With the help of other 'diarists, particularly Trevor Kerr, we've been tracking the very human story of bird flu for some time now. We've uncovered many interesting news items and examined various aspects of what is happening and what could happen. Today Henry Miller a fellow at the Hoover Institution, Stanford University tells some of the hard truths about bird flu. Henry Miller was an FDA official from 1979 to 1994 and was a member of the OECD Group of National Experts on Biotechnology.
Hard Truths About Bird Flu
by Henry Miller
The issues surrounding the possibility of a pandemic of the H5N1 strain of avian flu are extraordinarily complex, encompassing medicine, epidemiology, virology, and even politics and ethics. Moreover, there is tremendous uncertainty about exactly when H5N1, which now primarily affects birds, might mutate into a form that is transmissible between humans, and how infectious and lethal it might be.
It is thus hardly surprising that commentaries about avian flu often miss the mark. A recent New York Times editorial, for example, decried wealthy countries’ “me first” attitude toward a possible H5N1 pandemic, because “[t]he best hope of stopping a pandemic, or at least buying time to respond, is to improve surveillance and health practices in East Africa and Asia, where one would probably begin.”
To be sure, good surveillance is needed in order to obtain early warning that a strain of H5N1 flu transmissible between humans has been detected, so that nations around the world can rapidly initiate a variety of public health measures, including a program to produce large amounts of vaccine against that strain. But the massive undertaking required to “improve health practices in the poorest countries of the world” plays better on the editorial page than on the ground.
Intensive animal husbandry procedures that place billions of poultry and swine in close proximity to humans, combined with unsanitary conditions, poverty, and grossly inadequate public health infrastructure of all kinds, make it unlikely that a pandemic can be prevented or contained at the source.. It is noteworthy that China’s chaotic effort to vaccinate 14 billion chickens has been compromised by counterfeit vaccines and the absence of protective gear for vaccination teams, which might actually spread disease by carrying fecal material on their shoes from one farm to another.
In theory, it is possible to contain a flu pandemic in its early stages by performing “ring prophylaxis” – using anti-flu drugs and quarantine aggressively to isolate relatively small outbreaks of a human-to-human transmissible strain of H5N1. According to Johns Hopkins University virologist Donald S. Burke, “it may be possible to identify a human outbreak at the earliest stage, while there are fewer than 100 cases, and deploy international resources – such as a WHO stockpile of antiviral drugs – to rapidly quench it. This ‘tipping point’ strategy is highly cost-effective.”
However, a strategy can be “cost-effective” only if it is feasible. Although ring prophylaxis might work in Minneapolis, Toronto, or Zurich, in the parts of the world where flu pandemics begin, the probability of success approaches zero. In places like Vietnam, Indonesia, and China – where the pandemic strain will likely originate – expertise, coordination, discipline, and infrastructure are lacking.
The response in Turkey – where as many as 50 possible cases have appeared in the eastern part of the country – is instructive. Officials in that region warned the government on December 16 of a surge in bird deaths, but it took 12 days for an investigation to begin. When a fourteen-year-old boy became Turkey’s first avian flu mortality last week (soon followed by two siblings), a government spokesman criticized doctors for mentioning the disease because they were “damaging Turkey’s reputation.” This is ominously reminiscent of China’s initial response to SARS in 2003.
For now, it seems that all of the human H5N1 infections have been contracted from contact with infected poultry. But the situation in Turkey is what the outbreak of a human to human pandemic could look like at its earliest stages: the rapid spread of confirmed cases (and deaths) from an initial site to nearby villages and cities. We would expect to see a large number of illnesses among both employees and patients in hospitals where the victims are treated, and soon someone (perhaps even a carrier who is not ill) would spread it to Ankara, Istanbul, Tbilisi, Damascus, Baghdad, and beyond.
The anti-flu drugs Tamiflu and Relenza are extremely expensive and in short supply. History suggests that if we were to make these drugs available to poor countries for ring prophylaxis, they would often be administered improperly – such as in sub-optimal doses – in a way that would promote viral resistance and only intensify a pandemic. Or perhaps they would be sold on the black market to enrich corrupt government officials.
A politically incorrect but rational strategy would be for rich countries to devote resources to developing countries primarily for surveillance. They would obtain timely warning of the existence of an H5N1 strain that is transmissible from human to human, but would focus the vast majority of their funding on parallel, low- and high-tech approaches – vaccines, drugs, and other public health measures – that would primarily benefit themselves.
If the pandemic were to begin relatively soon – say, within a year or two – there would be little that could be done to attenuate significantly the first wave of infections. But, if we’re ready to rush the pandemic strain into an emergency program to manufacture vaccine, we could possibly blunt the second wave.
A flu pandemic will require triage on many levels, including not only decisions about which patients are likely to benefit from scarce commodities such as drugs, vaccines, and ventilators, but also broader public policy choices about how best – among, literally, a world of possibilities – to expend resources.
