Effect Measure

Wanted: leadership in public health

An excellent story from Bloomberg News by John Lauerman brings us up to date on an issue we raised yesterday concerning giving breaks on biologicals (like vaccines) to countries who deposit sequence data in publicly accessible databases like Genbank:

Poorer countries where bird flu is spreading may license virus strains isolated from their residents and poultry as a way to leverage better access to drugs and vaccines that come from studying those strains.

The plan is being advanced by a new program, announced today, that urges participating countries to place genetic information about their individual bird flu strains into central databases in return for rights that will allow the countries to control who uses the data. (Bloomberg News)

This is close to a suggestion we made in our previous post and we are glad that experts in public interest intellectual property issues were there ahead of us. Viral strains have not usually been licensed, no matter their country of origin, because this was an obstacle to the periodic revision of seasonal influenza vaccines, which are based on worldwide surveillance of circulating viruses. Bit the concern that in a pandemic developing countries will not be able to afford vaccines made from seed strains they contributed, however, has prompted some new thinking:

The new program will collaborate with Cambia, a Canberra, Australia-based non-profit research organization, and Science Commons, based in Cambridge, Massachusetts, to write agreements and patents that will allow the flu strains to be shared, said Peter Bogner, the program’s director.

“Intellectual property is the most important part of this,” he said yesterday in a telephone interview. Bogner said his background is in licensing media, and that he became involved in a healthcare project for the first time because of the threat of a pandemic.

Countries that join the data-sharing program will post their genetic sequence data in public databases, such as those at GenBank, run by the U.S. National Institutes of Health, and the European Molecular Biology Laboratory, Bogner said. Companies that want to use the viruses will be able to obtain them from laboratories that do bird flu testing, such as those affiliated with the World Health Organization.

[snip]

The new program’s approach appears to offer benefits for all parties that might be involved, said Michael Gollin, founder of Public Interest Intellectual Property Advisors in Washington, which also gives assistance to developing countries on intellectual property rights.

“f the countries that have the viruses can get preferential treatment on access to vaccines and drugs, then there’s incentive to participate,” said Gollin, who said he has helped Kenyan tribes negotiate rights to a molecule used in a fabric softener, among other projects. “The leverage seems to be there.”

According to a news article in Nature accompanying the letter outlining the new Global Initiative on Sharing Avian Influenza Data (GISAID; see our post here), the moral force behind this development was Italian virologist Ilaria Capua, who rebelled against the “old boy” system of holding flu sequences in secret:

Instead of placing her flu sequence data in the WHO-linked, password-protected database, she chose to enter it into the publicly available GenBank, and called on colleagues to do the same. “When you’re facing a pandemic, you have to get your priorities straight,” she says.

The idea of favouring freely available databases then started to gain ground. Capua joined forces with well-connected Peter Bogner, who runs an advisory group called The Bogner Organisation in Santa Monica, California. Bogner travelled around the world talking to scientists and policymakers about the issue. The avian flu expert group formed by the World Organisation for Animal Health and the Food and Agriculture Organization of the United Nations, called OFFLU, subsequently endorsed the idea. (Nature)

There still seems to be a lot to work out, however, and there is real urgency to get it done. At least an agreement in principle is needed quickly, made publicly by vaccine manufacturers and pledging favorable treatment in the event a viral isolate is used for commercial purposes. In addition, there needs to be a public commitment that any final agreement would be retroactive to the present, so there would not be an incentive to withhold data pending a formal and binding agreement.

There is a simple description for what Ilaria Capua did. It’s called leadership. Now WHO, CDC and the community of flu scientists have an important role to play in getting an agreement in principle done with all possible speed. It’s time for some real leadership and statesmanship by the international public health community. With some notable exceptions like Capua, we’ve seen precious little leadership to this point.

Precious little.

Comments

  1. #1 Tom DVM
    August 25, 2006

    Revere. Could this be a slippery slope?

  2. #2 revere
    August 25, 2006

    Tom: To what?

  3. #3 caia
    August 25, 2006

    I thought Ilaria Capua was cool when she appeared to be leading by example; now we know she was leading by organization as well. A gold star for Dr. Capua.

