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PubMed1997

Impaired antibody response to pneumococcal capsular polysaccharides and phosphorylcholine in adult patients with a history of bacteremic pneumococcal infection.

The serum antibody response after immunization with a pneumococcal vaccine was analyzed in 46 patients with a history of bacteremic pneumococcal infection and in 36 healthy controls. Seven patients with IgG/IgG2 deficiencies had significantly lower preimmunization and postimmunization levels of antibody to pneumococcal capsular polysaccharides (serotypes 3, 6A, 19F, and 23F) and phosphorylcholine than did the control subjects, while the patients with normal IgG/IgG2 levels did not have a deficient antibody response. For the whole patient group, postimmunization levels of antibody against the serotypes that caused the bacteremias were lower than the levels against other tested serotypes (P < .05). Ten patients vs. one control subject were unable to mount a postimmunization antibody response to the four tested serotypes (P < .05). Six of these 10 nonresponding patients had low IgG/IgG2 levels. The results demonstrate that a poor antibody response to vaccination with capsular polysaccharides, often associated with IgG/IgG2 deficiency, is common in patients with a history of bacteremic pneumococcal infections.

Adolescent↗

PubMed1985

The influence of splenic weight and function on survival after experimental pneumococcal infection.

Splenectomy impairs survival after pneumococcal challenge in rats, while preservation of sufficient splenic tissue can be protective. This study investigated the effects of methylcellulose on stimulation of splenic weight, splenic histology, reticuloendothelial (RE) activity, and survival after pneumococcal infection. Methylcellulose increased spleen weight four- to five-fold but did not improve RE function or survival after infection. These parameters correlated best with the weight of the remnant in animals that did not receive methylcellulose. The functional limitations of splenic autotransplants were not corrected by methylcellulose stimulation of splenic weight. Preservation of a splenic remnant with intact blood supply is preferable to autotransplantation of the spleen to conserve RE capability.

Animals↗

PubMed2002

[Pharmaco-economic aspects of vaccination against invasive pneumococcal infections in persons over 65 years of age; review of the literature on cost effectiveness analysis].

OBJECTIVE: To assess the cost-effectiveness of vaccination to prevent invasive pneumococcal disease in the elderly. DESIGN: Review of the literature. METHODS: Articles in Dutch or English reporting studies into the cost-effectiveness of vaccination for the prevention of invasive pneumococcal infection in persons over 65 years of age were retrieved from Medline (1980-2000; search terms: 'pneumococcal' and 'vaccine' in combination with 'costs' or 'economics') and on the basis of the reference lists in the articles found. The following aspects of the selected studies were assessed: the net costs per year of life gained, the incidence of invasive pneumococcal disease in the elderly, the mortality due to invasive pneumococcal infections, the effectiveness of the vaccine in the prevention of invasive pneumococcal infections, and the costs of the vaccine and its administration. Attention was also given to specific age categories and to the effects of varying certain crucial assumptions. RESULTS: We retrieved a total of five studies: one each for the USA, Canada, the Netherlands and Spain and a multinational study for five European countries. The cost-effectiveness of vaccination of the elderly against invasive pneumococcal infections varied from cost savings to [symbol: see text] 33,000,-per life-year gained. The Dutch study estimated the cost-effectiveness at [symbol: see text] 10,100,-per life-year gained (price level 1995). Almost all the studies selected based their estimate of the effectiveness of vaccination on the same case-control study from the USA. The potential effects on cost-effectiveness of more extensive influenza vaccination and of the inclusion of re-vaccination against pneumococci were not included in the analyses. CONCLUSION: The cost-effectiveness of vaccination against invasive pneumococcal infections in persons over 65 years of age (in the Netherlands as well as in several other countries) was below the previously accepted threshold of [symbol: see text] 20,000,-.

Aged↗

PubMed2002

The effect of cephalosporin resistance on mortality in adult patients with nonmeningeal systemic pneumococcal infections.

