Immunogenicity of pneumococcal vaccine in heart transplant recipients.

To assess the immunogenicity of pneumococcal vaccine in recipients of heart transplants, we immunized 35 long-term transplantation survivors with pneumococcal vaccine and measured the pre- and postvaccination IgG antibody titers to 5 representative vaccine capsular polysaccharides. Responses of heart transplant recipients to pneumococcal vaccine antigens were generally suppressed.

Nonspecificity of assaying for IgG antibody to pneumolysin in circulating immune complexes as a means to diagnose pneumococcal pneumonia.

Detection of immunoglobulin G (IgG) antibody to pneumolysin (PLY) in precipitated circulating immune complexes (CICs) has been used to diagnose pneumococcal pneumonia. With care to include appropriate controls, we precipitated and dissociated CICs and then assayed for IgG antibody to PLY. We detected IgG antibody to PLY in CICs that were precipitated from serum samples that were obtained at the time of admission to the hospital from 5 (23%) of 22 healthy adults, 7 (44%) of 16 subjects with stable chronic obstructive pulmonary disease, 10 (63%) of 16 subjects colonized with Streptococcus pneumoniae, and 9 (60%) of 15 patients with nonbacteremic pneumococcal pneumonia. Of the 16 patients with bacteremic pneumococcal pneumonia, 4 (25%) had IgG antibody to PLY at the time of admission, and 8 (50%) had IgG antibody to PLY in convalescence. Levels of IgG antibody in CICs closely correlated with serum levels of IgG antibody to PLY, implicating precipitation of free serum antibody in tests with false-positive results. Detection of IgG antibody to PLY in precipitated CICs is not a reliable method for diagnosing pneumococcal pneumonia.

Protection against bacteremic pneumococcal infection by antibody to pneumolysin.

Pneumolysin is an important virulence factor of Streptococcus pneumoniae. This study examined the hypothesis that human antibody to pneumolysin provides protection against pneumococcal infection. At the time of hospital admission, patients with nonbacteremic pneumococcal pneumonia had higher levels of serum anti-pneumolysin IgG than did patients with bacteremic pneumococcal pneumonia or uninfected control subjects. IgG levels rose significantly during convalescence in patients with bacteremic pneumonia, reaching levels observed in nonbacteremic patients. Purified human anti-pneumolysin IgG protected mice against intraperitoneal challenge with S. pneumoniae types 1 or 4 in a dose-related fashion; mice that received anti-pneumolysin IgG had a greater likelihood of surviving challenge and had negative blood cultures. Pneumolysin damages epithelial cells and inhibits phagocytic function of polymorphonuclear leukocytes. One hypothesis that might explain the study results is that, early in infection, IgG to pneumolysin blocks these effects in the alveoli, thereby protecting the host against bacteremic pneumococcal disease.

Bacteremic and nonbacteremic pneumococcal pneumonia. A prospective study.

We prospectively identified cases of pneumococcal pneumonia and used stringent criteria to stratify them into bacteremic and nonbacteremic cases. Although patients were distributed among racial groups in proportion to all patients seen at this medical center, the proportion of African-Americans with bacteremic disease was significantly increased. All patients had at least 1 underlying condition predisposing to pneumococcal infection, and most had several. Although the mean number of predisposing factors was greater among bacteremic patients than nonbacteremic patients, only alcohol ingestion was significantly more common. Nearly one-third of patients had substantial anemia (hemoglobin < or = 10 g/dL) on admission, which may have predisposed to infection. In the case of other laboratory abnormalities, such as albumin, creatinine, and bilirubin, it was difficult to determine which abnormality might have predisposed to pneumococcal infection and which might have resulted from it. The radiologic appearance was varied. Airspace consolidation and air bronchogram on chest X-ray were highly associated with bacteremic disease, as was the presence of pleural effusion. Although the Pneumonia Patient Outcomes Research Team (PORT) risk score was a predictor of mortality, it did not help to predict the presence of bacteremia in an individual case. Most patients who died in the first week in hospital were bacteremic, and a high PORT risk score with bacteremia reliably predicted a high likelihood of a fatal outcome. Eleven patients had extrapulmonary disease with meningitis, empyema, and septic arthritis predominating; all of these patients were bacteremic. The antibiotic susceptibility of our strains correlated well with those that have been reported in the United States during the years of this study. The use of numerous antibiotics of different classes in many patients, especially those who were the most ill, precluded analysis of outcome based on antibiotic therapy. Only 17 patients had been vaccinated. Since nearly all patients had conditions for which pneumococcal vaccine is recommended and more than one-third had been hospitalized in the preceding 6 months, the low rate of vaccination can be regarded as a missed opportunity to administer a potentially beneficial vaccine.

Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for Pneumococcal pneumonia.

IgG to capsular polysaccharide (CPS) of Streptococcus pneumoniae is thought to provide the greatest degree of protection against pneumococcal disease. Serum obtained at hospital admission from 14 (27%) of 51 patients with bacteremic pneumococcal pneumonia and 11 (37%) of 30 with nonbacteremic pneumococcal pneumonia contained IgG to CPS of the infecting serotype; these percentages are similar to the prevalence of IgG to CPS in a control population. However, when compared with antibody from healthy adults, this IgG had far less capacity to opsonize the infecting pneumococcal serotype for phagocytosis in vitro by normal human polymorphonuclear leukocytes or to protect mice against experimental challenge. Failure to opsonize correlated closely with failure to protect mice, and each of these parameters correlated well with poor avidity for CPS. Future vaccine studies may need to examine the functional capacity of antibodies as a surrogate for infection, in addition to measuring their concentration in serum.

Association between FcgammaRIIa-R131 allotype and bacteremic pneumococcal pneumonia.

Human FcgammaRIIa has 2 codominantly expressed allotypes, which differ greatly in their ability to ligate immunoglobulin G2 (IgG2). Whereas FcgammaRIIa-R131 binds only weakly to IgG2, FcgammaRIIa-H131 binds to it efficiently and might be primarily responsible for the phagocytosis of IgG2-opsonized bacteria. IgG2 plays a pivotal role in defense against pneumococcal infection. This prospective study showed that 50% of patients with bacteremic pneumococcal pneumonia were homozygous for FcgammaRIIa-R131, compared with 28% with nonbacteremic pneumococcal pneumonia and 29% of uninfected controls (P<.05). The gene frequency of FcgammaRIIa-R131 was 0.67 in bacteremic patients, significantly higher than in the other groups (P<.05). All bacteremic patients who died within 1 week of hospitalization were homozygous for FcgammaRIIa-R131. Therefore, the severity of pneumococcal infection may, in part, be genetically mediated. Taken together with similar findings in cases of meningococcal disease, these results suggest that such genetic factors may be generalizable to infections caused by encapsulated bacteria.

Genetic relatedness among nontypeable pneumococci implicated in sporadic cases of conjunctivitis.

Nontypeable Streptococcus pneumoniae is a common cause of epidemic conjunctivitis. A previous molecular fingerprinting study identified a clone of nontypeable pneumococcus that was responsible for a recent outbreak of conjunctivitis. In the present study, we examined the extent to which pneumococci that cause sporadic cases of conjunctivitis are related to this epidemic strain. Using arbitrarily primed BOX-PCR, we have determined that, of 10 nontypeable pneumococci causing sporadic conjunctivitis, 5 were clonal and closely related to a previous outbreak strain, whereas 5 others were genetically diverse.