  4. #4 bangvap
    August 25, 2006

    I appreciate Ilaria Capua and her leadership in public health

  5. #5 william
    August 25, 2006

    There is an urgent and immediate need to collect the sequences of mammals at the locations in Indonesia where there are clusters of human infection. At present there are 5 human clusters in Indonesia. And there is also a need to immediately test humans with bird flu symptoms, where there is an absence of contact with dead birds.
    Peter Roeder is taking sequences of cats in Indonesia. This is very positive. But much more effort should be dedicated to this effort to collect mamalian sequences of cats, dogs, rats, and pigs, and any other mammal that might be a source.
    An exclusive concentration on dead chickens as the source is insanity, and may result in many human deaths. If a mammalian source is discovered, that source must be destroyed, in exactly the same way that sick chickens are destroyed.
    But Westerners feel killing dogs or cats is repugnant. They immediately think of their own dog or cat, and say no way buddy. Andre Jereminko, a virologist who worked in Indonesia many years, stated it is necessary to find a match for the human H5N1 sequences. But so far the only match is from a cat.
    It is very possible sick chickens are at times a vector for human H5N1, and it is completly reasonable to kill them.
    But what if there are multiple vectors? What happens if cats, for example, are also a vector? Do you ignore cats as a vector, and allow them to infect humans with H5N1? Do you think that would be a reasonable response, meaning we should destroy the sick chicken vector, but not destroy the cat vector. Will the transmission of H5N1 to humans be reduced in that way? Will the risk of a pandemic be reduced in that way? What do you do if people refuse to kill their infected cats? Do you use force to kill those cats? What about all the Indonesians that refuse to cull their chickens. Do you use force to kill those chickens?
    Of course you will respond that if H5N1 goes to sustained H2H, it will not make any difference. But is that a logical response? For example, if there are 3 vectors for the transmission of H5N1 to humans, meaning: 1. human to human,
    2. Bird to human, and 3. Cat to human; will you say it useless to kill sick cats and chickens because humans are the third vector?

  6. #6 Juliet
    August 25, 2006

    If you’re talking about potential cat vectors in the US, it’s totally different. They get it from eating sick birds. They are not exactly social creatures, nor can they fly, so it’s difficult to imagine them passing it beyond perhaps a single colony of feral cats. I’m not saying they’re not a danger, but this whole alarmism about having to cull household pets is silly.

    My cats stay indoors anyway – actually, that’s probably what they’d advise when AI hits the US. As to cats passing it between one sick family member and another – well, you’d have to isolate that family member from people and animals – if you can do the one, you can do the other.

    And as to cats in Indonesia, more should be tested before culls are considered. Unfortunately a lot of developing countries have a lot of free-roaming and stray animals which are very much at risk for all kinds of diseases, least of all H5N1.

  7. #7 william
    August 25, 2006

    Juliet,
    Dead cats in Germany and Thailand were determined to have been infected with H5N1. The only match Andrew Jereminko can find is a sequence from a cat.
    Are you telling me people always keep their cats inside the house. Have you ever seen a cat outside a house? Your position regarding pet cats is absurd. You are a perfect example of the fierce resistance that will result if cats in the US are ever determined to be a vector for H5N1, if and when a pandemic hits, which it probably soon will. There are now 5 different clusters of human H5N1 in Indonesia, and 5% of the 6000 patients with pneumonia in Thailand died. This is a very high death rate, and may imply many were infected with H5N1.
    Would you refuse to allow your cat to be killed if it was determined it was infected by H5N1? Would you prefer to see humans die in the US instead of cats?

  8. #8 Juliet
    August 25, 2006

    I’m not telling you people always keep their cats inside a house. I’m telling you that if H5N1 were detected in the US, cats would be forced to stay inside the house, as mine are already. However, cats do not fly on the air, and rarely fly in airplanes. They’re just not as effective a vector, unless you’re talking about spreading H5N1 within a household, especially assuming in-home quarantine, which I think is being recommended in Germany.

    Of course I would euthanize my cats if they had H5N1. There would be no way to save them. What a silly argument this is, overall. It’s almost like you’re looking for opposition.

  9. #9 Juliet
    August 25, 2006

    1. when I said quarantine, I meant of cats.

    2. Also – these clusters you mention are suspected. They may well turn out to be clusters, and then again they may not. I guess what I’m wondering mostly is “where are all the deaths” if the 20 in Cikelet really had AI? I mean, 5 deaths out of 20 is a much better rate than we’re used to in Indonesia.

