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PubMed2003

Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination.

Rates and severity of pneumococcal infections in children with sickle cell disease were examined before licensure of pneumococcal-conjugated vaccine (PVC). Rates of peak invasive infection rates in 1-year-old children with hemoglobin SS and mortality in those 0 to 10 years of age were 36.5 to 63.4 and 1.4 to 2.8 per 1000 person-years, respectively (>10 and 100 times as frequent as in the general population). Overall, 71% of serotyped isolates (n=80) were PVC serotypes and 71% of nonvaccine serotype strains were penicillin-sensitive. Clinical presentation in children with hemoglobin SS (n=71; more with hypotension) and hemoglobin SC (n=18; more with acute chest syndrome, otitis media) differed. Penicillin nonsusceptibility (38% of isolates) varied between geographic study sites. Penicillin prophylaxis appeared less effective against intermediate and resistant strains. Of all infected children, meningitis developed in 20% and 15% died (hemoglobin SS, n=15 and 11; hemoglobin SC, n=1 each). Factors associated with death included age >4 years (58%), serotype 19F, and not being followed by a hematologist (42% each). The pneumococcal-polysaccharide vaccine was 80.4% effective within 3 years after vaccination (95% CI, 39.7, 93.6). Children with sickle cell disease of all ages may benefit from PVC boosted with polysaccharide vaccination.

Anemia, Sickle Cell↗
PubMed1983

An epizootic of pneumococcal infection occurred in inbred guinea pig colonies.

Epizootiological observations were made on an outbreak of pneumococcal infection occurred in 14 inbred guinea pig colonies during January to October, 1981. Monthly incidences of diseased animals ranged from 16.6 to 0%, showing the highest rate in the first month of the occurrence. Affection rates were remarkably different according to guinea pig strains, being 75% in JY-1 but 0% in JYG and Strain 2. Affected animals showed ruffled fur, dry-dirty noses, emaciated abdomen and dyspnea, and some of them were resulted in death. At necropsy, the fibrinopurulent pneumonia, pleuropneumonia and pleuritis were found as the major pathological features, and in addition, the fibrinopurulent pericarditis and peritonitis with a large amount of exudate were also observed in some cases. Streptococcus pneumoniae was isolated from nearly all the affected organs, and also from the external nares and trachea. Isolation rate from the external nares was especially high, thus 97.1% of infected guinea pigs including healthy carriers were detected by cultivation of nasal swab samples. Carrier rates of healthy animals were gradually increased from 17.2% in April to 36.5% in October, but the organism was not detected from JYG strain at all. During the observation period, vaccination, advance of weaning age of animals and administration of high vitamin C dose were taken as preventive measures of the epizootic, but no remarkable effect was obtained. The same diseased conditions were successfully produced in Hartley guinea pigs by experimental nasal infection of a pneumococcal strain isolated from this epizootic.

Animals↗
PubMed1999

Severe pneumococcal infection at a Thai hospital.

OBJECTIVES: To determine clinical manifestations, prognostic factors, and therapeutic outcomes of severe pneumococcal infection. METHODS: Hospitalized patients with specimens cultured positive for Streptococcus pneumoniae were identified retrospectively by reviewing hospital records from 1992 to May 1998 at Siriraj Hospital. RESULTS: Of 205 evaluable cases, 130 (63.4%) patients were male. Nineteen (9.3%) patients were less than 2 years old, 29 (14.1%) were between 2 and 13 years, 99 (48.3%) were between 14 and 60 years, and 58 (28.3%) were over 60 years of age. From 1992 to 1997, the average admission rate was highest (36.4%) between January and March (range = 20-45%). Average admission rates during other periods ranged from 20.0% to 23.1%. Pneumonia (50.7%) and acute exacerbation of chronic obstructive pulmonary disease or infected bronchiectasis or bronchopneumonia (21.0%) were the most frequent diagnoses, followed by meningitis (14.6%) and primary sepsis without localized lesion (8. 3%). The mortality rate during the first 7 days of hospitalization was 28.8%, and thereafter, 11.7%. The odds ratios (95% CI) of old age, congestive heart failure, and alcoholism for death were 3.4 (1. 4-8.2), 8.6 (0.97-76.1), and 8.0 (3.1-20.9), respectively. For pneumonitis only, mortality rates among alcoholic and nonalcoholic patients were 76.9% and 39.6%, respectively (P = 0.025). CONCLUSIONS: Patients who were alcoholic, over 60 years of age, or had congestive heart failure were vulnerable to severe pneumococcal infection with significant mortality, in spite of proper selection of empirical antimicrobials. Diabetes mellitus and multiple myeloma also contributed to late mortality after 7 days of hospitalization.

Adolescent↗
PubMed2005

Predicting antimicrobial resistance in invasive pneumococcal infections.

