viruses on a keyboard, but I wouldn't say it's impossible. The article says that while there might be many ways to clean your keyboard (like what?), PC for Everyone's advice for avoiding keyboard transmitted colds and influenza is the simplest: wash your hands after using.

Hat tip, Slashdot for alerting me to the article, which is here (of course, it's in Swedish).

". . . how can you not be for a cancer vaccine?"

While a vaccine against cancer sounds too good to be true, for the Christian Right it is too true to be good. Because there is such a vaccine for at least one cancer, cancer of the cervix, and the Christian Right doesn't like it.

The problem of course is one of their usual hangups, sex. Because cervical cancers are strongly linked to infection with the human papilloma virus (HPV), which can be and often is sexually transmitted. Papillomas are benign, wart-like tumors that can be found in lots of different organs. Many are caused by a family of viruses, the papilloma viruses, of which there are more than a hundred. About thirty of them are transmitted by sexual contact. Most of them don't cause malignant tumors (cancers) but about a dozen subtypes are strongly associated with a variety of cancers, including cancers of the soft palate, vulva, vagina, penis, anus and cancer of the cervix. It is this last connection which is most solidly established, to the point that we believe most cervical cancers are caused by papillomaviruses of particular subtypes. There is a good rundown at a National Cancer Institute site here.

Because HPV can be transmitted sexually, a major risk factor is having multiple sexual partners. And because infections can be silent or difficult to identify, the public health goal is to prevent infection in the first place. You know how the Bush administration wants to do this--abstinence. Public health professionals have nothing against this (except maybe for themselves!), but they are also realistic about the biological forces connected with reproducing the species. "Just say No" is not one of the more effective preventive measures.

But vaccines are. And what it is preventing--cervical cancer--is a nasty disease, killing a quarter of a million women each year. That's eighty World Trade Centers worth of deaths--each year. Now two companies have developed effective HPV vaccines. Good news? Not if you are the Family Research Council and other forced childbirth activists:
Conservative groups, including the Family Research Council, Concerned Women for America, and the National Abstinence Clearinghouse, have already suggested that vaccinating young girls would send them a message that premarital sex is acceptable. Christian-oriented Web sites have also been following objections to the vaccines more closely than mainstream news organizations.

[Dr. Joel Palefsky, a UC San Francisco professor who is an expert on HPV] characterized concerns that the HPV vaccines will encourage promiscuity as "nonsense."

"There's no evidence to suggest that the risk of HPV is a factor in someone's decision whether or not to have sex," he said. (He also pointed out the vaccine is somewhat of a boon to HPV education efforts since news coverage of its development is probably acquainting many people with the virus for the very first time. (SF Bay Guardian)
One of the new vaccines, Cervarix, is made by GlaxoSmithKline and is about to be marketed in Europe. The other, Gardasil, made by Merck, is working its way through FDA approval. Given FDA shenanigans that kept Plan B (the "morning after pill") off drugstore shelves against the advice of its own scientists, it is not sure FDA will act on this lifesaving vaccine in a timely manner, and even if approved, whether the government will include it in its official vaccine recommendations. These recommendations find their way onto state lists of inoculations required for school and also affect insurance reimbursements.
Alan Kaye, who became the executive director of the National Cervical Cancer Coalition after the disease killed his wife, told us he hopes critics of the vaccine back down. "I can tell you, with a ripped heart, that anyone who's ever battled cancer themselves or with family or friends would be for it," he said. "I mean, how can you not be for a cancer vaccine?" (SF Bay Guardian)
I guess we know the answer to that.

Sunday, January 22, 2006

No beef with Japan

Who said the US Department of Agriculture (USDA) has no backbone? They do. Unfortunately, it's in the wrong place. Ask the Japanese:
Japan announced Friday it would hold all American beef at ports until the U.S. delivers a report on how prohibited cattle backbone got into a shipment from Atlantic Veal & Lamb Inc. The measure came two weeks after Tokyo lifted a two-year ban on U.S. beef imports.


Once the most lucrative market for American beef, Japan imposed a blanket ban on imports in December 2003 after mad cow disease was first discovered in a U.S. cow.

