Catharina Svanborg Edén

Correlation of P Blood Group, Vesicoureteral Reflux, and Bacterial Attachment in Patients with Recurrent Pyelonephritis

Bacterial attachment to urinary-tract epithelium is important in the pathogenesis of urinary-tract infection. Most pyelonephritogenic Escherichia coli bind specifically to epithelial-cell receptors, which are glycolipids of the globoseries and also antigens in the P blood-group system. Among 36 girls with recurrent pyelonephritis who did not have vesicoureteral reflux, we found that attaching bacteria were common and the P1 blood-group phenotype was present in 97 per cent, as compared with 75 per cent of 84 age-matched children without urinary-tract infection (P less than 0.01). In 32 girls with recurrent pyelonephritis who had reflux, attaching bacteria were rare, and the frequency of the P1 phenotype was not significantly higher than in controls (82 per cent, P greater than 0.05). In the group of patients with the P1 phenotype, 68 per cent of the urinary bacterial isolates from those without reflux, but only 25 per cent of isolates from those with reflux, bound to globotetraosylceramide, as determined by a receptor-coating technique (P less than 0.001). Our data suggest that, in the absence of reflux, the P1 blood group contributes to susceptibility to recurrent pyelonephritis due to bacteria that bind to the glycolipid receptors of the globoseries. In the presence of reflux, uroepithelial attachment does not seem to confer an advantage to bacteria that infect the kidney.

Bacteriuria and mortality in an elderly population

Bacteriuria detected in the screening of adult and elderly populations has been associated with an increased mortality rate, but it is not clear whether the increase is a result of the bacteriuria itself or of differences in age, concomitant disease, or both. We screened a representative sample of the elderly population of Göteborg, Sweden (n = 1966), for bacteriuria. The mean (+/- SD) age at the time of screening was 70 years +/- 2 months. The five-year mortality among women with bacteriuria was 13.4 percent, whereas that among women without bacteriuria was 9.4 percent. The nine-year mortality in the two groups of women was 23.9 and 23.3 percent, respectively (P not significant). When the women with indwelling catheters were excluded from the analysis, the five-year mortality was 9.0 and 9.2 percent, respectively. Men with bacteriuria had an increased frequency of cancer (27.3 vs. 5.8 percent at age 70; P less than 0.002) and a higher five-year mortality than the other men; however, among the men with bacteriuria but not cancer the mortality was not increased. We conclude that fatal diseases associated with bacteriuria may account for the increase in mortality among elderly patients with bacteriuria.

Bacterial attachment as a predictor of renal abnormalities in boys with urinary tract infection

The development of renal scarring was analyzed prospectively in 241 boys with their first known episode of symptomatic urinary tract infection (140 acute pyelonephritis, 61 acute cystitis, and 40 nonspecific). Of 197 boys undergoing urography, 22 (11%) had scars; 20 were in the pyelonephritis group. Vesicoureteral reflux occurred in 81% of those with scarring, compared with 20% of those without scarring. The bacteria causing the first episode of urinary tract infection in each patient were saved, and Escherichia coli organisms were characterized for the expression of both galactose-alpha (1----4)galactose-beta (Gal-Gal)-specific adhesins and pap homologous DNA. Scarring occurred in 41% and other renal abnormalities in 11% of boys infected with bacteria that did not bind Gal-Gal (Gal-Gal negative), compared with 5% and 1%, respectively, in those infected with Gal-Gal-binding strains (Gal-Gal-positive) (relative risk 8.3; 95% confidence limits 3.3 to 20.4; p less than 0.001). That boys infected with Gal-Gal-negative strains more often had reflux did not explain the increased risk for renal scarring in this group. The possibility that the phenotypically negative strains could be induced to express Gal-Gal adhesions in vivo was excluded by dot blot analysis, which showed the absence of pap homologous DNA in all but one of the Gal-Gal-negative strains. The results suggest that the absence of Gal-Gal-specific adhesins in E. coli can be used as an indicator of risk for renal scarring and the need for radiologic examination.

Gamma-globulin treatment of recurrent acute otitis media in children

This study examined the hypothesis that children prone to acute otitis media have a reduced concentration of circulating antibodies of the IgG2 subclass and that this defect can be compensated for by gamma-globulin treatment. Infants and children below 18 months of age with at least three episodes of acute otitis media were randomized to intramuscular gamma-globulin or no treatment and were followed for 6 months. We could demonstrate neither reduced IgG2 nor specific anti-polysaccharide antibody activity in the otitis-prone children. In contrast they had higher concentrations of IgG2 and antibodies to phosphorylcholine than did age-matched controls. There was neither a relationship between the IgG2 concentration and the number of otitis episodes prior to enrollment nor a reduction in otitis frequency in the gamma-globulin-treated group.