  10. #10 Michael
    August 25, 2006

    I think what is being suggested is a little impractical. If we find the virus in pigs, dogs, horses, and wolfs, do we kill them all? I think there is a point at which we need to develop some other strategy than killing everything in the world that harbors a virus, H5 or otherwise.

  11. #11 william
    August 25, 2006

    Juliet,
    “I’m not telling you people always keep their cats inside a house. I’m telling you that if H5N1 were detected in the US, cats would be forced to stay inside the house, as mine already are.”
    Do you really believe the solution stated above is realistic? You obviously love your cats. But how many US citizens are capable of keeping their cats inside the house, 24 hours a day, 7 days a week? How many would comply?
    I am not looking for opposition, and I apologize for using the word absurd. It is just that your statement above is an unrealistic solution to the problem, since those who did let their cats out might be guilty of allowing an H5N1 cat vector to infect and kill humans.
    I am trying to show just how painful and difficult it would be for US citizens to kill their H5N1 infected cats. Just as dogs in Thailand were asymptomatic, but were infected with H5N1; meaning the dog was infected but appeared healthy, the same could apply to cats, if they also become infected. That means your perfectly healthy cat might have to be killed, if tests showed it was infected,since it might infect humans. Would you allow your cat to be killed, if it appeared it was healthy, but tests determined it was infected?
    Please be aware the Indonesians are facing the exact same problem right now. They often have to kill their pet birds.
    To an Indonesian child, this is a terrible tragedy, since Indonesians love their pet birds the way we love our pet cats and dogs.
    And if the vector is dogs, then the idea of keeping all dogs inside will not be possible. How many dog lovers out there in the US would suffer great pain if they had to kill their pet dog?
    I apologize if I sound argumentative. I sincerely thank you for responding to my post, and I only hope virologists will soon begin to take blood samples of mammals in Indonesia and Thailand soon.
    I believe the real mammal vector is rats. Rat fleas carried bubonic plague during the middle ages, killing thousands in Europe. If rats are the vector, there will not be any discussion about culling them. There will be no way to stop rats, infected with H5N1, from infecting humans in large numbers, especially in poor countries.
    I hope others also get involved in this discussion, and post here, because I obviously do not have the answer to this problem.

  12. #12 Juliet
    August 25, 2006

    Let’s be real – the main reason people don’t want to kill their chickens is because they’re a livelihood. Pet birds are not what are infecting most people – in fact, fighting cocks aren’t even the majority of the vector. We don’t eat cats in the US, and indeed they cost us money. They don’t make it for us.

    Also, my cat, personally, wouldn’t be infected, asymptomatic or no. My cats don’t go outside. There are many other diseases out there other than H5N1.

  13. #13 william
    August 25, 2006

    Michael,
    I agree with you. I do not think culling sick chickens will stop a human H5N1 pandemic. Obviously, it may allow H5N1 to mutate into a form that is transmissible H2H. But can sick chickens really be culled effectively in Asia and other poor countries, where many cannot read? I doubt it. I live in Medellin Colombia, and am an American. I see children in the parks playing with their pet parrots. There are birds all over Colombia. People sell live chickens in the center of Medellin. And as far a getting farmers in Colombia to kill their cats and dogs, forget it. On the farms, there are chickens running around free like pets. It just cannot be done. If you want to come to Colombia and tell a farmer to kill his chickens, go ahead, but I am not going to do it. It might be the last thing you do.
    And as far a killing other animals that are infected, just forget it, people will not kill their pet cats and dogs in the US. They would prefer you shoot the owners first. They would rather take a chance on dying from H5N1, than kill their pets.
    Humans should leave the animals alone, and accept their fate. The world is overpopulated with humans anyway. Of course, I do not want to be the one that has to die to reduce the excess population.
    In Colombia there are plenty of other ways an American can get killed besides dying from bird flu. But if bird flu arrives as a pandemic in Colombia, it will be like a volcano exploding. The situation will go from bad to total disaster really fast.