The ban was lifted Dec. 12, but only for meat from cows ages 20 months or younger, which are believed unlikely to have the disease. The deal excluded spines, brains, bone marrow and other cattle parts thought to be at high risk of containing the ailment. (AP via Yahoo)
Japanese Prime Minister Koizumi, a US sock puppet, was coming under increasing criticism for caving to American cattle interests applied through the Bush Administration:
Japan imported about $1.4 billion worth of U.S. beef in 2003. It was unclear how much the country bought after lifting the ban, but a Kyodo News survey last month showed 75 percent of Japanese were unwilling to eat American beef even if imports resumed.

Criticism was also directed at Prime Minister Junichiro Koizumi's government for too hastily resuming imports.

"The government bowed to U.S. pressure and put President Bush's wishes ahead of the safety of Japanese consumers. I consider that a huge error of judgment," said Yukio Hatoyama, secretary-general of the main opposition Democratic Party of Japan.

Koizumi ordered the resumption of imports based on recommendations made by an expert panel after several U.S. officials, including Bush, expressed growing impatience with the ban.

The premier has defended the decision, saying it was based on scientific grounds.
I don't know what "scientific grounds" Koizumi was referring to, but if based on the likelihood of neural tissues winding up in the Japanese beef supply they got it wrong. But since we know what kind of "science" the Bush Administration likes (the kind that comes up with their answers), maybe Koizumi is telling the truth. It was based on "Bush science."

Meanwhile, the eventual result of paying lip service to "sound science" while simultaneously ignoring it is going to cost Bush's cattle baron patrons dearly in the Japanese export market. Maybe they don't care, because they can sell their potentially tainted beef here to fast food chains. Who knows?

But if they keep this up and BSE appears again in US animals (or worse, people), they'll soon find that burgers will be rare.

Freethinker Sunday Sermonette: Kate

I like old movies and sometimes watch them on Sundays. While I'm not a big Katherine Hepburn fan, I do like her well enough. But then I don't know much about her, although the glimpse that emerges in Scorsese's movie The Aviator is intriguing.

I ran across this quote, uttered towards the end of her long life.
In an interview in the October 1991 Ladies' Home Journal that was advertised as her "most candid" ever, Hepburn said,

"I'm an atheist, and that's it. I believe there's nothing we can know except that we should be kind to each other and do what we can for each other."
[LHJ, October 1991, p.215; via Celebatheists]
My sentiments. Exactly.

Saturday, January 21, 2006

Talking Turkey with the neighbors

Turkey is unhappy with its neighbors, who are undoubtedly unhappy with Turkey. With 21 human cases and outbreaks in poultry throughout the country, Turkey is a focus for infection on the border of Europe. But they doubt they are alone:
Turkey said on Friday its battle against a bird flu outbreak in people and poultry was being made harder by the failure of neighboring countries to admit to having the deadly H5N1 virus.

"It is unofficially known that this illness exists in our neighboring countries which are ruled by closed regimes, but these countries do not declare this because of their systems," Agriculture Minister Mehdi Eker told a news conference.

He did not name the countries but Iran and Syria are two likely targets of the criticism. Health experts are concerned neighboring countries are not taking enough preventive measures against bird flu. (Reuters)
And while states like Iran have not admitted to any infected birds, they have culled tens of thousand of them in a strip 15 km deep into their own territory on the borders with Turkey. The Kurds in northern Iraq are also terrified, but do not admit to any cases:
"We are afraid and in a state of high alert in the face of what could be a time bomb," says Azad Ezzeddin Mulla Afandi, the chief agricultural official for the Kurdish Democratic Party (KDP), one of two Kurdish parties running the northern provinces, which provide a large amount of poultry and eggs for the rest of the country.

"Despite all the precautions we have taken, we are terrified that the disease will appear here," he says.


Imports of poultry from Turkey were banned in October, while the trade of live chickens in Kurdistan itself was outlawed last week.

"Strict orders were given to poultry farmers to install basins at the gates of their farms to decontaminate vehicles going in and out," says Afandi.

According to him, these measures are being carried out not just in the provinces of Arbil and Dohuk, which are under KDP control, but also in Suleimaniyah, the Kurdish rival run by the KDP's sometime rival, the Patriotic Union of Kurdistan (PUK).

