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PubMedDate not supplied

[Host reactions against bacteria. Application to pneumococcal infections].

Pneumococcal infection remains a public health problem, because of its important incidence, as well for pneumonias (2 cases per 1,000 persons per year) as for bacteremias (0.5% among hospitalized patients). The fatality rate in the bacteremic cases is 37.3% and reaches 89% in the fulminant sepsis cases, which are observed especially in splenectomized patients: the spleen takes part in the host defences against Streptococcus pneumoniae, together with the phagocytosis, the antibody production and the complement activation, essentially through the alternative complement pathway-activated C3b. Bacterial opsonization remains the fundamental mechanism of the host defence in the early stages of the pneumococcal infection.

Antibodies, Bacterial↗
PubMed2000

The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection.

Pneumococcal proteins, alone, in combination with each other, or in combination with capsular polysaccharide-protein conjugates may be useful pneumococcal vaccine components. Four proteins with a potential for use in vaccines are PspA, pneumolysin, PsaA, and PspC. In a mouse model of carriage, PsaA and PspC were the most efficacious vaccine proteins. Of these, PsaA was the best at eliciting protection against carriage. However, a combination of PspA and pneumolysin may elicit stronger immunity to pulmonary infection and possibly sepsis than either protein alone. Recently, a phase one trial of a recombinant family 1 PspA was completed in man. PspA was observed to be safe and immunogenic. Injection of 0.1 ml of immune serum diluted to 1/400 was able to protect mice from fatal infection with S. pneumoniae. Under these conditions, pre-immune serum was not protective. The immune human serum protected mice from infections with pneumococci expressing either of the major PspA families (1 and 2) and both of the pneumococcal capsular types tested: 3 and 6.

Adult↗
PubMedDate not supplied

Pneumococcal infections and pneumococcal vaccine: an update.

Pneumococcal pneumonia continues to be an important disease in terms of prevalence, morbidity and mortality. With the discovery of penicillin and its wide clinical use, the overall mortality of pneumococcal pneumonia has been significantly reduced, but problems remain. These include: 1) death rate is uninfluenced by the antibiotic in the first five days of illness; 2) death rate in certain high risk groups and in patients infected with type 3 pneumococcus exceeds 25%; and 3) penicillin resistant strains of pneumococci have emerged. Because of these and other considerations, a modern 14-valent pneumococcal vaccine has been developed by Robert Austrian and his co-workers. The vaccine has been found to be immunogenic and effective in a number of populations studied. Additional efficacy studies are needed, however, particularly in certain high risk groups, such as the elderly and immunocompromised patients.

Bacterial Vaccines↗
PubMed1999

Unusual manifestations of invasive pneumococcal infection.

Unusual pneumococcal infections occurred frequently in the preantibiotic age but rapidly declined with the advent of the antibiotic era. Unfortunately, the morbidity and mortality associated with invasive pneumococcal disease remain high despite antibiotic therapy and monumental advances in medical technology. The incidence of invasive pneumococcal disease has increased recently because of the onset of the human immunodeficiency virus (HIV) epidemic and the emergence of antibiotic-resistant pneumococcus. Robert Austrian described the clinical triad of pneumococcal pneumonia, meningitis, and endocarditis, a syndrome that now bears his name. Although seen infrequently today, unusual manifestations of pneumococcal infection such as those Austrian reported still occur. A review of these cases is warranted because, as drug-resistant organisms continue to emerge worldwide, more unusual pneumococcal infections will be seen. Streptococcus pneumoniae is responsible for a remarkable array of disease processes; our literature review uncovered 95 different types of unusual pneumococcal infections representing 2,064 cases. Examples of these infections included pancreatic and liver abscesses, aortitis, gingival lesions, phlegmonous gastritis, inguinal adenitis, testicular and tubo-ovarian abscesses, and necrotizing fasciitis. We also reviewed predisposing underlying illnesses and conditions. Alcoholism, HIV infection, splenectomy, connective tissue disease, steroid use, diabetes mellitus, and intravenous drug use remain common risk factors for invasive pneumococcal infections. Currently, multidrug-resistant S. pneumoniae remains susceptible to vancomycin and several new third-generation fluoroquinolones. As what some fear will be a possible postantibiotic era approaches, clinicians must be able to recognize and manage unusual pneumococcal infections.

