Friday, June 09, 2006

Effect Measure has moved!

We have moved the blog, at the invitation of the folks at ScienceBlogs, publishers of Seed Magazine. is fast becoming the premier venue for science-oriented blogs and we couldn't pass up the opportunity to join some wonderful bloggers already there and new ones in our cohort. At Sb you'll find Pharyngula and Aetiology, already ensconced, and Coturnix's new blog and Mad Mike the Biologist arriving with us. Plus many more. Quite a varied selection and all of high quality. Several have already established themselves as A-list sites among the science blog community. We were pleased to be asked.

To our regular readers (now numbering in the thousands) the only things that will change are the address (new URL: and the appearance. We will be on a MovableType platform instead of Blogger, which will give us the ability to have categories and subcategories. Commenting will now have a "Preview" function, so you won't have to post again to correct a typo. There are probably a bunch of other things that will be enhancements we haven't figured out yet, too. So it's a big plus as far as we are concerned, and we hope you will think so, too.

There are still some 1200 posts on this site, which will remain here. It isn't feasible at the moment to move all the posts and archives over to the new site. Unfortunately there is no way to categorize them here. You can still find things by using the Google Bar in the upper left of this site or Googling the subject with the words Effect Measure (e.g., Googling, biodefense Effect Measure, will get you to our post on biodefense, way back when).

If things get a little glitchy in the transition, we'll use this as a fallback site until things are straightened out, so if you have trouble you might check back here to see if it is a migration problem. We're not expecting it, except that we expect it. That's the nature of the world, especially the computing world.

We enjoyed our time here on Blogger (well, mostly; there were a lot of pesky outages but hey, it's free hosting). If you want to start your own blog, it's incredibly easy. It can also be dangerous if you have a tendency to obsessive compulsive disorder, so be warned. Just go over to and click the button that says "Create a Blog." We did it on Thanksgiving Day of 2004, just to see what it was like. We're still here.

We're already at the new address and that's where Effect Measure will be from now on. Our first post introduces ourselves to the new neighbors. So bookmark the


and come on over.

Update, 2:23 pm EDT: heh, heh. Oh, well. First glitch. Entry text is up on the first post (Housewarming) but no extended entry (Read More). Have a query in to the Sb tech folks to fix. Moving is always a pain.

Update, 2:31 pm EDT: Temporary fix. No extended entry, just the whole post on the page, like you are used to here.

Reader beware

When you read news reports, you have to be circumspect. There are some excellent reporters on flu but most don't know much about it and have a tendency to transcribe whatever some official spokesperson says. Even large news organizations depend on local stringers who send in bits and pieces they think might be of interest.

A good example comes this morning in the form of two short filler pieces, one from Associated Press (AP) and one from Bloomberg News Service. Both report the failure of a WHO reference lab (neither tells us which one) to confirm H5N1 in a seven year old girl who died June 1 near Jakarta. Her ten year old brother had died three days earlier with similar symptoms but no specimens were obtained. Contact with sick poultry was alleged. "Local tests" of the little girl were positive for H5N1. Who does the local tests is not stated, but it is my impression the US Naval Lab NAMRU2 is involved and they are technically expert and all previous local tests have been confirmed for H5N1 by WHO reference laboratories. Apparently that isn't the case this time.

Here is the AP version, run under the headline,"Indonesian girl's flu death questioned," (RSS headline, "WHO lab indicates Indonesian girl did not die of bird flu"). The piece cited the Indonesian Ministry of Public Health:
A lab approved by the World Health Organization said a seven-year-old Indonesian girl who tested positive locally for bird flu did not have the virus, a senior Health Ministry official said Friday.


"This is the first time local tests came back positive and Hong Kong laboratory tests negative," said Kandun, adding WHO needs to carry out new tests to reconfirm its findings. (AP via CANOE Network, Canada)
Believing the Indonesian Ministry of Health on bird flu these days is like believing Donald Rumsfeld on torture.

Here is the Bloomberg version, run under the headline "Bird flu tests are inconclusive on Indonesian girl: WHO":
Confirmatory tests for bird flu on a 7-year-old girl in Indonesia were inconclusive and more specimens will need to be tested, a World Health Organization spokeswoman said Friday.

"Test results are pending further analysis, and more samples are to be collected" for testing by a laboratory in Hong Kong, said Sari Setiogi, a spokeswoman with the WHO in Jakarta. (Bloomberg via Jakarta Post)
In this case it is pretty clear which is the more accurate report. But if you'd only seen the AP report and didn't read it carefully (it is only a small filler piece) you could easily have gotten the impression that WHO had determined the Jakarta case was not bird flu. So far, that hasn't happened (although it may). There are many reasons why a truly positive test may be inconclusive.

The internet brings us information of epidemiologic interest at unprecedented speed nowadays. But the usual cautions apply: caveat lector.

Banned in China

Indonesia is a known problem spot for bird flu. An impotent central government, infected poultry everywhere, a huge but far flung population on thousands of small islands, and a poor and primitive health care system. Not a pretty picture.

But China may be as bad as Indonesia. A long story in Asia Times online is well worth reading. I'm surprised the reporter isn't in jail for revealing "state secrets" (infection with H5N1).
Having learned a bitter lesson from covering up the severe acute respiratory syndrome (SARS) epidemic in early 2003, the central government of China now is said to be taking a more positive, responsible attitude in dealing with avian influenza, or bird flu. But that hasn't filtered down to the provinces.

As the market economy has taken root in China, the country has become increasingly decentralized. Because of this, Beijing's tough orders regarding the prevention of a bird-flu outbreak may not necessarily be carried out at all levels. Overwhelmingly concerned with economic growth, some local officials still tend to cover up any outbreak of bird flu, defying Beijing's order to report new cases immediately.

Beijing has punished some local officials for their incompetence in dealing with bird-flu outbreaks. For instance, in May it was announced that five officials in Dazhu county in Sichuan province had been sacked for of dereliction of duty because they did not report and contain the local outbreak in time.

But during an investigative reporting trip to three locations in China, Asia Times Online found that in rural areas, local officials and residents really don't like any action that might expose a possible bird-flu outbreak, fearing the damage it would do to the economy. Because of this, they hate individuals who dare to inform authorities of any bird-flu case. (Asia Times online)
There follows chilling examples of cover-ups, retributions and missed diagnoses, not specifically at the hands of the Chinese government, but of the people in the rural countryside. It isn't just ignorance. It is deliberate cover-up. We posted in December about one of these instances, retribution against a local farmer who notified authorities there was infected poultry in his village. The Asia Times story has a follow-up and additional details. They aren't pretty, either. The reasons the whistleblower, Mr. Qiao, has become a pariah aren't hard to find:
Owing to wide coverage of Qiao, the poultry market in Gaoyou has slumped. "The price of eggs has dropped from 3 yuan [37 US cents] to 1 or 2 yuan per 500 grams, chicken prices are also down from 5 yuan to 2 yuan for half a kilo, even below the raising cost," Chen noted. "So no one wants to raise chickens now, even though chicks are free."


More than half a year has passed since the bird-flu epidemic in Tianchang city, Anhui province, was exposed to the outside world. A recent visit by ATol found residents there still eager to see their hated local informer turned into a criminal defendant, while little attention has been paid to prevention of a possible return of the epidemic.

Ducklings and goslings roamed all over Liangying village, showing that no one was paying attention to the Animal Epidemic Prevention Law. Among other things, the law stipulates a six-month ban on breeding poultry after an outbreak, and the current ban only expired on May 24. "We started raising poultry after the Chinese New Year, and village leaders never stop us," a local farmer said.

The poultry population of Liangying village and the surrounding area is growing again, and some households even raise birds, dogs and lambs together, despite warnings to separate them to prevent cross-breeding of diseases between various kinds of livestock. "We're poor, and raising poultry is the only way to enrich our tables and honor guests," an elderly farmer said, herding a gaggle in the fields.

All these words and scenes reveal a complete and willful ignorance of basic precautions against a possible revival of bird flu, as well as a deadly apathetic attitude toward epidemic prevention that is shared by the local authorities and residents alike.

To the local farmers in Tianchang, Qiao was just a "bad guy". Because of his tip-off, the government decided to destroy all reared poultry in the neighborhood, but the state compensation did not suffice to cover the colossal loss. This seething resentment against Qiao even extends to his his fellows from Gaoyou. "Gaoyou guys dare not come here to trade anymore. They are afraid we will beat them up," grinned a local Tianchang farmer.
The reporter goes on to tell the story of Li Juhua and her 6 year old son Ouyang, so far China's youngest bird flu case. Ouyang was diagnosed with bird flu, received treatment, and recovered. His mother was never diagnosed, although her symptoms were similar. She took sick first and died. The onset of symptoms was several days apart, suggesting possible human to human transmission in this small two person family cluster. The family details are revealing:
Last December 21, the family had dinner to celebrate the winter solstice. They were not rich enough to kill a live bird and could afford only dead chickens dumped by owners, which the poor collect and preserve for festivals.