  14. #14 william
    August 25, 2006

    Juliet,
    You are correct. People in the US do not eat cats and dogs.
    But in Asia, especially in China, they do eat cats and dogs.
    And as Michael just stated, how can we actually kill all of these animals, especially if they are asymptomatic? Who has the time to take blood tests of all the cats in the US, if they are determined to be a vector? What do you do if both cats and dogs are both vectors?
    So the best solution may be to leave the cats and other animals alone, and let the people die.

  15. #15 Juliet
    August 25, 2006

    You know, if these people who love their pets so much are given a choice between killing their pets and keeping them inside, they’ll keep them inside.

    The other thing is that, again, cats dont fly, and they don’t flock.

  16. #16 william
    August 25, 2006

    juliet,
    I want to thank you for your posts here. Your comments have helped me to better understand what may happen if a mammal is determined to be a vector of H5N1.

  17. #17 Trina
    August 25, 2006

    If the companies and countries are set up to benefit from viral strains, will individuals then start to bargin when they go to the hospital? You can define what I have — if you give my family and I free care?

  18. #18 Tom DVM
    August 25, 2006

    Revere. What I meant was that this may be another opportunity for pharmaceutical companies. Another way to corner a market. The pharmaceutical company offers a poor country a few million dollars for complete access to their disease raw materials…similar to coke and pepsi in schools…maybe the drug company throws in a hospital or two for good measure.

    In return they apply for patents on the material and have a twenty year plus monopoly as to the price they can charge.

    I am not sure that this is what Dr. Capua had in mind but it may be an unintended consequence.

    If anyone owns defective genes, it should be the group of people with the defective genes…but of course, that horse is long out of the barn and down the road.

    Maybe this presents an opportunity to step back and have another look at things…because in the future the pharmaceutical companies’ president’s children will be as susceptible as the poorest person in the world and in the 1950’s and 1960’s making money was not the first consideration in public health…and they say we are more advanced today?

  19. #19 tan06
    August 25, 2006

    The proposal from Nancy Cox and others is, ( quote)that “countries can take ownership of rights to biological organisms isolated from their residents and poultry and DECIDE WHICH companies or researchers USE THEM.”

    This cannot be misunderstood. Further on in the article:

    “International legal groups such as the Geneva-based World Intellectual Property Organization, an agency of the United Nations, help protect those rights.
    In the past, countries have not protected rights to virus strains used to create vaccines for seasonal flu, Cox said.
    “There’s been a tradition developed over the years where the flu viruses isolated anywhere in the world were considered to be part of the global domain,” she said. “If we had concerns about intellectual property, we wouldn’t be able to update the annual vaccine in a timely manner.””

    http://deseretnews.com/dn/view/0,1249,645195875,00.html

    IMO, it’s a very good thing to reinforce sharing flu sequences, but to say these countries “decide which companies or researchers use them” is the most complicated piece in the matter. There is the risk that international policy prevales (again) and some countries are allowed to use the ‘intellectual property’ and others are being denied the use of it. Every factory should be able to manufacture an updated vaccin, knowing what sequence(s) is (are) relevant at that very moment. In fact, there will be a shortage of vaccins anyway. Even when every factory in the world started producing it.
    (Today my pharmacy called me and told me the Relenza definitely will not be delivered to private buyers, because our government confiscates all from GSK, and the big central pharma distributor will not get any of it. The government wants to have all in store just in case. A bit totalitarian, I think. But it’s because of the shortage.)
    I’d rather change the proposal of Cox and others in a guaranteed and in advance fixed percentage of the production of vaccines by someone who uses the knowledge of the specified BF strain. When this is agreed on and a contract is signed, the production could start and a commitee should be supervising a fair way of keeping this promis. And a kind of punishment for not delivering the amount and medicins laid down in the contract.

    Another point is that also in my view we cannot continue to cull livestock and pets in the way it is happening until now. We dispose of valuable genes in some animal races and we cannot cull humans. At least, that’s the general opinion on human ‘culling’. Must we be glad a patient died? For a dead end of the virus and a set back in the number of mutations that happened? And the losses never really can be compensated.
    Some infected animals and humans die from H5N1, others survive. Finally we want everyone to survive. Why not keep the strong animals who have eliminated the H5N1 from their blood and bodily tissues?
    Of course, we don’t want living reservoirs of potentially mutating viruses, but we will never be able to have total control by culling most of them. Some tend to escape.
    Maybe it’s better to start (more) substantial research on means that kill viruses when they try to infect one. What should one eat, drink, do about body temperature, do on hygiene and the like to kill as much virus particles as possible, to overcome the infection?
    It’s very interesting a patient (in Sumatra) fled the hospital and got alternative treatment and was the only one who recovered.
    Because he was the only member of the family who could walk when infected with H5N1? And was to overcome the BF anyway? Or did he make a very sensitive decision in fleeing the hospital and get some ‘better’ treatment than Tamiflu?