P Blood Group and Proneness to Urinary Tract Infection in Japanese Children

The globoseries of glycolipids are antigens in the P blood group system as well as epithelial cell receptors for uropathogenic Escherichia coli. The P1 blood group is overrepresented in Swedish girls with recurrent pyelonephritis. In this study, Japanese children with urinary tract infection (UTI) were analyzed for P blood group phenotype. Out of 26 children with recurrent UTI, 50% were of the P1 blood group compared to the 31% of P1 individuals in the Japanese population at large (p less than 0.05). Of children defined as having febrile UTI 62% were P1. The P1 blood group was thus significantly enriched (3.5 times) in the children with febrile UTI. These results support the hypothesis that individuals of blood group P1 run an increased risk for recurrent pyelonephritis.

Recent progress in the understanding of the role of bacterial adhesion in the pathogenesis of urinary tract infection

There is extensive evidence indicating that the capacity of Escherichia coli to attach to the mucosal lining of the urinary tract is a virulence factor in acute pyelonephritis in the unobstructed state. In vitro results using human uroepithelial cells and clinical E. coli isolates as well as in vivo work on ascending urinary tract infection in mice and E. coli strains with genetically defined adhesins support this notion. The biochemical characterization of the bacterial ligands and epithelial cell receptors important for the attachment of most pyelonephritogenic E. coli provides a more sophisticated means of evaluating the role of bacterial adhesion in urinary tract infection: 1) It allows precise diagnosis of the receptor specificity of clinical isolates; 2) The receptor can be used to isolate the relevant bacterial adhesins; 3) The localization and quantity of the receptor in the patient may be of prognostic importance; 4) The administration of soluble receptor analogues or antibodies to the adhesins may be useful for prophylactic and/or therapeutic purposes.SummaryThere is extensive evidence indicating that the capacity ofEscherichia coli to attach to the mucosal lining of the urinary tract is a virulence factor in acute pyelonephritis in the unobstructed state.In vitro results using human uroepithelial cells and clinicalE. coli isolates as well asin vivo work on ascending urinary tract infection in mice andE. coli strains with genetically defined adhesins support this notion. The biochemical characterization of the bacterial ligands and epithelial cell receptors important for the attachment of most pyelonephritogenicE. coli provides a more sophisticated means of evaluating the role of bacterial adhesion in urinary tract infection: 1) It allows precise diagnosis of the receptor specificity of clinical isolates; 2) The receptor can be used to isolate the relevant bacterial adhesins; 3) The localization and quantity of the receptor in the patient may be of prognostic importance; 4) The administration of soluble receptor analogues or antibodies to the adhesins may be useful for prophylactic and/or therapeutic purposes.ZusammenfassungEs gibt zahlreiche Hinweise dafür, daß die Adhäsionsfähigkeit vonEscherichia coli an der Schleimhaut der Harnwege ein Virulenzfaktor für die Entstehung der nicht obstruktiven, akuten Pyelonephritis ist. Diese Vorstellung stützt sich auf Ergebnisse vonIn-vitro-Studien an menschlichen uroepithelialen Zellen mit klinischen Isolaten vonE. coli sowie vonin vivo-Studien am Modell der aufsteigenden Harnwegsinfektion der Maus unter Verwendung vonE.-coli-Stämmen mit genetisch definierten Adhäsinen. Die biochemische Charakterisierung der Bakterien-Liganden und der für die Adhäsion der meisten pyelonephritogenenE. coli-Stämme wichtigen Epithelzell-Rezeptoren ermöglicht eine methodisch differenziertere Abklärung der Rolle der Bakterienadhäsion für die Harnwegsinfektion: 1) Sie ermöglicht eine exakte Diagnose der Rezeptorspezifität klinischer Isolate; 2) Der Rezeptor kann zur Isolierung der relevanten Bakterien-Adhäsine eingesetzt werden; 3) Die Lokalisation des Rezeptors und seine Quantität kann für den Patienten prognostisch bedeutsam sein; 4) Die Anwendung löslicher Rezeptoranaloga oder von Antikörpern gegen Adhäsine ist möglicherweise von prophylaktischem und/oder therapeutischem Nutzen.

Fever, bacteriuria and concomitant disease in children with urinary tract infection.

