Epidemiology of Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae in children in the Valencia Community, Spain. Acute diseases study group

OBJECTIVE: To asses the incidence of Haemophilus influenzae type b (Hib), Neisseria meningitidis and Streptococcus pneumoniae meningitis in children of de Valencian Community (VC), Spain, and to describe the microbiologic characteristics. MATERIAL AND METHODS: Prospective surveillance system with paediatrician and microbiologist participation of all public hospitals of the VC. Cases are children less than 15 with clinical meningitis and with isolation of Hib, N. meningitidis or S. pneumoniae from CSF of blood. RESULTS: From 1st December 1995 to 30th November 1996, 51 cases were declared, 33.3% were Hib, 49.0% N. meningitidis and 17.7% S. pneumoniae. The annual incidence of meningitis was 7.6 cases/100,000 < 15 years, 20.5/100,000 < 5 years and 56.2/100,000 < 1 year. 84.3% of the cases occurred in children younger than 5. S. pneumoniae had the highest mortality. CONCLUSIONS: Hib is a frequent cause of meningitis in spite of that one third of children are vaccinated. 43% of the N. meningitidis isolated in meningitis are serogroup C. S. pneumoniae meningitis are more frequent in children less than one, and has a high mortality rate.     

Prospective study of bacterial meningitis in North East Thames region, 1991-3, during introduction of Haemophilus influenzae vaccine

OBJECTIVE: To describe the epidemiology of primary bacterial meningitis in the North East Thames region over a three year period before and during the introduction of the vaccine for Haemophilus influenzae type b. DESIGN: Analysis of information on cases of primary bacterial meningitis identified by microbiology laboratories in the region, with collection of case data by questionnaire. MAIN OUTCOME MEASURES: Annual incidence rates for types of meningitis according to age and ethnic group. RESULTS: The annual incidence rates for the three major causes of bacterial meningitis in the general population were 1.9/100,000 for Neisseria meningitidis, 1.6/100,000 for Haemophilus influenzae before vaccination, and 1.0/100,000 for Streptococcus pneumoniae. Higher rates of H influenzae meningitis were found in Asians compared with white people (3.6/100,000 v 1.5/100,000, P = 0.01). As a result of the vaccine programme introduced in October 1992 the number of cases of H influenzae meningitis in children under 5 years has fallen by 87%. CONCLUSIONS: Bacterial meningitis is a serious problem especially in preschool children. There are differences in the incidence of some causes of bacterial meningitis in different ethnic groups; with H influenzae type b being significantly more common among black and Asian people than among white people. The immunisation programme for H influenzae type b in the North East Thames region has been successful in reducing the incidence of this type of meningitis in Asian and white populations. The numbers were too small to evaluate in the black population.     

Pediatric meningitis in the Western Cape Province of South Africa

During the 9 years 1985-1993 a prospective survey of all cases of meningitis in children < 13 years of age presenting to our hospital in the Western Cape Province of South Africa was carried out. Two-thousand-nine-hundred-and-twenty cases of meningitis were identified. The commonest form of bacterial meningitis was tuberculous meningitis (TBM) diagnosed in 282 children (mean age 2.94 years). N. meningitidis identified in 220 children (mean age 2.87 years), Haemophilus influenzae in 156 children (mean age 1.15 years) and S. pneumoniae in 106 children (mean age 2.14) were the next commonest causes of bacterial meningitis diagnosed. One-hundred-and-eighteen cases of bacterial meningitis were confirmed in infants < 1 month of age and the commonest bacteria identified were group B beta-haemolytic Streptococcus in 27, E. coli in 21, Klebsiella species in 11, and Candida species in 15 neonates. The emergence of TBM as the predominant cause of bacterial meningitis in childhood at our hospital is probably a reflection of the worsening tuberculosis situation in the Western Cape Province of South Africa.     

Bacterial meningitis in the United States in 1995. Active Surveillance Team

BACKGROUND: Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS: Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS: On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS: Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.     