  20. #20 Ground Zero Homeboy
    August 25, 2006

    Ha! Cats are very social when you’re not looking. Cat-specific diseases (Feline HIV f.x.) don’t come out of thin air.

    The book “Catwatching” by Desmond Morris is wonderful.

    http://www.amazon.com/gp/product/0517880539/sr=8-1/qid=1156550745/ref=pd_bbs_1/102-0446110-7818560?ie=UTF8

    Used copies starting at 49c US

  21. #21 Trina
    August 25, 2006

    Tom, you worded and ordered the worries floating around in my mind.

    Would it not suit a company who manufactures a cure for a virus not to slow the spread of the virus? Let everyone buy the vaccine.

  22. #22 revere
    August 25, 2006

    Tom, tan06: The drug companies already are licensing the vaccines and taking the money. This at least gives the originating country of the seed strain some benefit and also encourages releasing the sequences.

    There is a lot to be worked out about these agreements. The Science Commons people are extremely good (a version of the Creative Commons movement) and Ihave confidence they will come up with usefl and innovative solutions. They are not beholden to Cox or WHO or CDC or anyone.

  23. #23 Tom DVM
    August 25, 2006

    Revere.

    Where I come from this would be called ‘a pig in a poke’.

    I have respect for what pharmaceutical companies do but they are now a little bit like the pesticide industry…give them an inch and they take a mile.

    If we want real advance lets have an arrangement similar to that at polio vaccine and Connaught Laboratories in Toronto in the 1950’s.

    When was it decided that public investment in vaccines was a bad thing and when was it decided that public/private partnerships was a bad thing and where was it decided that non-profit pharmaceutical development would be a bad thing?

    Trina. Thanks.

  24. #24 mara
    August 26, 2006

    Attempting to kill all “threatening” mammals is a no brainer,which-ever way you approach it.Ever tried to herd wild cats? heh…Let’s some of us try to hate pharmaceutical corps.. a bit less for now and make it as “feasible” as possible to deliver a vaccine which I believe would be our only saviour.

  25. #25 DebP
    August 26, 2006

    I have a question(forgive me if it is nonsense or off topic). If the tamiflu blanket really does effect the testing results- to give a false negative, shouldn’t they go back and do bloodwork a few weeks later, after the tamiflu is done? Wouldn’t the person have antibodies from the ai? Couldn’t this provide more clues, by sequencing these, to tell where it came from?

  26. #26 revere
    August 26, 2006

    Tom: You have more confidence in the benefits of Big Pharma than I do. That’s why I like any initiative that starts to constrain them, as this one does. We have argued here numerous times for national/international vaccine institutes that takes vaccines out of the private sector and puts them in the public one. When was it decided to put them private? When the US voted for right wing presidents like Reagan and Canada did the same. We voters are getting what some of us deserve (and the rest of us have to suffer with them).

    DebP: Yes, you could do seroprevalence surveys later, after RX with Tamiflu. This may or may not tell you what you want (assumes infection produces seroconversion for your antibody). However it wouldn’t help much, because the person would already have been sick (or not) and possibly shed the virus (or not) by the time seroconversion was determined. And the problem some suspect is that Tamiflu prevents isolation of the virus, so there is nothing to sequence.

  27. #27 kent nickell
    August 26, 2006

    This would seem like a good area to do a seroprevalence test. If they were worried enough to do a Tamiflu blanket it would seem a good indication to try and figure out how many people actually were infected. However, as Revere alluded to this also is not perfect. The virus may not induce enough antibody to be measured or it may be changed enough to not be picked up by the testing. (Also this is an antibody to the virus and not the actual virus so sequencing can’t be done). Ideally parts of these blood samples would also be frozen in case better testing becomes available.