The wife, Li Juhua, soon felt sick and was taken to the county hospital on December 23. At that moment, a grisly thought occurred to Ouyang that his wife might have been infected with bird flu, as he had watched news of the epidemic on television. Yet none of the doctors heeded his fears. Li died the next day, to which the hospital only gave a single-sentence explanation citing some rare dermatological disease.

A few days later, the son developed the same symptoms as his deceased mother. At the county hospital, the diagnosis given was tuberculosis. Ouyang dared not take a chance with the county hospital again and took the little boy to a hospital in Chenzhou, where the medical staff were concerned and referred the child to Changsha. There his affliction was finally diagnosed as bird flu infection.
The mother's quick death induced the father, now a widower with two young children, to get his son to the better equipped hospital in Chenzhou. Otherwise Ouyang would be another undiagnosed, faceless death instead of the China's youngest case. To date the mother's case has not been discussed or reported by authorities.

The local attitude is clearly a difficult problem for Chinese authorities. But the central authority's claim to openness on bird flu has more problems than this. The Health Ministry and the Agriculture Ministry are not always on the same page regarding transparency. And information is still carefully managed in China.

If you live in China you are not likely to read that information is managed, however. Not even on Effect Measure. We are banned in China.

Thursday, June 08, 2006

Transgenic chicken paradox

Maybe if I didn't spend a lot of time thinking about bird flu and chickens I wouldn't have noticed this. But I did, so I bring it to you.
Origen Therapeutics announced today that it has succeeded in developing a robust and versatile technology for genetically modifying chickens that, for the first time, puts avian transgenics on a par with transgenic mice. The company made the announcement in conjunction with the publication of an article this week by Origen scientists and a collaborator from the University of California, Davis on its transgenic technology in the journal Nature. Using the new technology, Origen can, in principle, make any genetic modification desired to the chicken genome, including the insertion of genetic elements for the production of human therapeutics and the modification of the chicken immune system to produce novel human sequence polyclonal antibodies. Moreover, the new technology opens up the possibility of producing chickens with enhanced agronomic traits, including resistance to avian flu. (Press release via rxpgnews)
The technology uses, interestingly enough, chicken embryonic stem cells. President Bush has yet to outlaw chicken stem cell research, so this is legal (so far; but you never know). The idea is to modify the chicken genome to produce drugs and biologicals.
"We believe a transgenic chicken system offers a number of advantages over either plant or other transgenic animal systems for protein production. Besides the ability to produce antibodies with enhanced cell killing properties, the time from antibody identification to production in eggs is a matter of months, the purification of proteins from eggs is relatively simple, and good manufacturing practices have long been established for vaccine production in chicken eggs. Moreover, the overall cost of facility and operations is a fraction of that associated with fermentation methods of manufacture. The ability to readily create transgenic chickens through this technology, and then to scale up production through conventional breeding further adds to the practicality of this technology for large-scale production of therapeutic proteins," [said Robert Kay, Ph.D., Origen Therapeutics president and chief executive officer].


"This work addresses a major biomedical issue -- how to produce antibody-based medicines in an easy, cost-effective way," said Matthew E. Portnoy, Ph.D., of the National Institute of General Medical Sciences, which partially funded the research.
The irony of this "breakthrough" is just too delicious. Consider. We are already terrified of one biological agent produced in chickens, H5N1 viral protein and its genetic material (in the form of a virus). We cannot rely on egg-based technology to make another badly needed biological, a vaccine against the first chicken-produced biological, so we are desperately trying to move to cell-culture techniques where the vaccine will be produced in large fermenters because it will be quicker and cheaper. Now we have the proposal to use transgenic chickens to make still other biologicals with an egg-based technology because using fermenters is too costly and not fast enough.

Go figure.

In defense of Juan Cole (as if he needs it)

I'm an academic and a blogger. So I feel compelled to come to the defense of another academic and blogger, the estimable Juan Cole of Informed Comment. Cole's blog on contemporary Middle Eastern affairs is one of the most highly regarded on the net. Unlike many of the pundits and experts confidently holding forth about the Middle East, Cole actually reads and speaks the languages of the area and is an acknowledged scholar of the subject. By all reports he is scrupulous in his scholarship (which is very specialized) and respectful and fair with his students at the University of Michigan. His classroom is a safe place for expressing ideas.

But he is no shrinking violet. Cole's blog is accurate in its facts, well documented and brutally honest. It is a very political blog, but that is the nature of blogs (including this one). He has been straightforward in criticizing the monumental incompetence that has gotten the US into a catastrophic war in Iraq and fearless in calling Israel to account for its often brutal occupation of the Palestinian state. These two things have earned him the hatred of the neocons, who brought us the Iraq mistake, and the Israel lobby, for whom no criticism of Israel is ever allowed.

Earlier this year Cole was recommended for a tenured position to teach modern Middle East affairs at Yale. The Yale Sociology and History Departments separately approved the offer. This would usually be the end of the matter. But last week, in what was described by some Yale faculty members as a highly unusual move, the University's tenure committee turned the appointment down. The central issue, according to the newspaper The Jewish Week (who described Cole as one of the country's top Middle East scholars), was the political commentary on his blog.
Cole, while refusing to comment on the tenure committee’s vote, told The Jewish Week he believes that “the concerted press campaign by neoconservatives against me, which was a form of lobbying the higher administration, was inappropriate and a threat to academic integrity.

“The articles published in the Yale Standard, the New York Sun, the Wall Street Journal, Slate, and the Washington Times, as part of what was clearly an orchestrated campaign, contained made-up quotes, inaccuracies, and false charges,” he said. “The idea that I am any sort of anti-Jewish racist because I think Israel would be better off without the occupied territories is bizarre, but I fear that a falsehood repeated often enough and in high enough places may begin to lose its air of absurdity.” (The Jewish Week)
The orchestrated attack, involving op ed pieces and letters to large donors to Yale who are Jewish, had the desired effect. Now an embarrassed Yale is trying to rewrite the history of the episode. First, anonymous sources are maintaining that Cole's scholarly work is too specialized to be of general interest. But here's what the Search Committee said:
Political science professor Frances Rosenbluth, who was part of the search committee, said that Cole emerged as a clear choice.

“The committee read his work very thoroughly, in conjunction with the work of other scholars,” Rosenbluth told The Jewish Week. “We interviewed other people, we sent out letters to the field of contemporary Middle Eastern studies, and [Cole] is very highly regarded as a scholar. That’s why the committee made its recommendation.” (The Jewish Week)
They are also floating the absurd idea it wasn't Cole's blog politics but his collegiality that was at issue:
Second, the source continued, Cole appears to lack in collegiality, as his penchant for combative blog entries and personal spats with detractors might make him an unnerving fixture on Yale.
That really made me laugh. I've seen Cole many times on PBS's Newshour and he is invariably low key, respectful and non confrontational when presenting his views. Moreover if a penchant for combative blog entries were a criterion for employability, the Reveres and most of the commenters who make this such an interesting place would be unemployed.

Not one of Yale's better moments, although I am sure alum George W. Bush approves.

Wednesday, June 07, 2006

Chrome plated fraud

In December we posted on a Wall Street Journal article about how a high priced corporate consultant (I hesitate to say, scientist) essentially ghost wrote an article which he signed for a now deceased Chinese doctor, apparently retracting earlier work the doctor had done showing exposure to chromium-VI was a risk factor for cancer. The orignal paper was some of the work relied on in the famous Erin Brockovich case featured in the movie starring Julia Roberts.

The Environmental Working Group, one of the environmental movement's more effective watchdog groups was all over the case and their efforts are bearing spectacular results.
In a real-life epilogue to "Erin Brockovich," a respected medical journal will retract a fraudulent article written and placed by a science-for-hire consulting firm whose CEO sits on a key federal toxics panel. The retraction follows a six- month internal review by the journal, prompted by an Environmental Working Group (EWG) investigation.

The July issue of the peer-reviewed Journal of Occupational and Environmental Medicine (JOEM), the official publication of the American College of Occupational and Environmental Medicine, will carry a retraction of a 1997 article published under the byline of two Chinese scientists, JianDong Zhang and ShuKun Li.