BACKGROUND: The prevalence of multiantimicrobial resistance among Streptococcus pneumoniae continues to increase worldwide. In patients presenting with infection possibly due to pneumococci, recognition of risk factors that would identify those likely to have an antibiotic-resistant isolate might assist clinicians in choosing the most appropriate empirical therapy. METHODS: A prospective cohort study of invasive pneumococcal infection was conducted in Toronto, Canada. Risk factors for antimicrobial resistance were evaluated by means of univariate and multivariate modeling. RESULTS: A total of 3339 patients with invasive pneumococcal infection were identified between 1995 and 2002. Multivariate modeling revealed that risk factors for infection with penicillin-resistant as opposed to penicillin-susceptible pneumococci were year of infection (odds ratio [OR], 1.28; P < .001), absence of chronic organ system disease (OR, 1.72; P = .03), and previous use of penicillin (OR, 2.47; P = .006), trimethoprim-sulfamethoxazole (TMP-SMX; OR, 5.97; P < .001), and azithromycin (OR, 2.78; P = .05). Infection with TMP-SMX-resistant pneumococci was associated with absence of chronic organ system disease (OR, 1.64; P = .001) and with previous use of penicillin (OR, 1.71; P = .03), TMP-SMX (OR, 4.73; P < .001), and azithromycin (OR, 3.49; P = .001). Infection with macrolide-resistant isolates was associated with previous use of penicillin (OR, 1.77; P = .03), TMP-SMX (OR, 2.07; P = .04), clarithromycin (OR, 3.93; P < .001), and azithromycin (OR, 9.93; P < .001). Infection with fluoroquinolone-resistant pneumococci was associated with previous use of fluoroquinolones (OR, 12.1; P < .001), current residence in a nursing home (OR, 12.9; P < .001), and nosocomial acquisition of pneumococcal infection (OR, 9.94; P = .003). CONCLUSIONS: Knowledge of antimicrobial use during the 3 months before infection is crucial for determining appropriate therapy for a patient presenting to the hospital with an illness for which S. pneumoniae is a possible cause. Nosocomial acquisition and nursing home acquisition are significant risk factors for infection with fluoroquinolone-resistant pneumococci.

Adolescent↗
PubMed1979

[Pneumococcal infections and pediatric intensive care (author's transl)].

During the period 1965 to 1978, 62 cases of severe pneumococcal infection were admitted in Saint-Vincent de Paul pediatric intensive care unit. Recovery without sequelae was observed in only 17 of 49 meningitis. 5 fulminant pneumococcal infections after splenectomy or other disorders were observed. This late condition may be preventable by vaccination.

Adolescent↗
PubMed2006

Human antibody response towards the pneumococcal surface proteins PspA and PspC during invasive pneumococcal infection.

IgG antibodies against pneumococcal surface protein A, family 1 (PspA1) and family 2 (PspA2), protein C (PspC), and protein Hic were investigated in 41 patients with invasive pneumococcal disease. Pre-existing antibody levels against the four pneumococcal proteins were not significantly different from those found in 40 patients with non-pneumococcal bacteremia or 80 healthy controls. However, during convalescense a strong immune response developed especially against PspA, and there was a high degree of cross-reactivity between PspA- and PspC-antibodies. Our findings on immunogenicity and cross-reactivity suggest that in a future pneumococcal protein based vaccine, only a limited number of proteins could be sufficient.

Adult↗
PubMedDate not supplied

Invasive pneumococcal infections: incidence, predisposing factors, and prognosis.

A retrospective analysis of the case records of 494 patients with 508 episodes of pneumococcal infections verified by cultures from blood or from cerebrospinal, pleural, and/or synovial fluid from 1964 through 1980 is presented and discussed in relation to the literature on invasive pneumococcal infections. The documented incidence (1976-1980) of pneumococcal meningitis in a defined area of southwestern Sweden was similar to that reported from the United States; 1.4 cases per 100,000 persons per year; for nonmeningitic infections (mainly bacteremic pneumonia) the incidence was 6.1 per 100,000 per year. The highest age-specific incidence was seen in infants younger than two years. In the vast majority of patients, predisposing conditions (young or old age or severe underlying diseases) were present. In adults, alcoholism was the most important risk factor. The fatality rate was 33% for patients with meningitis and 15% for patients with non-meningitic infections, figures that were strikingly similar to those reported in other studies. Underlying diseases and young or old age contributed significantly to the high mortality rates.

Adolescent↗
PubMed1989

Pneumococcal infection of a prosthetic hip joint.

A case of late haematogenous pneumococcal infection of a prosthetic hip joint is presented. In view of the relatively benign nature of pneumococcal arthritis, the patient was treated with parenteral antibiotics and surgical drainage without removal of the prosthesis. This was followed by complete resolution.

Aged↗
PubMed1986

Invasive pneumococcal infection in Israel. Review of 90 cases.