    It seems one theory is that Tamiflu may inhibit replication of the virus causing less viral shedding and therefore less likely to pick up especially with relatively superficial testing like in the nose. Deep testing is probably almost always preferable and would also more likely give a good sample for the gold standard of actual viral isolation in the lab for sequencing.

    This is also a chance to look for Tamiflu resistant strains in anyone who may have gotten sick while taking the meds.

    Here is the USDA sequence of testing being used on wild birds..

    http://www.usda.gov/wps/portal/usdahome?contentidonly=true&contentid=2006/06/0223.xml

    STAGES OF USDA TESTING

    I. Rapid screening tests

    A series of AI rapid screening tests are performed that cannot differentiate between HPAI and LPAI viruses. Varieties of this test can screen for the presence of all strains of AI virus, specifically for H5 or H7 subtypes and the N1 subtype.

    NVSL conducts the following rapid screening tests:

    1) Matrix test ? used to screen for AI viruses

    2) H5 test ? used to screen for H5 subtype

    3) H7 test ? used to screen for H7 subtype

    4) N1 test ? used to screen for N1 subtype

    These results can be expected within 4-7 hours after receipt by NVSL.

    II. Confirmatory tests

    1. Virus isolation test and H/N subtyping tests

    Virus isolation is the gold standard test used to diagnose AI virus infections. The virus is isolated in embryos inside chicken eggs. A series of tests follow to specifically identify H and N subtypes of the AI virus. These tests cannot determine pathogenicity.

    2. Genetic sequencing test

    This test involves identifying the genetic sequence of the virus grown and comparing it to known AI genetic sequences. These known sequences, such as that of the highly pathogenic H5N1 AI virus, are stored in databanks. If the genetic sequence matches that of a known highly pathogenic AI virus, the sample is considered to be highly pathogenic.

    3. Chicken pathogenicity test

    This test involves the inoculation of 4- to 8-week old disease-free chickens and observation for signs of AI for 10 days. According to the USDA and OIE, highly pathogenic AI is defined as any AI virus that is lethal for 6 or more of 8 chickens (75% mortality).

    Confirmatory AI test results can be expected within 5-10 days

  28. #28 mary in hawaii
    August 26, 2006

    Just to add to the last 3 comments. It would seem important to do the follow up testing deb and kent suggest for one very important reason: if it turns out that there are more than 25 people in that cluster of cases, then WHO would be able to make a more accurate assessment of whether or not it is time to raise the pandemic alert level to phase 4. If tamiflu masks a large number of cases it makes it appear we are still in the very limited H2H stage. Thus, without restrictions imposed, the disease is able to spread silently through the area to then pop up full blown somewhere else as unsuspecting people carry it in their travels.

  29. #29 Trina
    August 27, 2006

    Looked at Science Commons. I am chastised. I did not even know they existed. Or created plos. They look like an awesome group of people.

    I am a person not in the science field. I was seeing things from a far too idealistic place; just help everyone I thought.

    The politics of who owns thoughts didn’t enter my mind. I had the utopian viewpoint that science was purely in the academic world, not the business one.

    I envisioned that a working collective of knowledge already existed, and did not understand that people are only beginning to think of moving in that direction.

    I am naive.

  30. #30 Ron
    August 27, 2006

    Back on the original topic, it is really kind of ironic that poorer countries would declare intellectual property rights in their disease organisms as leverage against Big Pharma that uses those organisms to make vaccines and medicines to sell back to them. A new twist on the IP debate.

  31. #31 g510
    August 28, 2006

    Back to cats for a moment here. If I’m not mistaken, a medieval Pope once declared that cats were “the Devil’s familiars” and ordered that good Christians kill cats wherever they could be found. Minus cats, rats and mice multiplied, and along with them, their fleas, and along with those, the plague. The rest, as they say, is history.

    So let’s not go on a cat-killing spree lest we end up with a population explosion of rodents and all of the public health consequences of that.

    And speaking of population explosions, ten points to William for not being cowed by the usual social taboos against speaking the truth on that topic. “Humans should leave the animals alone, and accept their fate. The world is overpopulated with humans anyway.” Exactly. 6.5 billion headed toward 9.3 billion on a planet that can support perhaps 2.5 billion sustainably. The idea that we can go so far past overshoot without a collapse is sheer hubris. Our natural compassion and desire to save lives can best be seen as a part of the overall mechanism of natural selection: cooperation is a survival trait.