Effect Measure

After spending more time than I wished “defending” WHO against what I considered a particular kind of scurrilous attack (it also seemed to raise the hackles of some unintended as targets, but the dialog with them was at least rational) — after all that, I now have to turn around and complain about WHO (again). Let me be constructive and offer their spokesperson, John Rainford (or whoever writes the statements he mouths), a little biology lesson. A mutation of a virus is a technical term that describes a replicable change in the sequence of bases that constitute the virus’s genetic blueprint and its heritable material (for influenza, RNA). The genetic blueprint is one of the main (but not only) determinants of how the virus behaves and spreads in a population of potential hosts — like birds or us. If you want to see if one has occurred you look at the sequence of bases in the virus’s RNA (or, almost equivalently, the sequence of amino acids in proteins coded for by the RNA). If you want to know what the mutations mean, you also have to know quite a bit about the biology of the virus in a particular host. We don’t know most of what we would like to know about that part of the picture for influenza A, especially the subtype of influenza/A we are most worried about these days, subtype H5N1. Why the lesson?

The World Health Organisation on Friday ruled out any mutation of the potentially fatal H5N1 strain of the bird flu virus after a case of inter-human transmission of bird flu may have been detected in Pakistan.

“There is no suggestion that the virus has changed into a form that poses a broader risk,” WHO spokesman John Rainford told AFP. “If that had been the case, we would have witnessed more cases of human transmission.”

Rainford said that the genetic sequencing of the virus involved in the latest case was being continued. (Agence France Presse)

What’s wrong with this? Suppose (for the sake of argument) it takes two changes to turn a virus into one that “poses a broader risk” and only one has occurred in this case. We wouldn’t know this by seeing if there were more cases. We would only know this if we looked at the sequence and further, we knew what to look for (which two changes to track). It isn’t clear that the viral sequence in this case has been examined completely (and we hope that when it is examined, the sequence will be deposited immediately into a publicly accessible database like GenBank). It is also quite clear we don’t know what to look for, so a categorical statement that “a mutation” has been “ruled out” isn’t true and cannot be true at this point.

It’s bad enough that WHO doesn’t release information it can release quickly enough; or that there is some information it cannot release or chooses not to release at all but doesn’t tell us why it cannot release it or chooses not to release it.

It’s worse that too often the information it does release is wrong.

Comments

  1. #1 daedalus2u
    December 30, 2007

    My understanding is that what (mostly) determines transmission is the composition of the part of the virus that binds to the human receptor. If genes for that part and that part alone had been sequenced and found to be not mutated, then it would not have changed to a form that posed a broader risk (most likely).

    Mutations in that part have been found that (presumably) do increase transmission. Presumably they could look for that very quickly (and would). If that were negative, they would still want to sequence the whole thing.

    http://www.ncbi.nlm.nih.gov/pubmed/17626098?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

  2. #2 revere
    December 30, 2007

    daedulus2: Not completely. As I noted in a post the other day, H1N1 circulating in birds has human receptor but poultry workers don’t get infected much. Human respiratory tract has plenty of “avian” receptor. So there is much more to it. What it is, we are just starting to disentangle. If the receptor were the only factor it would be difficult but not anywhere near as difficult as it is in reality. The part they have will almost certainly have genetic differences with the avian consensus sequence. That is almost always true. It is what they mean that is the difficult part.

  3. #3 davidp
    December 30, 2007

    It sounds like the reporter may be to blame – if the reporters were asking “Is this the mutant epidemic causing Bird Flu we’ve been fearing?” John Rainford could say what he said without any misunderstanding of mutation etc. The reporter writes what was “ruled out” not the spokesman. I’ve read the whole AFP release and find it consistent with this.

  4. #4 AlbertAFT
    December 30, 2007

    Good post revere.

    Feel free to stop by AFT sometime.

    Kind regards,
    A

  5. #5 revere
    December 30, 2007

    davidp: Could be but not likely IMO. This is rather typical of the loose talk of WHO spokesmen. It has a long history. They are not at all careful and they careless in ways that serve their objective of reassurance. They are the World Health Organization, not the World Reassurance Organization. They have many parts, but the PR part frequently doesn’t understand this. Moreover it is the job of the spokesperson to speak in ways the reporter understands and can’t get it wrong.