The article appeared to be a reversal of an earlier study by Zhang that found a significant association between chromium pollution of drinking water and higher rates of stomach cancer in villages in rural northeast China. Since its publication, the fraudulent article has influenced a number of state and federal regulatory decisions on chromium.

"It has been brought to our attention that an article published in JOEM in the April 1997 issue by Zhang and Li failed to meet the journal's published editorial policy in effect at that time," says the retraction, signed by JOEM Editor Dr. Paul Brandt-Rauf and obtained by EWG. "Specifically, financial and intellectual input to the paper by outside parties was not disclosed."


Under the state Public Records Act, EWG obtained and posted online documents from California regulators and court records that showed the article was actually the work of ChemRisk, a San Francisco-based consulting firm whose clients include corporations responsible for chromium pollution. The documents and the story they outline are at


ChemRisk's founder and CEO, Dennis Paustenbach, is a Bush Administration appointee to a U.S. Centers for Disease Control advisory panel on toxic chemicals and environmental health. His firm holds a lucrative contract with the CDC and the Energy Department to investigate radioactive and toxic releases from Los Alamos National Laboratory in New Mexico.

In this case, ChemRisk was working for Pacific Gas & Electric (PG&E), a San Francisco-based utility whose dumping of the industrial chemical chromium-6 had contaminated the drinking water of the small town of Hinkley, Calif. Hinkley residents' lawsuit against the company, which PG&E eventually paid $333 million to settle, was the basis for the film "Erin Brockovich," starring Julia Roberts as the legal investigator who uncovered the dumping.

PG&E hired ChemRisk to conduct a study to counter Hinkley residents' claims of cancer and other illnesses from chromium-6 in their water. ChemRisk tracked down Zhang, a retired Chinese government health officer, and paid him about $2,000 for his original data. ChemRisk distorted the data to hide the chromium-cancer link, then wrote, prepared and submitted their "clarification'" to JOEM under Zhang and Li's byline, and over Zhang's written objection. (Environmental Working Group)
This affair is not a tempest in a teapot. It has had real life implications for all of us. California regulators used the fraudulent paper to revise chromium-VI standards for drinking water, on recommendations from a panel upon which Paustenbach sat. And the EPA also used it to allow continued use of chromium as a wood preservative. CDC is refusing to remove Paustenbach as a member of the toxics advisory board or ChemRisk as a contractor.

EWG's coup comes on top of its recent victory to force DuPont to disclose drinking water tests on the teflon ingredient perfluorooctanoic acid (PFOA; posts here, here and here) and an earlier unmasking of ABC hack reporter John Stossel, whose use of fraudulent (non-existent) test results in one of his hatchet jobs (on organic food) forced him to make an on-air retraction and apology.

Kudos (once again) to EWG. I'm glad these guys are on our side.

WHO, part V: end of the beginning

[This is the last post in the series about WHO (part I, part II, part III, part IV). We try to sum up where the story has (unexpectedly) brought us.]

For everyone reading this series of posts wondering where we were going, we were wondering, too. The Reveres started blogging because for us, "writing is thinking," and we believed strongly then and continue to believe now that the progressive public health movement did too little thinking and too much sloganeering. We started writing as a way of trying to think things through, doing it publicly because we beleived there was much raw brain power "out there" to help us move things forward. We haven't been disappointed, despite the occasional aggravation that goes with asking people what they think and giving them an opportunity to answer.

The WHO series originated because of our distress over criticisms leveled at WHO regarding their transparency, their honesty and their motives, especially the issue of sequence release and their incomplete recording of case data. If you read the comments here you will find us defending WHO and flu scientists and trying to parry accusations we felt were unfair and misdirected. It was our thought that one way to have a more persuasive response was to explain where WHO fit into the whole scheme of things. Hence this series.

But a funny thing happened on the way to the last installment. Our original ideas began to evolve, and we must acknowledge that some of our readers' criticisms of WHO had more force than we gave them credit for, and some of the optimism we had about WHO's own recognition of the problems has been tempered. We still have respect for the many highly competent professionals in WHO, some of whom risk their lives in the cause of public health. We still have sympathy for the extremely difficult position WHO finds itself in as an intergovernmental agency trying to work with governments whose highest priority is not the health of the world's people, or even, in some cases, the health of their own people. We still think the imputation of base motives to many in WHO is misguided, misdirected and unfair. And along with our wiki colleague anon_22, we still think we are better off having WHO than not having WHO -- by a long way. But we no longer see WHO as the principal engine safeguarding global public health.

One of the fundamental problems is that WHO, however global its vision, can act only through the same sovereign states that constitute its membership and are the instrumentalities through which any actions are taken. WHO's success in the SARS outbreak rested on its authority as a source of global alert, best clinical practice, and most dramatically, geographically-specific travel advisories. These products all depended on WHO's ability to provide information. But as the H5N1 threat has evolved in relative slow motion, old Westphalian habits hve reasserted themselves, as WHO scrambles to manage information and reveal it simultaneously. Cumulative missteps -- contradictory stories, clear spinning towards less threatening outcomes, unfounded claims of certainty and authority when uncertainty and powerlessness were the reality, lack of transparency about sequence information and case data, overstatement and understatement -- have seriously weakened the only real source of WHO power, its credibility and authority.

Three years ago WHO would have been able to weather these self-inflicted wounds. Now WHO must compete with an abundant free flow of information on the internet, information which is sometimes correct, sometimes not, but often as accurate or more accurate than WHO's. It comes from the same raw sources as WHO's but its interpretation is not bound by WHO's rules, traditions or constraints. If those rules and constraints were the source of discipline to make WHO's version superior, it would be one thing. But they aren't. They are another source of distortion. Thus one of the sources of WHO's enhanced powers after the revision of the IHR, the management of the flow of epidemiological information and surveillance, has been overtaken and perhaps made irrelevant by the advance of technology and the new social structures it fostered.

WHO's complementary role in coordinating global resources for control of local and regional disease outbreaks remains an important one, but it is moot for a pandemic which happens everywhere. There is not much ability to focus and coordinate resources that are needed everywhere. The "national system" upon which WHO depends is also clearly incompatible with the demands of reacting to infectious diseases that care nothing for national borders. For an evolving pandemic where managing the consequences is paramount, the main tool is information.

In that sphere, WHO and its sovereign member nations must not only share the stage with many non-state actors, but it must share them with actors that can rise to the demands of a pandemic better than WHO itself. WHO's epidemiological intelligence function has been superseded by a global internet that ferrets out, assembles and interprets information faster than WHO and often arrives at plausible interpretations at odds with the ones advanced by WHO.

Where does this leave us? We wish we knew the answer, but the H5N1 pandemic threat has left WHO and the world suspended in a kind of global public health limbo, recreating the anarchy of Westphalian public health but enlarging it to include all the other actors as well: states, intergovernmental agencies, NGOs, multinational corporations, public-private partnerships, and the increasingly influential world of information fed internet subcultures. Like the nations of the world, we need to find a way to work together. Information has become the currency in this world. We all want more of it and we want real gold, not fool's gold.

Information is a type of product that isn't depleted with use. It is not a counter in a zero sum game, with your gain my loss. Just the reverse. When it is distributed and redistributed, everyone gains. The lesson is that we all need to treat that resource with the greatest respect and the utmost of generosity. If WHO wants to regain some credibility and effectiveness, the single most important thing is to open the spigots of information full bore. We know it hasn't done so yet.

The same is true of my scientific colleagues. If you work on infectious diseases of pandemic importance, you will have to change your customary way of doing things. For some this is hard but it is necessary. For students and their mentors who fear this will put them at a competitive disadvantage in the academic world, that's going to be the price you will have to pay to be in this field. There are a lot of other subjects you can pursue if this is unacceptable to you. To health agencies like CDC, you will also have to provide the same kind of information, without regard for political, career or commercial considerations. It's not a choice. Do it or lose your authority and credibility. This is a constraint the outside world is placing on you.

For us, the distributed and global world of obsessed information harvesters, purveyors of hopes and fears, cassandras and hucksters, prophets and ordinary folks, there are also responsibilities. We need to practice fairness, consideration, empathy, constructiveness, and the desire to help each other and others engaged to the same ends, including WHO and CDC, in this increasingly turbulent drama against a virus that doesn't think, doesn't care and isn't even alive.

Maintaining that balance and openness ourselves may be the toughest job of all, as we struggle to push others to do their jobs, too.

Tuesday, June 06, 2006

Next question

This is what WHO is up against in Indonesia. The largest bird flu cluster to date occurred in North Sumatra, Medan, Karo regency in Kubu Simbelang village. On May 30 and June 4 emergency shipments of protective equipment with spraying tools, boots, masks and medicines arrived in Medan's Polonia Airport. There were four packages, weighing 265 kilograms.
According to WHO's liaison officer in Medan, Elia Ginting, the four packages are labeled 'protective equipment bio packaging' and were sent via Singapore.

