The Action of Type-Specific Hemophilus Influenzae Antiserum

Abstract

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.

On the Behavior of Hemophilus Influenzae in Certain Diseases of Children

“…This finding accords well with Pittman's observation of the superior viability of M strains in the blood and tissues of experimental animals (7,8 assaying the importance of mucoid influenza bacilli in these patients. We may note that Pittman has found that most of her meningeal strains are Type B (7,8) …”

Incidence and Type Distribution of Capsulated H. influenzae Strains

“…Experimental evidence to support the second suggestion is not available, although it has been found by various authors (Pittman, 1931;Chandler et al, 1937;Raettig, 1939-40;Allison et al, 1943) that capsulated strains are more virulent for white mice than non-capsulated H. influenzae strains. It is known that the capsular polysaccharides of the six H. influenzae types are serologically (Pittman, 1931(Pittman, , 1933 and chemically different (MacPherson et al, 1949), and these differences might account for differences in virulence.…”

“…It is known that the capsular polysaccharides of the six H. influenzae types are serologically (Pittman, 1931(Pittman, , 1933 and chemically different (MacPherson et al, 1949), and these differences might account for differences in virulence. In this context it is interesting to note that it was shown recently that the antigenic composition of the capsule of freshly isolated H. influenzae type e strains is more complex than had been supposed hitherto (Williamson and Zinnemann, 1951)., Whether the presence of capsulated H. influenzae strains in the nasopharynx causes distinct clinical symptoms is difficult to decide from this study, as many of the children in whom no pertussis and no capsulated H. influenzae strains were found suffered from a persistent cough.…”

Clinical Memoranda

“…Of fifty cases treated in this way (Ward and Wright, 1932;Pittman, 1933;Huntington and Wilkes-Weiss, 1936;Ward and Fothergill, 1932) only three recovered. This shows no improvement over ordinary methods.…”

“…Throat strains of H. inifluenzae form a heterogeneous group of antigens, whereas nearly all strains of meningeal H. influenzae have similar antigenic properties (Pittman, 1933). Pittman also showed that all meningeal strains possessed a similar type of soluble specific antigen derived from the supernatant fluid from a centrifuged culture.…”