Induction of antibody response to Chlamydia trachomatis in the genital tract by oral immunization.

Groups of BALB/c mice were orally immunized with Chlamydia trachomatis serovar L2/434/Bu in order to characterize the nature and kinetics of the chlamydial antibody response in the cervix and other mucosal sites. These animals were subsequently challenged intravaginally to determine whether oral immunization offers protection against chlamydial antigen shedding in the genital tract. Following oral immunization, immunoglobulin A antibody activity was detected in the genital tract as well as other mucosal sites. Subsequent intravaginal challenges exhibited booster effects on preexisting antibody activity in the genital tract. Significant protection against challenge infection in the genital tract was observed by oral immunization. This was indicated by the absence of any chlamydial antigen shedding in cervical secretions. On the other hand, passively administered chlamydial-specific serum immunoglobulin G antibody did not significantly influence the course of cervical shedding of the organism and did not confer any protection against a subsequent intravaginal challenge. It is concluded that prior oral immunization can induce a secretory antibody response in the genital tract and provide protection against subsequent infection.

Incidence of catheter-associated gram-negative bacteremia in children with short bowel syndrome.

Children with catheter-associated bacteremia were evaluated for the type of bacteria recovered and the relationship of the bacteria to the predisposing disease. A previously unrecognized observation was that gram-negative isolates, namely, Escherichia coli and Klebsiella sp., were almost exclusively recovered (11 of 12 isolates [92%]) from children with short bowel syndrome (SBS) compared with those from children with other underlying diseases, such as inflammatory bowel disease, malignancies, and other disorders (P less than 0.001). Furthermore, children with SBS had a higher frequency of repeated infection (3.1 catheter-associated infections compared with 1.3 catheter-associated infections in children with other disorders during the same period). Only gram-positive bacteria were isolated from children with malignancies and other predisposing disorders. The very high frequency of catheter-associated gram-negative bacteremia in children with SBS compared with that in children with other bowel disorders, malignancies, and other predisposing diseases requires attention by the clinician in the management of patients in this group.

Immunoprophylaxis of Chlamydia trachomatis lymphogranuloma venereum pneumonitis in mice by oral immunization.

Groups of BALB/c mice were orally immunized with chlamydiae and challenged intranasally to determine whether oral immunization offers protection against pulmonary disease and to characterize the nature and kinetics of the chlamydial antibody response in the lung and other mucosal sites. Protection by oral immunization from chlamydial lung disease was demonstrated by lack of replication of the organism and the lack of chlamydial antigen in lung tissue. The chlamydial immunoglobulin A (IgA) antibody response was present at all body sites, reaching peak levels in the lung as well as in the serum. Classical IgA booster effect kinetics was observed after intranasal challenge, especially in the lung. Specific IgG antibody was detected at all body sites but at lower levels. Furthermore, animals immunized orally had no pneumonic process, as determined by histopathology. These studies also suggest that passively acquired specific serum IgG antibody may not significantly influence the course of mucosal replication of the organism. These observations indicate that oral immunization activating the gut-associated lymphoid tissue system gave total protection against chlamydial lung disease, suggesting migration of immunologically competent cells from the intestine to the lung.

Immunization of the gastrointestinal tract with bacterial and viral antigens: implications in mucosal immunity.

The effects of oral immunization with Pseudomonas aeruginosa (PAOI), Chlamydia trachomatis or respiratory syncytial virus (RSV) on the development of specific antibody responses in the intestine, respiratory tract and genital secretions was studied in several animal models. Oral immunization resulted in the development of specific immunity in distant mucosal sites. However, its role in influencing the outcome of reinfection challenge at the distant site varied with the antigen. Little or no protection was observed against infection with Pseudomonas aeruginosa in the respiratory tract. Limited protection was observed against respiratory tract infection with RSV. On the other hand oral immunization appeared to be quite effective in preventing respiratory or genital infection with Chlamydia trachomatis. Finally, preliminary studies have suggested that intestinal immunization via the process of breast feeding can also be employed as an effective means to induce anti-idiotypic immunity against RSV in the breast feeding neonates.