The relationship between fatty liver and hyperinsulinemia in obese Japanese children

During 1994, 603 cases of bacterial meningitis were reported in Italy. Seventy-five percent of cases with determined etiology was due to three agents: Neisseria meningitidis (33.4%), Streptococcus pneumoniae (23.4%) and Haemophilus influenzae (18.6%). The majority of cases due to N. meningitidis and H. influenzae occurred in subjects below five years of age (35.7% and 84.8%, respectively) while S. pneumoniae accounted for 52.8% of meningitis cases in subjects older than 44 year of age. The estimated incidence of N. meningitidis on the national population in 1994 was 0.27 per 100,000. Serogroup B accounted for 62.5% of the serotyped isolates, group C for 23.1%, group A for 7.2%, group W135 for 3.6%, group Y for 1.8%. All tested meningococcal strains were susceptible to penicillin as well as to rifampin. Incidence of meningococcal meningitis in 1994 has been low suggesting that its relative importance compared to other bacteria causing meningitis is likely to change in the future. Therefore, extended surveillance on bacterial meningitis by other etiological agents has to be maintained and implemented in order to undertake the appropriate control measures and evaluate their effect.     

Color doppler ultrasonography in peripheral artery occlusive disease: continuous application of a signal enhancer

OBJECTIVE: The purpose of this study was to evaluate the clinical and epidemiological characteristics of meningitis in our environment. PATIENTS AND METHODS: A retrospective study of 166 cases of meningitis diagnosed in our hospital during a 10 year period (1986-1995) was performed. The patients were between 1 month and 14 years of age. RESULTS: Sixty-six percent of the patients were male and 34% female. Eleven cases were younger than 2 months (6.6%), 122 cases (73.5%) were between 3 months and 5 years of age and 33 cases (19.9%) were older than 5 years. The most frequent symptoms and signs were fever (96%), vomiting (60%), impairment of consciousness (24%) and meningeal signs (49%). CSF cultures were positive in 52% and blood cultures in 32%. The pathogen isolated was N. meningitidis in 53 cases (32%), H. influenzae in 38 (23%), S. pneumoniae in 9 patients (5%) and others in 3 children (2%). Meningitis due to H. influenzae increased each year. No microorganism was isolated in blood and CSF in 63 cases (38%). Meningitis in children between 3 months and 5 years of age was due to N. meningitidis in 40 children (33%) and H. influenzae in 36 (29%). The mortality rate was 3%. The most frequent complications were sepsis (36%) and seizures (16%). CONCLUSIONS: The most frequently isolated agent in our study was N. meningitis. Meningitis due to H. influenzae is increasing such that H. influenzae and N. meningitis currently show similar frequency in children between 3 months and 5 years of age.     

Pattern and antibiotic susceptibility of bacteria in pyogenic meningitis in a children's emergency room population in Maiduguri, Nigeria, 1988-1992

From January 1988 to November 1992, 107 (3.5%) of 3074 postneonatal children admitted to the Children's Emergency Room, University of Maiduguri Teaching Hospital, Nigeria, had sporadic pyogenic meningitis; 66 (61.7%) were aged < or = 12 months. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae together were responsible for 77.3% (58) of 75 culture-proven cases, 13.4% (10) had Enterobacteriaceae, 5.3% (4) had Staphylococcus aureus and 4% (3) untyped alpha-haemolytic streptococci. Fifty percent of 62 bacteria were resistant to ampicillin, 47.2% of 36 to penicillin and 10.7% of 56 to chloramphenicol; none of 21 bacteria was simultaneously resistant to all three antibiotics. Up until 1992, we have encountered treatment failure with a regimen containing chloramphenicol in only 2 of 53 patients; the 2 patients had coliform meningitis. Non-meningococcal bacteria are an important cause of sporadic pyogenic meningitis in sub-Saharan Nigeria and chloramphenicol is the most appropriate initial drug of choice at the present time for the management of sporadic meningitis.     