90 cases of invasive pneumococcal infection hospitalized during the period 1975-1984 were reviewed. The organism was recovered from blood, cerebrospinal fluid or other normally sterile body fluids. 40 of the patients were adults, most of whom had pneumonia, and 50 were children who had pneumonia, primary bacteremia or meningitis. 90% of the adults and 14% of the children had underlying conditions. Nosocomial infection was remarkably more common among adults (25%), than among children (2%). Mortality was similar to that reported by others: 37% for adults and 10% for children. The most important predictive factors for fatal outcome were: old age (greater than 80), meningeal infection, presence of malignancy or chronic lung disease, and failure to mount leucocytosis. 13% of the strains were moderately resistant to penicillin.

Adolescent↗
PubMed1995

The molecular basis of pneumococcal infection: a hypothesis.

New insight has been gained into the mechanisms underlying the tissue tropism and inflammation of pneumococcal infection. Virulence has been linked to a transparent colonial morphology. Adherence has been characterized at the molecular level, and the importance of receptors arising upon activation of eukaryotic cells in promoting the progression to disease has been established. The contribution of peptidoglycan and teichoic acid to the generation of inflammation has suggested the need to couple anti-inflammatory therapy with antibiotic treatment in order to improve the outcome of invasive disease. Elucidation of the pathogenesis of pneumococcal infection, including the identification of virulence determinants by recently developed genetic strategies, can provide a paradigm for new mechanisms that are active in gram-positive bacterial infections and that are clearly distinct from the familiar pathways triggered by endotoxin.

Bacterial Adhesion↗
PubMed1990

Does naturally acquired IgG antibody to cell wall polysaccharide protect human subjects against pneumococcal infection?

Antibody to the non-serotype-specific cell wall polysaccharide (CWPS) of Streptococcus pneumoniae has been said to confer a degree of non-serotype-specific protection against pneumococcal infection. The hypothesis underlying the present study was that if this antibody is protective, relatively higher levels are likely to be detected in patients who are colonized by pneumococci but do not have infection, those who have febrile bronchitis but do not have pneumonia, and those who have pneumococcal pneumonia but are not bacteremic. Mean IgG reactive with CWPS by ELISA in 15 healthy young adults was 43.9 micrograms/ml and in 126 randomly selected hospital patients of all ages was 41.9 micrograms/ml. In subjects with chronic bronchitis with or without known pneumococcal carriage, mean anti-CWPS IgG was 87.7 micrograms/ml. In three groups of patients (3 with acute purulent tracheobronchitis, 13 with nonbacteremic pneumococcal pneumonia, and 14 with S. pneumoniae bacteremia) at the time of admission, mean antibody levels were essentially identical, 104.9-110.1 micrograms/ml. The data suggest that naturally present anti-CWPS IgG does not protect against the evolution of acute pneumococcal infection from colonization to acute purulent bronchitis, from bronchitis to pneumonia, or from pneumonia to bacteremia.

Adsorption↗
PubMed1981

[Early neonatal pneumococcal infections (author's transl)].

Five newborn infants with early pneumococcal infection are presented, two of them died. Until 1978 no cases of this infection were found in our Nursery. In the last three years pneumococcal septicemia has been responsible for nine percent of early neonatal infections. The clinical findings are identical to those seen in type-B beta hemolytic infections. The maternal genital tract colonization maight fetal colonization.

Apnea↗
PubMed2000

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants.

Incidences of and risk factors for Streptococcus pneumoniae sepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P =.03) and chronic GVHD (10-year probability, 14% vs 4%; P =.002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127; P =.07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16; P =.04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk. (Blood. 2000;95:3683-3686)

Adolescent↗
PubMed1999

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i. n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections.

Administration, Intranasal↗
PubMed1981

Pneumococcal infections in children with sickle cell disease: increased incidence, immunological defects, vaccine failure, and prospects for the future.

There has been an increased incidence of pneumococcal infections in patients with sickle cell disease. Two immunological defects, functional asplenia and decreased pneumococcal serum opsonins due to a defect in the alternate pathway, have been shown to have a causal relationship to this increased incidence. The pneumococcal vaccine has been tried in children with sickle cell disease and failures have been reported in the literature. Clinical trials are now underway to determine the best method to prevent pneumococcal infections in children with sickle cell disease, that is by use of a vaccine, penicillin, or both.

Adult↗
PubMed1999

The epidemiology of pneumococcal infection in children in the developing world.

Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio-economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing countries. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide-protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Review of recent pneumococcal infections with attention to vaccine and nonvaccine serotypes.

Conflicting data on the efficacy of the pneumococcal vaccine have continued to evolve. One important aspect of vaccine efficacy is related to the percentage of disease-causing serotypes contained in the vaccines. If disease-causing serotypes were to vary from place to place and population to population, vaccine efficacy would be variable and difficult to assess. We reviewed the literature on serotypic distribution of pneumococcal infection. Percentage of disease-causing serotypes covered by the 14-valent vaccine varied significantly from one study to another. Differences in age, hospital type, and source of isolation showed statistically significant serotypic distribution.

Bacterial Vaccines↗