The two provinces, which are close to the parts of Turkey that have reported cases of bird flu, are also major producers of eggs and poultry, supplying much of the Iraqi market. (via Kurdmedia)
It is more than plausible that the virus is already in Iraq, as we noted in a post yesterday. Both Iraqi government and WHO sources are discounting the possibility, but samples have been sent to the UK reference lab to confirm the 14 year old girl didn't have the disease. She came from a town near the Turkish border where bird flu is known to exist in poultry flocks and where Turkey's first human cases were discovered. WHO is accepting word of the Iraqi government that she died of heart disease, although they admit that hasn't been confirmed (Dow Jones). WHO seems very quick to discount what, on its face, is a highly probable case of bird flu in this unfortunate young girl.

Which brings us back to Turkey's suspicions. Is Iraq one of those neighboring countries covering up a bird flu problem? If so, it couldn't happen without US cooperation and collaboration. But US authorities have been silent on the issue. One wonders about the effect on US opinion on the war if news emerged there were human cases of bird flu in Iraq.

I would be more inclined to accept the word of WHO and Iraqi authorities if it were based on more solid evidence (see previous post). WHO seems to be taking everyone's word for the fact it isn't bird flu. If it turns out the true diagnosis is H5N1, a scenario that has played itself out numerous times in the past, this will be yet another blow to their credibility. Prudence alone would dictate more caution in WHO's remarks, unless they are under other pressures.

I guess I'm with Turkey on this one. I'm suspicious.

Friday, January 20, 2006

Background science for the Turkish mutations, IV (conclusion)

In the first three posts of this series (here, here and here) we have given an overview of what the cell surface looks like to the influenza virus and set out the ideas and vocabulary virologists use to discuss the sugar molecules on the cell's surface the virus hooks on to, the viral receptor. The many possible configurations of sugars on a cell's surface serve important biological functions, like cell to cell communications and anchoring, structural uses and as receptors for important biological molecules the organism needs to function properly. These surface sugars are essential to the internal communication of the organism. But other organisms can also take advantage of them and that is how pathogens like viruses, bacteria and parasites find their way to the particular tissues and cells they need for their life cycles. Viruses use these sugar signposts as receptors to grab on to a cell in preparation for entering it and hijacking its genetic replication and protein manufacturing machinery to make new viruses.

At the risk of belaboring the point, here is yet another cartoon picture that gives the general idea (I'd credit the source if I could find it):

This picture shows the cell surface structures we have been talking about. From the first post you can see the cell membrane (the wall around the cell, also called the plasma membrane). It is a lipid bilayer, seen here as the blue and yellow archway from lower left across the picture to lower right. The blue area below it is the inside of a cell. The blue balls with yellow sticks (backed up against each other) are the phospholipid units that make up most of the cell membrane structure, but there are also some glycolipids, where instead of the blue balls you see a string of colored hexagons, which are sugar units. You see one at the left in the archway. In the first post we also talked about proteins which are anchored to and through the cell membrane. These also often have sugars attached to them, so they are called glycoproteins. There is an example second from left. The string of attached sugars is called an oligosaccharide. See the first post for details.

Items (b), (c), (d) and (e) in the picture show ways that viruses, toxins, bacteria and lymphocytes (a white cell that is part of the body's immune system) interact with glycolipids, glycoproteins and in one case, (e), an odd shaped protein that has no sugars on it but which interacts with the sugars on a glycoprotein of the lymphocyte. One of the things to notice in this stylized depiction is that the docking of the virus, the toxin or whatever, has a sort of "lock and key" aspect to it. The lock is usually a protein or glycolipid with a chain of sugars on it. The "key" is usually a protein that is shaped in just such a way that it can fit together perfectly with the sugar chain. When that kind of "perfect fit" occurs it will set in motion biological processes, often mechanisms that allow the "key" to enter into the cell or make the cell do something like manufacture a protein. Hormones work this way. They are part of the body's internal signaling system, where the signals (the hormones) travel through the blood and activate particular cells through receptors those cells have on their surfaces. Cells that don't have the receptors are unaffected. Neat system.