  6. #6 Dipl.-Ing. Wilfried Soddemann
    December 31, 2007

    Transmission of avian flu by drinking water

    Transmission of avian flu by direct contact to infected poultry is an unproved assumption from the WHO. Infected poultry can everywhere contaminate the drinking water. All humans have contact to drinking water. Special in cases of decentral water supplies this pathway can explain small cluster in households. In hot climates/tropics the flood-related influenza is typical after extreme weather and natural after floods. Virulence of Influenza virus depends on temperature and time. If young and fresh H5N1 contaminated water from low local wells, cisterns, tanks, rain barrels or rice fields is used for water supply water temperature for infection may be higher (24�C: virulence of influenza viruses 2 days) as in temperate climates with older water from central water supplies (7�C: virulence of influenza viruses 14 days).
    Human to human and contact transmission of influenza occur – but are overvalued immense. In the course of Influenza epidemics in Germany recognized cluster are rarely (9% of the cases in the season 2005).
    In temperate climates the lethal H5N1 avian flu virus will be transferred to humans strong seasonal in the cold via cold drinking water, as with the birds feb/mar 2006.
    Recent research must worry: So far the virus had to reach the bronchi and the lungs in order to infect humans. Now it infects the upper respiratory system (mucous membranes of the throat e.g. when drinking and mucous membranes of the nose and probably also the conjunctiva of the eyes as well as the eardrum e.g. at showering). In a few cases (Viet Nam, Thailand) stomach and intestine by the H5N1 virus were stricken but not the bronchi and the lungs. The virus might been orally taken up, e.g. when drinking contaminated water.
    The performance to eliminate viruses of the drinking water processing plants regularly does not meet the requirements of the WHO and the USA/USEPA. Conventional disinfection procedures are poor, because microorganisms in the water are not in suspension, but embedded in particles. Even ground water used for drinking water is not free from viruses.
    In temperate climates the strong seasonal waterborne infections like norovirus, rotavirus, salmonellae, campylobacter and – differing from the usual dogma – influenza are mainly triggered by drinking water dependent on the drinking water temperature (in Germany minimum feb/mar � maximum august). There is no evidence that influenza primary is transmitted by saliva droplets. In temperate climates the strong interdependence between influenza infections and environmental temperatures can�t be explained with the primary biotic transmission by saliva droplets from human to human with temperatures of 37.5�C. There must be an abiotic vehicle like cold drinking water. There is no other appropriate abiotic vehicle. In Germany about 98% of inhabitants have a central public water supply with older and better protected water. Therefore in temperate climates like in Germany cold water is decisive to virulence of viruses.

    Dipl.-Ing. Wilfried Soddemann
    eMail soddemann-aachen@t-online.de
    http://www.dugi-ev.de/information.html
    Epidemiological Analysis:
    http://www.dugi-ev.de/TW_INFEKTIONEN_H5N1_20071019.pdf

  7. #7 M. Randolph Kruger
    December 31, 2007

    Politics and bird flu are not a good mix

    Emmy Fitri, Jakarta

    People will do so much to be called a hero, even if it’s too late or way too early to be one. That’s a dreadful afterthought having read an interview in the journal Nature with Indonesian Health Minister Siti Fadilah Supari.

    In the interview, published online on Dec. 19, Siti explained why Indonesia has persistently refused to share its H5N1 virus samples with the WHO until it is assured of a vaccine supply in the event of a pandemic.

    She was quoted as saying “Indonesia is open to international collaboration but this must be fair, transparent and equitable. The WHO’s Global Influenza Surveillance Network system is obviously unfair and opaque. Samples shared become the property of the WHO collaborating centers in rich countries, where they are used to generate research papers, patents and to commercialize vaccines. But the developing countries that supply the samples do not share in these benefits.”

    With those strong words against the world, are we off the hook simply because we are be poor and bear the huge burden of a population over 220 million? Are we excused for being ungrateful after so long relying on the generosity of donors and international agencies in fighting diseases, including the big three — AIDS, tuberculosis and malaria?

    Most of all, is it the right time to challenge a long-standing protocol after decades of compliance? Why now? Why not 10 or 20 years ago, or next year?

    By and large, are we really aiming at contributing to a better world by stubbornly holding the samples with one hand while the other hand fumbles about so clumsily for international aid?

    Many meetings have been held by the WHO to settle the standoff with Indonesia, and many talks held by Indonesia to win allies from neighboring countries, but none ever seems to settle the dispute.

    Maybe Indonesia is barking up the wrong tree. The country has turned a blind eye to the fact that battling bird flu and other diseases is not a matter of playing victim before the international community and seeking attention over nothing.

    Isn’t it natural that if we want to fly, we cannot just wait for angels to lend us wings? We have to learn how to make aircraft. There is so much to be done to show the world that we are not so poor and needy.

    Preventing more deaths by educating the public about proper poultry handling is the top concern. Unlike diplomacy and politics, viruses don’t discriminate. It is just irrelevant to bring up a political perspective in the name of the nation’s dignity. The minister could have better used a little politics to butter up parliament members and provincial and regental officials in order to get more funds and resources to battle the virus.

    Indonesia is not the first country to be offended by the protocol; the system is not flawless. Some countries, such as China and Thailand, have had similar complaints, but their problems were settled amicably.

