Anatomy of a potential pandemic

You know your phone number, even your Social Security number. Now you’ll have to learn a new number: H5N1.

That number is the serotype of avian influenza, or “bird flu.” While currently attacking migratory fowl, poultry farms and other bird populations, the virus has claimed more than 60 human lives. But scientists fear the bird flu could become a pandemic more deadly than the one that hit in 1918.

While the seasonal influenza seen every year kills about 30,000 to 50,000 people in the United States, primarily due to pneumonia, the 1918 Spanish flu pandemic killed an estimated 20 to 50 million people worldwide, including 675,000 in this country.

That is exactly the scenario world health officials are trying to avoid with the avian flu.

The avian flu currently has not reached pandemic status because it has not mutated into a form where it is easily transmitted between humans.

Flu viruses are notorious for their adaptability, which is why flu vaccines are given every year instead of once a lifetime like many other viral inoculations.

Right now, the avian flu virus is transmitted between birds, often in crowded poultry farms or in migratory fowl, through saliva, nasal secretions or feces.

Humans can become sick from direct contact with infected birds or, in very limited situations, from another person who had close contact with sick birds. This is probably due more to a case of also picking up the virus from infected material because of close proximity than actually from a form of communicable disease.

Scientists have noted subtle mutations in the virus that is fatal in bird species, but the disease has not yet mutated to a form where it can be passed directly from person to person. Yet.

How likely is the human-to-human transmission mutation?

“The odds are 0 to 100. We’re dealing with Mother Nature,” said Richard DiPentima, deputy director of the Manchester Health Department. “History has shown us that pandemics do occur, and there is no reason to believe that another one will not occur again in the future. But when is anybody’s guess.”

DiPentima said there is concern about the avian flu because the strain is so widespread in bird populations.

“It’s in Asia, now in Europe. It’s not controlled in the wild.”

According to the World Health Organization, the most telltale sign that a pandemic is occurring is when multiple human victims are identified coming from the same area under similar circumstance, such as a cluster of infections in health-care workers.

While it’s more likely a new virus strain is dangerous, history also has shown that some influenza mutations are not quite so harmful.

“The flu pandemics in 1957 and 1968 were not deadly, even though they were novel viruses,” said DiPentima.

A vaccine?

Avian flu is not one of the strains contained in flu vaccines people are currently receiving.

Vaccines work by presenting the body’s immune system with dead or weakened viruses or viral components, called antigens. The body sees this material as foreign and makes white blood cells with portions specifically created to attack the invaders, called antibodies. They fit something like a lock and key, whereby the virus would be neutralized. The body “remembers” this culprit, so if it is ever detected again, the virus can be attacked and destroyed all the more quickly.

Because the H1N5 virus is new to humans, we have no antibody crusaders to fight off the infection.

A pandemic form of the virus would even be different from H1N5, so a vaccine based on today’s version of the virus would do little, if any, good against a pandemic strain. While scientists can and are working on vaccines against the current H5N1 strain, they cannot start making commercial doses of a pandemic version avian flu vaccine until such a virus is confirmed.

And if it does become a global human influenza, one “shot” might not help stave off the disease.

“A novel strain may take two doses to confer a lasting immunity,” said DiPentima.

The “swine flu” of 1976 had a similar history.

Another problem scientists have to contend with in manufacturing a vaccine against the avian flu is the disease itself. It is pathogenic to chickens, and embryonic chicken eggs are the medium in which the vaccine is created.

“They have to do some reverse work to manipulate the virus so it won’t kill the chicken egg,” said DiPentima.

Tamiflu and Relenza

Two antiviral medications belonging to a class of drugs called neuraminidase inhibitors show promise in preventing the disease.

Oseltamivir, manufactured by Roche under its more commonly known name Tamiflu, and Zanamivir, also known commercially as Relenza, made by GlaxoSmithKline, can reduce the length and severity of the seasonal flu, but must be administered within 48 hours of the onset of symptoms.

While the Swiss drug manufacturer Roche appears to be able to keep up production with the relatively innocuous common flu, it is the sole producer of the drug, and scientists are concerned about a sudden worldwide demand for it.

Gilead Sciences invented Tamiflu and sold the licensing and developing rights to Roche in 1996. But in June 2005, Gilead announced it was seeking to terminate its licensing agreement with Roche for not “adequately demonstrating the requisite commitment to Tamiflu since its launch in the United States nearly six years ago, nor has it allocated the necessary resources to realize the potential of the product as a treatment and preventive for influenza.”

John C. Martin, president and chief executive officer of Foster City, Calif.-based Gilead, said, his firm “is taking this action in the interest of our shareholders and, importantly, because it is essential for public health that health-care professionals and consumers have improved access to information about Tamiflu, as well as to the product itself.”

In 2004, Gilead earned $44.6 million in royalty revenues from Tamiflu, and has netted $36 million in the first six months of this year.

According to its 2005 mid-year report, Roche is in discussions with Gilead to resolve the dispute.

At the request of WHO, some 40 countries across the globe are already stockpiling the drug in the event of a widespread outbreak. The United States has approximately 2.26 million adult doses of Tamiflu stockpiled and the U.S. Department of Heath & Human Services in September awarded a $2.8 million contract to GlaxoSmithKline for 84,300 treatment courses of Relenza.

Health and Human Services Secretary Michael Leavitt said he wants to stockpile as many as 20 million antiviral doses and has granted French pharmaceutical company Sanofi Pasteur a $100 million contract to develop and produce another 20 million doses of an avian influenza vaccine.

Some are calling for the rights to make their own generic versions of Tamiflu, bypassing stringent patent controls.

That might be wishful thinking on the part of erstwhile drug manufacturers eager to make their own flu medications — and subsequent profits that would come with a global outbreak. Tamiflu is made under a highly sophisticated — and potentially explosive – process, taking a full year to complete and involving extracting starter components from a spice called star anise.

Despite ramping up production fourfold and donating 3 million doses to the international rapid response stockpile, WHO estimates it would still take Roche a decade to produce enough Tamiflu to treat 20 percent of the world’s population.

As of Oct. 17, the 10-pill course of treatment of Tamiflu costs an average of $89 in New Hampshire and is stocked at seven pharmacies, according to the drug finder on the state’s Web site. Relenza averages $80 for a 20-dose prescription and was available at just one pharmacy, in Rochester.

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