“The equipment was sent after the WHO's laboratory recommendation about bird flu transmission in Karo was issued. It was sent in special stages for bird flu eradication personnel in Karo,” she said.

However, she acknowledged that the import documentation for the packages was not yet completed by WHO at the time of shipment from Singapore.

Meanwhile, according to Jontara Siburian, Head of the Customs Section of the Customs and Excise office at Polonia Airport, told Tempo that Customs and Excise was not going to release all of WHO's goods because it has not received the import documents until now.

“Although they are for emergency purposes, Customs will not release the equipment yet,” he said. (Tempo Interactive)
Yes, get the paperwork done, by all means. But the real truth is the Indonesians don't want to cull birds. We posted on this last September and nothing has changed. A mass killing of birds there is as likely as a mass killing of cats and dogs in the US.

It is easy to wag our fingers at the Indonesians because they won't put their own house in order and they are endangering us. Probably the Columbians feel the same way about the US because we won't stop the drug demand that is fueling the culture of vicious violence in their home country.

The Indonesians are at fault, here. No question.

So are we regarding substance abuse. Next question.

WHO, part IV: one door closes, another door opens

[This is the fourth of several posts (part I, part II, part III, part V) giving some background to the place of WHO in the international system. I am trying to explain some things about WHO behavior and positions I think might be useful to interpreting their actions and statements. It is not meant as a defense of either.]

Westphalian public health, as embodied in the International Health Regulations, was obviously a failure, and revision of the IHR was in order. The revision process began quietly in 1995. Early on it was realized that just adding to the list of notifiable diseases (including HIV/AIDS, for example) was not going to solve the serious structural problems caused by reliance on states as the only legitimate actors and sources of information. The member states were often blatantly disregarding their obligations to notify WHO, and through WHO, other member states. Adding to the list of diseases wasn't going to help much. The goal of the revision remained the same, however: to prevent the cross-border spread of infectious disease while interfering a little as possible with trade and travel (see also, the excellent monograph by David Fidler, SARS, Governance and the Globalization of Disease). The key move was to include information of non-state origin as legitimate sources of epidemiological information. This was a conscious break with Westphalian principles because it shared governance with non-state actors.

It was also a formal recognition of a fact. On the one hand, depending on states to divulge information that might damage them was unrealistic and obviously a failure. On the other hand, WHO and global health experts were already using to good effect non-state sources of information: newspapers, websites, chatrooms and email lists -- all the capabilities of the exploding new information technologies we know as the internet. In the mid nineties the Program for monitoring emerging Diseases (ProMED) was formed to harness the internet for a rapid dissemination of diverse sources of information. Today ProMED has tens of thousands of subscribers in more than 150 countries. Many of us receive it by broadcast email and its website is open to the world. It is currently sponsored by the International Society for Infectious Diseases, an NGO.

This kind of information was not just harvested, but also used by WHO in a new Global Outbreak Alert and Response Network (GOARN), which started operation in 1998. On paper GOARN was impressive:
This overarching network interlinks, in real time, 110 existing networks which toegether possess much of the data, expertise, and skills needed to keep the international community alert to outbreaks and ready to respond . . . .[o]ne of the most powerful new tools for gathering epidemiological intelligence is a customized search engine that continuously scans world Internet communications for rumors and reports of suspicious disease events. (WHO, as quoted in Fidler, p.. 66 - 67).
WHO claimed to have used GOARN to identify and investigate 538 outbreaks of international concern in 132 countries between 1998 and 2002. I have no way to verify this. But Karl Greenfeld, in his new book on SARS (The China Syndrome), points out that at the time of the SARS crisis, GOARN was in reality just three full-time medical professionals operating out of two offices on the first floor of the WHO annex building in Geneva. GOARN got its information from the same sources we do at Effect Measure: ProMED, media reports, websites, local correspondents and rumors.

On February 11, 2003 GOARN detected a developing respiratory disease outbreak in southern China, about a month after the Chinese government sent a team of doctors to Heyuan Number One Hospital to see the first cases of what later came to be know as SARS that came to its attention (they did nothing about it). Initially, the WHO suspected this was the start of an H5N1 outbreak and they alerted their laboratory network immediately, although public notification didn't come until weeks later. One might say that GOARN had "worked" much better than leaving it to China to report, but there was still a sufficiently long lag time that hads it been the start of a flu pandemic it would have cost many lives.

The SARS outbreak was resolved with the help of hard work on the part of many people, including heroic doctors in Hong Kong and WHO epidemiologists, one of whom died identifying the disease. Had this truly been H5N1, however, we would almost certainly have had a pandemic. This, despite even more dramatic departures from WHO's Westphalian heritage. In trying to stop the global spread of SARS, WHO issued travel advisories against the wishes of powerful member states and suffered a backlash from Canada as a result. And while WHO had made progress, SARS showed its capabilities were probably inadequate to stop a pandemic from the influenza virus.

In 2005 the IHR were officially de-Westphalianized, the culmination both of their failure in an age of global pandemics or threatened pandemics (HIV/AIDS, SARS, now avian influenza) and the "facts on the ground" regarding new actors on the global public health stage (discussed in Part III). The revised IHR don't seem up to the task, however, despite their departure from their Westphalian roots. In particular, there are many loopholes, long timelines, gaps and vague clauses, problems that to any lawyer's eyes, would vitiate the force of the new regulations.

Given the nature of this intergovernmental agency it may be as good as it can do. We don't have a world government and the US have done all in its power to circumscribe and weaken the UN, the world's only and already weak supranational force. And the revisions may prove very useful for other, regional or more localized outbreaks of disease. But it is hard to see how they will change much in WHO's ability to affect the evolution of an evolving pandemic threat from avian influenza. (You can read the IHR here and some thoughtful and heated commentary on it on The Flu Wiki in this Forum Thread. The Forum is the freewheeling discussion section of the Wiki and is separate from the "informational" side. In particular you will find useful annotations of the IHR by anon_22 at 10:35.)

If the revised IHR have any significance it lies elsewhere. In the final post, we broaden the question of where WHO fits in, not with respect to the international system, but with respect to the new global health system that includes WHO, NGOs, multinational and national businesses -- and the new communities growing up around the internet. In other words, us. This is a critical discussion we need to shape our response to the other actors who share the global public health stage with us: our own countries, NGOs, intergovernmental organizations like WHO, FAO, OIE and the World Bank, and the various internet communities that rub shoulders, sometimes cooperatively and sometimes in opposition.

Monday, June 05, 2006

Public-private default

In today's post about WHO we mention public-private partnerships, one of the ways WHO was accommodating to a world stage that had more than national states participating in international health activities. One of the more pertinent examples is in the news today, the alleged effort of countries, NGOs and intergovernmental organizations to battle bird flu using $1.9 billion pledged by the parties in January. That was then. This is now.
Just $286 million has been spent to fight bird flu out of nearly $1.9 billion pledged last January by nations and organizations that said they wanted to make a "massive effort" against the virus, according to a World Bank report.

Only Japan, Switzerland and the Czech Republic have fully spent the money promised at a meeting of big donors in Beijing last January, according to the report, a copy of which was obtained by Reuters.
Africa in particular needs more money, the report said.

"Japan has fully committed its pledge in Beijing of $158 million to a range of countries and organizations at the regional and global level," the report reads. Switzerland pledged and has spent $4.7 million while the Czech Republic promised and has spent $200,000.

The report, prepared for a meeting of senior officials in Vienna on June 7, also singles out the United States, which pledged and committed $334 million, but which has spent $70.95 million. Of $500 million in loans promised by the World Bank, just $113 million has been committed and only $1.97 million sent out. (Leslie Wroughton and Maggie Fox, Reuters)
The money was meant to improve animal health systems and surveillance, poultry vaccination and rapid response measures, all critical to slowing the spread of avian influenza. The money is slated for projects in Vietnam, Indonesia, Nigeria, Turkey and Cambodia, all bird flu hot spots.

So it's just Japan, Switzerland, the Czech Republic (and an AP story adds Finland to the list) that have met their obligations. The European Community has disbursed nothing and the US only a small fraction of its pledge.

Pretty pathetic.

WHO, part III: the world changes

[This is the third of several posts (part I, part II) giving some background to the place of WHO in the international system. I am trying to explain some things about WHO behavior and positions I think might be useful to interpreting their actions and statements. It is not meant as a defense of either.]