    A tropical country, Indonesia is a hotbed for germs, viruses and bacteria. Yet people show scant awareness of good sanitary practices. They are not the only ones to blame for their ignorance, since apparently the government’s development and education programs have not yet picked up on the fact that we are all living with lots of microbes.

    Not only is there no effort to translate the threat of disease into public policies and educational content, but generally speaking, health issues are treated as second-class.

    It’s not surprising that Indonesia is so dependent on the private sector and the international community’ generosity in containing diseases, even those endemic to this country. It stems from the government’s failure to prioritize money and strategies to strengthen the health sector.

    Bird flu is just one of many health problems facing Indonesia. With, according to the World Bank, more than 45 percent of this country’s population impoverished, perhaps it is natural for the public and even officials to think of bird flu as just another disease. But it is not.

    Globally, bird flu has vaulted into the limelight because of fears that the H5N1 virus could mutate so that it can be transmitted from human to human, thus laying the groundwork for a pandemic.

    The 1918 flu virus caused one of the worst pandemics in human history. It’s frightening to think how quickly a disease spread through a cough or handshake might travel today, as people fly from one continent to another at the drop of a hat.

    To imagine a pandemic hitting Indonesia — heaven forbid — is unbearable.

    Do we need human vaccines in a time of pandemic? Even if we do, the global production capacity, currently estimated at less than 500 million doses per year, will never meet the need.

    A down-to-earth effort which is less costly than waging war against the world must be devised. As recommended in the December Ministerial Meeting in New Delhi, non-pharmaceutical measures must be pursued vigorously.

    We must prepare officials, both civilian and military, to respond in a quick and organized way to pandemics. Because Indonesia is an agricultural country, coordinated efforts to manage the human and animal health sectors also cannot wait.

    If anything has to be politicized, let’s use political diplomacy to convince state officials that the threat is real and people’s lives at stake because of their ignorance.

    The author is a staff writer at The Jakarta Post

  8. #8 anon
    December 31, 2007

    “ruled out” is just common speak. Like “I’m sure that”
    or “we know that”. It’s never 100%, just considered likely,
    how much – that’s individual.
    I read it, that he thinks >90% that no
    significant mutations will be mentioned later
    (1-2 years ?-( ) in a paper concerning that virus.

  9. #9 revere
    December 31, 2007

    anon: No. “Ruled out” is a medical term that means “ruled out,” as in, “that isn’t it.” This is a common phrase in medicine that means what it says.

  10. #10 medlclinician
    December 31, 2007

    Whenever you have organizations and countries staffed by doctors and scientists releasing information which is untrue, this is not a casual oversight or blooper. These are educated and informed career health professionals who know their fields and the information release is deliberate, not some slip or accident. Eventually, and there are many intelligent peoples who eyes read Revere posts, the obvious will become more obvious. People know the truth, an organizations know the truth. Intelligent people stop defending them when what they are saying isn’t. M.C. R.N. and Medical Research Team Leader

  11. #11 Marissa
    December 31, 2007

    WHO needs a better spokesperson. There are always nearly mutations, but (we believe) most of them are inconsequential. For the mutations affecting key parts of the HA, NS1 subunits it may be easy to see in some cases whether these changes are likely to have altered some of the virus characteristics, but we do NOT know for sure since we have never looked at all the permutations and linked those to the results of chip-array models, which are only an approximation in the end, anyway.

  12. #12 SusanC
    December 31, 2007

    revere,

    davidp: Could be but not likely IMO. This is rather typical of the loose talk of WHO spokesmen. It has a long history. They are not at all careful and they careless in ways that serve their objective of reassurance. They are the World Health Organization, not the World Reassurance Organization. They have many parts, but the PR part frequently doesn’t understand this. Moreover it is the job of the spokesperson to speak in ways the reporter understands and can’t get it wrong.

    I agree. This is not the first time. It’s hard enough to get any media interest on this subject. It really sucks when they can’t use these opportunities to put out correct information.

  13. #13 AnnieRN
    December 31, 2007

    I think the statements made in this post are exactly why there are so many responses to revere’s previous “WHO-bashing” post. I remember a comment scrawled on the bathroom wall in college, when the college prez was trying to get rid of two professional schools which had 99% women faculty and students. “[Prez’s name] is treating us like mushrooms. He’s keeping us in the dark and covering us with s—.” WHO’s reporting looks a bit too mushroom-y to me, and this post appears to raise those same concerns. AnnieRN

  14. #14 Sock Puppet of the Great Satan
    January 2, 2008

    ‘anon: No. “Ruled out” is a medical term that means “ruled out,” as in, “that isn’t it.” This is a common phrase in medicine that means what it says.’

    Yeah, but the “ruled out” isn’t a quote from the WHO spokesman. Assuming this isn’t a reprint of a WHO press release, it’s a phrasing from the France-Presse agency.

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