Six newly recognized types of Streptococcus pneumoniae.
The serological properties of six new pneumococcal capsular types are described. A table listing all 90 pneumococcal types and their cross-reactions is included.
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Publications and source records attributed to J Henrichsen.
The serological properties of six new pneumococcal capsular types are described. A table listing all 90 pneumococcal types and their cross-reactions is included.
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Patients with B cell chronic lymphocytic leukemia (B-CLL) have decreased capacity to mount relevant antibody responses upon immunization, and development of hypogammaglobulinemia is part of the natural history of the disease. We investigated the influence of histamine type-2 (H2) receptor blockade by ranitidine on the in vivo antibody production in B-CLL patients following vaccination. Anti-polysaccharide antibodies in B-CLL patients, vaccinated with a tetanus-toxoid conjugated vaccine against Haemophilus influenzae type-B (Hib), reached long-term protective levels in more than 90% of B-CLL patients randomized to ranitidine treatment, as compared to 43% of the untreated patients (P = 0.024). No difference in the response to vaccination against influenza virus types A and B protein could be detected between the two groups. Plasma histamine levels were 2-fold to 20-fold higher in 23 out of 31 B-CLL patients, compared to normal controls, and these levels showed a significant positive correlation to disease duration. These findings indicate the possibility of improving in vivo antibody production against a highly relevant pathogen in B-CLL patients by histamine type-2 receptor blockade, and the combined finding of an immune-stimulatory effect of ranitidine and increased plasma histamine levels, strongly suggests the involvement of histamine in the pathogenesis of B-CLL immunodeficiency.
BACKGROUND: A substantial proportion of patients admitted to the hospital for pneumonia have been treated in a hospital during the preceding 4 to 5 years, and patients previously treated in a hospital for pneumonia seem to be at an especially high risk for another episode of pneumonia. Many cases of pneumococcal infection might therefore be prevented by immunizing admitted patients with pneumococcal vaccine at discharge or at follow-up. The aim of this study was to investigate the type-specific antibody response to pneumococcal vaccine in middle-aged and elderly patients at follow-up 8 weeks after hospital treatment for pneumonia. METHODS: A total of 92 individuals, 50 to 85 years old, participated in the study. One group consisted of 65 individuals treated in the hospital for pneumonia 8 weeks before vaccination (mean age, 67 years), and another group consisted of 27 individuals who had not recently been treated for pneumonia (mean age, 67 years). All 92 individuals received a single dose of a 23-valent pneumococcal vaccine. The type-specific antibody responses to six pneumococcal capsular polysaccharide antigens included in the vaccine as well as antibodies against the 23-valent pneumococcal vaccine were measured before and 3 to 4 weeks after vaccination by use of an enzyme-linked immunosorbent assay. RESULTS: The antibody concentrations before and after vaccination were comparable in the two groups, as were antibody fold increases from prevaccination to postvaccination serum. No serious adverse events were recorded. CONCLUSIONS: Pneumococcal vaccination at follow-up 8 weeks after treatment in the hospital for pneumonia seems to elicit an adequate antibody response without notable adverse reactions.
Countercurrent-immunoelectrophoresis (CIE) was used to detect pneumococcal capsular polysaccharide and C-polysaccharide (C-Ps) antigens in urine. The neutral capsular polysaccharides of types 7F and 14 were detected by coagglutination. We found pneumococcal polysaccharide in urine with the same frequency in two groups of patients, i.e. a non-bacteraemic pneumonia group (68%) and a group of patients with pneumococcal bacteraemia (66%). C-Ps was detected in the urine of two patients (4%) and, therefore, this test has no value in the diagnosis of pneumococcal infections. Since there is no sensitive, non-invasive, single procedure for the diagnosis of non-bacteraemic pneumococcal pneumonia we conclude that attempts to detect pneumococcal capsular polysaccharide by CIE in combination with coagglutination (types 7F and 14) may be a useful diagnostic supplement in the search for the etiological agent in pneumonia in adults until new, more sensitive diagnostic methods have been developed.
Penicillin-resistant clinical isolates of Streptococcus pneumoniae contain mosaic penicillin-binding protein (PBP) genes that encode PBPs with decreased affinity for beta-lactam antibiotics. The mosaic blocks are believed to be the result of gene transfer of homologous PBP genes from related penicillin-resistant species. We have now identified a gene homologous to the pneumococcal PBP2x gene (pbpX) in a penicillin-sensitive Streptococcus oralis isolate M3 from South Africa that diverged by almost 20% from pbpX of penicillin-sensitive pneumococci, and a central sequence block of a mosaic pbpX gene of Streptococcus mitis strain NCTC 10712. In contrast, it differed by only 2-4% of the 1 to 1.5 kb mosaic block in pbpX genes of three genetically unrelated penicillin-resistant S. pneumoniae isolates, two of them representing clones of serotype 6B and 23F, which are prevalent in Spain and are also already found in other countries. With low concentrations of cefotaxime, transformants of the sensitive S. pneumoniae R6 strain could be selected containing pbpX genes from either S. mitis NCTC 10712 or S. oralis M3, demonstrating that genetic exchange can already occur between beta-lactam-sensitive species. These data are in agreement with the assumption that PBPs as penicillin-resistance determinants have evolved by the accumulation of point mutations in genes of sensitive commensal species.
