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Invasive pneumococcal infections in pediatric cardiac transplant patients.

BACKGROUND: Bacterial infections cause significant morbidity and mortality in cardiac transplant patients. Because Streptococcus pneumoniae is the most prominent bacterial pathogen of childhood, the objective of this study was to define the role of S. pneumoniae as a pathogen in the cardiac transplant population. METHODS: Medical records of cardiac transplant patients from March, 1990, through November, 2000, were reviewed to identify invasive pneumococcal infections after transplantation. Demographic, clinical and microbiologic data were reviewed. RESULTS: Nine (11%) of 80 patients had 12 episodes of pneumococcal bacteremia for an incidence rate of 39 cases/1,000 patient years. Patients who were African-American, transplanted before 2 years of age and transplanted because of idiopathic dilated cardiomyopathy were at increased risk of invasive pneumococcal disease (P < 0.05). Six patients were eligible for the 23-valent pneumococcal polysaccharide vaccine before their first invasive infection, but only 1 had received it at the recommended age. Most isolates (82%) were penicillin-susceptible, and no single serotype predominated. There were 2 deaths in the study group, but each was unrelated to infection. Three patients (33%) had recurrent invasive disease with a second serotype an average of 12 months after the first infection. CONCLUSIONS: The incidence of pneumococcal bacteremia in cardiac transplant patients is higher than in the general pediatric population. Risks for infection were being African-American, being younger than 2 years at the time of transplant and being transplanted because of idiopathic cardiomyopathy. It is plausible that pneumococcal vaccine would decrease this risk.

Arkansas↗

Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey.

Streptococcus pneumoniae (S. pneumoniae) may cause severe and lethal infections months and years following stem cell transplantation (SCT). In a prospective survey over a 3.5-year period, we assessed the incidence, risk factors and outcome for invasive pneumococcal infection (IPI) following SCT. Fifty-one episodes of IPI were reported: 43 episodes after bone marrow transplantation (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after allogeneic SCT and 16 after autologous SCT. Seven IPI episodes, all bacteraemias, were defined as early, occurring 1-35 d (median 3 d) post transplantation. Forty-four episodes were defined as late (> or = 100 d post SCT), occurring 4 months to 10 years (median 17 months) post transplantation. The incidences of early and late IPI were 2.03/1000 and 8.63/1000 transplantations respectively (P = 0.001). A higher incidence of late IPI was observed after BMT than after PBSCT (10.99 versus 3.23/1000; P < 0.01) and after allogeneic versus autologous SCT (12.20 versus 4.60/1000; P < 0.01). There was a higher estimated incidence of IPI in allogeneic patients with than in those without graft-versus-host disease (GVHD) (18.85 versus 8.25/1000; P = 0.015). The mortality rate was 20%, including 2/7 of early and 8/44 of late IPI. S. pneumoniae is a rare but important complication during the aplastic phase after SCT. In conclusion, S. pneumoniae is a significant cause of morbidity late post-transplantation, especially in allogeneic patients, and particularly those with GVHD. The high IPI mortality rate, both early and late post-transplantation, requires preventive approaches, mainly effective immunization.

Adolescent↗

[The pneumococcal infection in a general hospital of a parisian suburb: a prospective study in Villeneuve-Saint-Georges hospital (author's transl)].

The authors have carried during one year, in the hospital of Villeneuve-Saint-Georges, a prospective study on 229 cases of pneumococcal infections with bacteriological findings. They emphazise the frequency, the high-exposed groups and the gravity of these infections despite of the antibiotherapy. The emergence of multiply resistant pneumococcus makes out another argument for proposing a preventive vaccination taking notice of the most frequent serotypes found in France.

Adolescent↗

Toll-like receptor 9 acts at an early stage in host defence against pneumococcal infection.

Toll-like receptor 9 (TLR9) induces an inflammatory response by recognition of unmethylated CpG dinucleotides, mainly present in prokaryotic DNA. So far, TLR9-deficient mice have been shown to be more sensitive than wild-type mice to viral, but not to bacterial infections. Here, we show that mice deficient in TLR9 but not in TLR1, TLR2, TLR4 and TLR6 or IL-1R/IL-18R are more susceptible to a respiratory tract bacterial infection caused by Streptococcus pneumoniae. Intranasal challenge studies revealed that TLR9 plays a protective role in the lungs at an early stage of infection prior to the entry of circulating inflammatory cells. Alveolar as well as bone marrow-derived macrophages deficient in either TLR9 or the myeloid adaptor differentiation protein MyD88 were impaired in pneumococcal uptake and in pneumococcal killing. Our data suggest that in the airways, pneumococcal infection triggers a TLR9 and MyD88-dependent activation of phagocytic activity from resident macrophages leading to an early clearance of bacteria from the lower respiratory tract.

