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The Terrorists Within 

Be afraid, be very afraid

Thursday, Nov 11 2004
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Deep in the countryside of Thailand and Vietnam, a pernicious army is gathering strength. While our administration has been obsessing about Muslim terrorists, a far more virulent sort has been quietly massing below the radar, a species that recognizes no human boundaries, national or religious. This is not an offshoot of al Qaeda but the alarming new form of flu virus that has emerged over the past year in birds throughout Southeast Asia. Known as H5N1, this lethal pathogen has the potential to morph into a radical new super-flu that could wreak deadly havoc on humans.

To date, H5N1 has killed 32 people, most of them rural poultry-farm workers in Thailand. Thirty-two may not sound like a great number, but it happens to be 73 percent of the 44 people who have contracted the virus so far. A statistic like this is every epidemiologist’s nightmare and heralds the potential for a disaster of biblical proportions. Even the bubonic plague when left untreated kills only 60 percent of its victims; treatment reduces mortality to around 15 percent.

Each year in the U.S., regular flu viruses cause the death of some 36,000 people, according to figures from the Centers for Disease Control and Prevention. Influenza kills by overwhelming the immune system, leaving the body vulnerable to other infections such as pneumonia. Super-influenzas, like the ones that caused the great Spanish flu pandemic of 1918-19 or the Hong Kong flu pandemic of 1968-69, are powerful new viral strains to which humans have little inherent immunity. During the period in which a super-flu runs rampant — before an effective vaccine is developed — tens of millions of lives may be lost. In the case of the 1918-19 pandemic, which it calls "the most deadly disease event in the history of humanity," the World Health Organization (WHO) estimates the death toll at 40 million to 50 million worldwide. A spinoff strain from the current bird-flu virus may be even more lethal.

Anyone who doubts this grim prognosis should consider what H5N1 has done to the birds it infects. Since the outbreaks began last December, more than 100 million domesticated fowls (mostly chickens and ducks) have died or been killed to prevent the virus from spreading. Birds that contract the virus can die on the same day they become symptomatic, and when flocks are found to be infected, the reaction must be swift and brutal — total annihilation of all animals and complete sterilization of equipment and pens. The WHO describes the outbreaks as "unprecedented in their geographical scope, international spread and economic consequences."

So far, H5N1 has not exhibited much tendency to spread directly between people — almost all human cases to date have been contracted by contact with infected animals or their droppings. But this class of virus is so inherently dangerous that should a version arise which can pass between humans, we could find ourselves in the midst of a pandemic against which we would be virtually powerless. There is currently no proven vaccine and no available treatment once illness becomes severe.

Dr. Arnold Monto, a University of Michigan epidemiologist who is part of the team that advises the U.S. government on vaccines, notes that a number of the major flu pandemics over the past century have originated from bird strains. That was certainly the case with the 1957-58 pandemic, and there is evidence, he says, that the 1918-19 strain may also have had its origin in birds. Monto stresses that avian-to-human flu morphing is not an unlikely event, saying, "We have to act now as though this is a possibility with H5N1."

IN THE TAXONOMY OF VIRUSES, influenzas are in a class of their own. Most viruses consist of just a single strand of genetic material — either DNA or RNA — packaged in a protein shell. But flu viruses have eight separate genetic strands. That means they have far greater potential for genetic variation and can mutate easily into new forms by the process known as antigenic drift. It is this normal evolutionary process that is responsible for the appearance of ordinary new flu strains each year, the ones that are covered by regular vaccines. Yet because flu viruses have eight genetic strands, they have another mechanism up their sleeve that enables them to generate radical new strains against which we may have no immunity.

Unlike living cells, which replicate by splitting into two "daughter" cells, viruses reproduce by making multiple copies of all their component parts and then assembling these parts into new virus wholes, much as in a factory production line. Normal viruses simply assemble new copies of their single genetic strand. But when a flu virus assembles its new "copies" it can exchange some of its eight strands with other nearby viruses, creating wholly new genetic combinations. The process is known as reassortment, and it is this, says Dr. Debiprosad Nayak, a flu expert at UCLA’s Department of Microbiology, Immunology and Molecular Genetics, that makes influenzas so dangerous.

Even more fiendishly clever, some flu viruses can exchange genetic strands across species barriers. The way this would come about is if a person was simultaneously infected with H5N1 and a regular human flu. The close proximity of the two viral strains would enable them to exchange genetic strands, thereby creating a major new strain that may have all the lethal power of the bird flu but also be directly transmissible between humans. Once that occurred, Nayak says, it would likely be only a matter of time before the regular mutations of antigenic drift would result in a strain that was highly transmissible between humans. In order to kill in large numbers a virus needs to be both individually lethal and easily passed on.

A further worrying factor is that while most flu viruses can only replicate inside the lungs, the H5 class are able to replicate almost anywhere in the body. They can therefore overwhelm the host’s immune system far more quickly. To date, Nayak says, there is no evidence that H5N1 has gone through reassortment with any human virus. "This is not like any virus we have seen in human history," he adds. "We should be doing everything we possibly can to prevent human infection."

As with most health issues, it is not just a matter of understanding the science better, but also the economics. One critical strategy to prevent reassortment between human and bird-flu viruses would be to make sure that all poultry-farm workers everywhere are vaccinated against human flu. Indeed, Thai authorities have expressed a desire to do just that, but they have only some 100,000 donated doses of flu vaccine, which is not nearly enough. Ninety-five percent of flu vaccine routinely goes to developed nations, leaving developing countries criminally short.

Moreover, there are very few companies working on new types of vaccines. Most of the techniques currently used to make flu vaccines were developed during World War II. Early next year the National Institute of Allergy and Infectious Diseases will begin conducting clinical trials of an experimental human vaccine against avian influenza, but much more needs to be done. Recently the WHO has warned of the need to speed up R&D. Should a new pandemic arise, the agency has estimated we would likely need 2 billion doses worldwide! The fact that the U.S. is now struggling to produce enough doses of regular flu vaccine should be a cause for extreme concern, says Monto. "If we don’t have the capacity to produce enough for regular flu, then we won’t have the capacity to produce for a pandemic."

Few countries have any significant stockpiles of vaccines on hand — or of antiviral drugs such as Tamiflu that can help to save lives when new strains appear. Although the effectiveness of Tamiflu against avian influenzas has not been rigorously proved, it is the only drug we have at the moment that may be effective. Poor countries like Thailand cannot afford to provide hundreds of thousands of doses of such an expensive commodity — in the U.S. a course of 10 capsules costs $75 and up. In Vietnam, which is poorer still, The New York Times has reported that the country’s military has been confiscating foreign donations of Tamiflu for their own use. Monto insists that we cannot let market forces rule here. Somehow the world must begin to take collective responsibility for protecting not just rich nations but also poor ones against this most dangerous enemy.

Bird viruses in Bangkok may seem a distant problem, but in the age of jet travel, novel viruses that arise in one corner of the world can soon spread everywhere. Influenza recognizes no national boundaries; driven by purely mechanical necessity, it will travel by any means possible. This is a foreign agent of which we should be truly afraid.

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