Drug Resistance, Microbial↗
PubMed2000

American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis.

Pneumococcal infections are the most common invasive bacterial infections in children in the United States. The incidence of invasive pneumococcal infections peaks in children younger than 2 years, reaching rates of 228/100,000 in children 6 to 12 months old. Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with human immunodeficiency virus infection have pneumococcal infection rates 20- to 100-fold higher than those of healthy children during the first 5 years of life. Others at high risk of pneumococcal infections include children with congenital immunodeficiency; chronic cardiopulmonary disease; children receiving immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases; children with chronic renal insufficiency, including nephrotic syndrome; children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American (American Indian and Alaska Native) or African American descent also have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal infection have occurred with increased frequency in children attending out-of-home care. Among these children, nasopharyngeal colonization rates of 60% have been observed, along with pneumococci resistant to multiple antibiotics. The administration of antibiotics to children involved in outbreaks of pneumococcal disease has had an inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in children younger than 5 years with SCD has been successful in reducing rates of pneumococcal disease by 84%. Pneumococcal polysaccharide vaccines have been recommended since 1985 for children older than 2 years who are at high risk of invasive disease, but these vaccines were not recommended for younger children and infants because of poor antibody response before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar) induce proposed protective antibody responses (>.15 microg/mL) in >90% of infants after 3 doses given at 2, 4, and 6 months of age. After priming doses, significant booster responses (ie, immunologic memory) are apparent when additional doses are given at 12 to 15 months of age. In efficacy trials, infant immunization with Prevnar decreased invasive infections by >93% and consolidative pneumonia by 73%, and it was associated with a 7% decrease in otitis media and a 20% decrease in tympanostomy tube placement. Adverse events after the administration of Prevnar have been limited to areas of local swelling or erythema of 1 to 2 cm and some increase in the incidence of postimmunization fever when it is given with other childhood vaccines. Based on data in phase 3 efficacy and safety trials, the US Food and Drug Administration has provided an indication for the use of Prevnar in children younger than 24 months.

Antibiotic Prophylaxis↗
PubMedDate not supplied

[A method for preventing experimental pneumococcal infection].

Lethal pneumococcal infection in mice, infected intranasally, can be induced only by highly virulent strains of pneumococci. The introduction of N-acetylglucosamine and/or D-galactose, both 1 hour before the introduction of pneumococci or simultaneously with their introduction, prevented the development of this infection in 83-91% of mice used in the experiment. The use of the mixture of these carbohydrates did not change the level of their activity. These carbohydrates were shown to be capable of protecting mice from the intranasal introduction of 100-1000 LD50 of Streptococcus pneumoniae highly virulent strains, adapted to the respiratory tracts and lungs of mice.

Acetylglucosamine↗
PubMed1984

[Contribution of pneumococcal serotyping and antibiotyping to the prevention and treatment of pneumococcal infections (1980-1982). Pneumococcal typing and vaccination (1980-1982)].

During a 3-year period (1980-1982), 594 pneumococcal strains taken from 565 patients were serotyped. The distribution of the serotypes and their prevalence varied by sample and year. The theoretic vaccinal coverage, evaluated for the four main pathologies: pneumonia, otitis, meningitis, bacteriemia, is 79,1%. Among vaccinal serotypes, the types 19, 7, 3, 6, 1, and 23 are the most frequent, representing a cumulative incidence of 57,7%. In our region (Grenoble), the pneumococcus remains very sensitive to antibiotics. No strain resistant to penicillin G was observed. Erythromycin, doxycyclin, chloramphenicol, and cotrimoxazole preserve their potency with, respectively, 2,1%, 1,8%, 1,1%, and 1,9% resistant strains.

