THE ACTION OF TYPE-SPECIFIC HEMOPHILUS INFLUENZAE ANTISERUM
Authors: Margaret Pittman
Journal: The Journal of Experimental Medicine (1933)

In this communication, further evidence has been given which supports the view that the majority of the strains of Hemophilus influenzae giving rise to meningitis are of the same serological type. Forty strains have now been examined, and thirty-seven have been of Type b. A horse has been artificially immunized with Type b strains isolated from the spinal fluid of patients. By precipitation tests with the capsular carbohydrate, the serum has been shown to be highly typespecific. For the first 3½ months of immunization, the type-specific antibody content of the serum increased steadily. Later, in spite of continued immunization, there occurred no apparent increase. By means of animal inoculations, it has been shown that the anti-serum has an anti-infectious action. If mice, inoculated intraperitoneally with Type b organisms, were also given serum, the bacteria did not invade the blood, or did so to only a limited degree. But the recovery of the treated mice was found to be inconstant. In rabbits infected intravenously and later treated by the same route, the number of bacteria in the blood stream was quickly reduced and sterilization followed. In the experiments it was necessary that the dosage of the culture be not too large, as influenza bacilli contain a substance which, artificially introduced into mice and rabbits, gives rise to marked toxic reactions. This substance is apparently not neutralized by the antiserum. However, it was found that among the surviving animals, those treated with immune serum returned to the normal state more quickly than did the animals not so treated. The anti-infectious action of the serum has further been demonstrated by a study of its effect on the lesions which follow inoculations of type-specific bacteria into the skin of rabbits. Again it was found that for any effect of the serum to be manifested it is necessary that the dosage of bacteria be limited, since if large numbers of bacteria are introduced into the skin the development of lesions cannot be completely inhibited, no matter how large doses of serum are employed. As the number of living S organisms which cannot be neutralized is roughly equivalent to the number of R or heat-killed bacteria which may produce a lesion, it seems that there is some preformed irritating substance in the bacterial cells which may give rise to lesions, even if the bacteria are killed or inhibited in their growth. In order to demonstrate the protective action of immune serum, therefore, it has been found necessary to employ a dosage of culture so small that if the bacteria are immediately killed, or their growth inhibited, no lesion results. Employing immune serum under these conditions, it has been found that the ability of the serum to prevent the occurrence of skin lesions has progressively increased with continuing immunization of the horse. A series of eighteen patients suffering from influenzal meningitis has been treated with Type b antiserum. Following the use of serum, recovery occurred in one patient of the series, and in two, although the patients ultimately died, the spinal fluid cultures became sterile and remained so for periods of 7 to 14 days. In four other cases, the spinal fluid cultures showed, temporarily, either no growth of bacteria, or a reduction of their number. Among five patients in whom septicemia was present before treatment, in four the blood cultures, after treatment with serum, became sterile. The number of patients treated has been small, and the treatments were carried out under widely varying conditions. It is difficult, therefore, to draw conclusions regarding the actual value of this form of therapy, or the best methods of procedure. The clinical results, however, indicate, as do the experimental, that the serum has a definite anti-infectious action. The experience is too limited to permit final conclusions regarding the importance of the addition of fresh (complement-containing) serum to the immune serum. Further experience, under more accurately controlled conditions, may show that the serum has greater practical value in treatment than is shown by the mortality results in this series of cases.