Animals↗

Prevalence of serotypes and antimicrobial resistance of streptococcus pneumoniae strains isolated from Brazilian children with invasive infections. Pneumococcal Study Group in Brazil for the SIREVA Project. Regional System for Vaccines in Latin America.

A laboratory surveillance study was developed in Brazil in 1993 to determine capsular types and antimicrobial susceptibility of Streptococcus pneumoniae strains. By studying 360 strains isolated from children with invasive infections in three different cities, 8 out of 34 types were identified as being the most prevalent and considered as the reference group for further analyses. This group comprised 77.7% of all strains studied, and includes the types 1, 5, 6A/B, 9V, 14, 19F, 19A, and 23F. The prevalence of this reference group was significantly higher among strains isolated from children with pneumonia than meningitis. Similarly, this group was more prevalent among strains isolated from children 3 to 6 years of age than from children under 2 years of age. Most strains (78.6%) were found to be susceptible to penicillin and only 1.4% showed high resistance to this antibiotic. However, intermediate resistance to penicillin was detected in 20% of the strains. This laboratory surveillance will be maintained and extended to other cities of Brazil to better define and monitor the trends of pneumococcal infections for proper control and prevention.

Brazil↗

Invasive pneumococcal infections: a clinical and microbiological analysis of 53 patients in Taiwan.

OBJECTIVE: To track penicillin susceptibility among Streptococcus pneumoniae causing invasive diseases and to evaluate risk factors for antibiotic resistance. METHODS: A retrospective study was performed in a medical center of all patients with invasive pneumococcal infections based on positive microbiological findings, confirmed by appropriate clinical and laboratory findings. MICs of penicillin and ceftriaxone were determined and interpreted by NCCLS methodology. RESULTS: Fifty-three episodes of invasive S. pneumoniae infections (ISPI) among 22 children and 31 adults were identified. The disease patterns of ISPI were similar between children and adults, and the most common modes were pneumonia (70%) and primary bacteremia (23%). The rate of penicillin-nonsusceptible S. pneumoniae (PNSP) isolated from pediatric patients was higher than that in adult patients (95.5% vs. 54.8%, P < 0.001). This finding was correlated to prior antibiotic use that was more common in children (36.4%) than in adults (18.9%). The rate of penicillin-resistance among S. pneumoniae isolates (PRSP) was extremely high in this area: 45.5% from pediatric patients and 41.9% from adult patients. More adults (90.3%) with ISPI had major underlying diseases than children (4.5%). This may explain why adult patients tended to run an unfavorable outcome (mortality rate, 51.6% and 4.5% in adults and children, respectively), although most of the cases with empyema were children. None of the patients enrolled in this study received pneumococcal vaccination. CONCLUSION: We suggest that vaccines be administered for young children and the elderly with major underlying diseases to prevent ISPI.

Adolescent↗

[Modern views on pneumococcal infections in infants and toddlers].

Pneumococci colonize the upper respiratory tract predominantly in sucklings and toddlers. By means of their factors of virulence (capsule, ahesines, peptidoglycan, and polysaccharides of the capsule, cytoplasmic membrane enzymes) they can either avoid or impair the immunity mechanisms causing thus severe infections especially in children younger than three years of age and in patients with immunity defects. Regarding the possibility of occurrence of pneumococci with altered susceptibility to penicillin and some other drugs (erythromycin, cotrimaxazol, ceftriaxon, chloramphenicol, tetracycline) it is necessary to treat severe pneumococcal infections on the basis of in vitro detected susceptibility.

Child, Preschool↗

Analysis by cDNA microarrays of altered gene expression in middle ears of rats following pneumococcal infection.