Anti-Bacterial Agents↗
PubMed2000

American Academy of Pediatrics. Committee on Infectious Diseases. Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis.

Heptavalent pneumococcal conjugate vaccine (PCV7) is recommended for universal use in children 23 months and younger, to be given concurrently with other recommended childhood vaccines at 2, 4, 6, and 12 to 15 months of age. For children 7 to 23 months old who have not received previous doses of PCV7, administration of a reduced number of doses is recommended. Two doses of PCV7 are recommended for children 24 to 59 months old at high risk of invasive pneumococcal infection-including children with functional, anatomic, or congenital asplenia; infection with human immunodeficiency virus; and other predisposing conditions-who have not been immunized previously with PCV7. Recommendations have been made for use of 23-valent pneumococcal polysaccharide (23PS) vaccine in high-risk children to expand serotype coverage. High-risk children should be given vaccines at the earliest possible opportunity. Use of antibiotic prophylaxis in children younger than 5 years with functional or anatomic asplenia, including children with sickle cell disease, continues to be recommended. Children who have not experienced invasive pneumococcal infection and have received recommended pneumococcal immunizations may discontinue prophylaxis after 5 years of age. The safety and efficacy of PCV7 and 23PS in children 24 months or older at moderate or lower risk of invasive pneumococcal infection remain under investigation. Current US Food and Drug Administration indications are for administration of PCV7 only to children younger than 24 months. Data are insufficient to recommend routine administration of PCV7 for children at moderate risk of pneumococcal invasive infection, including all children 24 to 35 months old, children 36 to 59 months old who attend out-of-home care, and children 36 to 59 months old who are of Native American (American Indian and Alaska Native) or African American descent. However, all children 24 to 59 months old, regardless of whether they are at low or moderate risk, may benefit from the administration of pneumococcal immunizations. Therefore, a single dose of PCV7 or 23PS vaccine may be given to children 24 months or older. The 23PS is an acceptable alternative to PCV7, although an enhanced immune response and probable reduction of nasopharyngeal carriage favor the use of PCV7 whenever possible.

Antibiotic Prophylaxis↗
PubMed1996

Invasive pneumococcal infections in human immunodeficiency virus-infected children.

Invasive pneumococcal infection (IPI) is the most common serious bacterial infection in human immunodeficiency virus (HIV)-infected children. Data from a population-based pediatric HIV surveillance project were used to determine the incidence of IPI in HIV-infected children and to conduct a case-control study assessing potential risk factors for IPI in HIV-infected children. There were 50 episodes of IPI and a cumulative incidence of 6.1 cases/100 patient-years through age 7 years. Children with IPI were more likely to have a prior AIDS diagnosis (odds ratio, 4.2; 95% confidence interval, 1.2-15.1) and higher levels of IgG and IgM (P=.01) than were controls. In a separate case-control study, the manifestations of IPI in HIV-infected children were compared with those in HIV-negative controls. Focal complication rates in the 2 groups did not differ; however, HIV-infected children were less likely than controls to have leukocytosis (P<.001) and more likely to have isolates with penicillin resistance (P=.03).

Age Factors↗
PubMed1984

A controlled evaluation of the protective efficacy of pneumococcal vaccine for patients at high risk of serious pneumococcal infections.

The protective efficacy of pneumococcal vaccine against systemic pneumococcal infections in adults with the current indications for the vaccine was evaluated in a case-control study. Six (7%) of the 90 cases and 16 (18%) of the matched controls had received pneumococcal vaccine for an odds ratio of 0.33 (p less than 0.05). The vaccine's protective efficacy was 67%, which remained virtually unchanged after adjusting for potential confounding variables. The vaccine's efficacy was 77% for patients at moderately increased risk of pneumococcal infections, but 0% for patients who were severely immunocompromised. The vaccine's protective efficacy was 70% (p less than 0.05) for all patients 55 years or older after controlling for indications for the vaccine in addition to age. Pneumococcal vaccine confers substantial protection against systemic pneumococcal infections on the elderly and patients with illnesses associated with a moderately increased risk of pneumococcal infections.