PURPOSE: To evaluate the clinical relevance of cephalosporin (ceftriaxone/cefotaxime) resistance among patients with nonmeningeal systemic pneumococcal infection. SUBJECTS AND METHODS: From January 1994 to October 2000, we prospectively studied 522 episodes of nonmeningeal systemic pneumococcal infections (448 pneumonias) in 499 adults who were treated according to hospital guidelines. In vitro antibiotic susceptibility, as the minimum inhibitory concentration (MIC), was determined by microdilution method. The MIC methods and breakpoints (cutoffs) were established by the National Committee for Clinical Laboratory Standards. RESULTS: Of the 522 pneumococcal strains, 413 strains (79%) were susceptible to ceftriaxone/cefotaxime, MIC < or =0.5 microg/mL; 79 (15%) were intermediate, MIC = 1 microg/mL; and 30 (6%) were resistant, MIC = 2 microg/mL. After adjusting for several variables, including pneumococcal serogroups/serotypes, infections due to nonsusceptible (intermediate and resistant) pneumococcal strains were independently associated with prior antibiotic therapy, with an odds ratio of 5.9 (95% confidence interval: 2.6 to 13.6). Thirty-day mortality among the 185 patients who were treated with ceftriaxone (1 g/d) or cefotaxime (1.5 g every 8 hours) did not differ by cephalosporin susceptibility: 18% (26/148) among those with susceptible organisms, 13% (3/24) with intermediate organisms, and 15% (2/13) in resistant cases (P = 0.81). CONCLUSION: Ceftriaxone or cefotaxime were effective in treating patients with nonmeningeal systemic pneumococcal infections caused by strains with MIC < or =2 microg/mL. These results support the newly established ceftriaxone/cefotaxime MIC breakpoints (cutoffs) for nonmeningeal pneumococcal infections.

Adult↗

PubMed2000

Epidemiology of invasive childhood pneumococcal infections in Greece.

UNLABELLED: A retrospective study was conducted to identify the epidemiologic characteristics of invasive pneumococcal infections among children <14 y of age in our geographic region. During a 5-y period, from 1995 to 1999, 590 cases of invasive pneumococcal infection were identified in Aghia Sophia Children's Hospital, Athens, Greece. The male to female ratio was 1.4:1 and 64% of patients were younger than 5 y of age. The overall annual incidence rate was estimated as 44/100,000 children <14y of age, whereas the incidence rate for children <5y of age was 100/100,000. The most common types of infections were pneumonia (472 cases; 133 definite and 339 probable), bacteraemia without focus (79 cases), and meningitis (33 cases). A seasonal variation of invasive pneumococcal infections was noted, with two peaks--one during spring and the other during autumn. Only two cases with meningitis died and one developed permanent neurological sequelae, representing a case-fatality rate for meningitis of 6%. Serogroups 14, 19, 6, 18, 23, 4 and 9 were the most prevalent, comprising 77% of 92 serotyped isolates. CONCLUSION: Invasive pneumococcal infections cause considerable morbidity in the paediatric population in the Athens metropolitan area. Sixty-six percent of the serotypes causing invasive pneumococcal disease in our region are included in the 7-valent conjugate vaccine.

Adolescent↗

PubMed1999

Pneumococcal infections in HIV-infected adults.

Bacterial pneumonia, specifically pneumococcal infection, is a frequent cause of morbidity and mortality in persons infected with human immunodeficiency virus (HIV). It causes morbidity directly and possibly progression of HIV infection. The clinical presentation and response to therapy are usually similar to that of patients without HIV infection, although radiographic presentations may be atypical. There is a higher incidence of invasive disease and extrapulmonary disease, and mortality may be increased in HIV-infected patients. HIV infection impairs the host response to pneumococcus in a variety of ways. Colonization with Streptococcus pneumoniae may be prolonged for reasons that are incompletely understood. Concern about the rising prevalence of resistant pneumococcal strains is increasing, but the clinical relevance is uncertain. At least 90% of the strains that cause invasive disease are present in the 23-valent pneumococcal vaccine. The response to vaccination declines as immunodeficiency progresses; however, the potential benefit to responders is great and the risk is minimal. Therefore, this vaccine is recommended for all HIV-infected persons.

AIDS-Related Opportunistic Infections↗

PubMed2006

Prevalence of Toll-like receptor signalling defects in apparently healthy children who developed invasive pneumococcal infection.

