One of the deadliest diseases in human history spread across the globe in 1918. The illness, now known as the Spanish influenza, killed an estimated 50 million people. Desperate to stem the tide of death, doctors began offering sufferers an unusual treatment: They transfused the blood of recovering patients into the bodies of the sick.

“They didn’t know much about the immune system, but there was this sense that there were immune factors in the blood that could be used to help other patients,” said Stephen Hoffman, a doctor and the chairman of Protein Potential LLC, a Maryland biotechnology company that works primarily in vaccine development.

Now, worried about the possibility that a strain of avian influenza might spark a new pandemic on a similar scale, a team of researchers from the U.S. Navy, led by Hoffman, has suggested resurrecting the decades-old therapy.

In a paper to be published in the Oct. 17 edition of the Annals of Internal Medicine, Hoffman’s team analyzed eight studies of these transfusions, known as passive serotherapy, published shortly after the 1918 pandemic. The reports, which covered a total of 1,703 patients, concludes that transfusions decreased the overall fatality rate—37 percent of those who didn’t get the transfusions died compared to only 16 percent of those who got passive serotherapy.

The technique works because patients who have recovered from the flu have antibodies for that particular strain in their bloodstreams. A transfusion of blood plasma, which is the liquid in which blood cells are suspended, transfers some of these antibodies into the bloodstreams of sick patients, whose immune systems can use them to fight the virus.

The researchers hope the same method will be effective for H5N1, the strain of avian flu appearing worldwide that many experts believe will cause the next pandemic.

If H5N1 patients in recovery agree to donate blood, its plasma could then be extracted, screened for diseases, and then frozen. Then, in the event of a bird flu outbreak, doctors would be ready to fight back; the plasma from one recovering bird flu patient could be used to treat several sick patients.

“We could pull that plasma from the freezer, thaw it out, and inject it like a blood transfusion,” Hoffman said.

Because the early flu studies analyzed in the current meta-analysis were conducted before blind, randomized, and placebo-controlled trials were the norm, the authors want to convene a group of experts to further discuss the potential of passive immunotherapy. They hope to begin organizing the studies that would be necessary before the treatment could be used in an H5N1 outbreak.

Though the researchers acknowledge that serotherapy is unlikely to become a first-line defense against bird flu, it could provide a good alternative to vaccines and antivirals, both of which have limitations.

“It might be the only intervention that a particular physician in a particular community hospital might have,” Hoffman said. “But that’s not something you can unleash on any medical community without proper study. It’s a disease for which there’s little else, and we have to prepare to study it now.”

The fear of a pandemic is prompting more research and investment in novel treatments for an avian flu, said Jeffrey Levi, a flu expert and the executive director of the nonprofit Trust for America’s Health.

“We don’t have a vaccine, and we don’t have the production capacity to produce an H5N1 strain vaccine at the beginning of a pandemic,” he said. “And antivirals are in relatively short supply. For H5N1, the cheaper and more readily available antivirals do not appear to work.”

But, Levi cautioned, the desire to find a unique new magic bullet, such as serotherapy, shouldn’t replace the effort to improve more standard interventions.

“One of the challenges that we face here is being as creative as possible in our science, but also addressing the basics—those being increasing our production capacity of vaccines,” Levi said.

Originally published September 27, 2006

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