The idea that states were the only legitimate actors was the essence of the system WHO was born into, guiding and constraining its activities for the first 50 years or so. It derived from the Peace of Westphalia, 1648 (seep part I):
The Westphalian moment in the seventeenth century represented the effective abandonment of the legitimacy of transnational, non-state actors, such as the Catholic Church, that had played governance roles in earlier times. The Peace of Westphalia stripped governance of international relaitons bare of such actors and grounded governance in the interactions of sovereign states. (David Fidler, SARS, Governance and the Globalization of Disease, p. 50)
In part II we saw how this was reflected in the International Health Regulations that governed WHO's activities in infectious disease, establishing the state as the only legitimate source of epidemiological information and the only actor that could authorize its dissemination. The idea of the IHR was to reduce the possibility that one state would needlessly harm another by the unilateral application of quarantine or product boycott for reasons of infectious disease. The IHR were international health treaty counterparts to the kind of standardization that was done in many places in the twentieth century to standardize regulations, screw sizes and many other things to lubricate the wheels of commerce, travel and trade.

Despite the state-centered basis, non-state actors like multinational corporations (MNCs) and non-governmental organizations (NGOs) were not absent from the WHO world. WHO had both formal and informal systems of relationships with them to allow cooperation and consultation in matters of health. The difference was that the MNCs and NGOs were not part of the WHO governance scheme. Only states were.

But NGOs and MNCs were neither inert nor passive and their power and influence grew in the last third of the twentieth century. An international campaign against infant formula in the developing world had significant success in altering marketing practices of MNCs and national maternal and child health agencies. The field of actors was being enlarged beyond the states, affecting intergovernmental agencies like WHO indirectly through effects on MNCs and governments. MNCs in turn also were players with national governments and sometimes NGOs. The stage was becoming more crowded.

At the same time a new kind of actor was coming into being, the "public-private partnership." A recent example is the Bill and Melinda Gates Foundation's Global Alliance for Vaccines and Immunization, directed at working with WHO and other intergovernmental agencies like the World Bank, governments, NGOs and pharmaceutical companies to provide vaccines for the world's children. This is about as un-Westphalian an endeavor as one can imagine. These partnerships are not treaty agreements between sovereign states but agreements between a wide range of actors that include WHO, sovereign states, NGOs, MNCs and others. Nor is it the only such example. There are many others, including the ambitious voluntary bird flu fund established in January.

Thus while the IHR remained stuck in a Westphalian world, the international system had changed radically. On paper, international health might be populated solely by state actors, in reality that world was gone. Whether it was NGOs, corporations, public-private partnerships or the new sub-cultures growing up through the internet, the prohibitions and constraints that kept WHO confined to horizontal relationships between state actors had broken down and numerous new actors were busily engaged in influencing, intervening, opposing or supporting what was going on inside state borders.

There is more to it. A fundamental change was occurring in how we looked at the world, perhaps best symbolized by the iconic blue marble view of the earth from space. The right to participate in international health governance was no longer seen as the sole right of nation states, whose existence is not visible in this view. Nor is it presumed that the Great Powers should be either the sole producers or sole consumers of products meant to enhance the health of the globe. The Westphalian standard of "the national interest" was no longer the obvious touchstone of all global health decisions.

Fidler discusses how the new view influenced such establishment sources as the 2001 action agenda of the Commission on Macroeconomics and Health on a matter which concerns us here, so I'll end this post with it:
The Commission's action agenda included the recommendation that the supply of global public goods, such as international disease surveillance, be bolstered through additional financing of relevant international organizations, including WHO. The Commission captured why [the idea of global public health good] differs from the policy objectives targeted in Westphalian governance when it observed that global public goods "are public goods that are underprovided by local and national governments, since the benefits accrue beyond a country's borders." (Fidler, p. 60).
In part IV, we'll discuss how WHO responded -- and failed to respond -- to the new reality and the growing threat of emerging and re-emerging infectious diseases.

Sunday, June 04, 2006

WHO, part II: Westphalian public health

[This is the second of several posts (Part I here) giving some background to the place of WHO in the international system. I am trying to explain some things about WHO behavior and positions I think might be useful to interpreting their actions and statements. It is not meant as a defense of either.]

In Part I we gave a brief background to the international system to which WHO is tied, the Westphalian system. When WHO was created it was the only game in town. Throughout its history, WHO has struggled to overcome the incompatibility between the legacy of a political and diplomatic world where actors are nation states and the real public health world where these actors are irrelevant.

The problem of the irrelevance of political borders (and state sovereignty) to a microbe was understood even before the germ theory. Quarantine goes back at least to the fourteenth century, and as time went on the practice and others like requiring a "bill of health" from the port of origin became an increasing source of interference to free trade and trravel between nation states. In principle one country couldn't intervene in the affairs of another to stop an epidemic, but it could prevent its ships from its shores or incarcerate its crews aand impound once landed.

As trade increased so did the costs in spoiled cargos and lost cartage times. By the middle of the nineteenth century the community of large trading nations was exploring ways to reduce the frictional loss caused by sovereignty, of each nation acting on its own. Westphalianism allowed supranational controls as long as all parties agreed. Thus began a series of international sanitary conventions from 1851 onward. They were voluntary but binding agreements negotiated by sovereign states on how to minimize interference with international trade and travel while maximizing protection from specified infectious diseases. In other words, they were rules that managed state interactions while leaving the core of sovereignty alone. The sanitary conventions didn't interfere with what went on inside borders. They covered quarantine and requirements for certain facilities at international ports and airports, the gateways for cross-border disease spread.

The classical example of a Westphalian structure in international health are the International Health Regulations (IHR), adopted by WHO in 1951 from the international sanitary conventions in force at that time. They are discussed in David Fidler's monograph, SARS, Governance and the Globalization of Disease. As he observes (p. 33), the objectives of the IHR are pure Westphalian doctrine: to ensure the maximum security against the international spread of disease with minimal interference with world traffic. At the heart of the IHR is a surveillance activity that requires notification of the international community through WHO. The IHR only covered diseases of interest to the great powers, cholera, plague and yellow fever ("Asiatic diseases"). The original IHR/1969, in force until next June when they will be succeeded by the revised IHR/2005, are Westphalian through and through:
The IHR seek to achieve minimum interference with world traffic by regulating the trade and travel restrictions WHO member states can take against countries suffering outbreaks subject to the Regulations. The IHR provide that the trade and travel measures prescribed for each disease subject to the Regulations are the most restrictive measures that WHO member states may take (IHR, 1969, Article 23). The IHR contain the maximum measures that a WHO member state may apply to address potential cross-border transmissions of cholera, plague, or yellow fever . . . . The IHR have provisions that prevent the departure of infected persons by means of transportation and that limit actions taken against ships and aircraft en route between ports of departure and arrival, against persons and means of transport upon arrival, and against cargo, goods, baggage, and mail moving in international transport . . .(Fidler, p. 34).
This is not all. The flow of epidemiologic information has also been regulated by Westphalian principles:
The [IHR] also reflect the state-centric framework, especially with regard to the flow of epidemiological information to and from WHO. Under the IHR, surveillance information that WHO can disseminate to its member states can only come from governments (IHR, 1969, Article 11). As WHO observed [cite omitted], '[t]he IHR wholly depend on the affected country to make an official notification to WHO once cases are diagnosed." WHO has no legal authority under the IHR to disclose disease outbreak information it receives from reliable non-governmental sources. (Fidler, p. 51).
This explains a great deal of WHO's seemingly irresponsible behavior regarding release of case and sequence information. It did not have the legal authority, under international law, to release information without the consent of the member state. We at Effect Measure or Henry Niman at Recombinomics might rail that WHO "must" release the Turkish sequence information, but WHO could not do so without the permission of the Turkish government. We could bemoan this restriction (as WHO did for many years) and demand WHO violate international law. But such an act could have serious consequences for WHO's position in the international system. It would be like asking the police to violate the law for a higher good. It might be justified in some circumstances, but they would have to be extraordinary and the undertaking would be fraught with difficulty and hazard. They also would not have many chances to do it again if it turned out to be unjustified.

It is clear the Westphalian IHR were inadequate to the task of safeguarding the world from pandemic disease, not only in the bird flu case but in many others where state actors have violated their obligations to notify WHO because they would suffer economic harm. WHO understood that the core principles for the Westphalian IHR were inadequate as well and by the mid nineties was undertaking to revise them. At the same time, changes were taking place in global public health, like a chrysalis developing within the Westphalian cocoon. In Part III we will take a look at them.

Correction, 6/4/06, 12:50 EDT: Inserted the word "not" to make the second sentence in the penultimate paragraph read correctly, viz., "…but WHO could not do so without the permission of the Turkish government." Sorry for any confusion. Thanks to the reader who pointed it out.

