Hypothermia and infection. III. Influence of hypothermia on the course of experimental pneumococcal infection in mice.
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Animals↗
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Invasive pneumococcal infection in a healthy infant caused by two different serotypes.
We present a case of invasive pneumococcal infection in a healthy 10-month-old infant from whom Streptococcus pneumoniae serotype 23F was isolated from the blood and serotype 23B was isolated from the cerebrospinal fluid. Both serotypes were penicillin nonsusceptible. Pulsed-field gel electrophoresis analysis demonstrated that the two serotypes had distinct DNA patterns, indicating that infection did not occur as a result of capsular transformation but as a result of a mixed infection with two distinct pneumococcal serotypes.
Bacteremia↗
[The role of hyaluronidase in the occurrence of a generalized pneumococcal infection].
The hyaluronidase activity of pneumococcal strains isolated from 39 patients with purulent meningitis, 26 patients with acute internal otitis and 130 healthy carriers was studied. All strains isolated from patients with purulent meningitis and meningoencephalitis and 84.6% of strains isolated in cases of otitis were found to have hyaluronidase, while in healthy children hyaluronidase-synthesizing strains were detected only in 11.5% of cases. Hyaluronidase titers in pneumococcal strains isolated from patients with meningitis and meningoencephalitis were significantly higher than in strains causing purulent otitis. At the same time strains with high hyaluronidase titers were also isolated from 7% of healthy carriers. Noncapsular pneumococcal strains had no hyaluronidase. The average value of the reverse correlation between hyaluronidase activity and the virulence of strains for mice was established. Hyaluronidase activity did not correlate with different serotypes of pneumococcal strains. The intranasal administration of hyaluronidase in high titers (> or = 1:8) to mice and rats led to the penetration of the infective agent through the hematoencephalic barrier of the animals and to their death from generalized pneumococcal infection. The role of hyaluronidase as the invasiveness factor of pneumococci was confirmed in experiments on the intranasal infection of mice with low active strains mixed with the preparation of exogenous hyaluronidase.
Acute Disease↗
Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections.
Levels of circulating cytokines were measured in 22 hospitalized patients with pneumococcal infections during the first week after admission, to test for age-associated differences. Twenty-two healthy age- and sex-matched subjects were included as controls. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-1 receptor antagonist, soluble TNF receptor I (sTNFR-I), and IL-10 were increased on admission (P<.05), but macrophage inflammatory protein (MIP)-1beta was not. Whereas levels of cytokines were similar on admission, levels of TNF-alpha and sTNFR-I after 1 week were higher (P<.05) in elderly (68-91 years) than in young (37-55 years) patients. Furthermore, plasma levels of IL-10 and sTNFR-I after 1 week were positively correlated with age, and the declines in sTNFR-I and in the TNFalpha/IL-10 ratio from day 0 to day 7 were correlated with age. Thus, aging was associated with prolonged inflammatory activity. This may reflect decreased ability to control the infection or a dysregulated cytokine response.
Adult↗
Comparison between cohorts vaccinated and unvaccinated against influenza and pneumococcal infection.
This study characterizes possible confounders that might make cohorts vaccinated and unvaccinated against influenza and pneumococcal infection different at baseline, with the hypothesis that the two cohorts are comparable. The similarity between health and demographic data was analysed by a randomized, multivariant study addressed to 10,000 persons aged 65 years and older in Stockholm County and was carried out in the form of a postal inquiry during the period December 2000 to May 2001. The study-population response rate was 78%. Of these, 66% (5,120 persons) had been given at least one influenza vaccination during the 3-year study period (1998-2000), 50% (3,780) had received one pneumococcal vaccination and 78% had received both vaccines during the period. The vaccination rate was lower in the age group 65-69 years (60%), compared with elderly cohorts aged over 70 years (67-72%, P < 0.001). Elderly persons living in nursing homes or institutions had higher vaccination rates than persons living in their own households (72 vs. 67%). Persons with underlying chronic diseases had higher vaccination rates (71%, P < 0.001) than those without underlying chronic diseases. Vaccine recipients had fewer days in hospital, compared with non-recipients. Unvaccinated persons with myocardial disease had nine times more days in hospital than vaccinated persons with myocardial disease. Vaccination against pneumococcal infection had an additional effect with influenza vaccination in reducing hospitalization for chronic lung diseases; influenza vaccination alone did not have this effect. In conclusion, the influenza and pneumococcal-vaccine recipients were older and had significantly more chronic lung and heart conditions than the unvaccinated cohort.
