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Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances pulmonary defenses against pneumococcal infections after splenectomy.

BACKGROUND: Splenectomized individuals are at risk for pneumococcal sepsis. Alveolar macrophage bactericidal function is depressed after splenectomy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has pronounced effects on the number and function of macrophages. We hypothesized that GM-CSF treatment could improve alveolar macrophage bactericidal activity against pneumococci, and improve survival with pneumococcal infection. METHODS: Two weeks after splenectomy or sham operation, mice were treated with GM-CSF or saline twice daily for varying times. Alveolar macrophages were obtained by bronchopulmonary lavage, and bactericidal activity was measured. Survival was assessed after pneumococcal aerosol challenge. RESULTS: Alveolar macrophage bactericidal activity was improved with GM-CSF treatment in both eusplenic and asplenic mice (p < 0.001). GM-CSF treatment improved survival in both groups (p < 0.001). CONCLUSIONS: GM-CSF can augment alveolar macrophage function and provide protection against pneumococcal infections. It may be a useful adjuvant therapy for normal and splenectomized individuals.

Animals↗

Pneumococcal infection and immunologic response to pneumococcal vaccine in chronic obstructive pulmonary disease. A pilot study.

We assessed the importance of Streptococcus pneumoniae and immunologic response to 14-valent pneumococcal vaccine in a randomized (saline placebo or vaccine) double-blind pilot study involving 103 patients with chronic obstructive pulmonary disease (COPD). Antibody titers, the flora of the sputum, respiratory infections or pneumonias, and deaths were monitored. The patients' antibody titers before immunization were higher than healthy control subjects. Titers rose normally in those vaccinated but declined more rapidly. Differences between the group receiving placebo and vaccine were not significant at 12 and 24 months. The incidence of pneumonia was high before and after vaccine (47/1,000 vs 41/1,000 patient-years). Nonpneumococcal causes predominated (73 percent of pneumonias; 83.4 percent of lethal pneumonias). Isolates from sputum were predominantly nonvaccine types (50 to 62.5 percent). Twenty-seven patients died; pneumonia occurred in six (one pneumococcal in a vaccinated patient) as a terminal complication of other diseases. Thus, although pneumonia occurred frequently in these patients with COPD and contributed to mortality in 22 percent (six) of the 27 deaths, the predominance of nonpneumococcal causes and the data on antibodies and sputum suggest that pneumococcal vaccine may not be as beneficial for patients with COPD as was hoped. More observations are needed.

Adult↗

Invasive pneumococcal infection in South and West England.

Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5.2 and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P = 0.019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines.

Adolescent↗

Latex agglutination in the diagnosis of pneumococcal infection.

A latex agglutination (LA) method for detection of pneumococcal antigens was evaluated and compared with counterimmunoelectrophoresis (CIE). LA was 2 to 10 times more sensitive than CIE for the detection of purified capsular polysaccharides in defined media, but only when a 1+ or 2+ agglutination reaction was interpreted as positive. LA was much less sensitive than CIE with clinical samples. In 50 cases of pneumococcal pneumonia, antigen was detected in the serum almost twice as often with CIE (40%) as with LA (22%). LA was positive in six cases of pneumonia where CIE was negative; however, in three of these cases, antigen was detected only in undiluted sera, which raised some question about the specificity of the result. With 18 samples of cerebrospinal fluid (CSF) from 11 patients with pneumococcal meningitis, the CIE test was positive more frequenlty (14 samples) than was LA (11 samples). Moreover, antigen was detected in CSF by LA in only one additional patient than was positive by CIE alone. There was one false-positive LA reaction among 45 samples of CSF from patients without pneumococcal infection. Although LA is a less complicated method than CIE, it is not a sensitive test for pneumococcal antigens and would be of little value as a routine diagnostic method.

Antigens, Bacterial↗

[Aneurysms of the cerebral vessels and pneumococcal infection].

Two cases of cerebral aneurysm rupture with repeat subarachnoidal haemorrhage are reported in patients with pneumococcal infection confirmed bacteriologically. It is concluded that in pathogenesis of the aneurysmal rupture in pneumococcal infection a significant role is played not only by pneumococcal tropism to the meninges, but also by affection of the endothelium and cerebral vascular membranes, hemostasis defects, arterial hypertension as manifestations of a general adaptation syndrome.

Acute Disease↗

Epidemiology of invasive pneumococcal infections in children in Finland.