Freethinker Sunday Sermonette: post deathbed conversion

Chicago Democratic ward healers used to confer voting rights on the deceased, and lately Republicans have revived the practice (although not the voters). But when it comes to proselytizing, nobody beats the Mormons.

From The Jerusalem Post:
Jewish leaders in a dispute with the Church of Jesus Christ of Latter-Day Saints over the practice of posthumous baptisms say there is new evidence that names of Jewish Holocaust victims continue to show up in the church's vast genealogical database.


Posthumous baptism is a sacred rite practiced in Mormon temples for the purpose of offering membership in the church to the deceased. Church members are encouraged to conduct family genealogy research and forward their ancestors' names for proxy baptism.

Church president Gordon B. Hinckley has said the baptismal rite is only an offer of membership that can be rejected in the afterlife by individuals. "So, there's no injury done to anybody," Hinckley said last November. (Jerusalem Post)
This is hilarious. No one's feelings should be hurt because the dead person can always refuse to be baptized?

What a timesaver. I don't even have to lampoon this, it's so daft.

Saturday, June 03, 2006

Vaccine vaporware?

There is no effective vaccine for H5N1 at the moment but there is a lot of activity. Whoever makes a vaccine will have a ready market if there is an outbreak and in a threatened pandemic, with production capacity inadequate to meet global demand, there will be room for more than one producer.

One of the first to announce it was well on the way to a practical vaccine was Hungary, whose partnership with a small vaccine developer, Omniverst, was touted as one of the first out of the gate late last year. Both the health minister and Prime Minister Ferenc Gyurcsany publicly took the vaccine and predicted Hungary would be able to protect its citizens against any pandemic. That was then.

Little has been heard since, according to a Bloomberg story reported in the Hungarian press. There have been no scientific publications and no one has ordered the vaccine from Omniverst. A large European pharmaceutical company looked at the technology and decided to proceed on its own. No regulatory approval has been applled for.
When contacted by Nepszabadsag, one of Omninvest's leaders, Tamas Laczko said that the Hungarian authorities had registered the vaccine and the company was in the process preparing the documentation necessary for European regulatory approval. The vaccine will only be deployed by the health authorities if there is an epidemic, he said. Therefore there is no urgency to get the European registration, which is costly for a small company like Omninvest, he added. (MTI)
No urgency. Of course not.

WHO, part I: 300 years old at birth

[This is the first of several posts giving some background to the place of WHO in the international system. I am trying to explain some things about WHO behavior and positions I think might be useful to interpreting their actions and statements. It is not meant as a defense of either.]

The World Health Organization (WHO) came into this world with a congenital deformity. Since then it has struggled, against the odds, to walk normally and do things that might seem difficult or impossible, given its disabilities. It hasn't stayed static, however, but is trying to perform reconstructive surgery on itself. To understand what is wrong and appreciate its achievements given the circumstances, we need to consult some textbook history.

WHO was established as the health agency in the United Nations system by an international charter in 1948. This is exactly 300 years from the year the modern system of international relations was crystalized in the Peace of Westphalia, ending the disastrous conflicts known as The Thirty Years War. This may seem a strange place to start an explanation of WHO's predicament, but we will try to show why it is important.

The Thirty Years War was a complex, chaotic and catastrophic convulsion that devastated continental Europe between 1618 and 1648. The causes were on many levels: Princes versus The Holy Roman Emperor; Protestants versus The Church in Rome; and internecine warfare between states and princes and everyone else. It was a War of All Against All and it decimated the continent and killed almost half the population of Europe, a three decade pandemic of violence more deadly than 1918 flu. The Peace of Westphalia, the Treaty that ended it (at least most of it), was known to contemporaries as The Peace of Exhaustion.

The Peace of Westphalia also gave rise to what political scientists call the Westphalian System of international relations, identified with the idea of sovereign national states subject to no higher authority. Each state actor could determine whith what other states and under what conditions they would have legal relations. The Westphalian system is "anarchic" in the sense there is no authority above a nationally sovereign state -- except such authority as the state agrees to in advance. Power is divided, and no "world government" is possible except to the extent a state agrees to be subject to some extra-national conditions.

Anarchy in this case doesn't mean confusion and disorder. On the contrary. There is a definite structure to Westphalian relations and its core is sovereignty -- states have sole power within their borders -- and its corollary is non-intervention: states do not interfere in the internal affairs of other states (I have used international legal scholar David Fidler's monograph SARS, Governance and the Globalization of Disease as a source for some of this exposition).

These principles are enunciated in the UN Charter (art. 2.7) which states that
"[n]othiing contained in the present Charter shall authorize the United Nations to intervene in matters which are essentially within the domestic jurisdiction of any State or shall require the Members to submit such matters to settlement under the present Charter." (quoted in Fidler).
This idea, the sovereignty and equality of nations, is the linchpin of the international system within which the UN, and hence WHO, operate. Again, from Fidler:
The Declaration on Principles of International Law Concerning Friendly Relations and cooperation Among States (1970, p. 42) states, for example, that "[e]very state has an inalienable right to choose its political, economic, social, and cultural systems, without interference in any form by another State." The principle of non-intervention excludes a great deal of sovereign behavior from being the subject matter of state interaction. (Fidler, p. 23)
Westphalian relations have a politics as well as a structure, however, and the politics are largely (but not exclusively) the politics of the Big Powers. Individual state actors are the units, but with no power acting over them, material resources, military power and strategic alliances affect how states relate to each other, just as they do in a democracy where the individual is the theoretical unit but some individuals are more equal than others.

In Part II we will examine how WHO's birth as a Westphalian institution has affected its functioning in public health, with particular emphasis on infectious diseases. Sovereign states are demarcated by borders, but viruses don't recognize those borders. The Westphalian System recognized this early on and developed ways to handle it. It is those ways WHO inherited at its birth in 1948.

Friday, June 02, 2006

Behind the Indonesian curtain

The curtain is being pulled back on the Indonesian bird flu control program and it reveals there is nothing there. In the last few days several major stories have highlighted the open secret that Indonesia is a No-Man's-Land of bird flu, a free for all with no one in control. This comes at the end of May, a month which saw 15 bird flu deaths in Indonesia and reports of several small clusters and one alarmingly large one. WHO is saying there is so far no evidence of spread beyond the family, information consistent with what we have heard through independent sources. But the ability of WHO and the Indonesian authorities to perform thorough contact tracing is limited.

Exasperation with the Indonesians is clearly evident. Even WHO epidemiologist Steve Bjorge, by all accounts a diplomatic and generous person, seems to be running out of patience:
"The situation is that there is a leak in the roof, and the Ministry of Health is just mopping up the floor every day," epidemiologist Steve Bjorge said.

Indonesia has the world's second- highest number of confirmed human bird flu deaths after Vietnam with 36 - and the most deaths this year.

Bjorge said Indonesia had to start mass culls of infected birds and more intensive testing of fowl suspected of carrying the H5N1 virus if it wanted to stem the spreading of the virus, which he said was "pandemic in poultry."

In Papua's Manokwari district, he said, "they have had three outbreaks in the last nine months, and each time they've culled and they've stopped it. That to me means, even in Indonesia, it is possible to do it."

But the sprawling country's hugely decentralized government - spread over 17,000 islands - means that preventing the spread of the virus among birds is a very complicated task, Bjorge said, adding there is no central authority that can order culling "on a minute's notice." (Marianne Kearney, AFP via The Standard, Hong Kong)
This is not just one person in WHO expressing a personal opinion. Almost exactly the same language was used by WHO spokesperson Dick Thompson, not previously known for the boldness of his pronouncements:
"We're tying to fix this leak in the roof, and there's a storm," World Health Organization spokesman Dick Thompson said. "The storm is that the virus is in animals almost everywhere and the lack of effective attention that's being addressed to the problem."

Indonesia, an archipelago of 17,000 islands with a population of 220 million people, has a patchwork of local, regional and national bureaucracies that often send mixed messages. The impression, health officials said, is often that no one is truly at the helm.

"I don't think anyone can understand it unless you come here and see it for yourself," said Steven Bjorge, a WHO epidemiologist in Jakarta. "The amount of decentralization here is breathtaking."

He said Health Ministry officials often meet with outside experts to formulate plans to fight bird flu, but they are rarely implemented.

"Their power only extends to the walls of their office," Bjorge said, adding that the advice must reach nearly 450 districts, where local officials then decide whether to take action.


But public awareness and bio-security standards remain low in the densely populated countryside, home to hundreds of millions of backyard chickens.