No high affinity melatonin binding sites are detected in murine melanoma cells and in normal human melanocytes cultured in vitro

Samples of 1815 cerebrospinal fluid (CSF) were studied in a meningitis outbreak during 1989 in S?o Paulo, Brazil. Neisseria meningitis 56% with 44% type B, Haemophilus influenzae 17%, from which 72% in children (days to 3-year-old) and Streptococcus pneumoniae 14% from which 60% in children (day to 1-year-old) of 443 (24%) of all strains. Cytochemistry study showed: purulent or turbidity aspects in 70 to 79% positive bacterioscopy or culture of CSF; white cells count > 500/mm3; glucose < 45 mg/dl; protein > 90 mg/dl in 90% of all patients. We concluded that: CSF prognostic factors: (aspect and cytochemistry) were correlated with bacterial meningitis. Bacterioscopy and positive cultures were correlated to NM, SP and HI isolation from these patients (Goodman Test).     

Recent developments in bacterial conjugate vaccines

Study of the epidemiology of childhood infection reveals that the brunt of disease for a number of invasive bacterial infections is borne by children under the age of 4 years. Haemophilus influenzae type b (Hib), Neisseria meningitidis and Streptococcus pneumoniae, the three most important causes of childhood meningitis, illustrate this phenomenon, which is caused by the inability of infants and young children to mount antibodies to the carbohydrates that form a capsule surrounding these organisms. Carbohydrates are traditionally viewed as T-independent antigens with a number of unique and important immunological properties that are not encountered when inducing an immune response to proteins. These properties include no overt requirement for the presence of T cells to induce an immune response, dominance of IgM, failure to induce memory following immunisation, an absence of affinity maturation following immunisation, and poor immunogenicity in infants, the elderly and the immunocompromised. These properties of carbohydrates have precluded the use of pure carbohydrate vaccines in those patients most at risk. Conjugate vaccine technology, where a carbohydrate antigen is coupled chemically to a protein carrier, has overcome the limitations of carbohydrates as vaccine antigens by rendering the carbohydrate moiety of such vaccines immunogenic, even in the very young. The dramatic success of the Hib conjugate vaccines, the first conjugates licensed clinically for human use, in reducing the incidence of invasive Hib disease has demonstrated the potential value of such conjugate vaccines. Similar technology is, therefore, being applied to a number of other vaccines in development, including N. meningitidis (groups A and C) and S. pneumoniae vaccines. The large number of pneumococcal carbohydrate serotypes that require inclusion in a vaccine makes this conjugate formulation far more complicated than that for Hib, and it is likely that the dramatic success of the Hib conjugate vaccines will be more difficult to repeat for the pneumococcus.     

Epidemiology of acute bronchopulmonary infections in children

In infants and young children acute lower respiratory infection is the most common cause of morbidity and death especially in developing countries. Factors that contribute to the increased susceptibility to respiratory pathogens include young age, season, sex, indoor pollution, large family size, malnutrition, low immunocompetence, socioeconomic disadvantage. The epidemiology of acute respiratory infections in childhood seems similar worldwide. In all countries, respiratory syncytial virus, parainfluenzae virus 1 and 3 influenzae A and B viruses and adenovirus are reported to be the main causes of acute respiratory infections. Six microorganisms are responsible of 90% of documented acute bacterial pulmonary infections, Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis, Haemophilus influenzae, Staphylococcus. Mixed viral and bacterial infections occur frequently (30%). The role of respiratory viruses in predisposing to colonization and invasion of bacterial organisms has often been suggested. In recent years acquired resistance against antibiotic for H. influenzae and S. pneumoniae has emerged.     