***
Henry Miller is a physician and fellow at the Hoover Institution and the Competitive Enterprise Institute. From 1979 to 1994, he was an official at the US Food and Drug Administration. His next book, The Frankenfood Myth: How Protest and Politics Threaten the Biotech Revolution, will be published later this year.
Copyright: Project Syndicate, 2006.
www.project-syndicate.org
Complexities of surveillance
NHS Direct Syndromic Surveillance program in the UK collates data on symptoms, as they are reported by people with illness in England and Wales. Results are presented in graphical format - see Latest NHS Direct Bulletin in the CDR.
The immediate problem in translating this means of surveillance to Australia is in "NHS Direct is a nurse-led telephone help-line which covers the whole of England and Wales." No prizes for spotting the flaw, and for guessing why the all-powerful Australian Medical Association would lobby strenuously against nurses taking leading roles in health care. (Like the AMA fought hard against the original Medibank, and now we are stuck with a crippling fee-for-service racket.)
The charts show current influenza-like illness is not more prevalent, compared to previous years. This type of surveillance, and the data, is essential to plans for moderation of influenza epidemics and pandemics.
The UK's Health Protection Agency also presented data on National increase of Vero-cytotoxin producing E. coli O157 phage type 8 – Case-control study. The relevant point here is that these particular strains of a common gut bug can cause a type of food-poisoning that can have severe consequences. But, the authorities need to be fairly careful about shutting down businesses. As the study shows, sophisticated analyses have to be done, as well as collecting precise information about the people who have become ill. It takes a carefully designed database to track diseases with this fine degree of granularity. The reason for that is each isolate of, say, E.coli, can have a range of extra attributes, as in this study. The ones of interest have been detected by at least three schemes of typing - serological type, toxin type and phage. It is obvious that the database fields for these three features may contain other values, if another kind of disease is caused. No-one would want to see Safeway stores shut down across the country, if the E.coli in their sausages was similar, but harmless.
See The significance of Salmonella, particularly S. Infantis, to the Australian egg industry for another example. The numerous types of Salmonella are grouped into the same species, differing only in fine detail. But it matters which type, since there are pecularities in some strains that make them more likely to colonise chooks. And it appears some Salmonella are able to make their way through eggshells, and that is an entirely different mode of transfer between fowls, than passage through the ovaries. The knowledge of whether or not chook-associated Salmonella cause illness in humans, and how they move around between chooks, will have immense practical implications for the poultry industries. There are clear responsibilities for improvements, but imperfect knowledge could lead easily to false moves and injustice.
Staph. aureus has to be assigned with different attributes, too. At the present, we concentrate on their various abilities to resist the effects of antibiotics, but as knowledge increases we will need to track them by other characteristics. But, in the end, it's the same need - to be able to identify the facts with precision, and avoid laying blame in the wrong place.
The consequences of this need, for several nested layers of attribution, impinge directly on design and power of the databases that store information about illnesses. Poorly designed, or underpowered, databases prevent us from storing accurate and accessible data.
As this work - St. Jude Conducts First Large-scale Bird Flu Genome Study - we may have to track influenza infections by variations in single genes of the virus:
Paul Krugman wrote for the New York Times (Health Care Confidential, it's pay-for-view) on the success of the Veterans Health Administration in the US:
"Electronic record-keeping" is the key to surveillance for infectious diseases, including influenza, also. In case anyone's listening, the VHA's system is called VistA, not to be confused with a Microsoft product of the same name.
SBS documentary - 5 stars
The SBS documentary on Pandemic Influenza (Super Flu - Race Against a Killer) broadcast Sunday Jan 15th, was a cracker. A number of international experts were interviewed, and their contributions woven skilfully into a pretty scary narrative. It started with the hypothetical situation based on the ease with which a recently infected returning traveller could bring to Sydney an early case of human-adapted H5N1 infection that was transmitting between humans in the same manner as ordinary, seasonal influenza.
A weakness in the production, at this point, was that it did not explain the essential differences between 'airborne' and 'droplets' as vehicles for transmission. The documentary laboured the 'airborne' aspect, as being necessary for pandemic spread, but the graphics were more appropriate for droplet spread. The illustrations showed the potential for spread of virus via handprints, but they failed to even mention hygienic precautions, such as decontamination of hands and disposal of soiled tissues, as part of daily living.
The central interlocutor was Robert Webster, a virologist (and native of NZ) based in a US laboratory. He was very keen about the frightening features of some of the latest experimental findings. I thought he was a trifle alarmist, but have since changed my mind. (I also thought that more information about his commercial relationships, involved in the production of his new vaccine for H5N1, was needed.)
The film went into mutations and reassortments, made the point that there are other candidates for the next pandemic (than H5N1) and all in all, was fairly balanced.
