Haemophilus influenzae type b infection in childhood: history of bacteremia and antigenemia.

Groups of children (mean age, 31.4 months) with Haemophilus influenzae type b meningitis, epiglottitis, or septic arthritis were tested for the presence and levels of bacteremia, capsular polyribophosphate (PRP) antigenemia, and development of specific antibody in serum after the onset of acute illness. Although bacteremia cleared promptly after antibiotic therapy, circulating PRP could be detected in serum for relatively long periods, with 51% of the patients still having detectable antigen after 30 days postinfection. Even in the presence of specific antibody, antigenemia persisted for as long as 47 days after admission. It was observed that there was no statistically significant correlation between the persistence of antigenemia and age (P greater than 0.2), the initial antigen concentration (P greater than 0.50), or the development of antibody (P greater than 0.20). The presence of a low magnitude of bacteremia (less than 300 organisms per ml) was associated with a maximum concentration of 10 ng of PRP per ml. On the other hand, bacterial counts in excess of 10(4)/ml were associated with greater than 1,000 ng of PRP per ml (r = 0.98, r2 = 0.96, P less than 0.001). It was observed that the amount of circulating PRP in the acute phase of illness was related to whether a child developed convalescent-phase antibody. Invariably, the younger children, who primarily had meningitis, had a PRP concentration of greater than 10 ng/ml and failed to develop an antibody response in any isotype, whereas the older patients, who primarily had infections other than meningitis, had a PRP concentration of less than 10 ng/ml and a 45.5% success rate in developing an antibody response (P = 0.006). These findings suggest that there is a direct correlation between the magnitudes of bacteremia and antigenemia, that antigen may persist for long periods even in the presence of antibody, and that the level of antigenemia in addition to the patient age is significantly related to the nature of the convalescent-phase antibody response.

Development of respiratory mucosal tolerance during Haemophilus influenzae type B infection in infancy.

Groups of patients with different forms of infection with Haemophilus influenzae type B (Hib), namely meningitis, epiglottitis, arthritis, and periorbital cellulitis, were evaluated for the appearance of serum IgG, IgA, IgM, and nasopharyngeal secretory (NPS) IgA (SIgA) antibody response to Hib capsular antigen at various intervals after the onset of clinical illness, by using an indirect enzyme-linked immunosorbent assay. The serum immune response was characterized by its predictable absence in infants under 23 mo of age, and in those with meningitis who, regardless of age, had high levels of circulating antigen. On the other hand, antibody response was frequently detected in the serum of older infants. Significantly, however, the appearance of SIgA antibody was demonstrated in virtually all patients with Hib infections under 23 mo of age. In addition, a positive correlation was observed between the concentration of antigen NPS, the level of SIgA activity in the NPS, and the absence of antibody response in the serum. These observations are strikingly similar to the development of systemic hyporesponsiveness (oral tolerance) observed after oral administration of certain infectious or nonreplicating antigens in experimental animals. It is suggested that similar mechanisms may underlie the immunologic abnormalities observed in the serum antibody response in infants with Hib meningitis.