Age Factors↗
Transformation during mixed pneumococcal infection of mice.
The recent demonstration by others of transformation during peritoneal infection of mice by two genetically distinct pneumococcal strains supports the notion that transformation may be significant in pneumococcal infection in nature. These studies confirm the occurrence of transformation during mixed infection of mice and define some conditions for its occurrence and its significance. Mice were inoculated with deoxyribonucleic acid (DNA) donor (small type III capsule, low virulence, streptomycin-susceptible) and recipient (noncapsulated, low virulence, streptomycin-resistant) pneumococci, and the bacteremia in mice that died was evaluated. Transformants (large type III capsule, virulent, streptomycin-resistant) were isolated from up to 80% of mice that died from mixed peritoneal infection. Transformation occurred in mice that received donor and recipient 6 hr apart; hence, active DNA was released and competence developed during growth in vivo. Transformation was detected only with progressive infection by both strains, and then transformants were few in the blood and apparently were not responsible for the death of the animals. In doubly infected mice treated with streptomycin, transformation was enhanced; transformants numerically dominated the bacteremia and seemed to cause the death of the mice. Transformation was also demonstrated for the first time during infection of the respiratory tract.
Animals↗
Clinical outcome of invasive pneumococcal infection in children: a 10-year retrospective analysis.
A retrospective study was conducted on 72 children admitted to a medical center in Taiwan due to invasive pneumococcal infections diagnosed between January 1990 and April 2000. Of these patients, 28 had meningitis and 44 had other invasive diseases. Forty-one (56.9%) strains of Streptococcus pneumoniae showed reduced susceptibility to penicillin by the oxacillin disc diffusion method. The total mortality was 20.8%, 32.1% for meningitis, and 13.6% for other invasive diseases. Ten (52.6%) of the patients survived from meningitis had long-term sequelae. Statistical analysis showed that initial presentation of coma, shock, respiratory distress requiring mechanical ventilation, and leukopenia (leukocyte <4,000 /mm3) were associated with mortality of invasive pneumococcal infections. Low cerebrospinal fluid leukocyte count (<50 /mm3) and high cerebrospinal fluid protein level (> or = 660 mg/dL) were also associated with mortality of meningitis. The presence of underlying diseases and high alanine aminotransferase level (> or = 100 U/L) were associated with fatal non-meningitic invasive diseases. Patients with shock and high alanine aminotransferase level but without high C-reactive protein level (> or = 20 mg/dL) were associated with rapidly fatal outcome. The outcome of invasive pneumococcal diseases was not associated with penicillin susceptibility.
Adolescent↗
Therapy of penicillin- and cephalosporin-resistant pneumococcal infections.
Streptococcus pneumoniae has recently developed resistance to almost every agent that has been used for therapy, including the extended-spectrum cephalosporins. The empiric therapy of penicillin-resistant pneumococcal meningitis should include cefotaximine or ceftriaxone plus vancomycin pending cephalosporin susceptibility results. Intermediate penicillin-resistant pneumococcal infections outside the central nervous system will usually respond to high dose intravenous beta-lactam antibiotic therapy. Highly penicillin-resistant pneumococcal infections may not respond to penicillin therapy, in which case therapy with vancomycin, imipenem or a macrolide (if susceptible) can be considered. Pneumococcal resistance to commonly used oral agents varies geographically and the efficacy of a particular agent can only be assured once the infecting strain is known to be susceptible. It is imperative to determine the susceptibility of every pneumococcal isolate to the agent(s) being used for therapy, particularly in cases of meningitis and to document rapid sterilization of infected body sites or fluids.
Administration, Oral↗
[Clinical study of 33 children with systemic pneumococcal infections].
We retrospectively analyzed 33 cases of children with systemic pneumococcal infections, 22 bacteremia and 11 meningitis, diagnosed and treated in Asahi General Hospital between 1985 and 1999. The median age at diagnosis was 15 months old and the incidence peaked in infants between 7 and 24 months of age (57.6%). Two cases showed low serum IgG2 levels. Fever was a common symptom in all cases and 13 (39.4%) presented convulsions. Meningitis [median age: 10 months] tended to occur, if not significant, in younger children than bacteremia [16 months]. All cases of meningitis were diagnosed 12 hours or later after the onset of fever, though 54.5% of the cases of bacteremia were diagnosed within 12 hours. The cases of meningitis showed statistically lower white blood cell counts [median: 9,700/mm3] and higher CRP levels [median: 25.6 mg/dl] than those of bacteremia [23,900/mm3 and 4.2 mg/dl, respectively] at diagnosis. Although all cases of bacteremia were cured without any sequelae by antibiotic treatment, 3 cases (27.3%) of meningitis died and 4 (36.4%) developed severe neurological sequelae. Our findings suggest that the putative pathogenesis by which pneumococcal meningitis results from bacteremia and, taking in the account of the poor outcome of meningitis, may justify the early antibiotic intervention against pneumococcal bacteremia.
