The idea of stopping an emerging influenza pandemic would have seemed ridiculous until a few years ago, but today the world just might have a chance to do that, according to two flu experts who published opinion pieces this week.
The World Health Organization (WHO) and many others have been warning frequently that the H5N1 avian influenza virus circulating in Southeast Asia could launch a human flu pandemic. The virus has infected more than 50 people in Vietnam and Thailand and killed most of them, but it has not yet found a way to spread easily from person to person.
Writing in the New England Journal of Medicine, Klaus Stohr, head of the WHO´s global influenza program, says the virus could acquire this ability suddenly by mixing with a human-adapted flu virus. Alternatively, he speculates, the virus might develop this ability more gradually by incrementally adapting to human hosts.
If the latter happens and is detected, Stohr writes, "Its detection could open an opportunity to intervene with antiviral drugs or a vaccine and thus forestall international spread or even eliminate a virus with low transmissibility.
"Though it is an attractive option, no attempt has ever been made to interrupt the transmission of an influenzavirus; the results of such an enormous and costly undertaking remain uncertain. The option deserves further investigation, however, particularly when viewed against the profound effect a delay in global spread and a flattening of the peak in disease prevalence could have during the initial phase of a pandemic."
One potential way to arrest an emerging flu pandemic would be to quickly treat patients and their contacts with the antiviral drug oseltamivir, which is known to inhibit H5N1 viruses, according to Arnold S. Monto, MD, professor of epidemiology at the University of Michigan in Ann Arbor.
In a separate commentary piece in NEJM, Monto writes, "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."
Both Stohr and Monto acknowledge that such an effort would face big obstacles. "A mobile stockpile of the drug would have to exist and be made available in the affected country," writes Monto. A number of developed countries are already stockpiling oseltamivir against the threat of a pandemic. Hence, stockpiling the drug in countries now affected by avian flu could require diverting supplies from other national stockpiles. "However, this diversion must happen," he states.
Monto adds that the idea of trying to stop a pandemic at its source "would have been considered laughable just a few years ago—but that was before SARS [severe acute respiratory syndrome] transmission was controlled by public health measures." Though no effective treatment for SARS has yet been developed, the disease was controlled through such standard measures as isolating patients, quarantining exposed people, and screening travelers.
But heading off an H5N1 flu pandemic with vaccination and antiviral drugs probably isn´t possible at this point, in the view of infectious disease authority Michael T. Osterholm, PhD, MPH.
It takes days to confirm a case of H5N1 avian flu, and treating the patient and his or her contacts with oseltamivir during that time would be a needless use of the drug if the illness turned out to be something else, he told CIDRAP News. "You wouldn´t want to use oseltamivir for everyone coming in with a flu-like illness, because you would quickly exhaust the world supply," he said.
Osterholm, who is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of this Web site, expressed doubt about the practicability of finding and treating the contacts of case-patients in time to stop transmission of H5N1. "I think the movement of humans today is so dynamic that we have a very leaky system," he said.
As for immunization, some H5N1 vaccines are under development, but no one knows whether they would work against an emerging pandemic strain, he said. "We don´t have a pandemic strain of vaccine yet, and we don´t have any idea whether any of the vaccines to date would be efficacious."
Osterholm said he currently knows of no other practical ways to stave off a flu pandemic, should the H5N1 virus soon become capable of spreading. "Once we have sustained transmission in humans, all the science, experience, and my gut tell me we´re going to be dealing with a worldwide pandemic," he said. He suggested that leaders should focus on finding ways to keep governments operating and protect infrastructures in the face of a pandemic.
Stohr writes that it is a mystery why the H5N1 virus hasn´t already evolved into a pandemic form by "reassorting" with human flu viruses, given the large numbers of Asian poultry workers and healthcare workers already exposed to it. He says the explanation could be sheer luck, or it could be "that reassortment has occurred but has resulted in viruses that are not viable, not pathogenic, or not more easily transmitted among humans than H5N1 already is."
The only way to answer the question is to produce reassortment in a secure laboratory, and one laboratory is doing that, Stohr writes. He doesn´t name the lab, but the US Centers for Disease Control and Prevention recently revealed that it would conduct reassortment experiments. Stohr´s article says this research may not be completed before the end of this year.
See also:
Stohr K. Avian influenza and pandemics—research needs and opportunities. N Engl J Med 2005;352(4):405-7
http://content.nejm.org/cgi/reprint/NEJMe048344v1.pdf
Monto AS. The threat of an avian influenza pandemic. N Engl J Med 2005;352(4):323-5
http://content.nejm.org/cgi/reprint/NEJMp048343v1.pdf
CIDRAP News story, "CDC to mix avian, human flu viruses in pandemic study"
http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jan1404hybrids.html
