The New England Journal's bird flu articles
On Monday The New England Journal of Medicine (NEJM) provided Early Release on-line versions of three articles related to avian influenza A(H5N1). [NB: These articles were available without subscription until today, when the print version was published. The NEJM's practice shutting off Open Access to material of such importance is not just annoying but irresponsible. Links are provided below for those wishing to purchase individual copies or who have subscriptions or access through their institutions.]
The main paper is an original research article, detailing an investigation into a cluster of three cases in Thailand in the summer of 2004. It shows likely person-to-person transmission from an 11 year old girl (who may have had contact with infected birds) to her mother and to her aunt who both cared for her during her fatal illness (Probable Person-to-Person Transmission of Avian Influenza A (H5N1), K. Ungchusak and Others ). The mother died but the aunt, treated with the antiviral oseltamavir (Tamiflu), survived. Examination of the genetic sequence of available viral specimens did not suggest that a fundamental mutation allowing facile human-to-human transmission had occurred in the virus. Thus this appears to be an example of the rare person-to-person transmission of the disease which has been suspected in some other circumstances, but not documented as here.
The paper was accompanied by a Perspective (The Threat of an Avian Influenza Pandemic, A.S. Monto ) and an Editorial (Avian Influenza and Pandemics — Research Needs and Opportunities, K. Stöhr ). Stöhr is with WHO's Global Influenza Programme. His Editorial adds little to what he and others have said previously. Monto's Perspective, however, deserves some additional comment. Here is the "money quote":
First, what are the US stocks of oseltamavir and where are they? According to speakers on Monday at the National Bioterrorism Conference in Ann Arbor, Michigan, the US Strategic National Stockpile (SNS) has only 2 million doses of oseltamavir, although Federal officials have "talked" about increasing it to 10 million, still a woefully inadequate supply. It is estimated that there may be another 4 million doses in regular commercial channels in the US (via Pathogen Alert). We note that Hong Kong alone has 1.7 million doses and expects to double this by mid year (via Reuters Alertnet). So much for adequate planning.
But Monto's Perspective also raises some important ethical questions. Oseltamavir can be used either for prophylaxis (prevention) or early treatment. In the face of short supply, who will get the drug and how will it be partitioned between prophylaxis and treatment? Thus there are important questions of rationing and allocation for our own population.
But there is an additional, international question. Monto's Perspective implies that a country not yet affected might send its scarce supply of antiviral agent to a country where an epidemic might be getting underway, like Viet Nam or Thailand. The hope would be that we could stop the epidemic before it becomes a pandemic, thus protecting people globally. But if we miss, then the donating country would have even less stock. Australia is a country with a relative (per capita) excess of oseltamavir. Alan Hampson, deputy director of WHO's Collaboration Centre for Influenza in Melbourne has already suggested the best use might be to send a portion of it to stamp out an outbreak elsewhere (via The Australian).
Thus among the broad range of experts we will need in the event of a pandemic, bioethicists will be among the most important.
Or maybe not. We could just leave it to the good, family values-based moral judgment of the Bush Administration. Do you feel safer now?
(See sidebar for links to other posts on bird flu.)
The main paper is an original research article, detailing an investigation into a cluster of three cases in Thailand in the summer of 2004. It shows likely person-to-person transmission from an 11 year old girl (who may have had contact with infected birds) to her mother and to her aunt who both cared for her during her fatal illness (Probable Person-to-Person Transmission of Avian Influenza A (H5N1), K. Ungchusak and Others ). The mother died but the aunt, treated with the antiviral oseltamavir (Tamiflu), survived. Examination of the genetic sequence of available viral specimens did not suggest that a fundamental mutation allowing facile human-to-human transmission had occurred in the virus. Thus this appears to be an example of the rare person-to-person transmission of the disease which has been suspected in some other circumstances, but not documented as here.