Human primary immunodeficiencies affecting Toll-like receptor (TLR) signalling reveal a non-redundant role for TLR function in defense against pneumococcal infection. To determine the clinical relevance of TLR abnormalities, we studied a population predicted to be enriched for TLR defects-healthy children who had developed invasive pneumococcal infection in the absence of classic risk factors for infection. We describe the development and optimization of a peripheral blood TLR assay. By testing 38 healthy control neonates, children and adults we demonstrated that TLR function was stable over the first six decades of life. We tested 50 children with a history of invasive pneumococcal infection and although TLR defects were predicted to be over-represented in this population, we did not identify any TLR abnormalities. Although TLR signalling defects are associated with greatly enhanced susceptibility to invasive pneumococcal infection, our results suggest that routine clinical screening for TLR defects in healthy children who develop invasive pneumococcal infection is not justified.

Adult↗

PubMed2000

[Invasive pneumococcal infections in children from Troms, Nordland and Sor-Trondelag 1980-95].

Invasive pneumococcal infections may be severe. We have examined epidemiology, risk factors and outcome of these infections. In the years 1980-95, 76 children below the age of 15 with invasive pneumococcal infections were admitted to the hospitals in the counties of Troms, Nordland and Sør-Trøndelag in Norway. The incidence rate in children 0-2 years old was 10.3 cases per 100,000 persons per year, and 1.8 in children 3-14 years. Of the patients 24 had meningitis and 52 bacteraemia. All bacteriological isolates were sensitive to benzylpenicillin. Seven patients died and five developed sequelae. Thirty-one of the children had risk factors prior to the infection. Children with hypo- or hyperventilation at the time of arrival, and/or impaired circulation fared worse than those with normal findings. Children with underlying risk factors have a much higher frequency of invasive pneumococcal infections than other children. Patients who had impaired circulation or ventilation on admission have a bad prognosis for healthy survival.

Adolescent↗

PubMed1999

Detection of antipneumolysin in invasive childhood pneumococcal infections.

Antibody levels against pneumolysin, a virulence factor in pneumococcal infections were evaluated by a neutralization test, using crude pneumolysin. A study population of 28 hospitalised children with culture proven pneumococcal meningitis and pneumonia were tested for detection of antipneumolysin antibodies in their serum. Results were compared with age and sex matched controls who were admitted with infections other than pneumococcal. Geometric mean titer (GMT) of antipneumolysin in serum of patients with pneumococcal infections showed a significant difference when compared with controls, GMT of 196.1 and 185.2 were noted in patients with meningitis and pneumonia respectively, in contrast to a titer of 40.32 among controls. A difference of more than 4-fold antibody titers between patients and controls was considered significant. Detection of antipneumolysin in serum can therefore be considered as a useful laboratory investigation in diagnosing invasive pneumococcal infections.

Antibodies, Bacterial↗

PubMed1985

Influence of splenectomy on lethal effects of pneumococcal infection.

To determine whether the splenectomized host is more sensitive to the toxic effects of pneumococcal infection and whether the known clearance defect accounts for the early, increased mortality seen in postsplenectomy infection, the authors studied 8-week-old C57B1 mice. They were divided into two groups: seven control nonsplenectomized mice and six splenectomized mice. All animals were inoculated intravenously with 10(3) colony forming units of Streptococcus pneumoniae. Microaliquots of blood were drawn from the tail of all mice into sterile, heparinized, capillary tubes at 1, 4, 8 and 16 hours. Blood bacteria were quantitated using a drop dilution method. The time to death was recorded. A form of survival analysis using the Cox proportional hazards model was performed on the data. The infection was uniformly fatal. An early decrease in the numbers of blood bacteria was seen in nonsplenectomized mice followed by a logarithmic linear increase. In splenectomized mice, there was early rapid bacterial growth greater than that in control mice. Splenectomized mice died earlier than control mice (p less than 0.05 at 24 hours, Fisher's exact test). The bacterial count had a highly significant effect upon mortality overall (p = 0.0017). A function describing the risk of dying versus bacterial numbers was generated and was the same for both groups. The splenectomized host does not appear to be more susceptible to the toxic effects of pneumococcal infection. Early mortality in bacteremic pneumococcal infection can be attributed to impaired bacterial clearance alone.

Animals↗

PubMed2001

Invasive pneumococcal infection in children.

