Convalescent Plasma Might Lessen H5N1 Mortality

WASHINGTON, Aug. 29 -- An empirical therapy used to battle the Spanish flu early in the 20^th century may be a valuable tool if the 21^st century avian flu turns into a human pandemic, researchers here suggested.

In the face of the 1918-1919 Spanish flu pandemic, physicians in several centers used serum from convalescing patients as a treatment for the pneumonia that was killing many of their patients, according to Thomas Luke, M.D., of the U.S. Navy's Bureau of Medicine and Surgery.

A meta-analysis of eight reports of those treatments suggested that they might have been on the right track, Dr. Luke and colleagues reported in the Aug. 29 issue of Annals of Internal Medicine.

Patients with influenza pneumonia had what appears to be a "clinically important benefit" when they were given blood products from those who were recovering from the illness, Dr. Luke and colleagues said.

The finding may be important if the H5N1 strain of avian influenza, now raging in parts of Asia, becomes a pandemic human strain, because one convalescing patient could produce plasma "sufficient to treat multiple patients with H5N1 influenza," the researchers said.

The eight studies involved 1,703 patients, the researchers said. Treated patients, often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward.

All eight showed a benefit for the treatment, with an overall crude case-fatality rate of 16% (54 of 336) among treated patients and 37% (452 of 1,219) among controls, for a 21-percentage-point difference in mortality risk.

Across the studies, the difference in mortality risk for treated patients compared to controls ranged from 8% to 26%.

There was also a benefit for early treatment -- before the fourth day of pneumonia complications. Overall, the crude case-fatality rate was 19% (28 of 148) among patients who received early treatment 59% (49 of 83) among patients who received treatment after four or more days of pneumonia complications.

Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients, the researchers said.

The finding, however, should not be taken as a gold standard, the researchers said. There were only a few studies and they all had methodological limitations. In particular, none of them was a blinded, randomized, placebo-controlled trial.

Also, there were no standard dosages and definitions, disruptions caused by World War I may have hindered the ability to record data, and wartime censorship may have led to publication bias, the researchers said.

Nonetheless, the data imply, Dr. Luke and colleagues said, that "convalescent human H5N1 plasma could be an effective, timely, and widely available treatment for patients with H5N1 influenza during outbreaks and pandemics."

Clinical trials should test the idea, they argued.

That suggestion was echoed in an accompanying editorial by John Treanor, M.D., of the University of Rochester (N.Y.) Medical Center. "Controlled clinical studies done now will probably pay a considerable dividend when the pandemic begins," Dr. Treanor argued.

Despite the limitations of the original studies, "the concept is important and it should be explored further, especially given our lack of proven interventions to prevent or treat illness due to H5N1 influenza," he said.

Many hurdles exist, Dr. Treanor noted. For one thing, it is not even known yet whether patients who recover from H5N1 influenza have high levels of antibody. Also, the understanding of the human immune response to H5N1 infection is not complete and it isn't known what level of antibody will confer protection, or what dose of serum would produce useful antibody levels in patients.

The H5N1 avian flu strain has so far shown little sign of easy human-to-human transmission, which would be essential for it to become a pandemic. However, when humans have caught the disease, usually from infected birds, it has had a high case fatality rate. As of Aug. 23, the World Health Organization reported 241 cases, resulting in 141 deaths.