"It's not quite so easy here, where you have to have the local authorities and provincial authorities and national all on board," said Jeff Mariner, an animal health expert from Tufts University working with the FAO in Jakarta.

"We find outbreaks every week scattered throughout Java. It's a diffusely endemic disease. In most districts, you can find it at any time," he said. "It's a staggering undertaking in a decentralized country." (AP)
Two things strike me about this. The Indonesian situation is probably mirrored in numerous countries in Africa. Who knows what's going on there? Second, WHO appears to be flexing its newly authorized muscles. We don't yet know if this is a sign of a sea change, and if it is, what its origin is. The agency is operating under the direction of an interim Director-General who may be taking advantage of international concern to do things differently, as WHO did during the SARS episode. Or maybe the newly revised International Health Regulations are starting to bite. Or maybe its a combination of factors.

Whatever it is, we can hope.

Indonesia "releases" the sequence data (sort of)

In a curious statement, Indonesia's director-general of disease control and environment at the Indonesian Ministry of Health, I. Nyoman Kandun, said his government may share the genetic sequences of the Medan cluster if it helps researchers and isn't an "opportunity for them to make money." (Bloomberg).
"We have not received any request to share it with GenBank,'' Kandun said yesterday in an interview from Jakarta. "If there was a request, and it's clear that it is in the public interest to do so, why not? I would surely recommend it to the health minister.''
WHO spokesperson Maria Cheng responded from Geneva:
"We think it's important to share this information so that everyone can have a better understanding of what's going on.''
So it's settled. Or should be.

WHO should take this as consent to deposit the sequences immediately in GenBank. Cheng is still saying WHO "can't compel countries to do things they don't want to do." But this is not the issue here. Under the revised International Health Regulations(2005), whose bird flu provisions went into effect last week (a year early), Indonesia is required to provide the information and has tacitly released it via their statement. WHO has the information. The sequencing was done by Dr. Malik Pereis in Hong Kong, at Indonesian government and WHO request.

The Indonesian Ministry of Health has a record of saying one thing and doing another (or more frequently saying one thing and doing nothing). In this case it doesn't matter. They've essentially released the sequences, subject to conditions met by Cheng's response.

Time for WHO to tell Dr. Peiris to deposit them in GenBank.


Thursday, June 01, 2006

New rules in a dangerous game

Declan Butler, senior correspondent for the scientific journal Nature, also has a blog and he used it to amplify on his piece in the journal today about the situation in Indonesia. In particular he quotes from correspondence we both have had with Dr. Andrew Jeremijenko, formerly with the influenza surveillance unit of the US Naval Medical Research Unit 2 in Jakarta (NAMRU-2).

Andrew is an astute observer of the scene there, and his correspondence is filled with worry about the inability of the Indonesian central government to cope with the endemic poultry infection throughout this vast country and the continual sporadic appearance of human cases, culminating two weeks ago in the large family cluster in Sumatra which infected all eight members of an extended family and killed seven of them. There was unmistakable evidence of human to human transmission, probably extending to three generations of cases (human to human to human). The actual response was such as to suggest the futility of the kind of almost instant response WHO says will be needed if there is any hope of smothering a pandemic at the source.

Declan gives us the bottom line:
Working at NAMRU-2, Andrew witnessed the enormous gap between the official rhetoric and the reality on the ground. Take the recent declaration by Michael Leavitt, US Secretary of Health and Human Services’ statement to the World Health Assembly: “In closing, I ask this Assembly today to pledge with me to abide by four principles of pandemic preparedness:
  • Transparency,
  • Rapid reporting,
  • Data sharing and,
  • Scientific cooperation.
In reality of course, for many political and cultural reasons — including those of the scientific community itself — although some progress is being made, lip service is often paid to these on the ground, and that includes the US’s own CDC. (Declan Butler's blog)
Declan goes on to reiterate what we have been saying here. WHO has had no inherent police authority over its member states. Under the international system WHO is bound by the principle of state sovereignty and its corollary, non-intervention in the internal affairs of a state. Under the International Health Regulations in effect until last week, WHO may only release information about infectious disease within a member state with the permission of that state. On one occasion only (cholera in Guinea, 1970), a strong and decisive Director-General (Marcolino Candau) ignored the IHR restrictions, but that was the only instance before the SARS outbreak of 2003 that WHO issued any epidemiological information or advice without the assent of a member state. SARS was the signal event that pushed WHO to a more drastic revision of the IHR, going into effect in 2007. WHO's governing body last week authorized it to ask for voluntary compliance for bird flu, one year ahead of time.

The newly revised IHR will require states to respond actively and provide immediate information. WHO hopes this will extend to the vexing problem of release of sequence information, bottled up in the no-man's land of fragmented authority and personal agendas. WHO works with scientists, laboratories and governments around the world and is privy to most of the sequence information. So far it has not gone outside the legal constraints on unilateral release of country information, but that doesn't mean it is powerless. It should be using whatever influence it has -- including withholding isolates from scientists who won't deposit sequence information immediately. Now that the WHA has authorized the early application of the revised IHR to bird flu, WHO should also begin pressuring recalcitrant states using the new authority. Indonesia is a prime candidate for this because it essentially has no central government at all. Instead it continually "yeses" international agencies, so WHO could take those empty assents as a signal the Indonesian sequences are released under the new IHR.

But it's not just state actors that are the problem. Prominent members of the community of flu scientists are also wearing out the world's patience. CDC, St. Jude's, Weybridge, Mt. Sinai and others have unreleased sequence data for H5N1. It is time to deposit them immediately in GenBank or risk losing the respect of colleagues and the public. WHO has no legal obligation to keep sequences that are not from a member state private and they shouldn't. As a data gathering scientist myself I have an appreciation for what this means to the scientists involved. But these aren't ordinary times and the failure of CDC and prominent flu scientists to release all their sequences is reckless, irresponsible and dismaying. Why should China, Turkey and Indonesia do it when the most famous flu scientists in the world won't? Currently they are setting an example of the worst kind. They should set a good one.

There's enough blame to go around here, but it should be placed where it belongs most, with the countries and the scientists. It is time for WHO to start exercising more muscle now that the WHA has authorized it for bird flu.

And there's a lot WHO can do besides issue unrealistic fireblanket scenarios few think will work. They can use the bully pulpit and their own new authority to push countries (including the UK labs and US CDC) to open up the spigot of epidemiological and genetic sequence information. This is an unaccustomed role, but they need to learn to use it quickly.

The revised IHR are new rules in a new game. And the game is dangerous.

Another thought on the sequences

Andrew Jeremijenko, the physician formerly in the influenza surveillance branch of NAMRU2 in Jakarta, has raised an interesting question about release of the sequences. The isolates come from patients and are sequenced elsewhere, often CDC or another WHO reference lab. One piece of information of interest to the treating doctors is whether the isolated strains have the genetic markers for adamantane-class and/or Tamiflu resistance. The adamantanes (amantidine, rimantadine) are older antivirals that are relatively inexpensive but little used in Indonesia, according to Jeremijenko. If the H5N1 strains there are sensitive to the adamantanes as some are elsewhere (although independent information suggests the ones in the Medan cluster were resistant), then this is important information for the treating physicians. There is an absolute moral obligation of the sequencing labs to provide the sequence information for use by treating physicians.

I don't know what, if anything, the Indonesian doctors have been told about the efficacy of amantadine. Jeremijenko suggests they have been told nothing. But this is just another case for releasing the sequences -- an urgent one. At the moment, post docs and young faculty (and their mentors) are aware that if they are sequencing H5N1 today they run the risk of having their work used by others who mine GenBank sequences for their own purposes. That's going to be a risk they must run if they want to work in this area. Meanwhile the profession should think of mechanisms to protect the sources of the sequences. GenBank might consider devising a policy requiring acknowledgment and credit (possibly co-authorship) for those using deposited sequence information so the careers of those providing the information will not be harmed.

But first things first. Scientists should not be the roadblock for H5N1 sequence release, despite the risk their work will be scooped by others. That's a hard case to make to someone who is trying to establish themselves in a competitive field. It should be one of the costs of entry, however. There are a lot of other scientific areas to work in, if that's unacceptable.

The sequence problem needs to be solved, and solved quickly. Time to cut the Gordian knot and for scientists to deposit them in GenBank on their own initiative and because its the right thing to do, career or no career. Maybe that will also shake some of the state actors loose.

Wednesday, May 31, 2006

Australia's best laid plans

Australia had a great pandemic flu plan. On paper. Now paper is confronting reality and reality is winning.