Streptococcus pneumoniae infections can involve multiple organs and cause high mortality and morbidity. In this retrospective study, we reviewed patients with invasive pneumococcal infection in the pediatric department of a teaching hospital in Taipei. From 1984 to 1998, 81 children with invasive pneumococcal infection were hospitalized. Twenty-eight patients had meningitis, 27 had pneumonia with pleural effusion, 60 had sepsis, and 4 had arthritis. Thirty-eight patients had more than one site of infection. Most of our patients (81.7%) were below 5 years of age. Pneumococcal infections were more common from October to March. Eight patients had a history of trauma that correlated with the site of infection. Thirteen patients (16.0%) expired and 20 (24.7%) had severe sequelae. Multi-regression analysis found that meningitis and complications were independent variables that affected the outcome. The percentage of penicillin-resistant strains increased beginning in 1990 and accounted for about four-fifths of the infections in the final 2 years of the study. Since invasive pneumococcal infections in children may have a poor prognosis and penicillin-resistant strains have become increasingly common, early and adequate antibiotic therapy should be given as soon as possible.

Adolescent↗

PubMed1984

Prevention of pneumococcal infection in children with homozygous sickle cell disease.

The efficacy of prophylactic penicillin and of 14 valent pneumococcal vaccine in preventing pneumococcal infection in homozygous sickle cell (SS) disease was investigated in 242 children aged 6 months to 3 years at entry. In the first five years of the trial there were 11 pneumococcal infections in the pneumococcal vaccine treated group, 10 by serotypes present in the vaccine. Type 23 accounted for five of these, and there was evidence of higher infection rates in those given the vaccine before age 1. No pneumococcal isolations occurred in the penicillin group while receiving penicillin, although four isolations occurred within one year of stopping penicillin. Probably the most effective prophylaxis against pneumococcal infection requires penicillin beyond the age of 3. The age at which pneumococcal vaccine should be given must await further data on antibody response and clinical efficacy in these patients.

Anemia, Sickle Cell↗

PubMed1984

Effect of exchange transfusion with an oxygen-carrying resuscitation fluid on the efficacy of penicillin therapy of pneumococcal infection in rats.

The effects of exchange transfusion with Fluosol DA (FDA) or stroma-free hemoglobin on the outcome of pneumococcal infection in rats were determined. Rats were sham transfused or exchange transfused with 25 ml of FDA or stroma-free hemoglobin. They were then challenged intraperitoneally with Streptococcus pneumoniae type 3 and treated with penicillin for 120 h. Only 2 of 15 (13.3%) FDA-transfused rats were alive at 312 h compared with 11 of 15 (73.3%) concurrently studied sham-transfused control rats (P = 0.0016). Of 10 stroma-free hemoglobin-transfused rats and 10 concurrently studied sham-transfused control rats (P = 0.98), 8 from each group (80%) were alive at 312 h. Penicillin therapy only suppressed pneumococcal infection in FDA-transfused rats, and relapse occurred after therapy was stopped. This effect could not be attributed to interference with the bactericidal activity of penicillin against pneumococci, to an alteration in the pneumococcal burden before penicillin therapy or to an alteration of the leukocyte and polymorphonuclear leukocyte response by FDA. In contrast, pneumococcal infection in stroma-free hemoglobin-transfused rats was cured with penicillin therapy. These data showed that FDA altered the ability of rats to respond to pneumococcal infection.

Animals↗

PubMed1990

Increased risk of pneumococcal infections in cardiac transplant recipients.

We observed 5 episodes of pneumococcal infection among 129 cardiac transplant patients between March 1985 and December 1987, giving an estimated incidence of 36 cases per 1000 patient-years. Infections occurred a mean of 58 days after transplantation and included bacteremia with empyema, bacteremia alone, and pneumonia. All patients recovered from their infections. There was no correlation between infection and age, sex, immunosuppression, or rejection episodes. We also measured antibody levels to 12 pneumococcal antigens in 6 unvaccinated, uninfected patients before and after cardiac transplantation, to see if baseline antibody levels decreased. Protective levels of antibody were defined as greater than or equal to 300 ng of anticapsular antibody nitrogen per milliliter serum. Before transplantation patients had protective antibody levels to a mean of 8.7 +/- 1.2 pneumococcal serotypes; after transplantation, the number of presumably protective antibody levels decreased to 6.5 +/- 1.4 (P = 0.021). One of these patients subsequently developed pneumococcal pneumonia. Cardiac transplant patients are at increased risk of pneumococcal infections. Vaccinating transplant candidates prior to transplantation may provide protection after transplantation.