The aim of this study was to examine the immunogenicity of a Haemophilus influenzae type b (Hib) vaccine (PRP-D) in Danish children younger than 18 months of age, given at the same time as a diphtheria-, tetanus- and polio-vaccine at the age of five, six and 15 months. The study was carried out as a multicentre study, where 21 children were vaccinated by their general practitioners. Blood samples were drawn just before and four weeks after each of the three vaccinations and the concentration of Hib-antibodies were determined using an ELISA-technique. Before the first vaccination none of the 21 children had antibody levels above 1 microgram/ml, which is believed to be the level which provides long-lasting protection, whereas after the first, second and third vaccination respectively 24, 48 and 100% of the children had antibody levels above 1 microgram/ml. There were only mild and short-lived side effects. The PRP-D vaccine given at the same time as Di-Te-Pol is safe, without serious side-effects and immunogenic in Danish children.
We have developed an ELISA for antibody determination, superior to others hitherto described, in which optimal coating is achieved using phenylated pneumococcal capsular polysaccharides as coating antigen. The specificity of the assay is ensured by complete inhibition of antibodies against the species-specific pneumococcal antigen, C-polysaccharide (C-Ps). The method is sensitive, specific, reproducible, fast and easy to work with and can be used for both immunoglobulin class and subclass antibody determinations.
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The ability of antibodies against C-polysaccharide (C-Ps) to protect against experimental pneumococcal infection was examined in a mouse model. No protection against types 6A and 14 pneumococcal infection could be demonstrated neither with mouse monoclonal antibodies against C-Ps, specific for phosphorylcholine (PC) or for C-Ps backbone, nor for polyclonal rabbit immunsera against C-Ps. The monoclonal antibody with PC-specificity was protective against infection with type 27 pneumococcus, that has PC as part of its capsular polysaccharide. Type-specific mono- and polyclonal antibodies were highly protective against infection with the homologous type. We conclude that no species-specific protection can be achieved against intraperitoneal Streptococcus pneumoniae infection with optimally capsulated bacteria in outbred mice by passive immunization with antibodies to C-Ps.
The molecular population genetics and pathogenic potential of North American and European invasive strains of Streptococcus pyogenes were assessed. Isolates from recent invasive infections and from infections in the 1920s and 1930s were characterized for multilocus enzyme genotype and allelic variation in the gene (speA) that encodes streptococcal pyrogenic exotoxin (SPE) A (scarlet fever toxin). A subset of strains was studied for allelic variation in genes that encode SPE B and streptokinase. All contemporary strains assigned to electrophoretic types (ETs) 1 and 2 that synthesize SPE A have the speA2 and speA3 allelic variants, respectively, and their relative virulence in two mouse models is similar to that of strains of the same ET and M protein types recovered earlier. In contrast, ET 1 and 2 isolates from disease episodes in the 1920s and 1930s contain the speA1 allele. The data suggest there may be temporal and geographic variation in the occurrence of clone--virulence factor allele combinations, an observation that may in part explain fluctuations in disease frequency, severity, and character.
Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae presents a challenge to clinical case management, particularly in programs for acute respiratory tract infection (ARI), including pneumonia, in developing countries. To determine whether nasopharyngeal isolates of S. pneumoniae and H. influenzae from a clinically defined group of children could be used to predict the prevalence of antimicrobial resistance of strains that cause disease, 601 urban children with ARI, 133 healthy urban children and 285 rural children were evaluated in Pakistan. Of the urban children with ARI, 216 (35.9%) were bacteremic, predominantly with S. pneumoniae (108 children) and H. influenzae (100 children). Overall 631 (61.9%) children carried S. pneumoniae and 381 (37.4%) carried H. influenzae. The proportions of nasopharyngeal isolates of both organisms from urban children with ARI resistant to penicillin or ampicillin, trimethoprim/sulfamethoxazole, chloramphenicol and erythromycin were similar to the proportions of resistant blood isolates. Nasopharyngeal isolates from rural children had lower rates of resistance to some antimicrobial agents. These findings suggest that nasopharyngeal isolates of S. pneumoniae and H. influenzae from children with ARI can be used to conduct surveillance for antimicrobial resistance in a defined geographic area. Such surveillance would aid programs in developing countries in making a rational choice of antimicrobial agents for use in clinical management of bacterial diseases, including pneumonia.
