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Analysis of Spanish flu cases in 1918-1920 suggests transfusions might help in bird flu pandemic

August 30, 2006

Transfusions with blood products taken from people who had recovered from Spanish influenza may have reduced risk for death and improved symptoms of hospitalized patients who contracted Spanish influenza complicated by pneumonia. Early treatment was superior to later treatment.

Researchers studied medical literature published shortly after the 1918 Spanish flu pandemic and found eight relevant studies.

Similar transfusions might be useful in treating victims of a bird flu pandemic, especially in light of the problems with existing vaccines and treatments, say authors of the Spanish flu study. They say that a single recovering bird-flu patient could donate "a weekly volume of plasma sufficient to treat multiple patients with H5N1 influenza."

The article "Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?" will be published in the Oct. 17, 2006, print edition of Annals of Internal Medicine and is available at http://www.annals.org/cgi/content/full/0000605-200610170-00139v1. An accompanying editorial is available at http://www.annals.org/cgi/content/full/0000605-200610170-00140v1.

Spanish flu (H1N1) and bird flu (H5N1) are subtypes of influenza A virus. The Spanish flu pandemic in 1918 to 1920 killed between 20 million and 100 million people worldwide.

The World Health Organization (WHO) says that a bird-flu pandemic is a serious possibility today. As of August 24, 2006, 241 cases of confirmed avian flu A/(H5N1) have been reported to WHO, resulting in 141 deaths.

WHO says H5N1 virus is widespread in birds, particularly poultry which seems to be the source of the Asian infections. Widespread prevalence of the virus in birds increases the chance of transmission from bird to human. When human cases become transmissible from human to human, a flu epidemic begins. If it is virulent, it will spread fast. If there are no effective antiviral drugs available, it will spread faster.

WHO says the world is not prepared to handle a bird-flu pandemic. Vaccines to prevent the particular flu strain of the pandemic will take time to manufacture and distribute after the first outbreaks.

Current recommended treatment is hospitalization and treatment with an antiviral drug, but studies of bird flu outbreaks in Asia have found that 30 percent to 80 percent of patients treated this way have died.

And WHO says the manufacturer of the most currently used drug (oseltamavir) does not have capacity to fill existing orders immediately. During an epidemic, antiviral agents, antibiotics and other medications may be rationed or not available to the most severely ill patients.

The WHO says that most developing countries will have no access to vaccines and antiviral drugs throughout a pandemic.

So the authors of the Spanish flu study believe blood product therapy has promising implications for the current situation.

The study has important limitations: the number of studies was small, the number of patients was small, and assignment to treatment or controls was not random, blinded or placebo-controlled; dosages and definitions were not standardized; disruptions caused by World War I probably affected medical personnel available to record data as well as exacerbated the spread of the disease; and wartime censorship may have affected publication of existing research. (The name "Spanish flu" came from the fact that Spain was not a partner in World War I and its press was freer to report details of the pandemic than press in combatant countries who did not want reveal information about deaths and sickness to enemies.)

The authors call for convening a body of experts "to consider H5N1 plasma therapy and to make recommendations for a research strategy and possibly treatment guidelines if therapy is required before the research is completed."

John J. Treanor, MD, says, in an accompanying editorial, that the idea that "passive serotherapy" might be useful in treating H5N1 virus infection has precedence in other viral diseases such as chicken pox, rabies and hepatitis A and B.

Treanor, of the infectious disease division of the University of Rochester Medical Center, identifies concerns with logistics, such as the ability to obtain, classify and prepare the blood materials in the midst of an outbreak, and missing information, such as whether people who recover from H5N1 infection actually develop high levels of an antibody or what is the most effective level of antibody or appropriate dose of plasma needed to achieve success in infected patients.

"Although many logistical hurdles exist, controlled clinical studies done now will probably pay a considerable dividend when the pandemic begins," Treanor says. "We can, should, and must explore these issues about serotherapy now, in advance of the pandemic."

American College of Physicians