Like a number of other places, it seemed only common sense that the priority for Tamiflu would be essential workers. Back in October the Australian government said it had enough Tamiflu for 1,000,000:
The Federal Health Minister, Tony Abbott, has been very frank about the inadequacy of Australian stockpiles:

"Certainly, we don’t have anything like enough antivirals to protect the entire population. At present, we have enough antivirals to protect one million essential service workers for about six weeks."

He has also been very candid about supply constraints being a clear reason for the limited stockpiles:

"[A]t the moment there are no additional antivirals anywhere in the world . . . If there were more antivirals to be had, by all means [we would expand stockpiles]. But on the best evidence we have, there aren’t."

Providing such protection will be essential in order to ensure that workers such as police, doctors, nurses, water and electricity staff and airport employees turn up for work and maintain essential infrastructure. When supplies run out after 6 weeks or so, Australia will then be competing to obtain preferential treatment for a scarce resource from Roche. (Medical Journal of Australia)
It turns out even this bit of pessimism was too optimistic. Australia has reversed direction and now will give Tamiflu only to the sick and those directly exposed to the sick:
"We came to the conclusion in consultation with the states that the attempt to keep prophylaxis going for the up to 1 million people who would normally be deemed essential was simply not going to work, there would never be enough anti-virals to do so," he said. (Australian Broadcasting Corporation)
Either a lot of Tamiflu disappeared since October, or the amount of Tamiflu was overestimated, or . . . they were just blowing smoke?

Score: Reality 1, Paper Plan 0.

Message to WHO: there is no barn door to close

I try hard to be fair to WHO. They've got an exceedingly tough job and not much to work with. Every time I write an opinion or criticize them I am conscious I could be very wrong.

But this fireblanket business just exasperates me. Let's get real.
The World Health Organization (WHO) issued a step-by-step plan on Tuesday, including the rapid mass use of the antiviral Tamiflu, for containing a bird flu outbreak if the virus starts to spread rapidly among humans.

The "rapid response and containment strategy" has a chance of quashing the deadly H5N1 virus only if people in the zone at risk receive massive doses of the drug within three weeks of a confirmed outbreak, it said.

"The success of a strategy for containing an emerging pandemic virus is strictly time dependent," the WHO said in its latest containment report, based on recommendations by 70 international experts who held closed-door talks in March.

"Mathematical models have indicated that a containment strategy, based on the mass administration of antiviral drugs, has a chance of success only when drugs are administered within 21 days following the timely detection of the first case representing improved human-to-human transmission of the virus."

Under the detailed timeline laid down, a country should notify WHO of a cluster of suspicious cases suggesting sustained human-to-human spread of the virus within 24 hours of detection.

A WHO-approved laboratory has another 24 hours to confirm that the H5N1 bird flu virus has changed, either through mutation or through reassortment with human influenza.

The strategy relies on WHO's global stockpile for rapid containment, three million treatment courses of Tamiflu, donated by Swiss drugmaker Roche. Quarantine, infection control measures and contact tracing must also be carried out.

Once the WHO officially asks Roche for Tamiflu doses to be sent, they should arrive at the international airport nearest the outbreak within 24 hours, the Geneva-based agency said. (Boston Globe)
On Saturday (May 27), The Globe goes on to report, WHO asked Roche to ready the stockpile for shipment to Sumatra in Indonesia after becoming aware of the bird flu large cluster that wiped out an entire extended family and bore unmistakable marks of human to human transmission. They did this after disease transmission had already been underway for at least four weeks and three of the patients had been released from the hospital to the general community before returning to the hospital to die. If ever there was a graphic demonstation of the futility of the fireblanket approach, this was it. It's not going to work.

This doesn't necessarily mean they shouldn't try. Maybe they'll succeed in getting a couple of days grace, although it's unlikely. What worries me more is the real possibility of self-delusion. Let me say it again, as clearly as I can: It's not going to work.

I don't know if this virus will evolve into a pandemic strain or not, and if it does, where and when it will happen (although Indonesia still tops my list of likely places). But if the biology and circumstances allow it, there is nothing we can do to prevent it. The best we can do is get ready to manage the consequences.

And there's plenty we can do along those lines, things that are more likely to save lives than elaborate and futile plans to close the barn door after the horse has bolted. Because there's no barn door to close for influenza.

Tuesday, May 30, 2006

What to expect next in Indonesia

What I think we can expect from Indonesia over the coming weeks is a fair amount of confusion. Sporadic cases of bird flu continue to be reported. WHO's latest update adds six to bring the Indonesian total to 48, of which 36 have been fatal. The wide publicity given the large cluster in Sumatra is likely to increase the index of suspicion that new cases of pneumonia, if there is a history of exposure to poultry -- common in Indonesia -- will be admitted to a bird flu isolation ward as a precautionary measure.

As we noted in an earlier post, there are a huge number of pneumonias every year in Indonesia -- 186,000 cases in the under five age group in West Java alone in 2005 -- many with exposure to poultry. If even a fraction of these is pegged a "suspect" case, the wards will fill up quickly with suspect bird flu cases. The result will be detection of some more genuine cases and more reports of crowded wards full of suspect cases, all possibly without any real change in the incidence of disease.

Add to this the chaos of a devastating earthquake, a government unable to cope at any level and a world peering in with trepidation and you have a recipe for -- a fair amount of confusion.

Unfortunately, expecting to be confused does not lessen confusion.

Revere's prep

If the SHTF, I am ready to go on blogging, thanks to this 1935 beauty from modern mechanix (h/t Boingboing):

Monday, May 29, 2006

Orent gets it (mostly) right

I've been tough on journalist Wendy Orent here because I thought her widely read op-ed pieces on bird flu were wrong-headed, inaccurate and unhelpful in getting people ready for a possible pandemic. Yesterday she had another op-ed in the LA Times and I'm glad to say it's on the right track. Not that I agree with everything she says, but it's informative and helpful to readers who want to understand some of the controversies. Here's the lede:
There's a lot of bird flu virus out there. Despite encouraging news from Vietnam and Thailand, neither of which has reported any bird or human cases of the lethal H5N1 strain this year, the situation in Indonesia continues to worsen. Eight members of a family contracted the disease, and seven of them died this month. The timing suggests person-to-person transmission. Although not the first instance of such transmission, it's the single largest cluster that has been seen, according to virologist Earl Brown of the University of Ottawa. Indonesia appears to lack the resources to combat the disease.

The virus is also active in Egypt and has spread to Israel, Jordan and the territories where Palestinians live. Africa has a wide belt of infection. With the disease spread over so much of the world, more people in contact with sick birds means more opportunities for humans to catch the virus. This appears how human influenza pandemics have begun — through human contact with sick birds.

But the factors that set off a pandemic remain unknown. No one has ever tracked the evolution of a new pandemic. All we have seen — in 1918, 1957 and 1968 — is the aftermath of that evolution. Still, we are told that all it would take for H5N1 to become a pandemic would be for the virus to mutate so it could spread in a sustained way from person to person. (LA Times)
The rest is a discussion of what she and others think this talk of mutation means. I might disagree in details, but essentially I agree we don't know much about what it would take. Most scientists don't believe a chicken virus turns into an easily transmissible human virus in one step (although it's possible). But Orent goes further. Her view is that natural selection is the key to the virus's evolution and it can't happen suddenly, requiring instead a period of adaption in mammalian and probably human hosts.

This isn't an unreasonable point of view, and this adaptation might be occurring now in Indonesia and elsewhere. But I think it's wrong to believe it is the only point of view. Here are a couple of other possibilities.

Whatever genetic changes are needed for transmissibility in humans may be traveling along with some that are useful for the virus in birds. Selection pressure doesn't explain everything, as we see in the sudden emergence of amantadine resistance in virtually all flu virus in the US. Amantadine is not used much in the US, so this isn't selection. Most likely it is a "hitchiker" effect with the amino acid change conferring amantadine resistance linked with another genetic feature that conveys some selective advantage (a point made by bioinformatician EC Holmes). Here's another possibility. It takes multiple genetic switches to be flipped to produce enhanced transmissibility in humans (let's say ten) but eight or nine are already flipped, leaving only one or two to go. Since we are largely ignorant of what it takes, we are also ignorant about how many switches are flipped already. Here's yet another point. Genetic changes that enhance transmissibility don't have to confer selective advantages or be linked to them. Without such an advantage the virus will eventually be replaced by another, more fit one, but the transient period could be very nasty. None of this is not a repudiation of Darwinism. It is consistent with the current neo-Darwinian synthesis ushered in by Sewall Wright, Ernst Mayr and others in the 1930s and 1040s.

So it's good to see Ms. Orent on board. A flu-denier has now become a useful source of information. I hope she's right about her viral evolution scenario. But the distinct possibility she isn't is good enough reason to prepare.