In the picture you can see how a virus might exploit this biological mechanism for its own purposes. If it can mimic the key of a receptor that serves another natural function (and we know only a few of these functions) it might be able to get the cell to do something useful for the virus, like set in motion processes which take the virus into the cell. But these mechanisms have to be very precise, and just like a real lock and key, if one of the bumps on the key isn't exactly right it won't work. Thus the influenza virus looks for very special sugar combinations on the cell surface. We spent most of the second post and part of the third discussing the specific signpost the virus looks for on the surface of a cell it will try to infect. These are the α-2, 3 and α-2, 6 linked Neu5AcGal two-sugar units you hear about in the flu world.

Today we look at the other side of the interaction, not the "lock side" but the "key" side, that is, the protein on the virus that fits exactly to the α-2, 3 or α-2, 6 linked Neu5AcGal units. As we noted in the third post, things now start to get really hairy. This double sugar unit is pretty specialized but it is still relatively common and is found in many species. We now know that there is a still finer structure, produced by the sugars next in line in the chain, an effect we hadn't appreciated before. Thus the next sugar might determine whether a bird virus that likes Neu5Ac α-linked to galactose through carbon #2 on Neu5Ac to carbon #3 on galactose (i.e., an α-2, 3 Neu5AcGal double sugar unit) will be more likely to infect a duck or a gull. So the basic idea is simple but its details certainly are not. What this means practically is that we still have a lot to learn about the consequences of changes in the key protein for what kind of lock it fits.

Back to the flu virus. The "key" protein, as most of you know, is the hemagglutinin (HA) protein spike that sticks through the surface of the virus. There are a lot of these spikes and they cover the surface pretty densely. Lots of "keys" to grap on to the right locks (α linked Neu5AcGal units plus whatever else might be involved we don't know about yet). The HA protein different parts and the outermost of them is called HA1 and it has a part that matches (or doesn't match) the cell surface receptor.

Now proteins are linear strings of amino acids, one linked to another, the sequence determined by the virus's genetic code. If there is a change in the genetic code, the viral protein will have a different sequence of amino acids. A change in the code is called a mutation. What is the effect of changing the sequence of the amino acids in the HA?

This turns out to be a difficult question, in general, although we know the answer in many particular cases and we are improving our abilities to predict what will happen by using computer models. One of the problems is that while the protein is one long string, like a real string it can fold into a huge number of different shapes. Proteins can be globular, ribbon shaped, elongated, threadlike, oblong or many other shapes, as the picture of the pink objects in the picture above shows. Predicting what shape a protein will take when you change the order or composition of the amino acid sequence is difficult. To show you how complicated the protein shape can be, here is a depiction of an HA protein:

The receptor binding site is at the top, indicated with an arrow. You can see how complicated this is. And because the way the long protein chain is folded, amino acids that are very far from each other in the sequence can wind up near each other after the folding is done or wind up in a place that the shape of one amino acid might hinder binding of the Neu5AcGal unit but another one might not -- or something in between.

When we look at the sequence of amino acids in avian flu viruses, the ones that bind efficiently to α-2, 3 linkages, we find that amino acids at certain positions are important. One of these is the position numbered 223 (amino acid 223 from the start of the whole sequence; this isn't exactly correct because there are some subtleties in the numbering, but this isn't too important for our purposes). When this is the amino acid serine, the HA binds nicely to α-2, 3. But if it changes to asparagine, it switches its allegiance to α-2, 6 linkages.

Mutations are designated by the giving the amino acid before the change followed by the position and then the amino acid after the change. Hence this mutation would be designated S223N, where the S is abbreviation for serine and N the abbreviation for asparagine (you can find the standard amino acid abbreviations here). S223N is one of the mutations seen in the Turkish isolate. In other words, it is a mutation that makes it easier for the viral HA to bind to α-2, 6 Neu5AcGal, characteristic of human influenza viruses. It is not new, having been seen twice before, in a father and son in Hong Kong in 2003 and a fatal case in Vietnam last year (see Declan Butler's piece in Nature).

What Butler also revealed in Nature a few days ago, however, was that there was another mutation in the HA protein, at position 153. WHO didn't mention it because, as their spokeswoman said, "it is not clear what role this particular change plays." From this description we don't know what the mutation was, but this position is adjacent to both the receptor binding site and the site that antibodies against HA attack, i.e., it is related to whether the host's immune response can protect against the virus. Evasion of antibody response has been associated with a change at or near this site achieved by attaching a sugar there. This has been seen in viruses from Hong Kong, Indonesia, Thailand, Vietnam and Yunnan, China (Li et al. in Nature 430, 209 - 212, 2004). While WHO is correct to say the significance is not known in this case, the fact that there is a change at or near a crucial area is additional cause for concern.