Adolescent↗

PubMedDate not supplied

[Pathomorphology of pneumococcal infection in children].

Clinical and pathological data on 10 children who died of pneumococcal infection were analyzed. The disease started as primary pneumococcal meningitis in 4 cases, secondary to otitis media meningitis in 1 and pneumococcal pneumonia in 5 cases. The latter complicated with secondary pneumococcal meningitis in 3 cases, pneumococcemia with hemolytico-uremic syndrome in 1 case. 9 patients died of infectious-toxic shock and 1 patient of massive bleeding from acute gastric and duodenal ulcers. The results suggest that a grave course of pneumococcal infection is due to development of the infectious-toxic shock. Emergence of metastatic suppurative focuses was indicative of sepsis. A fulminant form of pneumococcal sepsis--pneumococcemia--has no large or evident primary focus. Neuraminidase produced by pneumococci is responsible for development of hemolytico-uremic syndrome.

Child, Preschool↗

PubMed1976

Complement system in pneumococcal infections.

The properdin or alternate complement pathway may function as a heat-labile opsonin for pneumococci, and evidence has been sought for its activation in pneumococcal infections. Twenty-two patients had determinations of C1q, C4, properdin factor B, C3, and hemolytic complement during hospitalization for pneumococcal infection. Measurements were made during the first 36 h after admission on 16 patients and later during recovery on 16. The admission and recovery values were compared statistically with each other and with the levels of 15 normal individuals. The admission and recovery mean values were normal and nearly identical for C1q and C4, which are two early components of the classical pathway. The mean level of factor N, a properdin pathway component, was significantly depressed on admission, but the mean recovery value was normal. Admission levels for C3, a component of the late common pathway, were depressed, and recovery values were normal. Total hemolytic complement was decreased on admission, although the decrease was not significant for the patients with both admission and recovery determinations. The findings are consistent with the hypothesis that factor B is turned over rapidly, or consumed, early in pneumococcal infections; alternatively, persons with low baseline factor B levels may be particularly susceptible to pneumococcal infection.

Adult↗

PubMed1997

Prophylaxis against pneumococcal infection after splenectomy: a challenge for hospitals and primary care.

OBJECTIVE: To evaluate prophylaxis against pneumococcal infection after splenectomy. DESIGN: Retrospective analysis. SETTING: District hospital, Denmark. SUBJECTS: 555 Patients who underwent splenectomy between 1 January 1984 and 31 December 1993. INTERVENTIONS: Splenectomy, pneumococcal vaccination. MAIN OUTCOME MEASURES: Pneumococcal vaccination rates and the time of vaccination related to different indications for splenectomy. Extent of information in hospital records about measures for prophylaxis against pneumococcal infection. Recording of splenectomy and vaccination in discharge letters. RESULTS: The total vaccination rate was 62% (344/555), but vaccination rates from 47% to 91% in five different groups of indications were observed. Patients undergoing splenectomy during cancer surgery or because of inadvertent intraoperative trauma to the spleen were particularly at risk of not being vaccinated. Vaccination rates increased from 59% to 70% during the period studied. Of the 235 patients alive on 1 April 1995, 87% (205) had been vaccinated. Only 23% of the patients were vaccinated at the appropriate time. Splenectomy had not been recorded in 10%, and vaccination status was mentioned in 35% of the discharge letters. Only 6% of the hospital records and 2% of the discharge letters mentioned one or more precautions to consider for asplenic patients. CONCLUSIONS: The pneumococcal vaccination rates of patients after splenectomy were not satisfactory. Most of patients were vaccinated at an inappropriate time in relation to the splenectomy. The discharge letters often lacked information about the patients' vaccination status. More effort is needed to reach an acceptable level of prophylaxis against pneumococcal infection after splenectomy.

Adolescent↗

PubMed1989

Severe pneumococcal infection: a one year survey.

Invasive pneumococcal infection is a major health problem with considerable mortality. In most patients the diagnosis is relatively straightforward but this study points out that in many, especially children, it is difficult because of a lack of clinical signs of septicaemia. While chronic respiratory disease is a major predisposing factor, malignancy and immune disorders are also common underlying features. Certain risk groups may benefit considerably from vaccination. The treatment of established infection is now complicated by the emergence of resistant strains, but penicillin remains the mainstay of therapy.

Adolescent↗