A total of 124 children aged 0.2 to 6 years were enrolled in a study of first time febrile urinary tract infection. The patient population was stratified in groups according to the stringency of criteria for fever and bacteriuria and the presence of concomitant disease. The major group of 88 patients consisted of children with fever greater than or equal to 38.5 degrees C measured at the hospital within 24 hours of diagnosis, bacteriuria verified by suprapubic bladder aspiration or repeated cultures of voided urine, but without concomitant disease. These children were mainly infected with attaching Escherichia coli specific for galactose alpha (1----4) beta galactose containing receptors and had laboratory evidence of inflammation. Another group of 11 children were distinguished with strictly defined bacteriuria and concomitant disease. These children were infected with nonattaching bacteria and had lower concentrations of C-reactive protein in serum and lower microsedimentation rates than the major group. Five of these children had a reduction in renal concentrating capacity. The study emphasizes the heterogeneity among patients with fever and bacteriuria but does not rule out the possibility of renal involvement in any subgroup.

High Anti-phosphorylcholine Antibody Levels and Mortality Associated with Pneumonia

Phosphorylcholine is an immunodominant determinant of pneumococcal teichoic acids. Antibodies to phosphorylcholine are naturally occurring in man and decline in amount with age. Since antibodies to phosphorylcholine are markers of the immune responsiveness to polysaccharides and since anti-polysaccharide antibodies are highly protective against most bacterial pneumonia we expected a higher rate of pneumonia in elderly individuals with low levels of antibodies to phosphorylcholine. The relationship between the levels of antibodies to phosphorylcholine and mortality was analyzed prospectively in a representative sample of elderly individuals. A significant anti-phosphorylcholine antibody response occurred in a subgroup of the probands. There was a strong association (p less than 0.0001) between high levels of antibodies to phosphorylcholine in the serum at 70 years of age and pneumonia related death up to 14 years later. A similarly strong association was not observed between mortality and the antibody titer to another naturally occurring polysaccharide antigen: the blood group B antigen. Furthermore, there was no association between mortality due to diseases other than pneumonia and the levels of antibodies to phosphorylcholine. The association between antibody levels and subsequent fatal pneumonia provides a means of detecting individuals at risk for pneumonia-related death.

Bacterial and host determinants of renal scarring

This review summarizes recent work examining the interaction between host and parasite in recurrent urinary tract infection (UTI) and renal scarring. Virulence in uropathogenic E. coli has been defined by the severity of acute disease. Isolates from patients with acute pyelonephritic strains differ from those causing asymptomatic bacteriuria by multiple traits which contribute to virulence, and which are coexpressed in a non‐random manner. The single marker most characteristic for the pyelonephritogenic clones is bacterial adherence to uroepithelial cells binding specifically to the disaccharide Galα 1–4 Galβ within the globoseries of glycolipids. The notion that the most severe consequence of acute pyelonephritis, i.e. renal scarring, was caused by the most virulent clones, was contradicted by comparison of pyelonephritic strains isolated from children with and without scarring. The virulent clones were significantly less frequent in patients with renal scarring (22%) than in patients with recurrent pyelonephritis not developing renal scars (62%). In view of the unexpected inverse association of bacterial virulence with renal scarring lack of Galα 1–4 Galβ binding capacity of E. coli strains was found to predict the risk for renal scarring among boys with first‐time acute pyelonephritis. Vesicoureteric reflux (VUR) is widely accepted as a host determinant of susceptibility to pyelonephritis and renal scarring. In our study the frequency of renal scarring was 57% among girls with VUR as compared to 8% of those without. The reflux alone did however, not explain the selection of bacteria of low virulence. Individuals prone to UTI and renal scarring were found to be a genetically selected subgroup of the general population. A correlation between P1 blood group phenotype and susceptibility to UTI and between blood group non‐secretor state and renal scarring was found. The mechanisms behind these relationships need to be defined. The bacterial and host parameters combined indicate that host parameters are essential for the tendency to develop renal scarring after acute pyelonephritis.

Protein serotyping of Streptococcus pneumoniae based on reactivity to six monoclonal antibodies

Six monoclonal antibodies to proteins of Streptococcus pneumoniae were tested in a dot blot assay for reactivity with 499 clinical isolates of pneumococci. Forty-four percent of the isolates reacted with at least one of the antibodies. Nineteen patterns of reactivity were identified and each designated as a provisional protein serotype. Protein serotyping identified pneumococcal strains independently of their capsular type and made it possible to differentiate strains within most capsular types. A protein serotyping system provides a new dimension to the phenotypic identification of S. pneumoniae and may eventually provide a basis for assessing the population structure of these organisms.