By John Fauber and Susanne Rust,Milwaukee Journal Sentinel

MILWAUKEE – If a deadly bird flu hits the United States, health officials will have two lines of defense against a catastrophe that could kill nearly 2 million Americans: vaccines and anti-viral drugs.

Despite years of warnings, the country is woefully ill-prepared to use either weapon. An approved vaccine does not exist, and mass-producing any experimental vaccines could take years.

And some experts say the plan to distribute these drugs – giving priority to the old and sick, instead of young, healthy children – is misguided and unwise, considering how flu spreads.

In addition, stocks of anti-virals, which may have some benefit, are minuscule compared with what would be needed in a pandemic.

How did the world’s richest country find itself in such a poor state of readiness?

Fearful of a pandemic, Tommy Thompson, the former secretary of the U.S. Department of Health and Human Services, said that beginning in 2002 he requested $100 million three years in a row to upgrade the country’s vaccine capability.

The money was to be used to help the vaccine industry switch over from using chicken eggs to make vaccines to a new cell-based technology.

The first year, Congress cut all of his request, Thompson said. The second year, he got half of what he asked for. Finally, in 2004, after a public outcry over a flu vaccine shortage that year, the entire $100 million was approved.

He actually sought more money, Thompson added – he doesn’t recall the exact figure – but even before his requests reached the Republican-controlled Congress, the White House’s Office of Management and Budget insisted that they be held to the $100 million mark.

“I’m upset people didn’t listen to me three years ago,” Thompson said.

As the result of action by Congress and President Bush this month, the United States now is planning to provide incentives to industry to switch to modern vaccine production methods.

But, “We’ve got a long way to go,” Thompson said.

Asked about the remark of his old boss, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, at first didn’t want to comment.

When pressed, he said, “I don’t think you can say we lost a year or two because of failure to act.”

Beyond that, the U.S. vaccine industry is a shell of its former self, a low-profit operation that uses 1950s technology.

As recently as the 1970s, there were 27 vaccine makers in the United States, said Shelley Hearne, executive director of Trust for America’s Health, a non-partisan group that advocates for improvements in public health and disease prevention.

Today, there are only two vaccine plants in the United States, and one is owned by a French company, she said.

Vaccines have been one of the greatest weapons against disease and a public health success story, but making them has fallen out of fashion, she said.

“It’s more lucrative to make Viagra than to make vaccines,” she said.

And the federal government’s failure to bolster the vaccine industry is part of the reason the nation now is highly vulnerable to a new pandemic flu strain and probably will remain at risk for at least a few more years, she said, adding that the industry also is at fault for failing to invest.

This month, the federal government finalized its pandemic influenza plan, after the 396-page document languished uncompleted for years. President Bush announced plans to spend $7.1 billion on the plan.

Infectious disease experts applauded the government’s newfound urgency in dealing with the problem.

However, they pointed to several concerns.

As part of the plan, the Department of Health and Human Services said it plans to buy 20 million courses of vaccine against each circulating flu virus with pandemic potential. At the moment, the one virus that meets that description is H5N1.

A vaccine against the H5N1 virus is in clinical trials. It’s a killed virus that was isolated from a patient in Vietnam who was infected by a chicken.

Why limit production of the vaccine to 20 million doses when the virus already has shown some ability to infect humans, and with a 50 percent mortality rate?

“I would like to have a lot more than 20 million doses,” said Kelly J. Henrickson, an infectious disease expert and associate professor of pediatrics at the Medical College of Wisconsin. “We need 100 million (nationally).” But Henrickson said 20 million is a good start, especially with the limited production capability of the vaccine industry.

Indeed, producing large amounts of the H5N1 vaccine poses a special problem.

Fauci said the H5N1 vaccine being tested appears to be safe in healthy adults and that it induces a positive immune response.

However, the amount needed to produce the desired response is extremely high and far beyond production capacity of the vaccine industry, Fauci said.

