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PubMed2000

Invasive pneumococcal infections in Canadian children, 1991-1998: implications for new vaccination strategies. Canadian Paediatric Society/Laboratory Centre for Disease Control Immunization Monitoring Program, Active (IMPACT).

We reviewed 2040 consecutive cases of invasive pneumococcal infection that were seen at 11 pediatric centers across Canada during 1991-1998 to determine if such infections could be prevented by new conjugate vaccines. Isolates from 1528 cases were serotyped. Most cases (61.5%) occurred in patients aged >2 years. Underlying medical conditions were present in 23.2% of case patients. Serotypes in the 7-valent conjugate vaccine matched isolates as follows: 85.8% of tested isolates from children aged 6 months to 5 years, but significantly fewer isolates in younger and older children; 72.9% of isolates from non-healthy children, but 83.9% of isolates from previously healthy children; and 95.4% of isolates with high-level penicillin resistance, but only 72.7% of those with intermediate-level resistance. Significant natural variation in the proportion of isolates matching 7-valent vaccines occurred from year to year and among centers. New conjugate vaccines have great potential but their effectiveness and limitations require ongoing study.

Bacteremia↗
PubMed1999

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.

Adjuvants, Immunologic↗
PubMed1987

Pneumococcal infection in hospitalized patients: a four-year study in Malaysia.

A total of 90 cases of pneumococcal infections were identified at a major referral hospital in Kuala Lumpur, Malaysia during a study period of four years. Pneumonia was the most common clinical presentation (41 cases) followed by meningitis (19 cases). Of 48 patients who were followed-up during the microbiology consultation round, 11 died, 9 were children below two years old. Capsular typing was carried out on 57 strains of Streptococcus pneumoniae isolated from blood and body fluids of 43 children and 14 adults. 38 strains isolated from pharyngeal specimens were also typed. Types 6A (11 strains), 6B (7 strains), 14 (8 strains) and 19A (8 strains) predominated in children. The strains from older patients comprised 3 isolates from cerebrospinal fluid (types 18B, 6B and 14), five from blood (4 strains, type 1 and 1 strain, type 4) and six from pus (1 strain, type 14, 3 strains type 23F and 2 strains type 34). The isolates from pharyngeal specimens belonged to capsular type similar to those implicated in infections. 90% of the types reported in this study are included in the 23 valent pneumococcal vaccines. Minimum inhibitory concentrations of penicillin, cefuroxime, chloramphenicol and rifampicin were determined for selected strains. 4.1% of isolates were resistant to penicillin (3/74), 4.5% to cefuroxime (2/44), 6.5% to chloramphenicol (3/46) and 14.6% to rifampicin (6/41).

Age Factors↗
PubMed2000

Epidemiology of invasive pneumococcal infections in children aged 0-6 years in Denmark: a 19-year nationwide surveillance study.

UNLABELLED: The impact of the new pneumococcal conjugate vaccines on invasive disease burden in Danish children was evaluated by analysing the results from the last 19 years of a nationwide surveillance of invasive pneumococcal infections. During 1981-1999, the Streptococcus Unit at Statens Serum Institut, Copenhagen, received 1123 invasive pneumococcal isolates from children aged 0-6 years. Nearly 72% (71.8%) of the pneumococcal isolates were from children aged <2 y. The median ages of children with pneumococcal meningitis and bacteraemia were 10.2 mo and 15.9 mo, respectively. The incidence of pneumococcal meningitis remained stable during the study period. The mean annual incidence rates of pneumococcal meningitis among children aged <1, <2, and <7 years were 17.4, 12.4, and 4.3 per 100,000, respectively, during 1981-1999 (overlapping age groups are used throughout this article to facilitate the comparison of incidence data from different countries or among different studies). The annual incidence of pneumococcal bacteraemia increased from 1981 to 1996, after which a slight fall was noted. During the last six years of the study period, the mean annual incidence rates of bacteraemia were 30.1, 32.5, and 14.0 per 100,000 children aged < 1, < 2, and < 7 years. In the 1990s, pneumococcal isolates with reduced sensitivity to penicillin (0-5% each year) and erythromycin (7.4% in 1999) emerged as a cause of invasive infections in children aged 0-6 years in Denmark. During 1981-1999, 10 serotypes (1, 4, 6A, 6B, 7F, 9V, 14, 18C, 19F, 23F) caused 82% of invasive infections in Danish children. Importantly, no significant temporal changes in overall serotype distribution or differences in serotype distributions between girls and boys could be documented during the study period. CONCLUSION: According to the Kaiser Permanente trial, the 7-, 9-, and 11-valent pneumococcal conjugate vaccines will probably cover around 60%, 70%, and 80%, respectively, of all invasive pneumococcal infections in Danish children aged 0-6y, corresponding to 12-14 episodes of meningitis and 40-60 episodes of bacteraemia per year.