OBJECTIVE: Streptococcus pneumoniae is the most common pathogen in otitis media. Infection of the middle ear with S. pneumoniae potentiates development of thick effusion in the middle ear which frequently causes hearing loss and communication disorders in children. What has changed immediately in the middle ear cleft following pneumococcal infection is extensively studied and characterized but what has changed ever after remains elusive. The purpose of this study is to explore the cellular and molecular basis that remains on a longer time after acute pneucmococcal middle ear infection and potentiates development of thick effusion in the middle ear. METHODS: 12 rats were intrabullarly inoculated with pneumococcus at 2.5x10(6) CFU/ear and profiles of gene expression in the middle ear were examined by cDNA microarrays in combination with reverse transcription-polymer chain reaction (RT-PCR) 6 weeks after infection while the morphologic changes in middle ear were simultaneously characterized by histopathologic techniques. Twelve rats receiving phosphate-buffered saline (PBS) served as controls. RESULTS: it demonstrated that pneumococcus infected ears had the expression of the following genes at a high level compared to the controls: mitogenic signaling proteins (mitogen-activated protein kinase [MEK1 and MEK2], helix-loop-helix transcriptional regulators (Id3 and Id1), ion channels (sodium channel beta 1 and sodium channel 2), and mucin glycoproteins (Muc2 and Muc5). The morphology demonstrated a thickened mucosa and submucosa with increased expression of macroglycoconjugates compared to the controls. CONCLUSION: the expression of several genes remains high even after the acute episode of pneumococcal otitis media has been resolved. The up-regulated expression of these genes may serve as the basis for the development of thick effusion and mucous cell metaplasia/hyperplasia once it is complicated with other factors such as dysfunction of the Eustachian tube.

Animals↗

Phosphocholine of pneumococcal teichoic acids: role in bacterial physiology and pneumococcal infection.

Pneumococci have an absolute nutritional requirement for choline. Choline is incorporated as phosphocholine (PCho) into lipoteichoic (LTA) and teichoic acid (TA). The PCho residues are required for transformability, the activity of autolysins, the separation of daughter cells after cell division and for anchoring a family of surface proteins which play important roles in pneumococcal infection. The genes encoding the enzymes for PCho incorporation are described. Two strains that acquired the ability to grow in the absence of choline are discussed.

Animals↗

Invasive pneumococcal infections in Denmark from 1995 to 1999: epidemiology, serotypes, and resistance.

Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described. Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored. Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed. The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively. Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%). These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.

Adolescent↗

[Costs of pneumococcal infections and cost evaluation of heptavalent conjugate vaccine].

The results of six economic evaluations on heptavalent conjugate pneumococcal vaccination in children are discussed. Although the data of most studies come from estimates, the last study from US, in which data are based on a large randomized trial, shows encouraging results. Similar results are obtained in an economic evaluation performed in Germany, although the study is based on estimated data. The paper concludes stressing the need to improve epidemiological, clinical and economical knowledge on the pneumococcal diseases, in order to identify the best cost-effectiveness strategy to prevent a diseases so important for children and the elderly.

Health Care Costs↗

Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A.

Pneumococcal surface protein A (PspA), a cell-surface protein present on all strains of pneumococci, has been shown to elicit protective antibody responses in mice in the absence of capsular polysaccharide. Whereas PspA is polymorphic, considerable cross-reactivity and cross-protection have been demonstrated among PspA proteins of pneumococci exhibiting different capsular and PspA serotypes. A gene segment encoding the nonrepetitive variable NH2-terminal portion of PspA has been cloned into three distinct recombinant Bacille Calmette-Guérin (rBCG) vectors, allowing for expression of PspA as a cytoplasmic or secreted protein, or a chimeric exported membrane-associated lipoprotein. All rBCG-PspA strains elicited comparable anti-PspA ELISA titers, ranging from 10(4) to 10(5) (reciprocal titers) in both BALB/c and C3H/HeJ mice. However, protective responses were observed only in animals immunized with the rBCG-PspA vaccines expressing PspA as a secreted protein or chimeric exported lipoprotein. In addition, anti-PspA immune sera elicited by the rBCG vaccines passively protected X-linked immunodeficient mice from lethal challenge with the highly virulent, encapsulated WU2 strain of Streptococcus pneumoniae and two additional virulent strains exhibiting heterologous PspA and capsular serotypes. These studies confirm previous PspA immunization studies showing cross-protection against heterologous serotypes of S. pneumoniae and demonstrate a potential for rBCG-based PspA vaccines to elicit protective humoral responses against pneumococcal disease in humans.

Animals↗