The typical flu vaccine uses 15 micrograms as a standard dose. The H5N1 vaccine requires an initial dose of 90 micrograms and another 90 micrograms four weeks later to generate the desired immune response, Fauci said.

“As it stands now, it would take forever” to produce enough to vaccinate the entire population, he said.

National Institutes of Health researchers now are working with adjuvants, substances that can be added to a vaccine to enhance the body’s immune response. Fauci said it should be known by next spring if that approach will work with the H5N1 vaccine.

If the adjuvants are effective, it still could be two years before large amounts of H5N1 vaccine are available for immunizing Americans, he said.

The Health and Human Services Department also outlined plans to entice the pharmaceutical industry to beef up domestic vaccine production. Ultimately, it wants enough production capacity to vaccinate the entire U.S. population within six months of the onset of a pandemic.

However, upgrading the U.S. vaccine industry to meet that goal could take five years.

And if the flu were to strike before vaccines were available for everyone, who would get them? The Health and Human Services Department has come up with a list. Health care workers and people who make the vaccine come first. These two groups would require about 10 million doses.

Then come the groups considered high-risk: people older than 65 with one or more conditions that make them susceptible to influenza, as well as those of any age whose immune systems are compromised. These groups account for approximately 25 million doses.

Curiously, school-age children are at the bottom of the government’s list – outranked by politicians, funeral directors and telecommunications workers.

Ira Longini, an epidemiologist and biostatistician at Emory University in Atlanta, says the best way to slow or stop a pandemic is to target the part of a population that is spreading it: children.

Longini published a model in the Journal of Epidemiology this year that showed by vaccinating 70 percent of schoolchildren between ages 6 and 18, the transmission of flu could be reduced to very low levels.

That’s because it’s children who are most likely to spread the disease. The reason: Their potential for exposure is higher – because they are at school – and they have less prior immunity than adults. He showed that even if 50 percent of schoolchildren could be vaccinated, transmission would be cut considerably.

“If you inoculate schoolchildren,” said Longini, “you can stop epidemics in entire communities.”

There are about 60 million schoolchildren in the United States, Longini said. Therefore, if you had enough vaccine for 30 percent of the U.S. population – or nearly 90 million doses – it would be optimal to give about half of that to schoolchildren, and the rest to high-risk people and preschool children.

Federal health officials also say they are trying to stockpile anti-virals, including Tamiflu, which may help reduce symptoms for those infected by the H5N1 flu strain as well as control the spread. However, the federal government has about 2.3 million courses – small compared with what may be needed for an unvaccinated public in a flu pandemic.

More Tamiflu is on order, but the wait could be long. Roche Laboratories Inc. – the company that makes Tamiflu – is working at its maximum capacity to produce the orders coming in from other countries, such as France, Great Britain and China, as well as the United States.

Under pressure from global health authorities, the Swiss pharmaceutical giant is talking about licensing Tamiflu production to generic drug-makers. It also says it will greatly boost its own capacity to make the anti-viral.

Still, it may take years before every order is filled.

The U.S. government said it plans to buy 20 million courses of anti-virals by the end of 2006.

However, it is doubtful those stocks will be adequate in a pandemic for a nation of nearly 300 million people, and it may be a long time before enough is available.

At the low end, 75 million courses of anti-virals such as Tamiflu probably would be necessary, Fauci said.

The U.S. anti-viral supply would go to 81 million courses by the summer of 2007, based on assurances from drug companies, federal health officials said. That’s enough for 25 percent of the population plus an additional 6 million doses in reserve.

However, groups such as the Infectious Diseases Society of America say that the ideal amount stockpiled should cover 40 percent of the population.

In the end, many say the best use of these drugs would be in Southeast Asia. If a human-to-human form of the disease were to sprout, it should be squashed at its source, said Longini, adding that the response would need to be almost instantaneous.

“If we get in there after a month,” he said, “we have no hope” in stopping the spread.

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