Age Distribution↗
PubMed1996

Antibiotic-resistant pneumococcal infection in children with sickle cell disease in the United States.

OBJECTIVE: The purpose of this report is to examine the increasing problem of antibiotic-resistant pneumococcal infection in children with sickle cell disease in the United States. PATIENTS AND METHODS: In this retrospective review, 16 children with sickle cell disease and penicillin-resistant pneumococcal invasive infection were identified. They had a median age of 2 years (range 1-15) and were treated in Memphis, Dallas, Los Angeles, and five other cities between 1987 and early 1995. RESULTS: At presentation, patients frequently had high fever (> or 40.0 degrees C in 75%) and a toxic appearance (44%). Meningitis was present initially in two and diagnosed on days 4 and 5 in two. All were treated with an intravenous cephalosporin and nine received vancomycin. The clinical course was variable: two died within 36 h of presentation. In 20-86% of cases the organisms were resistant to cephalosporins, chloramphenicol, trimethoprim/sulfamethoxazole, erythromycin, and clindamycin; none were resistant to vancomycin. CONCLUSIONS: (a) The increasing prevalence of antibiotic-resistant Streptococcus pneumoniae infection in the United States poses special problems for patients with sickle cell disease. (b) Prompt antibiotic susceptibility testing of pneumococcal isolates should be performed. (c) Initial antibiotic management for patients suspected of sepsis/meningitis should include intravenous cephalosporin and vancomycin. (d) No alternative to penicillin prophylaxis is currently available. (e) An effective conjugated pneumococcal vaccine is needed.

Adolescent↗
PubMed1981

[Immunodiagnosis of pneumococcal infection in lung diseases].

The possibility of the identification of pneumococcal infection by means of serological tests was demonstrated. The etiological importance of pneumococci was determined on the basis of the presence of the pneumococcal antigen and the corresponding antibodies in the blood of patients with acute pneumonia. Simultaneously the level of circulating antibodies and their breakdown were studied. This allowed to evaluate the intensity of the elimination of the antigen from the body and enhanced the sensitivity of tests.

Acute Disease↗
PubMed2006

[EVAN-50 study: Effectiveness of polysaccharide pneumococcus vaccine in preventing pneumococcal infections in the over-50 population].

OBJECTIVE: To assess the effectiveness of 23-valent polysaccharide vaccine in preventing severe pneumococcal infections in adults over 50 years old. DESIGN: Case-control study. SETTING: Primary Health Care Service, Tarragona, Spain. PATIENTS: A total of 270 patients >50 with severe pneumococcal disease (invasive pneumococcal disease and non-bacteraemic pneumococcal pneumonia) and 540 control patients randomized from the primary care Centres of the case patients. Case and control patients will be matched for age, sex, family physician, and level of risk for pneumonia. MAIN MEASUREMENTS: Odds ratio (OR) will be used to measure the vaccine effect. Multivariate logistical regression, adjusted for age, sex, and comorbidity, will be conducted. Vaccine effectiveness (VE) will be calculated by the formula, VE = 1-OR. Vaccine effectiveness will be distinguished for the various age groups and at each risk stratum. It will also be estimated by means of indirect cohort analysis, taking as cases the infection caused by vaccine serotypes and as controls infection caused by non-vaccine serotype. DISCUSSION: The study will give an answer in terms of effectiveness of the vaccine for several age and risk strata. It will contribute to taking a decision regarding the controversial question of the systematic indication, or otherwise, of this vaccine for the elderly.

Case-Control Studies↗
PubMed1992

Epidemiology of invasive childhood pneumococcal infections in Israel. The Israeli Pediatric Bacteremia and Meningitis Group.

OBJECTIVE: To study the epidemiology of childhood pneumococcal invasive infections in Israel as a background for immunization programs. DESIGN: A 2-year (October 1988 through September 1990) prospective, nationwide surveillance of all invasive pediatric pneumococcal infections. SETTING: All 25 medical centers hospitalizing children in Israel, including all laboratories performing blood cultures from pediatric patients. PATIENTS: Infants and children aged 0 to 12 years visiting the pediatric emergency department or hospitalized in pediatric departments were included if Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid. RESULTS: Four hundred sixty-nine invasive infections were diagnosed. Pneumonia, bacteremia without apparent focus, meningitis, and cellulitis were found in 39%, 37%, 17%, and 3%, respectively. The annual incidence was 42 per 100,000 for children younger than 5 years of age (104 per 100,000 for those < 12 months old). The two most common serotypes were 1 and 5, which are rare in Western Europe and North America. Eight groups comprised 82% of all invasive infections. Extrapolated to a population in which 100,000 live births occur yearly, the total annual hospitalizations for pneumococci infections was calculated to be 1928 days. The overall case-fatality rate was 2.2%, but it was 30% during the first month of life. CONCLUSIONS: Pneumococcal invasive infections are common in children in Israel and carry considerable morbidity.

