010 and 011 - On the Treatment of Acne, Furunculosis, and Sycosis by Therapeutic Inoculations of Staphylococcus Vaccine

Next up is a pair of articles by the same researcher that helped develop the antityphoid vaccine (009), Almroth Edward Wright. Apparently he is quite a character, worth reading about; he predicted the rise of antibiotic-resistant bacteria and was a big advocate of preventative medicine.

In this pair of articles, Wright was attempting to develop a therapeutic (rather than preventative) vaccine against Staphylococcus, a common cause of skin infections such as boils (aka furunculosis) and hair follicle infection (sycosis). The preparation of the vaccine was similar to that of the antityphoid: grow up the bacteria, kill them somehow, and inject this into the patient. Often he used bacteria cultured from the patient’s own infection.

The first paper is a series of case reports, with some in-depth data and graphs(1). The second is another series of descriptive case reports of patients treated with this therapy(2). In each case, it appeared to help the patient’s current problem, but each patient seemed to suffer recurrences, the same or different, pretty often.

One interesting aspect to these reports is the measurement of phagocytic/opsonic index, a measure of how well the treatment increased the immune response. It did seem to increase after the vaccination. Other articles citing these papers give some more details:

Wright and Alexander Fleming developed technique called opsonic/phagocytic index to measure levels of antibodies against pathogen.

"This was considered necessary because by giving too large a dose of vaccine one could lower the antibody level in what was called a 'negative phase' to such an extent that the patient might become worse because he did not have a sufficient margin of resistance to safeguard him against any generalization of the infection....Fleming and his colleagues carried out no less than 16,000 opsonic tests in one year, each of which required half an hour."(3)

"Here again, a lack of adequate controls confounds the analysis. Wright's methods for measuring opsonizing activity were criticized by the renowned biostatistician Karl Pearson who deplored his cavalier indifference to statistical tests of significance: Pearson concludes one paper critical of Wright's data analysis with the exhortation 'Statistics on the table, please!'"(4)

"No adequately controlled clinical trials were undertaken to demonstrate the effectiveness of these forms of therapy."(5)

Sums it up pretty well, I think: not great quality. I hope to learn more about vaccine therapy in future reading though.

References:
1. Wright, A.E. Notes on the treatment of furunculosis, sycosis, and acne by the inoculation of a staphylococcus vaccine,: and generally on the treatment of localised bacterial invasions by therapeutic inoculations of the corresponding bacterial vaccines. The Lancet 159, 874–884 (1902).

2. Wright, A. E. On the Treatment of Acne, Furunculosis, and Sycosis by Therapeutic Inoculations of Staphylococcus Vaccine. Br. Med. J. 1, 1075–1077 (1904).

3. Hare, R. The scientific activities of Alexander Fleming, other than the discovery of penicillin. Med. Hist. 27, 347–372 (1983).

4. Burke, D. S. Vaccine therapy for HIV: A historical review of the treatment of infectious diseases by active specific immunization with microbe-derived antigens. Vaccine 11, 883–891 (1993).

5. Stein, D. S., Timpone, J. G., Gradon, J. D., Kagan, J. M. & Schnittman, S. M. Immune-Based Therapeutics: Scientific Rationale and the Promising Approaches to the Treatment of the Human Immunodeficiency Virus-Infected Individual. Clin. Infect. Dis. 17, 749–771 (1993).