The biggest surprise was a segment on the work with H5N1 in domestic cats. Having just read the paper, I can understand the alarm expressed by Webster and the others, and expect more to come. But, the paper was published only two weeks ago, yet the film must have taken more than a month to put together. It was produced in Australia, and is very well informed. So, by whom? The credits went by too quickly. They said it will be available on DVD.
As an aside, there must be better water in NZ. How's this for forward thinking? They are running advertisements for 'Leading influenza pandemic planning – psychosocial recovery' (See Project Manager - KC214).
PS - The Dilemma of Personal Tamiflu Stockpiling by Sandman and Lanard.
Influenza, innovations and secrets.
This phrasing incorrectly ascribes a type of intent to viruses. Viruses do not think. Although, in the current paradigm of specialness being assumed by citizens of the US, George Bush will probably claim that the viruses that infect Americans are doing it out of deliberate malice.
An extension of that type of magical thinking is found in Mutation found in Turkish bird flu:
Once again, viruses are not equipped to "try" anything. However, the interest in mutations is intense, and molecular analyses are performed on viruses from various geographical locations. Results from H5N1 analyses is helpful.
The mutations being referred to in the last article are based on findings from recent genetic analyses. But, mutations are only one pathway to change in the genetic makeup of an influenza virus. Of equal importance, at this stage in our (rapidly accumulating) knowledge, is genetic reassortment. It is believed that sudden changes can occur when a person (or bird, or mammal) is infected at the same time with viruses from two sources, say, a human H3N2 and an avian H5N1.
In the case of the outbreak of human infections with H5N1 in Turkey, observers would be keen to know if there was any evidence of co-existing transmission of H3N1. As far as I can tell, there is none. At the Fluwatch website in Canada, the incidence of 'ordinary' influenza - H3N2 - is rather low. As the charts show, several other respiratory viruses typically circulate, and cause infections, during winter.
See Flu Not The Only Germ Threat This Time Of Year.
There is great potential for huge profits in anti-virals and vaccines. The investment dollars will be attracted to projects like New Technique For Detecting Ability Of Flu Viruses To Infect Humans and Gene-specific Ebola Therapies Protect Non-human Primates From Lethal Disease.
But, as more knowledge about influenza is discovered, proportionately more of it will be sequestered into the domain of 'commercial in confidence'.
From Drug lobby preparing a bitter pill by Thomas Faunce and David Henry:
But, in the context of appalling living conditions for at least one billion of humankind, is a rotavirus vaccine money well spent? It would be, if the first world got stuck into providing everyone else with drinkable water and sewerage systems. In the end, though, villagers will still be dying of preventable infections, including diarrhea, and malnutrition, after the wealthy nations have pledged to "donate" rotavirus vaccine. "Well, we've spent a ten billion dollars of our money to stop rotavirus infections for one year, but you ungrateful people are still complaining. We prefer to sell F16s and sophisticated missiles to your impoverished governments, anyway."
There's another call for more innovation, in Bioterrorism — Preparing to Fight the Next War by D. A. Relman:
The tone of Relman's article is that amateur evil-doers, perhaps millions of them, are flat out at work in their kitchens, trying to construct "super-bugs". And they have one prime target - America. He writes "large-scale industrial processes are not necessary for the development of potent biologic weapons", but does not give an example. I doubt, very much, that any of the genetic manipulations he mentions can be achieved with a cook-book approach. I believe there are serious logical flaws, let alone a kind of cultic hyper-alarm, in his paper, and I hope someone gives it a good thrashing.
In 'Targeting Bioterrorism', a review of three books at New England Journal of Medicine Jan 12th (no free access), Karl Johnson takes a more measured posture in addressing the same themes as Relman:
Matthew Meselson is a renowned authority on bioterrorism; more from him at New York Review of Books and PBS.
I wonder what Bush, Cheney, Rumsfeld and their puppetmasters think of biological agents, in the broader concerns of manifest destiny, and how easily our leaders could be duped into setting up covert laboratories.
Announcing EU aid worth $100 million
Seems decision-makers are not listening to Mr Miller's prescription for a "politically incorrect but rational strategy".
Announcing aid worth $100 million at a news conference in Brussels, European Union External Relations Commissioner Benita Ferrero-Waldner said, "The costs of tackling bird flu are indeed substantial, but I am convinced that it is better to spend now on controlling avian influenza at the source than have to spend much more at a catastrophic event of a human pandemic." (see SBS World News)
Commissioner for Development and Humanitarian Aid, Louis Michel said, “We must take a global approach to this pandemic and we must anticipate and not just react to events. Hence, the European Commission stands ready to support all developing countries fight this potential threat. We will also have a special focus in Africa to counter the epidemiological risks and in particular the potential vulnerability of animal health systems in Africa.”
Personally I'm glad they are saying what they are saying and putting their money where their mouth is.