Eighty-four mono- and dizygotic Caucasian twins randomly chosen, except for age and sex distribution, were vaccinated with a 23-valent pneumococcal vaccine. Blood samples were drawn before and after vaccination and the concentration of IgG, IgG1 and IgG2 pneumococcal antibodies was measured using an ELISA technique which only detects type-specific capsular antibodies, since C-polysaccharide antibodies in serum were removed. A significantly closer correlation was found regarding mean IgG and IgG2 antibody concentrations after vaccination in mono- compared with dizygotic twins, and this correlation was seemingly type-specific. Since environmental factors in our study population should not contribute more to the immune response in one type of twins compared with the other, we conclude that genetic factors influence the IgG and IgG2 antibody response to pneumococcal vaccination, and that this influence seems to be type-dependent.
By means of the capsular reaction test, we typed 2,294 pneumococcal strains isolated from blood or cerebrospinal fluid (CSF) in Denmark during 1983-88.91% of the strains belonged to types included in the 23-valent vaccine. Among 254 pneumococcal isolates from blood and CSF from Danish children, types 6A + 6B, 18C, 14, 7F, 1 and 19F, in that order of frequency, were the most common ones, accounting for 68%. Among 2,031 pneumococcal strains from adults, the most common isolates were types 1, 3, 14, 7F, 4, and 6A + 6B, accounting for 50% of all pneumococcal strains isolated from patients with invasive disease. Penicillin-resistant invasive strains of Streptococcus pneumoniae are rare in Denmark (< 1%).
Streptococcus pneumoniae still causes serious infections especially in elderly people, despite relevant antibiotic treatment and intensive therapy. At present, Statens Serum-institut annually receives about 650 pneumococcal strains isolated from blood and cerebrospinal fluid for typing from the departments of Clinical Microbiology in Denmark. Of these strains about 55% were isolated from persons aged 60 years or older. The incidence of pneumococcal pneumonia in elderly people is said to be 4-8/1000 persons/year in countries similar to Denmark. In the USA, pneumococcal vaccination is recommended for groups at risk including immunocompetent adults > or = 65 years old. Since 1978, pneumococcal vaccine has been available in Denmark, where the only indication for vaccination has been and still is intended or already performed splenectomy in persons older than two years of age. According to the literature, the protective efficacy of vaccination of elderly persons is 60-70%. Since vaccination is, furthermore, without risks we believe that vaccination of elderly people in Denmark should be advised.
Hyperimmune and high-titered polyclonal pneumococcal antisera, specific for cross-reactive types within groups, were produced in adult rabbits. Purified capsular polysaccharide was injected intravenously into adult rabbits. One week later, these rabbits were given multiple intravenous injections of formalin-inactivated pneumococci of the cross-reactive type by an established method. Each of the resultant antisera were specific for the cross-reactive type indicating that the previous injection of the polysaccharide had induced epitope-specific tolerance. This method was successful for production of antisera against pneumococcal types 6A, 6B, 9N, 9V, 19F and 19A. Polyclonal rabbit pneumococcal antisera have some advantages over murine monoclonal antibodies for serologic studies and this method should be applicable for producing type-specific antibodies to cross-reactive polysaccharides of clinical interest. Further, this method is simpler and generally produces higher titered monovalent (factor) reagents than absorbed antisera.
A prospective investigation of patients admitted to the local hospital during a period of one year was undertaken. A total of 107 patients participated. 50% of the cases of pneumonia were found by Streptococcus pneumoniae. The diagnosis was established partly by demonstration of antigens and increase in antibody titre and also employing the traditional methods: Blood culture, microscopic examination and culture of the expectorate or tracheal secretion. 70% of the patients were over the age of 60 years. The mortality was found to be 17%. The difficulties in etiological investigations of infections in the lower respiratory tract are discussed.
Knowledge about the type distribution of Streptococcus pneumoniae is fundamental to ensure an effective formulation of pneumococcal vaccine, especially with the possibility of producing a polysaccharide-protein-conjugated vaccine for the prevention of invasive disease in children. During the 6-year period 1982-1987, we received and typed 10,298 isolates from patients with invasive pneumococcal disease: 7,812 (76%) from blood and 2,486 (24%) from CSF. Of all isolates, 81% were recovered from individuals in Europe and 23% were from children. In order of frequency, S. pneumoniae types 6A + 6B, 14, 18C, 19F, 1, 7F, 23F, 19A, 4, and 5 were most commonly isolated from children, and types 3, 1, 14, 7F, 4, 6A + 6B, 8, 23F, 9V, and 19F, from adults. The pneumococcal types in the currently available 23-valent vaccine represented 87% of all isolates in this study, but the proportion of vaccine types varied somewhat with age and source. In all pneumococcal groups included in the vaccine, the vaccine types represented > 80% of the isolates, except in groups 6, 15, and 18.