The sky is falling and millions of us are going to die.
By Alan Zelicoff, MD

That’s the lesson one would take from the cover headlines of generally staid journals, including Nature, Science and even Foreign Affairs, where entire issues have been devoted to fears of a coming pandemic of influenza due to a new subtype of bird flu called H5N1, first identified in 1996 in SE Asia and now circulating widely among birds – both migratory and agricultural – in China, Russia, and most countries of east Asia. Are the fears of and Washington’s preparations against spread of this new “killer” influenza to humans justified? The short answer is no: The threat is extremely remote and the $7 Billion plan the President offered is vastly over priced and ignores the one relatively inexpensive thing that might truly make a difference if this or similar threats were every realized: establishing a real-time national health monitoring system.

First, a review of basic biology is in order. The influenza virus is primarily a bird disease; humans appear to be an unnecessary host. The virus types circulating at any given moment are characterized by two chemicals on their surface: hemaglutinin (“H”) and neuraminidase (“N”). Both are necessary for the virus to invade cells in birds or other species and multiply. So the annual vaccine contains the “H” and “N” proteins of the currently circulating strains which induce antibodies in the recipient that then blocks the ability of the proteins to allow viral spread among host cells. At least 16 “H” types have been identified in birds and 9 distinct “N” types, but only about half a dozen combinations of various H and N proteins result in viruses that are known to cause disease in humans.

The flu fear-mongers advance the following rationale for worry: first, that “pandemic” flu (that is influenza that is truly global in spread and high in incidence) comes in more-or-less regular “cycles” and that we are “overdue” for a new subtype of flu since it has been nearly 40 years since the last flu pandemic. Next, since some humans (about 100 to date) have clearly acquired H5N1 influenza, most probably from birds, it appears that this new subtype does not seem to require an intermediate species (typically pigs) on its way to human adaptation. Half of the 120 people known to have become infected with H5N1 have died. And lastly they say since H5N1 is carried by migratory birds, it is only a matter of time that highly lethal influenza (for humans) is spread around the globe.

Each of these arguments is scientifically specious. Let’s begin with the belief in periodicity of influenza. There is no evidence that pandemic influenza comes at regular intervals. There have been three only in the 20th century (1918, 1957, 1968) and any high school math student will tell you that 3 points in time don’t define a periodic “cycle”. Rather, pandemics occur from random mutations in influenza genes (most of which result in viruses that infect no species, so they die out). Just like flipping a coin, pandemics are thus random, not periodic. We are not “overdue”, just simply no more due this year than we have been in any year.

Second, of the hundreds of billions of interactions between humans and infected birds in Asia, there have resulted but 120 cases of H5N1 disease. It may be that other humans have acquired the virus, but got no symptoms at all; Nature Magazine reports that tens of million of rural Chinese already carry antibodies to some varieties of H5N1 indicating they have become infected in the past 7 years but their immune systems eliminated the virus without resulting illness.

Third, in the single prospective study where we have good data on the likelihood of human-to-human transmission from those few people actually ill due to H5N1, staff (including janitors) at a hospital in Thailand designated to care for all H5N1 patients were tested to see if they developed antibodies to the virus. Not a single healthcare worker did -- indicating no infectious spread at all from patients, let alone serious disease.

Fourth, since dead birds don’t fly, it is IMPOSSIBLE for migratory fowl to spread a lethal virus (lethal to them, at least) over large distances. Just two months ago, geese and ducks were dying by the thousands in Asia from H5N1. They no longer are, though they continue to carry subtypes of H5N1. What happened? The H5N1 virus strains that killed birds couldn’t get into other hosts, so other less lethal varieties arose to replace them.

Fifth, just about everyone in the US is already carrying antibodies to the “N1” component of the virus. In animal studies where mice (which are exquisitely sensitive to H5N1) are immunized against N1 alone and then challenged with aerosol exposure to virulent H5N1, they are fully protected against death and get only a mild disease. This may explain why there have been so few human cases of N5N1 in Southeast Asia where “N1” containing flu virus has been circulating among humans for 20 years.

Finally, the conditions of crowding in 1918 – troops in trenches and massive hospital wards, people living in tenements without air circulation or central heating crowded into the kitchen to keep warm all day – simply don’t obtain today, even in the worst slums in the US. It is crowding itself that permits a lethal strain to maintain its survival chain because a susceptible host is always just a few feet away. It is highly unlikely that a human dying from a lethal form of H5N1 would be up and around spreading the virus to others.

None of this is to say that some variety H5N1 will not enter the US; I would be surprised if it didn’t. Nor are chickens – tightly packed in filthy conditions in the chickenhouses of high volume egg laying or meat production facilities – safe (indeed, an outbreak among domestic fowl is far more probable than not unless our husbandry practices change).

There even remains a very distant possibility that avian H5N1 could adapt to humans, could be lethal and could spread from person to person. But it isn’t anywhere near the probability of threat of other infectious diseases (including garden variety influenza strains already well suited for human infection). To understand the problem and respond rationally, we must advance our understanding of the dynamics of influenza in animals and humans, which in turn requires a real-time surveillance disease monitoring system.

Fortunately, of the $7 billion of new funding requested in the president’s recently released “National Strategy for Pandemic Influenza” some $500 million is earmarked for research and development of a robust real-time surveillance system. But it already exists. The Syndrome Reporting Information System (SYRIS) – which has proven its extraordinary cost effectiveness for human AND animal disease surveillance in extensive testing in parts of Texas and California over the past 2 years -- is ready for national use. Physician, veterinarians, rescue personnel and even wildlife rehabilitators share data in true real-time, unlike the CDC’s decade-old, failed electronic reporting system. The cost of implementing SYRIS is 15 cents per capita, or about $50 million for the entire country. I’ve testified four times on Capitol Hill about it, including before Sen. Frist who applauded its use and numerous successes.

By failing to read the record, the danger is that the Administration’s new funding line may actually delay implementation of nationwide disease surveillance – largely because the CDC and countless vendors will scuffle at the federal trough doubtless claiming they can do better. Because an unexpected variety of novel infectious diseases have already visited our shores in the past 20 years the a proven surveillance system today beats the “promise” of a better one tomorrow.

More details on SYRIS can be seen on the SYRIS web site at: http://syris.arescorporation.com/demo/ Time is of the essence, and the solution is staring us in the face. Hundreds of millions need not be squandered reinventing the wheel or preparing for a threat that probably will not materialize.