Bacteremia↗
Epidemiology of pneumococcal infections in Swedish children.
OBJECTIVE: This paper provides an overview of pneumococcal infections in Swedish children. METHOD: Data supplied by the Swedish Institute for Infectious Disease Control (SMI) provided information on invasive pneumococcal isolates and on isolates with reduced susceptibility to penicillin. Disease burden was estimated from data collected in northern Stockholm and Malmöhus County. RESULTS: Only 3-6% of the total number of invasive pneumococcal isolates came from children 0-15 years of age. Predominant serotypes in descending frequency were 7, 6, 14, and 23. Strains from all sources with reduced sensitivity to penicillin (MIC > or = 0.5 mg/l) were found in 3% of children and varied between 0.2% and 11%, with the highest value found in Southern Sweden (predominating strains were 9, 19, 15, 6, and 23). A 10-year review of all cases of meningitis in Northern Stockholm reflected an incidence of 10/100,000 (0-2 years) or 5.8/100,000 (0-5 years), with severe sequelae occurring in 20% of children. This information can be used to predict an annual incidence of 30 cases of meningitis in Sweden. CONCLUSION: The large proportion of serotype 7 among invasive isolates is distressing since this serotype is not represented in the present 7- and 9-valent protein-conjugated vaccines under development. However, the heptavalent vaccine, including serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F would (at a serotype level) provide coverage against 83% of the resistant isolates in Southern Sweden.
Adolescent↗
Pneumococcal infections in splenectomized children are preventable.
Through the Danish National Patient Registry we identified all children 0-15 years old who had been splenectomized during the period 1979-87 and all children of the same age who, during the same period of time, had been admitted to a hospital because of either meningitis or bacteraemia caused by Streptococcus pneumoniae. We wanted to see whether any of the splenectomized children had developed invasive pneumococcal infection during the observation period. A similar Danish study covering the period 1969-78, when pneumococcal vaccine was not available, has already been published (3). Four per cent of the children splenectomized during that period developed invasive pneumococcal infection in contrast to none of the children splenectomized and vaccinated during the period 1979-87. Since 1982 antibiotic treatment of splenectomized patients running a fever has been recommended, and we show that the program of pneumococcal vaccination and defined antibiotic prophylaxis has been highly efficacious in preventing post-splenectomy infections in children.
Adolescent↗
Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in healthy children and in children at increased risk of pneumococcal infection.
Splenectomized children as well as those suffering from nephrotic syndrome or recurrent asthmatic bronchitis have an increased susceptibility to systemic pneumococcal infections compared to healthy children. To determine the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPV), 119 children (21 healthy, 26 splenectomized children, 48 with nephrotic syndrome and 24 with recurrent asthmatic bronchitis), aged 2-18 years, received one subcutaneous injection of a 23-valent PPV. Anti-capsular antibodies (Ab) to types 6B, 9V, 14, 18C, 19F and 23F were measured by ELISA before and 4 weeks after immunization. In all cases the adverse reactions were mild and transient, consisting of local pain and/or erythema or swelling in 41% and fever above 38.5 degrees C in 2% of the children. The healthy children responded well to vaccination with a mean fold increase (FI) of 2.6 in postvaccination Ab titers compared to prevaccination titers. The combined geometric mean Ab concentrations in the high-risk children were significantly lower than those of healthy children both before and after vaccination. However, the combined geometric mean FI were not significantly different between high-risk and healthy children. These results indicate that PPV is immunogenic and safe in high-risk as well as in healthy Korean children.
Adolescent↗
[Pneumococcal infections in intensive care. Retrospective 8 year study].