OBJECTIVE: To study the epidemiologic characteristics of invasive infections in children caused by Streptococcus pneumoniae to provide background data for vaccination programs. DESIGN: A nationwide laboratory-based prospective surveillance of all invasive pneumococcal infections in children during 1985 through 1989. SETTING: A network of all microbiologic laboratories and pediatric wards in Finland. PATIENTS: Children aged 0 to 15 years who were admitted to a hospital with S pneumoniae isolated from blood, cerebrospinal fluid, or deep aspirate sample. RESULTS: Four hundred fifty-two invasive pneumococcal infections were diagnosed in 1985 through 1989. The annual incidence rate was 8.9 per 100,000 children less than 16 years of age (24.2 per 100,000 among children less than 5 years of age and 45.3 per 100,000 among those less than 2 years of age). The most common clinical entities were bacteremia without focus (310 cases), pneumonia (66 cases), and meningitis (51 cases), with other focal infections seen in 25 cases. The pneumococcal groups/types 14, 6, 19, 7, 18, and 23 comprised 78% of all invasive infections. CONCLUSIONS: Streptococcus pneumoniae is a common cause of invasive infections in children in Finland. A pneumococcal conjugate vaccine containing the six most common groups/types could prevent up to 70% of invasive pneumococcal infections of children in Finland if fully protective in infancy.

Adolescent↗

Variant mannose-binding lectin alleles are not associated with susceptibility to or outcome of invasive pneumococcal infection in randomly included patients.

Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people. Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor for pneumococcal infections. To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined. All patients included had positive blood cultures for Streptococcus pneumoniae. The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome. Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role in the pathophysiology, in contrast to earlier observations in patients with other concomitant immune abnormalities.

Adolescent↗

Pharmacoeconomics of elderly vaccination against invasive pneumococcal infections: cost-effectiveness analyses and implications for The Netherlands.

We performed a review of cost-effectiveness of elderly pneumococcal vaccination to prevent invasive disease. It concerns studies in the USA, Canada, Netherlands and Spain and a multinational study of five European countries. Cost-effectiveness of elderly vaccination against invasive pneumococcal infections varies from cost-saving to EUR 33,000 per life-year gained. The Dutch study estimates cost-effectiveness at EUR 10,100 per life-year gained (price level: 1995). This is below the level that has recently been defined for treatment of high cholesterol (EUR 20,000 per life-year gained) and may therefore be considered as favorable. Almost all studies base their estimate of vaccine efficacy on the same case-control study from the USA. We identify a need for a systematic review on the efficacy of the pneumococcal vaccine. Also, we suggest further analysis with respect to potential effects on cost-effectiveness of extended influenza vaccination for the Dutch elderly in recent years and inclusion of pneumococcal re-vaccination. Pending this additional information, we conclude that cost-effectiveness of vaccination against invasive pneumococcal infections for Dutch elderly is favorable (as in several other countries) and justifies implementation from a pharmacoeconomic point of view.

Aged↗

Clinical aspects and importance of pneumococcal infections.

Annualy in the USA, the estimated occurence of pneumococcal disease exceeds 500 000 cases of pneumonia (50 000 deaths), 1 200 000 cases of otitis media and 5 000 cases of meningitis. The pneumococcus remains the single most important pathogen which can cause pneumonia. When bacteremia accompanied pneumococcal pneumonia (one-fifth of these), the case fatality rate is approximately of 25% and exceeds 50% in individuals over 50 years of age. Most of the deaths (60%) occur within the first five days of illnesses, despite prompt antibiotic treatment of these patients. Emergence of pneumococcal strains with diminished sensitivity for penicillin, or resistant to tetracycline and other antibiotics is also a factor which lend increasing support to the concept that high risk patients should be protected from pneumococcal infection by immunoprophylaxis. A change of capsular types associated with bacteriemic disease has occured, in the USA, during the past three decades. The types 1 and 3 are less common than in the pre-antibiotic era, and the types 4, 8, 12, and 14 have become more prevalent. Infections with type 2, an epidemic type, have occured infrequently in the past 20 years. In the USA, at the present time, nearly four-fifths of bacteremic cases are associated with only 14 of the 84 pneumococcal capsular type ; in descending frequency : 8, 4, 1, 14, 3, 51, 12, 6, 56, 9, 19, 23, 5 and 20 (American system of nomenclature). The predominant capsular types of otitis media are : 1, 3, 6, 7, 14, 18 and 23. The polyvalent pneumococcal polysaccharide vaccine newly developed in the USA, is safe, antigenic and effective. Its widespread use can be expected to reduce the number of deaths attribuable to pneumococcal bacteremia.

Adolescent↗

Pneumococcal infections and the possible need for a vaccine.