The paper was accompanied by a Perspective (The Threat of an Avian Influenza Pandemic, A.S. Monto ) and an Editorial (Avian Influenza and Pandemics — Research Needs and Opportunities, K. Stöhr ). Stöhr is with WHO's Global Influenza Programme. His Editorial adds little to what he and others have said previously. Monto's Perspective, however, deserves some additional comment. Here is the "money quote":
But what if recognized transmission does begin to occur in a limited geographic area? Isolation and quarantine, which have proved effective against the severe acute respiratory syndrome (SARS), will probably not be sufficient to stop the spread of such an infection. Vaccine specific for the new strain will not be available for months after its appearance in humans . . . .It should be noted that Monto properly reported he received consultation fees and grant support from Roche, the drug company that makes oseltamavir (Tamiflu). Since he is advocating the use of this antiviral it presents an unfortunate appearance of a conflict, but it is probably true that for the moment oseltamavir is the only (medical) game in town and his comments seem reasonable and plausible. Assuming this, it raises several questions.
We know that the neuraminidase inhibitor oseltamivir inhibits the type A (H5N1) viruses. It might be possible to achieve local control of an incipient outbreak among humans by using oseltamivir for prophylaxis in the contacts of patients as well as for treatment in the infected persons themselves. Treatment of patients alone would not prevent further spread, but it might reduce the shedding of the virus and would, in any event, be required for ethical reasons. All these actions rely on early recognition through good surveillance and the ability to deliver the antiviral drug at a time when transmission might still be inefficient.
The logistic hurdles are formidable. A mobile stockpile of the drug would have to exist and be made available in the affected country. Oseltamivir is now being stockpiled by a number of developed countries for use once a pandemic virus becomes established and begins to spread rapidly around the globe. Developing a stockpile in an attempt to restrict the spread of the new virus at its source might mean diverting drugs from other national stockpiles. However, this diversion must happen. The notion of trying to control a pandemic at its source would have been considered laughable just a few years ago — but that was before SARS transmission was controlled by public health measures. We have no idea whether a type A (H5N1) virus that was fully adapted to humans would continue to be highly lethal, but it is nevertheless incumbent on the global community to try to contain it.
The avian origin of previous pandemic viruses was recognized only after the fact; this time, we have been given a warning. We really are not sure when, or whether, the type A (H5N1) virus will start to spread among humans, but we must be ready to stop it if we can — and, if we cannot, at least to mitigate its effects through the use of stockpiled antiviral drugs and, eventually, strain-specific vaccine.
First, what are the US stocks of oseltamavir and where are they? According to speakers on Monday at the National Bioterrorism Conference in Ann Arbor, Michigan, the US Strategic National Stockpile (SNS) has only 2 million doses of oseltamavir, although Federal officials have "talked" about increasing it to 10 million, still a woefully inadequate supply. It is estimated that there may be another 4 million doses in regular commercial channels in the US (via Pathogen Alert). We note that Hong Kong alone has 1.7 million doses and expects to double this by mid year (via Reuters Alertnet). So much for adequate planning.
But Monto's Perspective also raises some important ethical questions. Oseltamavir can be used either for prophylaxis (prevention) or early treatment. In the face of short supply, who will get the drug and how will it be partitioned between prophylaxis and treatment? Thus there are important questions of rationing and allocation for our own population.
But there is an additional, international question. Monto's Perspective implies that a country not yet affected might send its scarce supply of antiviral agent to a country where an epidemic might be getting underway, like Viet Nam or Thailand. The hope would be that we could stop the epidemic before it becomes a pandemic, thus protecting people globally. But if we miss, then the donating country would have even less stock. Australia is a country with a relative (per capita) excess of oseltamavir. Alan Hampson, deputy director of WHO's Collaboration Centre for Influenza in Melbourne has already suggested the best use might be to send a portion of it to stamp out an outbreak elsewhere (via The Australian).
Thus among the broad range of experts we will need in the event of a pandemic, bioethicists will be among the most important.
Or maybe not. We could just leave it to the good, family values-based moral judgment of the Bush Administration. Do you feel safer now?
(See sidebar for links to other posts on bird flu.)
posted by Revere at
1/26/2005 08:04:00 PM
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