Circulating polyribophosphate in Hemophilus influenzae, type b meningitis. Correlation with clinical course and antibody response.

Abstract

A B S T R A C T In systemic infections caused by Hemophilus influenzae, type b, the capsular polysaccharide, polyribophosphate, is released into the circulation. Polyribophosphate was quantitated in serial serum and cerebrospinal fluid samples from 45 children with H. influenzae, type b meningitis by means of a radiolabeled antigen-binding inhibition assay. Polyribophosphate was regularly found in acute serum and cerebrospinal fluid samples and could be detected in unbound form for periods of 1-30 days after initiation of effective therapy. Complexes of polyribophosphate dissociable with acid and pepsin were detected in serum samples from 17 patients, in one case for a period of 145 days after hospitalization. Polyribophosphate levels and patterns of clearance were studied in relation to hospital course and antibody response. Patients with prolonged antigenemia had protracted fevers and severe neurological symptoms during hospitalization, frequently with focal complications. Antipolyribophosphate antibody responses were detected during the first 100 days of convalescence by radioimmunoassay in 79% of the patients studied, including 60% of the children 1 yr or less in age. The intensity of antibody response although clearly related to the age of the patient, was more reliably predicted by the efficiency of antigen clearance. Antibody responses were uniformly of low magnitude in patients with prolonged antigenemia, irrespective of age. Paients who failed to develop antibody to polyribophosphate after meningitis also exhibited impaired antigen clearance. These studies suggest that mechanisms necessary for clearance of polyribophosphate may influence

A mucosal antibody response following systemic Haemophilus influenzae type B infection in children.

“…Even Hib infection in the young infant only induces a low titer ofserum anti-PRP antibody (22), a result confirmed in this report. The effects of parenteral PRP immunization on secretory anti-PRP antibody production are cur-rently under investigation in our laboratory.…”

“…These first samples were possibly obtained at sufficient time after nasopharyngeal bacterial colonization to allow the patients to produce nasal antibody. It is not uncommon to find anti-PRP antibody in the initially collected serum after the onset of apparent infection (22).…”

“…Received for publication 22 September 1980 and in revised form 30 December 1980. 1 Abbreviations used in this paper: ELISA, enzyme-linked immunosorbent assay; Hib, Haemophilus influenzae type b; PRP, purified capsule of Hib.…”

The paradox of Hemophilus infuenzae type B bacteremia in the presence of serum bactericidal activity.

“…Serum antibodies to PRP were titered by radioantigen binding (12). The content of soluble PRP in the serum-incubated or broth-incubated H.i.b cultures (approx.…”

“…The content of soluble PRP in the serum-incubated or broth-incubated H.i.b cultures (approx. 10/ml) was estimated by adding formaldehyde to 0.4%,o, holding the suspension for 5 days at room temperature, centrifuging, and assaying the supernate for PRP by radioantigen-binding inhibition (12 Table I. On admission, bacteremia was demonstrated in 12 of the 22 patients.…”