Antibiotics and chemotherapeutics have been available for about 40 years, but still bacterial infections constitute some of the greatest problems in medicine. Pneumococci causing pneumonia, bacteremia, meningitis and otitis are a leading cause of illness and death. The exact incidence and lethality of pneumococcal infections is not known, however, since they are not reportable diseases in most countries and since microbiological diagnosis is difficult. In the latest years some significant progresses have been made for the diagnosis of infections caused by pneumococci, especially pneumonia. This is for example the counterimmunoelectrophoresis (CIE) for antigen determination, the transtracheal aspiration (TTA) for direct bacterial cultivation from trachea, and serological assays like radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) for pneumococcal capsular antibody determination. These techniques have further emphasized the significance of pneumococcal infections. The recent finding of pneumococci resistant to penicillin and some other antibiotics also emphasizes the need for immunological prophylaxis. In recent years a vaccine consisting of the purified, most common pneumococcal polysaccharides has been introduced. It has been shown to protect against pneumonia, pneumococcal infections in splenectomized individuals and people with spherocytosis and probably partly against otitis media. Indications for the vaccine are suggested.

Adult↗

Pneumococcal infections after human bone-marrow transplantation.

Seven of 26 long-term survivors (greater than 7 months post-transplant) of bone-marrow transplantation developed penicillin-sensitive pneumococcal infections more than 7 months after transplantation. One patient had two infections. Six of eight infections were associated with pneumococcal bacteremia, and Streptococcus pneumoniae type 6A was isolated in three cases. Two infections were fatal. All patients had normal nematopoietic function, and none was receiving immunosuppressive therapy. The development of pneumococcal infection was significantly associated with males and with abnormally low or high serum IGG and IgM levels but not with graft-versus-host disease. Serum opsonic activity for S. pneumoniae type 6A was decreased in six of the seven patients when compared to normal pooled serum in an in-vitro bactericidal assay. Four of the six patients with impaired opsonic activity had low serum antibody levels for S. pneumoniae type 6A capsular polysaccharide, while the other two patients had low serum CH100 complement activity. Bone-marrow transplant recipients have an increased susceptibility to pneumococcal infections and should be evaluated for prophylactic penicillin or pneumococcal vaccination.

Adolescent↗

Epidemiology of pneumococcal infections in the elderly.

The risk of invasive Streptococcus pneumoniae infection (primarily bacteraemia and meningitis) is greatest among the very young and the very old. Persons in certain racial groups, including African-Americans, American Indians, Native Alaskans and Australian Aborigines, are also at increased risk of disease. Other factors that appear to increase the risk of pneumococcal infection are lower socioeconomic status, recent infection with influenza and possibly other viral respiratory tract infections, chronic medical conditions, and immunosuppressive medications. Reported annual incidences of invasive pneumococcal disease among persons aged > or = 65 years in North America and Europe range from 25 to 90 cases/100,000 persons. In the US and Canada, these rates represent between 15,000 and 30,000 cases annually among the elderly. Mortality caused by pneumococcal infections is highest among the elderly, with nearly 1 in 5 cases resulting in death. Worldwide, S. pneumoniae is the leading cause of community-acquired pneumonia requiring hospitalisation. The high fatality rates, as well as recent outbreaks of pneumococcal infection among unvaccinated nursing home residents and the emergence of drug-resistant pneumococcal strains, highlight the importance of preventing invasive infection by vaccination.

Aged↗

Emergence of drug-resistant pneumococcal infections in the United States.

OBJECTIVE: To estimate drug susceptibility patterns of Streptococcus pneumoniae in selected hospitals in the United States and to characterize the epidemiology of invasive drug-resistant pneumococcal infections. DESIGN: Minimum inhibitory concentrations (MICs) for a variety of commonly used antimicrobial drugs were determined for pneumococcal isolates submitted to the Centers for Disease Control and Prevention (CDC). Risk factors for drug-resistant pneumococcal infection were evaluated. SETTING: Hospital laboratories in the United States submitting pneumococcal isolates to the CDC between October 1, 1991, and September 30, 1992. PARTICIPANTS: A total of 544 persons with pneumococci isolated from normally sterile sites. RESULTS: A total of 13 hospitals in 12 states actively participated in an ongoing pneumococcal surveillance study. Resistance to penicillin was detected in 6.6% of isolates, including 1.3% of isolates with MICs of 2.0 micrograms/mL or more (compared with < 0.02% of isolates with MIC > or = 2.0 micrograms/mL identified by CDC surveillance from 1979 to 1987). A total of 16.4% were resistant to at least one of the following drugs or drug classes: penicillin, cephalosporins, macrolides, combination trimethoprim and sulfamethoxazole, and chloramphenicol. Six serotypes (6B, 23F, 14, 9V, 19A, and 19F) accounted for nearly 85% of strains resistant to at least one drug class. Children were more likely than adults to be infected with strains resistant to trimethoprim-sulfamethoxazole, erythromycin, or chloramphenicol. CONCLUSIONS: Emergence of drug-resistant pneumococcal infections will present critical challenges to clinicians for treating patients with pneumococcal disease. Widened and intensified surveillance is needed. These data suggest that current recommendations for use of 23-valent pneumococcal capsular polysaccharide vaccines should be aggressively promoted and that development and evaluation of new conjugate pneumococcal vaccines may be a crucial part of strategies for prevention.