OBJECTIVE: The aim of this study was to analyze the clinical presentations and severity of S. pneumoniae infections requiring hospitalization in an intensive care unit and evaluate the incidence and severity of infections caused by penicillin-resistant strains. PATIENTS AND METHODS: This retrospective study reviewed cases in our intensive care unit from January 1989 through December 1996 including all patients with pneumococcal infection. RESULTS: The study included 102 patients, mean age 59.6 years. Pneumonia was the most frequent (83 cases) followed by bacteriemia (31 cases) and meningitis (15 cases). Mortality was high (43%) and influenced by age, simplified severity score, and presence of shock at admission. Antibiotic resistance appeared in 1991 and increased over the years reaching, in 1996: 24% for penicillin, 38% for macrolides, 20% for sulfamides, 19% for tetracyclins, and 14% for phenicols. Penicillin-resistance was not found to modify clinical expression nor severity of infection. Amoxicillin and third-generation cephalosporins were the most widely used antibiotics. CONCLUSION: Pneumococcal infections in intensive care patients are severe with high mortality. The emergence of more and more resistant strains has little clinical consequence on severity or treatment.
Aged↗
Periodicity of susceptibility to pneumococcal infection: influence of light and adrenocortical secretions.
Circadian periodicity of susceptibility to pneumococcal infection was altered but not abolished in blind or adrenalectomized mice. Serum corticosterone concentrations 24 hours after pneumococcal challenge were greatest in animals challenged at 0400 hours, a time when circulatory corticosterone is lowest; the smallest absolute increase in serum corticosterone followed challenge at 1600 hours.
Adrenal Cortex Hormones↗
Invasive pneumococcal infections in adult lung transplant recipients.
An increased risk of invasive pneumococcal infection (IPI) has been described among kidney or heart transplant recipients, but the epidemiology of IPI among lung transplant recipients has not been previously reported. We undertook a single center, retrospective cohort study to define the incidence, timing, clinical, and microbiologic features of IPI in lung transplant patients. Fourteen out of 220 recipients (6.4%) developed IPI at a median of 1.3 years after transplantation (incidence rate: 22.7 cases per 1000 person-years). All patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis, and 10 (71%) had TMP-SMX-resistant isolates. All isolates were from the 23 valent polysaccharide vaccine-associated serogroups. The high incidence of IPI in lung transplant recipients is similar to that reported in kidney and heart recipients. Alternative prevention strategies, including use of the conjugated pneumococcal vaccine, should be explored in future studies.
Adult↗
The biology of pneumococcal infection.
For 100 y, the study of the molecular mechanism of pneumococcal infection has richly rewarded biomedical science and pediatrics. More recently, a framework has emerged for how the pathogen engineers colonization, invasion of the lung and bloodstream, and finally, entry into the brain. This trafficking is then followed by a separate set of events to generate the symptoms of disease. Understanding the ligand receptor interactions that dictate these events has suggested new concepts for how to control the course of an infectious process and improve the morbidity and mortality of encounters with this prevalent pathogen of children.
Child↗
Pneumococcal infections in humans are associated with increased apoptosis and trafficking of type 1 cytokine-producing T cells.
Streptococcus pneumoniae infections are associated with considerable morbidity and mortality throughout the world. The immunopathology is characterized by an intense inflammatory reaction, including a strong acute-phase response and increased numbers of neutrophils in the circulation. However, little is known regarding the T-cell response during in vivo infections in humans. The purpose of this study was to test the hypothesis that activated T cells producing type 1 cytokines were engaged in the host response to pneumococcal infections. The phenotype and function of T cells were studied in 22 patients at admission to a department of infectious diseases and after antibiotic treatment for 1 week compared with an age-matched, healthy control group. Pneumococcal infections induced lymphopenia in the circulation due to the disappearance of activated T lymphocytes with a type 1 cytokine profile. In contrast, the numbers of naive T cells and interleukin-4-producing T cells did not change. Activated type 1 cytokine-producing cells reappeared in the circulation in relation to the treatment and clinical improvement. The underlying mechanisms during infection may include sequestration in the peripheral tissues and/or apoptosis. In fact, increased activation-induced apoptosis in the remaining peripheral lymphocytes and elevated levels of soluble Fas ligand were detected at admission to the hospital. In conclusion, these data suggest that activated T lymphocytes with a type 1 cytokine profile are highly engaged in the in vivo immune response to S. pneumoniae.
Adult↗
Update on pneumococcal infections of the respiratory tract.
Respiratory illnesses are the leading reason for seeking medical care here in the United States. Streptococcus pneumoniae is the most common bacterial pathogen causing acute otitis media (AOM), sinusitis, and community-acquired pneumonia in both the pediatric and adult populations. The continued development of antibiotic resistance to an increasing number of different antibiotic classes by this organism has made the treatment of some of these infections more difficult. Recently, a heptavalent pneumococcal conjugate vaccine was approved for infants and toddlers, beginning at 2 months of age. Widespread implementation of this vaccine in the childhood population may have a significant impact on the amount of systemic disease seen with this organism.
Adult↗