Bacterial meningitis in children and adults. Changes in community-acquired disease may affect patient care

Despite improved understanding of how bacterial meningitis develops, the infection remains a potentially life-threatening emergency capable of causing significant morbidity and mortality. Since the introduction and widespread use of H influenzae type b vaccine in infancy and childhood in North America, the epidemiology of community-acquired bacterial meningitis has changed. S pneumoniae is now the most common cause in children and adults overall, although N meningitidis causes most disease in patients between ages 2 and 18 years. Broad-spectrum cephalosporins (eg, ceftriaxone, cefotaxime) are considered the agents of choice for empirical treatment of bacterial meningitis. However, use of these agents will have to be reconsidered if the incidence of invasive infection from drug-resistant S pneumoniae continues to increase. The role of adjunctive corticosteroid therapy needs to be better defined. Improved conjugate pneumococcal and meningococcal vaccines may soon make bacterial meningitis a preventable disease.     

Where''s the cash?

This study was done to analyze the epidemiology of invasive Haemophilus influenzae disease in Bochum city area. Forty-eight children with invasive Haemophilus influenzae infections were treated at the University Children's Hospital in Bochum during the study period from January 1971 to June 1992. Clinical manifestations included meningitis (n = 34), epiglottitis (n = 8), pneumonia (n = 2), bacteremia (n = 2), cellulitis (n = 1) and osteomyelitis (n = 1). The overall yearly incidence rate for all invasive Haemophilus influenzae infections was 13 per 100,000 children younger than five years of age, with a marked increase in the last six years. Haemophilus influenzae meningitis showed no significant change during the study period with an overall yearly incidence of 9 per 100,000 children younger than five years. Twenty-eight cases (58%) of all invasive Haemophilus influenzae infections occurred in patients under two years of age and five cases (10%) were younger than six months. Invasive Haemophilus influenzae disease showed no seasonal prevalence. All isolates were susceptible to ampicillin. No deaths occurred, but severe bilateral deafness resulted in one patient with meningitis. Prospective epidemiologic studies are needed to estimate clinical efficacy of the Haemophilus influenzae type b immunization program in Germany.     

Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen

Four-day dexamethasone therapy has been used to treat bacterial meningitis. This prospective, randomized study compared the effect of a 2-day versus a 4-day regimen. Children (n = 118, ages 2.5 months to 15 years) were evaluated; 50% of the cases were due to Neisseria meningitidis and 40% to Haemophilus influenzae type b. Patients were treated intravenously (iv) mainly with conventional antimicrobial therapy and were randomly assigned to receive dexamethasone, 0.15 mg/kg iv every 6 h for 2 or 4 days. The clinical response was similar for both dexamethasone regimens. The meningococcal meningitis patients survived without neurologic or audiologic sequelae. On long-term follow-up, neurologic sequelae or moderate or more severe unilateral or bilateral hearing impairment (or both) were found in 1.8% and 3.8% of patients treated with dexamethasone for 2 and 4 days, respectively. The 2-day regimen appears appropriate for the treatment of H. influenzae and meningococcal meningitis.     

Inhibition of peripheral blood mononuclear cell proliferation by cardiac glycosides

We prospectively studied the epidemiologic, clinic signs and outcome of bacterial meningitis in 125 children who were admitted into a PICU (Pediatric Intensive Care Unit) of 11 hospitals of Spain and whose meningitis was diagnosed between May 1994 and April 1995. RESULTS: The median age of the children was 3.55 +/- 3.32 years (range 1 month to 16.5 yrs). Eighty-eight were bacterial meningitis, probably bacterial 30 and aseptic 7. The most frequently isolated organisms were N. meningitidis (52), H. influenza type b (17) and S. pneumoniae (8). Twenty-five percent of N. meningitidis had C serotype. Incidence rate of each germen was depending of age. All patients diagnosed of H. influenza type b meningitis were less than 3 years old. H. influenza type b and meningococcus had similar incidence rate during the first year of life (27% versus 31%). During the first three years of life H. influenza type b produced one third of bacterial meningitis. A mortality rate of 5.6% (seven patients: 3 S. pneumoniae, 1 N. meningitidis, 1 H. influenza type b and 2 unknown germen) was observed. Patients who die had lower Glasgow coma score (p = 0.034) and seizures (p = 0.001) at admission. At discharge of PICU, 9 survivors (7.2%) had sequelae: mental retardation in 7 patients and hearing loss in two. One third of patients needed hemodynamic support and a 15% of them ventilatory support. CONCLUSIONS: Age is an important epidemiological factor in the etiology of pediatric acute meningitis. H. influenza type b and N. meningitidis had similar incidence rate during the first year of life. S. pneumoniae had the highest mortality rate (37.5%). The presence of coma and seizures at admission were associated with mortality.     

