Convalescent Plasma: Future H5N1 Treatment?

Since we are all sitting here and waiting and waiting for bird flu to hit, we have some extra time to look at what has happened during the Spanish flu between 1918-1920. Military docs from the Bureau of Medicine and Surgery, U.S. Navy and Uniformed Services University of the Health Sciences have published a meta-analysis study of research published in those dark days of the early 20th century. Their paper, in the latest Annals of Internal Medicine, shows that using influenza-convalescent human blood products (i.e. human plasma containing H5N1 antibodies from survivors) might possibly save lives. From an accompanying editorial:

In a thorough review and analysis of the historical literature, Luke and colleagues document the effects of passive immunotherapy. They found 8 studies that evaluated the effects of therapy with serum or plasma from convalescent patients on the course of clinically diagnosed influenza pneumonia during the 1918 Spanish influenza pandemic. Although the quality of these studies was relatively poor by modern standards, they all reached similar conclusions. In 6 of these studies, treatment was compared with a control group that received standard care, and in each of these reports, the mortality rate was lower in treated patients, although the decrease was statistically significant in only 3 reports. Two of the studies also compared the outcomes in those who received early treatment and those who received late treatment. An additional 2 reports compared early and late therapy but did not have an untreated control group. These studies demonstrated that only those who received early intervention experienced a beneficial effect of serum therapy, which is consistent with reports of serotherapy for other human infectious diseases. Luke and colleagues discarded multiple other reports that did not meet the methodologic criteria for inclusion in their meta-analysis. These weaker studies also supported the hypothesis that passive serotherapy was useful in treating Spanish influenza.
Would a similar approach be effective and feasible in the event of a pandemic of H5N1 influenza? Passive immunotherapy to treat infection with influenza viruses, including H5N1, has been effective in a mouse model. Other viral diseases offer ample precedent: Passive antibody prevents many human viral diseases, including varicella, rabies, hepatitis A and B, and respiratory syncytial virus (RSV). However, the distinction between prevention of disease and treatment of active disease is important. Few recent data support the use of passive antibody therapeutically after disease manifestations have already begun. For example, although passive antibody is highly effective at prevention of RSV infection in high-risk infants, systemic administration of antibody with high levels of RSV neutralizing activity is not useful therapeutically in infants with RSV disease.
Nevertheless, the concept is important and it should be explored further…

The press release…
The paper at the Annals of Internal Medicine…
The editorial…