Acute Disease↗
PubMed1985

[Immunoenzyme analysis in pneumococcal infection].

Complex protein preparations obtained from pneumococci have been used for the serological examination of patients with pneumococcal infection. The proposed system of ELISA permits the detection of positive results in about 70% of cases. The specificity of the method is 95%. Special attention is paid to the determination of the criterion indicating the presence of positive results.

Bacterial Proteins↗
PubMed2006

Streptococcus pneumoniae serogroups 15 and 33: an increasing cause of pneumococcal infections in children in the United States after the introduction of the pneumococcal 7-valent conjugate vaccine.

BACKGROUND: After the widespread use of the 7-valent pneumococcal conjugate vaccine, replacement serotypes have emerged. Serogroups 15 and 33 have emerged as nonvaccine serotypes causing invasive disease. We describe the clinical characteristics of children with infections caused by these serogroups and determined the genetic relationship of the strains. MATERIALS AND METHODS: The United States Pediatric Multicenter Pneumococcal Surveillance Group has prospectively identified children with pneumococcal infections since 1993. Charts were reviewed retrospectively, isolates were serogrouped and serotyped and randomly selected strains were fingerprinted with the use of pulsed field gel electrophoresis. Selected strains were further characterized by multilocus sequence typing. RESULTS: Between January 1994 and December 2004, 103 children had pneumococcal disease caused by serogroup 15, and 40 children had infections caused by serogroup 33. There was an increase from a mean of 7 cases per year for serogroup 15 in the prevaccine period to 14 cases per year in the postvaccine period and from 2 cases per year for serogroup 33 to 7 cases per year in the same periods. Isolates were susceptible to penicillin and ceftriaxone in both periods. A predominant clone was found in each serogroup representing 60% (30 of 50) of serogroup 15 strains and 83% (24 of 29) of the serotype 33F strains. The serogroup 15 clone comprised strains of serotypes 15B and 15C, whereas the 33 clone contained only serotype 33F strains. One isolate from each of the 15 and 33 clones was characterized by multilocus sequence typing and were found to be ST199 and 100, respectively. CONCLUSIONS: Pneumococcal disease in children caused by penicillin-susceptible clones of serogroups 15 and 33 is increasing in the United States. Clinicians should consider replacement serotypes when encountered with invasive pneumococcal disease in vaccinated children.

Adolescent↗
PubMed2006

[Serotype distribution and penicillin-binding protein genes of Streptococcus pneumoniae in children with invasive pneumococcal infection].

Between August 1998 and July 2005, we studied the serotypes and mutation of penicillin-binding protein (PBP) genes of 46 strains of Streptococcus pneumoniae isolated from children with invasive pneumococcal infection in Hokkaido. The clinical diagnosis was pneumonia in 16 cases, occult bacteremia in 15, meningitis in 8, upper respiratory infection in 6, and arthritis in 1. Patients ranged in age from 2 months to 9 years old. Prevalent serotypes were 6B (39.1%), 23F (17.4%) 6A (8.7%), and 19F (8.7%). The serotype coverage rate by the 7-valent pneumococcal vaccine was greater than 70% in children. Mutation of 3 genes (Penicillin-binding S. pneumoniae, PRSP) was detected in 18 isolates, mutation of 10 genes (pbp1a and pbp2x, or pbp2x and pbp2b) in 2, and of pbp2x alone in 15. PRSP was found in serotypes 6A, 6B, and 23F, and the rate of PRSP in 6A, 6B, and 23F was 75.0%, 62.5%, and 55.6%, respectively.

Bacteremia↗
PubMed1994

Recurrent systemic pneumococcal infection in an immunocompromised patient.

A case is reported of a splenectomized patient who experienced four episodes of systemic pneumococcal infection after receiving appropriate therapy in every instance. Serogrouping showed at least two different strains to be responsible for these infections. Immunological investigations showed a reduction in immunoglobulins, a decrease in in vitro immunoglobulin synthesis and a disorder of immunoregulatory T-cells, but immunological changes could not be readily explained by splenectomy alone.