Anti-Bacterial Agents↗

Invasive pneumococcal infection in children, 1981-92: a hospital-based study.

OBJECTIVE: To document the pattern and sequelae of invasive pneumococcal infection in hospitalized children. METHODOLOGY: Retrospective review of Streptococcus pneumoniae (Sp) isolates from normally sterile sites from 1981 to 1992 at three paediatric centres in Sydney for demographic data, spectrum of disease, predisposing conditions, mortality, and sequelae from meningitis. RESULTS: Four hundred and thirty-one episodes in 417 patients were identified. Foci of infection were: meningitis, 34%; pneumonia, 29%; bacteraemia without apparent focus, 30%; and other foci, 7%. Sixty-one per cent of all cases and 64% of cases with meningitis were less than 2 years old. Predisposing conditions were present in 37%, were significantly more common in patients over age 2 years and were more common with foci other than meningitis. Overall mortality was 6.6% whereas the mortality for those with meningitis was 8%. Neurological sequelae were identified in 34% of previously normal children, and severe hearing loss occurred in 11.5%. CONCLUSIONS: The high morbidity and mortality from invasive pneumococcal infection in children justifies further evaluation of preventive strategies.

Adolescent↗

Epidemiology of invasive pneumococcal infections in infants and young children in Metropolitan Santiago, Chile, a newly industrializing country.

AIM: To study the epidemiology of invasive pneumococcal infections in infants and young children in Santiago, Chile, as a representative pediatric population in a newly industrializing country where pneumococcal conjugate vaccines may be used in the future. METHODS: A 5-year retrospective laboratory-based review (1989 to 1993) was followed by a 3-year prospective laboratory and hospital surveillance study in two of the six health administrative areas of Santiago to detect all hospitalized cases of invasive pneumococcal disease (defined as Streptococcus pneumoniae isolated from blood, cerebrospinal fluid or another normally sterile site) among infants and children (0 to 23 months of age in the retrospective and 0 to 59 months of age in the prospective study). RESULTS: During the 5-year retrospective survey the incidence of invasive pneumococcal disease was 90.6 cases per 10(5) infants 0 to 11 months old and 18.5 cases per 10(5) toddlers 12 to 23 months old. Similar rates (60.2 per 10(5) infants and 18.1 per 10(5) toddlers) were recorded during the 3 years of prospective surveillance. Among the 110 cases in children 0 to 59 months of age detected during the 3-year prospective surveillance, 2 clinical forms, pneumonia and meningitis, accounted for 87.2% of all cases; 13 of the 49 pneumonia patients (26%) had empyema as a complication. Notably 40 of the 110 cases (36.4%) occurred before 6 months of age (63.4% of the 63 infant cases). Serotypes 1, 14, 5 and 6B were the most prevalent. Overall 76 and 69%, respectively, of S. pneumoniae isolates were antigenic types that would be covered by the 11- or 9-valent conjugate vaccines under development. CONCLUSIONS: Invasive pneumococcal infections in Santiago, Chile, exhibit an epidemiologic pattern intermediate between that of developing and industrialized countries. The high burden of disease in early infancy dictates that an accelerated immunization schedule (beginning in the perinatal period) or maternal immunization with pneumococcal vaccines should be explored.

Age Factors↗

Invasive pneumococcal infections. A comparison between adults and children.

A similar number of adults and children had invasive pneumococcal infection. There was male predominance, and different ethnic distribution between children and adults. The majority of adults (78%), had underlying diseases, but this was less frequent in children (24%). The presenting illness differed between adults and children. Complications of invasive pneumococcal infection occurred more frequently in adults than in children. The mortality rate in adults was 21.5%; in children, only 3.8%. The rate of penicillin-resistant pneumococci at our hospital was 23%, while cefotaxime resistance was 4.2%. Penicillin-resistant pneumococci were not isolated more frequently from children than from adults. Patients with penicillin-resistant pneumococci had longer duration of hospitalization and more nosocomially acquired infections. No difference in the mortality rate was found between patients with resistant or sensitive pneumococci. Ninety-five percent of strains were included in the current vaccine, but less than 2% of patients had been vaccinated. Isolates prevalent in Europe and the United States (19, 5, 1, 14, 6, 18, 12, 4, 9, 23, 7) were also most prevalent in Jerusalem. The distribution of serotypes differed between children and adults, and between patients from whom resistant organisms were isolated as opposed to sensitive organisms.

Adolescent↗