Bacterial meningitis in southwestern Alaska

Between July 1, 1971, and June 30, 1974, thirty-nine cases of bacterial meningitis were diagnosed at the Alaska Native Health Service Hospital at Bethel, Alaska. Thirty-two (82%) occurred in infants less than one year of age. Haemophilus influenzae (H. influenzae) was the predominant causative agent, and was isolated from 23 (72%) of the 32 patients under one year of age. The annual incidence of H. influenzae meningitis in the Bethel area was 63/100,000, and the annual incidence of H. influenzae meningitis in children less than five years of age was 474/100,000 cases.     

Central venous access: low internal jugular vein approach using imaging guidance

We reviewed the results of microscopic Gram stain examination and routine culture for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital microbiology laboratory during 55 months. There were 56 instances of bacterial or fungal meningitis (16 associated with central nervous system [CNS] shunt infection), four infections adjacent to the subarachnoid space, four cases of sepsis without meningitis, and an additional 220 CSF specimens with positive cultures in which the organism isolated was judged to be a contaminant. Because 121 of these contaminants were isolated in broth only, elimination of the broth culture would decrease unnecessary work. However, 25% of the meningitis associated with CNS shunts would have been missed by this practice. The most common cause of meningitis was Cryptococcus neoformans, followed by Streptococcus pneumoniae and Neisseria meningitidis. In 48 of 56 (88%) of cases, examination of the Gram-stained specimen revealed the causative organism. If patients who had received effective antimicrobial therapy prior to lumbar puncture are excluded, the CSF Gram stain is 92% sensitive. Microscopic examination incorrectly suggested the presence of organisms in only 3 of 2,635 (0.1%) CSF examinations. Thus, microscopic examination of Gram-stained, concentrated CSF is highly sensitive and specific in early diagnosis of bacterial or fungal meningitis.     

Young Malaysian children with lower respiratory tract infections show low incidence of chlamydial infection

OBJECTIVE: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period. METHODOLOGY: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods. RESULTS: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively. CONCLUSION: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia.     

Percutaneous large-core biopsy of papillary breast lesions

Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae possess the ability to cleave human IgA1 antibodies, and all successfully colonize and occasionally invade the human upper respiratory tract. N. meningitidis invades the bloodstream after a period of nasopharyngeal colonization. We directly compared levels of IgA1 protease activity in strains (n=52) derived from the cerebrospinal fluid or blood of patients with meningococcal disease with strains of N. meningitidis obtained from asymptomatic carriers (n=25). IgA1 protease activity was determined by a sensitive semiquantitative ELISA assay. Levels of IgA1 protease activity were significantly higher (P<0.0001) in strains associated with invasive meningococcal disease (98% with detectable activity, mean = 580 mU) than with those obtained from asymptomatic carriers (76% with detectable activity, mean = 280 mU). Despite marked variation in enzyme activity, almost all strains (96%) possessed the gene for IgA1 protease. Given the panmictic population structure of the bacterial isolates investigated, these data, obtained from two groups infected with N. meningitidis, but with markedly different clinical outcomes, provide the first quantitative evidence that IgA1 protease activity is a virulence determinant that contributes to the pathogenic phenotype, and suggest IgA1 protease as a potential target for prophylaxis.     

Pathogens isolated during treatment failures in otitis

OBJECTIVES: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure. METHODS: The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid. RESULTS: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14. CONCLUSIONS: Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.