Butler also reported that WHO had found a third mutation in the Turkish viruses, this one in another gene which we haven't discussed. It is associated with increased virulence in mammals, including humans, and has been found in migratory birds. Butler's news piece says this mutation might make the virus more amenable to a lower temperature, such as might be found in the nose. I don't know what data backs this up. Perhaps a reader can supply a cite. And while this mutation (E627K in the PB2 gene) has also been seen before, this is the first time all three of these mutations have been seen in the same virus.

The Nature piece concludes that there is still much to learn:
Establishing what effects these changes are having on the epidemiology of the current outbreak is a top priority for research teams working in Turkey. "We must learn more about the mild cases and be absolutely sure of whether these viruses are behaving differently from those we have seen elsewhere," says Hay. "It is early days in terms of what we know about the viruses causing these infections."

Researchers are sequencing more strains from the Turkish cases, to see whether they share the mutations and to check for further changes. Samples were expected to arrive in London on Wed 18 Jan 2006, after being held up for more than a week in Turkey because of the Eid-ul-Adha holiday period.
While it is the beginning of an evolving story of the Turkish mutations, it concludes our odyssey through some of the basic science behind them. Some might feel it was been one long shaggy dog story. We could have gotten there faster and more easily by just summarizing the last couple of paragraphs. But then we wouldn't have had the opportunity to survey some of the science. By doing so we had the chance to set out a lot of the basic vocabulary used in the world of research on flu, which because of events, is moving directly from lab bench to bedside.

Thursday, January 19, 2006

Iraq bird flu "all clear" is cloudy

Here's the scenario. A 14 year old girl lives in Kurdish Iraq near the Turkish border next to a lake that is a stopping place for migratory birds and some of the chickens her family kept in the house died. She was admitted to the hospital in Sulaimaniya with a severe lung infection after a two week illness and died the next day.

Bird flu? Authorities are now saying, no, after tests carried out by Irasqi health authorities were negative.
A group of Jordanian doctors arrived at Sulaimaniya hospital to help conduct further tests. But Dr Najmuddin, head of the Sulaimaniya health department, said there had been no cases of bird flu found, either in humans or birds. referring to Tijan, Dr Najmuddin said: "After she arrived at the hospital and after she was tested, symptoms were discovered that indicated that it wasn't bird flu. Then the veterinary division confirmed that they had tested lots of chickens and birds in the area where the incident took place, and there were no cases of bird flu."

Iraqi doctors are already overwhelmed by victims of insurgent suicide bombings and shootings. Iraq has been trying to secure porous borders with its neighbors, particularly Syria, since 2003 to stop the flow of foreign insurgents but with little success. Tribes living along border areas also make a living from smuggling goods.

Health officials say they need more money and expertise (Reuters)
WHO is also saying it is not H5N1, but dosn't say on what basis:
"It has been investigated and discounted. It is not an H5N1 (bird flu) case," spokesman Dick Thompson told Reuters.
The dismissal of bird flu seems to be based on three things: the claim that no birds in the vicinity tested positive for the virus; that the victim developed symptoms the doctors didn't think were typical of bird flu; and some kind of test was negative. We now have enough experience with this disease to know that none of these things singly or collectively are sufficient to rule out H5N1 infection, especially in view of the medical and environmental history. Samples are supposedly being sent to the UK WHO reference laboratory for confirmation, but there is no information yet as to the results or even if the samples actually got there.

Human cases of bird flu in a war-torn country with no effective medical or civil infrastructure and overwhelming needs is a classically fertile ground for epidemic disease. There are also 160,000 foreign troops there. Because the safety and security of US troops in Iraq is a sensitive political topic for a beleagured President Bush, the appearance of bird flu could have an unpredictable effect on American public confidence and might further shake already shaky support for the war. Given the striking medical scenario, the limited ability of the area doctors to confirm or disconfirm the diagnosis and the political domestic political dimensions, I will confess I am not completely confident this isn't a cover-up by virtue of a weak an insincere investigation.

So pardon me for not believing the "all clear" signal yet. Convince me. Give me the results from the UK reference lab.