Adolescent↗
PubMed1994

Pneumococcal infection and immunization in children.

Pneumococcal infection persists as a major cause of pneumonia, bacteremia, and otitis media and is the important cause of meningitis in young children. Children less than 2 years of age show the highest incidence of pneumococcal diseases. Pneumococcal types 6A + 6B, 7F, 9V, 14, 18C, 19F + 19A, and 23F account for the large majority of disease isolates in the pediatric population. Bacterial clearance and antibody response were studied in young mice from mothers injected with pneumococcal type 9V polysaccharide (PS) conjugated with the inactivated pneumolysin to examine the protective immunity of young mice to pneumococcal infection. The injection of mice with pneumococcal PS-protein conjugate conferred the protective immunity to pneumococcal infection. The efficacy of pneumococcal vaccine might be enhanced by addition of inactivated pneumolysin in the form of PS-protein conjugate. The molecular size of pneumococcal type 19F PS or oligosaccharide used for preparing the PS-protein conjugate has a profound effect on the antibody response to the PS. The conjugate immunogen prepared from a large molecule of 19F PS produced a high antibody response to the PS in young mice. Development of a PS-protein conjugate vaccine for selected pneumococcal types will help in solving problems of poor immunogenicity of pneumococcal PS vaccine in young children.

Adolescent↗
PubMed1999

Molecular and cellular biology of pneumococcal infection.

The complete pneumococcal genome sequence was released in November, 1997. This advance has been combined with new understanding of physiology and pathogenesis including characterization of a family of surface proteins adducted to choline, regulation of virulence, and the regulon for natural DNA transformation. These developments in our understanding of molecular and cellular biology of pneumococcal infection will allow the development of new vaccines and antibiotics against this community acquired pathogen.

Animals↗
PubMed2000

Pathogenesis of pneumococcal infection.

The pathogenesis of pneumococcal infection is a complex interplay between pneumococcal virulence determinants and the host immune response. Molecular studies have considerably advanced our knowledge and understanding of the precise structures and functions of the different determinants and their pathogenic roles. This review describes the mechanisms by which pneumococci attach, invade, evade lung defences and cause severe disease. Better understanding of the critical steps in this complex process will enable more effective clinical intervention to be developed to reduce the mortality exacted by this versatile pathogen.

Animals↗
PubMed1997

Penicillin-resistant pneumococcal infections in children.

Penicillin-resistant pneumococcal infections have been reported worldwide, but rarely reported in Taiwan. From 1990 to 1995, the rate of penicillin-resistant Streptococcus pneumoniae (PRSP) infections in our hospital increased from less than 10% during the first 2 years (1990-91) to 45% during the last 2 years (1994-95). From 1990 to 1995, twenty-four patients with systemic pneumococcal infections were diagnosed in the Department of Pediatrics at Mackay Memorial Hospital. Pneumococci were isolated from blood in 20 patients, cerebrospinal fluid in 12 patients, joint fluid in one patient and pleural effusion in one patient. Four patients had underlying diseases, including ileal atresia, Wiskott-Aldrich syndrome, congenital heart disease, and perilymph fistula. Of the 24 isolates of S. pneumoniae, 17 (70.8%) were intermediately penicillin resistant (minimum inhibitory concentrations between 0.1 and 1.0 microgram/mL), and 7 (29.2%) were highly resistant (minimum inhibitory concentrations > 1.0 microgram/ml). Fourteen patients recovered completely, two had minor sequelae, two had major sequelae, and six died. Four of the 12 patients with meningitis died. In this study, both the rate of PRSP as well as the mortality of patients with PRSP meningitis were high, as compared to previous reports. To reduce the mortality and morbidity of systemic pneumococcal infections, the oxacillin disc diffusion test is important in addition to appropriate antibiotic therapy.

Child, Preschool↗
PubMed2002

Intranasal immunization with pneumococcal conjugate vaccines with LT-K63, a nontoxic mutant of heat-Labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal mice.

Immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus toxoid (TT) (Pnc-TT) elicits protective immunity in an adult murine pneumococcal infection model. To assess immunogenicity and protective immunity in early life, neonatal (1 week old) and infant (3 weeks old) mice were immunized intranasally (i.n.) or subcutaneously (s.c.) with Pnc-TT of serotype 1 (Pnc1-TT). Anti-PPS-1 and anti-TT immunoglobulin G (IgG) and IgM antibodies were measured in serum and saliva, and vaccine-induced protection was evaluated by i.n. challenge with serotype 1 pneumococci. Pnc1-TT was immunogenic in neonatal and infant mice when administered s.c. without adjuvant: a majority of the young mice were protected from bacteremia and a reduction of pneumococcal density in the lungs was observed, although antibody responses and protective efficacy remained lower than in adults. The addition of LT-K63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant significantly enhanced PPS-1-specific IgG responses and protective efficacy following either s.c. or i.n. Pnc1-TT immunization. Mucosal immunization was particularly efficient in neonates, as a single i.n. dose of Pnc1-TT and LT-K63 induced significantly higher PPS-1-specific IgG responses than s.c. immunization and was sufficient to protect neonatal mice against pneumococcal infections, whereas two s.c. doses were required to induce complete protection. In addition, i.n. immunization with Pnc1-TT and LT-K63 induced a vigorous salivary IgA response. This suggests that mucosal immunization with pneumococcal conjugate vaccines and LT-K63 may be able to circumvent some of the limitations of neonatal antibody responses, which are required for protective immunity in early life.

Adjuvants, Immunologic↗
PubMed2000

Proportion of invasive pneumococcal infections in German children preventable by pneumococcal conjugate vaccines.

The incidence and serotype distribution of Streptococcus pneumoniae as a cause of invasive diseases are unknown with regard to most European countries. From January 1997 through December 1998, population-based nationwide prospective surveillance was undertaken for invasive pneumococcal disease (IPD) in children in Germany, based on monthly independent reports from all pediatric hospitals and from clinical microbiology laboratories. On the basis of 896 reported IPD cases (including 404 with meningitis), the incidences per 10(5) children in different age groups were as follows: children aged <1 year, 18.9 (9.7 for meningitis); children aged <2 years, 16. 0 (7.2 for meningitis); for children aged <5 years, 8.9 (3.9 for meningitis); and for children aged <16 years, 3.2 (1.4 for meningitis). The proportions of cases involving strains (304 serotyped) included in conjugate vaccines were as follows: for the 7-valent vaccine, 52%; for the 9-valent, 62%; and for the 11-valent, 71%. None of the isolates were resistant to penicillin or cefotaxime. Although the rate for meningitis is similar, other manifestations of IPD are less commonly diagnosed in Germany than in other countries. The serotype distribution only partially matched that used in the recent development of pneumococcal conjugate vaccines.

Adolescent↗
PubMed1986

Risk factors for acquiring pneumococcal infections.

To identify risk factors for developing pneumococcal infections, we carried out a case-controlled study on a retrospectively constituted cohort of 3074 clinic patients in a presumed high-risk population. Culture-proved pneumococcal infections were identified in 63 men over a period of 5.5 years, yielding an estimated incidence of 6.3 cases per 1000 person-years. By comparing these patients with 130 uninfected control patients, the relative risk of pneumococcal infections related to various exposures was calculated by logistic regression analysis. Statistically significant independent risk factors (and their relative risks) were as follows: dementia (5.82), seizure disorders (4.38), current cigarette smoking (4.00), congestive heart failure (3.83), cerebrovascular disease (3.82), institutionalization (3.13), and chronic obstructive pulmonary disease (2.38). Risk was increased with age and previous hospitalizations, and, to a nonsignificant degree, by hotel residence (3.93), lung cancer (2.24), previous smoking (2.14), corticosteroid use (1.81), and alcoholism (1.35); but not by diabetes mellitus (0.99), nonlung malignancies (0.93), nonwhite race (0.89), or ischemic heart disease (0.58).

Aged↗