Neisseria meningitidis bacteremia in children: quantitation of bacteremia and spontaneous clinical recovery without antibiotic therapy.

The relationship between the magnitude of bacteremia due to Neisseria meningitidis and the clinical diagnosis was determined for 43 children who had fever in the presence or absence of focal signs of infection. Bacteremia was quantitated by the previously described procedure using heparinized blood (0.2 to 1.0 mL). Additionally, blood was cultured by means of the radiometric Bactec technique. Seventeen patients had meningitis, 12 had meningococcemia, 13 had unsuspected or "occult" bacteremia, and five had other diagnoses. "Occult" bacteremia was diagnosed initially in four patients, but subsequently meningitis was diagnosed. All 13 patients with 500 or more organisms per milliliter had meningitis or meningococcemia in contrast to 12 (55%) of 22 patients with less than 500 organisms per milliliter (P less than or equal to .0035). Only 18 (42%) of these patients bacteremic with N meningitidis presented with petechiae or purpura. All 13 children with occult bacteremia were sent home after blood cultures were obtained; six of the 13 received a regimen of oral amoxicillin for otitis media. At reexamination (interval 16 to 119 hours) four had meningitis, seven were clinically improved (afebrile, negative blood culture, without invasive disease), and two were still mildly febrile with negative blood culture. Three of these bacteremic children experienced spontaneous clinical and bacteriologic resolution without antibiotic treatment. This has not been previously reported.

Fimbriation of Haemophilus species isolated from the respiratory tract of adults.

Twenty-two clinical isolates of Haemophilus species were studied within two passages of their original isolation for the presence of fimbriae by negative-staining electron microscopy. Six isolates were identified as fimbriated, including three strains of nontypable Haemophilus influenzae, one strain of Haemophilus parainfluenzae, and two strains of Haemophilus haemolyticus. In fresh isolates of fimbriated strains of nontypable H. influenzae, approximately 40%-50% of cells had fimbriae; after five passages in vitro, less than 1% of the cells had fimbriae. Thus, a variety of Haemophilus species that colonize the human respiratory tract can be fimbriated, and this fimbriation is rapidly lost on passage in vitro.

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.

Relationship between the magnitude of bacteremia in children and the clinical disease.

The relationship between the magnitude of bacteremia due to Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis and the clinical diagnosis was determined on 79 children who were not receiving prior antibiotic therapy and had fever, either in the presence or absence of focal signs of infection. Bacteremia was quantitated by the recently described Quantitative Direct Plating procedure in which heparinized blood (0.5 ml each) is plated onto blood and chocolate agar plates. Additionally, blood was cultured by means of the radiometric Bactec technique. In the case of H. influenzae and S pneumoniae, 23 (92%) of 25 patients with more than 100 organisms per milliliter of blood had meningitis or epiglottitis in contrast to only four (9.5%) of 42 patients with less than 100 organisms (P less than .001). No significant difference was noted in the magnitude of bacteremia due to N meningitidis among 12 patients with meningitis or other serious infections. The possible predictive value of the quantitation of bacteremia is illustrated by the observation of three children with seemingly mild respiratory infection and counts in excess of 100 organisms per milliliter who, within 20 hours, developed meningitis or epiglottitis. High bacterial counts of H influenzae and S pneumoniae in excess of 100 organisms per milliliter of blood should alert the physician to the existence or possible development of serious disease.

Infectivity of Chlamydia trachomatis in tissue culture with newborn calf serum.

By using representative strains of Chlamydia trachomatis serotypes, the efficacy of substituting fetal bovine serum with newborn calf serum for the isolation of this organism in tissue culture was examined. The criteria used were the quality and quantity of the iodine-stained cytoplasmic inclusions and the characteristics of the McCoy cells. Complete substitution of fetal bovine serum with newborn calf serum produced a detrimental change in the quality of the cytoplasmic inclusions and a dramatic decline in the inclusion count (P less than 0.001) with all of the chlamydial strains tested. There appeared to be no significant alteration in the characteristics of the McCoy cells. It is recommended from this preliminary investigation that newborn calf serum should not be used for the isolation of C. trachomatis in tissue culture.