(CIDRAP Source Osterholm Briefing) – How are you explaining the current risk of an H5N1-related influenza pandemic to your boss, the emergency preparedness committee, or the executive suite today? Is the task daunting? Are you being waved off with the comment that all this attention to pandemic preparedness is just public health’s version of Y2K?If so, you are not alone. After all, while sporadic human cases and bird-related outbreaks continue, the last worrisome cluster of human cases emerged more than a year ago. And the much-anticipated trigger that would launch many pandemic plans—sustained human-to-human transmission of the deadly H5N1 strain of influenza—has yet to occur. Maybe you are even questioning whether this current level of bird and human virus activity is the “new normal.” Perhaps you’re wondering if you can relax your preparedness efforts a bit.The answer is absolutely not. The risk of H5N1 causing a pandemic remains very real. Yet no one with a credible understanding of influenza virology can put odds on that risk. Given that quandary, what are responsible planners supposed to say and do? Let me see if I can offer help.Companies built to last take the long viewWe routinely plan for disasters that we can anticipate but for which we are unable to predict the exact time or place. Ten pandemics have been documented in the last 300 years, and we know more will happen in the future. So why has the much-watched H5N1 virus suddenly fallen off the radar screen?Ten years ago in May, H5N1 claimed its first human victim in Hong Kong. Public health authorities documented what they considered an apparent isolated case of human H5N1 infection. Later that year, an outbreak of H5N1 in domestic waterfowl sold in Hong Kong markets resulted in another human outbreak. By November 1997, 18 human cases of H5N1 infection, with six deaths, were documented. Sustained person-to-person transmission did not occur, and the outbreak stopped when all birds in the Hong Kong commercial poultry industry (about 1.4 million) were slaughtered.With a backdrop of international news coverage, some public health and animal health officials claimed that the prompt and unprecedented avian control efforts likely averted the next influenza pandemic. This event and such statements likely “set up” an expectation that H5N1 could cause the next pandemic. The public felt that if we didn’t control the threat at that moment, a pandemic would begin. Then everyone felt relief, which led to the sense that we could quash the threat.But H5N1 resurged in Asia in the fall of 2003 and spread in domestic poultry farms at an historically unprecedented rate. Human cases with bird contact followed. Obviously, the success claimed in eradicating the virus as a future pandemic risk was premature. The 2003 outbreak tapered off in spring 2004, but in summer it reemerged in several Asian countries (including Cambodia, China, Laos, Thailand, and Vietnam), where the virus continues to infect and kill people.But because sustained human-to-human transmission has yet to happen, we see much of the public and many preparedness officials confused about the risk. Unfortunately, many seem to believe that, like a severe weather warning that ends without incident, the risk of H5N1 causing another pandemic will pass with time. Companies built to last won’t be fooled by such short-sightedness.Why you should keep watching H5N1The H5N1 strains currently causing outbreaks across Asia and elsewhere are genetically distinct from the strain isolated from humans in Hong Kong in 1997. The virus continues to produce a virtual kaleidoscope of new strains. And that’s dangerous.Leading influenza experts who gathered in Toronto last week at the International Conference on Options for the Control of Influenza offered some sobering observations:Southeast Asia, the area from which the virus began spreading in late 2003, has seen multiple H5N1 bird outbreaks just in the past month, along with Vietnam’s first human death in 2 years, noted Dr. Watanee Kalpravidh of the United Nations’ Food and Agriculture Organization. “Freedom from infection has not been sustained in the region,” she said. “There has been a recurrence of cases in most of the affected countries, with some countries having continuing outbreaks. The virus may be endemic in some countries.”Dr. Ian Brown of the British government’s Veterinary Laboratory Agency noted that in Europe and the Russian Federation, “the reemergence of the virus in a number of countries does suggest we are moving toward endemicity,” even though some countries have deployed vaccinations against the disease.The apparent endemic threat means that every day this virus is replicating, and with each reproduction of itself, such viral activity leads to another chance for a critical pandemic-related genetic mutation.Remember H3N8I would also remind every pandemic preparedness planner never to forget our experience with the H3N8 influenza virus. What the heck is H3N8, you may ask?This strain of avian influenza virus emerged as an important cause of illness in horses in the early 1960s. No one understands from either a genetic or transmission standpoint why it jumped from birds to horses. Then, after more than 40 years of ongoing transmission in horses, this virus was suddenly able to infect dogs. Initially the infection only occurred in racing greyhounds, a breed of dogs that has close contact with race horses.Since 2004 when the first isolated cases of greyhound infections were documented, H3N8 has become widespread in pet dogs throughout the United States. No one can provide a clear explanation why this new disease problem has occurred except to say some unexplained changes along the bird-to-horse, horse-to-dog transmission road took place.Such a phenomenon very well could be a model of bird-to-human transmission of H5N1. A critical genetic change that results in a human pandemic strain might occur today, tomorrow, or even 10 years from now. Maybe it will never occur. But we can never rule out that one day an unexpected genetic change will take place in the widely circulating H5N1 virus that will suddenly change the potential for H5N1 to be transmitted by and between humans.The bottom line for businessAnother influenza pandemic will occur one day in the future—we just don’t know when. As one of my colleagues has said: “The pandemic clock is ticking; we just don’t know what time it is.” So, no, of course we don’t have a public health Y2K. How could we? We don’t have a clue when the next pandemic’s “Jan 1, 2000” will be. And I sure wouldn’t want to bet my family’s life on H5N1 not becoming the next pandemic strain—the unknowns are too many, while the knowns are abundant enough to raise alarms. When you find yourself challenged by myopic colleagues about the waning risk of an H5N1 pandemic, cite the H3N8 example.I don’t know if H5N1 will cause the next pandemic. It might. It might not. What I do know is that some strain of influenza will cause a pandemic. If you expect the unexpected—just as you would with any disaster—you and your company will be far better off.—Michael T. Osterholm, PhD, MPH, Director of the Center for Infectious Disease Research & Policy (CIDRAP), Editor-in-Chief of the CIDRAP Business Source, Professor in the School of Public Health, and Adjunct Professor in the Medical School, University of Minnesota.