Diphtheria anti-gravis serum: its action on experimental infection and in the treatment of patients

Abstract

Antibacterial sera against C. diphtherias gravis (serological type I), intermedius and mitis were prepared in horses. The details of the immunization and the preparation of the sera are described. The sera contained a minimal amount of antitoxin.The anti-gravis serum in the dose used, when it was given to guinea-pigs 1 hr.before the subcutaneous injection of ten lethal doses of the homologous organism, saved the life of 75 % of the animals. Those which died lived longer than the controls, and C. diphtheriae was recovered less often from the local lesion and the liver than at the same sites in the controls; it was not recovered from the heartblood of the animals which received the experimental serum, whereas cultures from the heart-blood were positive in about 40 % of the controls.In these experiments the degree of invasiveness of the strain, as judged by the frequency of its recovery in cultures from the heart-blood and the liver of the control animals, corresponded with earner observations (Robinson & Marshall,1934), which showed that in routine virulence tests carried out by the subcutaneous inoculation of guinea-pigs C. diphtheriae could often be cultivated from the local lesion, the liver, the pleural fluid and the heart-blood, and that gravis and intermedius strains were more invasive than mitis strains. This was one of the main facts which suggested that an antibacterial factor might prove to be a useful adjunct in the treatment of diphtheria.The anti-gravis serum, when given as a supplement to the routine doses of antitoxin to patients with severe diphtheria, had a definitely beneficial influence on the local lesion. Moreover, the serum improved for a time the general condition of some of the patients, including those who died later. The death rate of the group to which anti-gravis serum was administered was similar to that of the control group but, on the other hand, the patients who received the serum lived, on the average, longer than the control patients notwithstanding that treatment of the former group was begun later in the disease. The clinical evidence in favour of the anti-gravis serum cannot be assessed quantitatively, but, since it is based on critical observations, it should not be disregarded.Consideration of the results as a whole leads us to conclude that the anti-gravis serum used in the tests contained a specific antibody which, within limits, had a beneficial action. We suggest, therefore, that the role of the antibacterial factor in the pathogenesis and control of diphtheria merits investigation.