Turning to Chickens in Fight With Bird Flu

Desperate times call for desperate measures. In the worst months of the 1918 Spanish flu pandemic, doctors flailing to save patients tried all sorts of outlandish "cures." Cupping and bleeding made comebacks. Intravenous hydrogen peroxide was tried, sometimes fatally. One doctor injected a mix of blister fluid, morphine, strychnine and caffeine. Typhoid vaccine was given, since it prompts immune reactions; so was quinine, because it breaks malarial fevers.
Skip to next paragraph
Related
More Coverage: Avian Influenza

Presumably, if the A(H5N1) avian flu turns into a pandemic, modern medicine will show more common sense. But at the moment, the common-sense response — an avian flu vaccine for humans — is in very short supply. A few million doses exist, earmarked for clinical trials and protection of the vaccine workers needed to make more.

Meanwhile, billions of doses, using crude versions of the same technology, exist for chickens. In desperation, could chicken vaccine be used on humans?

Several experts asked about it were aghast at the idea.

"It hasn't even been discussed," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which is spending hundreds of millions of dollars in pursuit of human flu vaccine. "It's not even on the table."

Dr. Albert Osterhaus, a veterinary virologist at the Erasmus Medical Center in the Netherlands, said he saw no reason it should be. "A vaccine that gave severe side effects in humans might be worse than a pandemic," he warned.

But some theorized that, in a dire enough emergency, it might help, although they emphasized "might."

"You'd have a very, very sore arm," said Robert G. Webster, a flu expert at St. Jude Children's Research Hospital in Memphis. "But if faced with a catastrophic situation, it could be tried. It may do something."

Dr. Carol Cardona, a poultry veterinarian at the University of California at Davis, noted that the immune system has several levels of protection. Even if an imperfect vaccine could not create antibodies to forestall sickness, she said, it might prime the immune system enough to just fend off death.

And Dr. Terrence M. Tumpey, a flu specialist at the Centers for Disease Control and Prevention, said he thought it "could provide some protection against death" but with some nasty side effects.

Makers of human and veterinary vaccines usually work in separate worlds, held to different standards. But last week, Dr. Klaus Stöhr, chief of the World Health Organization efforts to develop flu vaccines, convened poultry vaccine manufacturers from China, Europe and North America to discuss upgrading lines for humans.

"If you went into one of those plants, you wouldn't initially see the difference," he said. "But no veterinary companies are producing human vaccines. It's not like 'O.K., you produce cars, so you can produce tanks.' "

On both production lines, virus is injected by hand into fertilized eggs to multiply as the embryo matures. After extraction, the virus is killed with formaldehyde or ultraviolet light, then concentrated in a centrifuge or by attachment to sugars, and then mixed with an "adjuvant" that spurs a stronger immune response.

But poultry vaccines, made on the cheap, are not filtered and purified to remove bits of bacteria or other viruses. They usually contain whole virus, not just the hemagglutin spike that attaches to cells. Purification is far more expensive than the work in eggs, Dr. Stöhr said; a modest factory for human vaccine costs $100 million, and no veterinary manufacturer is ready to build one.

Also, poultry vaccines are "adjuvated" — boosted — with mineral oil, which induces a strong immune reaction but can cause inflammation and abscesses. Chicken vaccinators who have accidentally jabbed themselves have developed painful swollen fingers or even lost thumbs, doctors said.

Effectiveness may also be limited. Chicken vaccines are often only vaguely similar to circulating flu strains — some contain an H5N2 strain isolated in Mexico years ago.

"With a chicken, if you use a vaccine that's only 85 percent related, you'll get protection," Dr. Cardona said. "In humans, you can get a single point mutation, and a vaccine that's 99.99 percent related won't protect you."

And they are weaker. "Chickens are smaller and you only need to protect them for six weeks, because that's how long they live till you eat them," said Dr. John J. Treanor, a vaccine expert at the University of Rochester. Human seasonal flu vaccines contain about 45 micrograms of antigen, while an experimental A(H5N1) vaccine contains 180. Chicken vaccines may contain less than 1 microgram.

"You have to be careful about extrapolating data from poultry to humans," warned Dr. David E. Swayne, director of the agriculture department's Southeast Poultry Research Laboratory. "Birds are more closely related to dinosaurs."

To risk it, doctors said, any medical authority would have to calculate how many lives would be saved against the risks.

Despite its lethal reputation, the 1918 flu killed only about 2 percent of its victims. A vaccine that killed 2 percent of those injected would be worse than no vaccine. Avian flu now kills about half its known victims — but flus that become more transmissible generally become less lethal, too.

Also, doctors have options that did not exist in 1918: antivirals, antibiotics and ventilators. Those may slow the epidemic until more human vaccine is made.