Adult↗
PubMed2004

Feasibility of radioimmunotherapy of experimental pneumococcal infection.

Streptococcus pneumoniae is an important cause of community-acquired pneumonia, meningitis, and bacteremia. The problem of pneumococcal disease is exacerbated by increasing drug resistance. Furthermore, patients with impaired immunity are at high risk for invasive pneumococcal infections. Thus, there is an urgent need for new approaches to antimicrobial therapy. Antibody therapies take advantage of the specificity and high affinity of the antigen-antibody interaction to deliver antibacterial compounds to a site of infection in the form of naked or conjugated antibodies. We have recently established that radioimmunotherapy (RIT) can be used to treat experimental fungal infections in mice. In the present study, we investigated the feasibility of applying a RIT approach to the treatment of S. pneumoniae infection by evaluating the susceptibility of S. pneumoniae to radiolabeled antibody in vitro and in an animal infection model. For the specific antibody carrier, we used human monoclonal antibody D11, which binds to pneumococcal capsular polysaccharide 8. We have selected the alpha particle emitter (213)Bi as the radionuclide for conjugation to the antibody. Incubation of serotype 8 S. pneumoniae with (213)Bi-D11 resulted in dose-dependent killing of bacteria. RIT of S. pneumoniae infection in C57BL/6 mice showed that 60% more mice survived in the (213)Bi-D11-treated group (80 micro Ci) than in the untreated group (P < 0.01). The treatment did not cause hematological toxicity, as demonstrated by platelet counts. This feasibility study establishes that RIT can be applied to the treatment of bacterial infections.

Animals↗
PubMedDate not supplied

Disseminated pneumococcal infection with pericarditis and cardiac tamponade: report of one case.

A 1-year-5-months-old female who had cough, rhinorrhea and prolonged fever for 19 days was admitted to the intensive care unit due to exertional dyspnea. She was intubated promptly in virtue of hypotension and cyanosis. The physical examination demonstrated diminished breathing sound over the right lung and distant heart sound; echocardiogram showed cardiac tamponade. Further X ray study showed right hydropneumothorax and cardiomegaly. Pericardiocentesis and chest thoracostomy were performed, and subsequently all the cultures showed growth of Streptococcus pneumoniae. Antibiotics therapy was started promptly after admission. Further investigation indicated osteomyelitis of the right ilium, so that surgical debridement was done. The patient was discharged 54 days later with complete recovery. After following up for 18 months, no restrictive heart disease developed. Purulent pericarditis with cardiac tamponade is an extremely rare complication of pneumococcal infection.

Cardiac Tamponade↗
PubMedDate not supplied

New vaccines for the prevention of pneumococcal infections.

Streptococcus pneumoniae is a major cause of acute otitis media, pneumonia, bacteremia, and meningitis. Because in recent years antibiotic-resistant pneumococcal strains have been emerging throughout the world, vaccination against pneumococcal infections has become more urgent. The capsular polysaccharide vaccine that has been available is neither immunogenic nor protective in young children and other immunocompromised patients. Several pneumococcal proteins have been proposed as candidate vaccines, but no human studies associated with them have been reported. Clinical trials of first-generation pneumococcal conjugate vaccines have shown that covalent coupling of pneumococcal capsular polysaccharides to protein carriers improves the immunogenicity of the polysaccharides. The protective efficacy of the conjugate vaccines against carriage, acute otitis media, and invasive infections is being studied.

Adult↗
PubMedDate not supplied

Pneumococcal infection in children: rational antibiotic choice for drug-resistant Streptococcus pneumoniae.

Streptococcus pneumoniae is one of the most common bacterial causes of otitis media, sinusitis, bacteremia, pneumonia and bacterial meningitis in the pediatric population. The resistance of S. pneumoniae to penicillin and other antimicrobial agents is increasing in many parts of the world. In Taiwan, extremely high prevalence (70%) of penicillin-resistant S. pneumoniae among children with nasopharyngeal carriage has been reported. The mechanism of resistance to penicillin is the alteration of penicillin binding protein (PBP) instead of the production of beta-lactamase. Thus beta-lactamase inhibitors are not the solution to the treatment of infections caused by penicillin-resistant S. pneumoniae. The adequate treatment of infections caused by penicillin-resistant S. pneumoniae should be based on (1) site of infection (2) degree of resistance. Currently, the MIC breakpoints for S. pneumoniae are divided to 2 categories; one for CNS infection and the other for non-CNS infections. For non-CNS infections caused by susceptible or intermediate S. pneumoniae, penicillin still remains the drug of choice with excellent bactericidal activity. Vancomycin should not be the first choice in treating all pneumococcal infections.

Adult↗