The Coming Pandemic?

Stephen DeAngelis

April 3, 2007

One cannot seriously consider the future without examining how resilient the economy would be if a pandemic were to sweep around the globe. We are all aware of the millions who died following the First World War when such a pandemic (the Spanish flu) did strike. Researchers have determined that Spanish flu was actually a strain of avian flu — must be a relief to the Spaniards. This only raises concerns about a new outbreak of avian flu since new Asian cases of “bird flu” have affected humans. Enormous efforts have been taken to prevent, track, and prepare for a new outbreak. Donald G. McNeil, Jr., recently provided an update on what is happening in this area. He writes:


Just exactly what is the bird flu virus doing? The virus, H5N1, which was first isolated in humans in 1997, has not started a pandemic in a full decade of trying, so a few flu experts think it never will. But the mainstream view is less optimistic. Viruses mutate constantly, many experts point out. And when one has already acquired the ability to jump species, occasionally spread from human to human and kill 60 percent of the people who catch it, it is far too early to dismiss it. So even though the human death toll from H5N1 is still below 200, scientists around the world are racing to study the ways in which it might mutate to spread easily among humans.”[1]


McNeil implies that scientists are pleasantly surprised with how slowly the H5N1 virus has mutated to date and they attribute this to the strategy that has been used to fight it. We all know that viruses are resilient. The health community is trying to become more resilient by putting a strategy in place that targets how the virus spreads instead of simply dealing with those affected. McNeil explains:

 

Today’s H5N1 flu is probably changing more slowly, because health officials have been vigilant about attacking clusters of cases, which presumably wipes out the most dangerous strains. Whenever several human cases appear, even in remote villages in Indonesia or Egypt, local officials and World Health Organization teams move in to kill all the local poultry and dose all the humans with antiviral drugs — the so-called Tamiflu blanket strategy. Each stifled outbreak robs the virus of the chance to carom wildly through dozens of human hosts as it does in a flock of chickens or ducks. That fends off what virologists most fear: gene-swapping in people infected with both human and avian flu. But the Tamiflu blanket may not be able to smother every spark, especially if countries cannot get their poultry epidemics under control.”


The big concern, according to McNeil, is the emergence of a human-bird hybrid. “A human-bird hybrid strain,” he explains, “has not yet been seen in nature. But if it did surface, that ‘would mean we might have a big problem on our hands,’ said Dr. Nancy Cox, chief of the influenza branch of the Centers for Disease Control and Prevention.” McNeil continues, “Last year, Dr. Cox and colleagues created a hybrid in their lab between a human flu of the H3N2 strain and samples of the H5N1 virus collected from 1997 to 2004. They infected ferrets with it to see if it would spread to ferrets in the same cage or those in nearby cages. The hybrid strain proved less lethal and was transmitted only once after long contact. But nature has a bigger laboratory than the C.D.C. does, and the agency’s director, Dr. Julie L. Gerberding, says the results do not mean that H5N1 cannot become more infectious.”
The fact that “nature has a bigger laboratory than the C.D.C.” is nowhere made clearer than in China. McNeil reports:

 

Geneticists at the University of California, Irvine, concluded that the H5N1 flu originated in Guangdong Province in Southern China, where millions of people and chickens live in close proximity. Guangdong is also believed to be the likely birthplace of previous flu strains — even if they later picked up names like ‘Hong Kong flu’ — and to be where the SARS virus jumped from horseshoe bats to masked palm civets to humans. But flus mutate incessantly wherever they move, and in viral samples from Asia, the Middle East and Africa, many individual changes that look potentially dangerous have been spotted. In May 2005, for example, the virus in China escaped in migratory birds going north and traveled across Russia, Europe and Africa. It became known as the Qinghai strain after the lake in Northern China where thousands of ducks and geese were found dead. (The older strain in Southern China and Southeast Asia is sometimes called the Fujian strain.) The Qinghai strain has a mutation known as PB2 E627K. (The abbreviation can be read this way: at position No. 627 on polymerase basic protein 2, the amino acid called glutamic acid, abbreviated by scientists as E, has been replaced by lysine, known as K.) The change helps the virus grow at the temperatures found in human noses, which are cooler than the insides of birds’ intestines. It is ‘characteristic of a gene that’s been in mammals,’ said Dr. Robert G. Webster, a virologist at St. Jude Children’s Research Hospital in Memphis. ‘It says to me that it was in a mammalian species in China, and got back into ducks. But what species? We don’t know.’ The Qinghai strain has now reached about 50 countries.”


Tiny mutations (for example, a change in just one of the 1,255 amino acids in the SARS) can have large consequences according to McNeil. It was such a mutation that allowed SARS to jump from bats to civets to humans. Similar mutations have been found in the avian flu virus. McNeil continues:

 

In avian flu, two mutations known to help viruses spread more easily — because they attach to the receptors in human noses and throats instead of those deep in the lungs — were found in outbreaks in Azerbaijan and Iraq in 2006. But those outbreaks were snuffed out. Another mutation, increasingly common in Egypt, where the disease is still raging through poultry and occasionally infecting humans, is called M230I. Scientists do not know what it does, but its persistence is worrisome, says Henry L. Niman, a Pittsburgh biochemist who runs a Web site tracking the genetics of flu cases. M230I is also found in typical annual flu strains like H1N1, H3N2 and influenza B; in H7 flus, which pass easily from birds to humans but usually cause nothing more serious than pinkeye; and in H3N8, the flu that has spread from dog to dog in many American kennels, often fatally. All the human cases in Egypt with M230I have been fatal, Dr. Niman said, and those without it have not been, although that may be coincidence. Mutations that confer resistance to Tamiflu have also been found in Egypt.”


A 100 percent fatality rate is certainly something to be concerned about as is the fact that drug resistant strains are emerging. McNeil reports:

 

After Tamiflu resistance was found in Egypt, the World Health Organization, moving to stave off panic, said the same change was seen in Vietnam years before. Still, the Vietnam cases led doctors to start doubling the typical Tamiflu dose, effectively halving the world’s stockpiles of it. An American Navy research lab in Cairo found that two Egyptian cases had a dangerous mutation known as N294S even before they got Tamiflu. That implies that it exists in Egyptian poultry, though it has not been found yet. Every flu virus is different, and it is impossible to predict exactly what constellation of changes will turn one into a pandemic strain.”


With so many uncertainties about our ability to contain an avian flu outbreak, nations and corporations seriously need to conduct some “what if” scenario planning. What if sick workers overseas close plants supplying parts? What if sick seamen shut down shipping? What if so many people die that bodies can’t be buried? The list goes on. I’m not trying to be gloomy, but a good “what if” approach can help organizations consider preventive strategies by walking the dog backwards (a reverse engineering approach). The World Health Organization has demonstrated that such an approach can be effective.


Footnotes
[1] Donald G. McNeil, Jr., “Scientists Hope Vigilance Stymies Avian Flu Mutations,” New York Times, 27 March 2007.