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.     

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.     

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.     

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.     

Bacterial meningitis in a rural Kenyan hospital

In a prospective study to investigate mortality and antibiotic resistance in meningitis patients, thirty two meningitis cases were seen over a three month period. Mean age was 11.3 years (range one month-60 years). Cerebrospinal fluid cultures were positive in 26 patients (81.3%). S.pneumoniae was responsible for 15 cases (46.9%), followed by H.influenzae in seven (21.9%). Salmonella infection was seen in two patients, and E.coli and N.meningitidis in one each. Twelve patients (37.5%) died during hospitalisation with most of the deaths occurring within 48 hours after admission. No patients presented with atypical signs of meningitis. No significant differences were found between delay and outcome. Malaria parasites were found in blood of thirteen patients (41%), but did not contribute to higher mortality. Three of H.influenzae isolates (42.9%) were resistant to ampicillin and penicillin. Reduced sensitivity to penicillin was found in two (13.3%) of S.pneumoniae isolates.     

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.     

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.     

Bacterial meningitis in the health sector of Virgen del Rocio, Spain

BACKGROUND: The aim of this study was review the epidemiology of the bacterial meningitis in our area. MATERIAL AND METHODS: A retrospective study was carried out of all the cases of bacterial meningitis in children with ages between two months and fourteen years, admitted in our hospital between 1986 and 1997. The following variables we analyzed: Sex, age of the patient, yearly and monthly incidence, previous antibiotic therapy, length of hospital stay, and analytical data of blood and cerebrospinal fluid. RESULTS: In the 755 cases analyzed, the 50% correspond to bacterial meningitis, the 47.6% to viral or aseptic and 2.3% to tuberculous. In of the bacterial meningitis Neisseria meningitidis was isolated in 55.7% of cases, Haemophilus influenzae in 20.4%, Streptococcus pneumoniae in 5.5%, other bacterias in 3.4%, and in 14.5% was not isolated any bacteria. We are assisting to an increase of Neisseria meningitidis serotype C during the last years. Haemophilus influenzae represents a more percentage of bacterial meningitis that in prior years. In meningitis by Streptococcus pneumoniae we observe a clear association with risk factors in children older than 2 years. CONCLUSION: Neisseria meningitidis is the main etiologic agent in children. The vaccination against Haemophilus influenzae serotype b and Neisseria meningitidis A and C can change the epidemiology in next years.     

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.     

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.     

Three cases of meningococcal pneumonia

Three cases of pneumonia due to Neisseria meningitidis are described. In all three cases the organism was isolated only from blood cultures, but in the presence of good clinical and radiological evidence of pneumonia. The isolates belonged to three different serogroups: B type 2b, C, and Y. The cases illustrate the fact that N meningitidis can cause pneumonia and that culture of blood plays an important part in the diagnosis. Clinically there is nothing to differentiate meningococcal pneumonia from other causes of community acquired pneumonia. Predisposing factors include aspiration, immunosuppression, influenza, and adenovirus infections. When diagnosed, pneumonia due to N meningitidis should be notified and prophylaxis given as for meningitis or septicaemia.     

Trend of bacterial meningitis in children over a 14 year period (1981 through 1994) in Japan--an analysis based on studies in 27 institutions]

We observed 266 children with purulent meningitis in 27 institutions in Japan during the 14 years from 1981 on dividing these years into 3 periods, 1981-1985, 1986-1990 and 1991-1994, and studied the trend of causative organisms identified in 254 among the 266 patients. Their ages were less than 3 months after birth in 50 children and 3 months or older in 216: there were 141 boys and 125 girls. The causative organisms were H. influenzae in 134 patients and S. pneumoniae in 50, most of them being aged 3 months or older. Next to the above bacteria ranked S. agalactiae in 29 and E. coli in 12, many of the patients were aged less than 3 months. Staphylococcus spp. was found in 7 patients and about 70% of them were aged 3 months or older. L. monocytogenes was found in 4 patients and N. meningitidis in 3 and they were aged 3 months or older in both patient groups. S. pyogenes, Enterococcus spp., Peptostreptococcus spp., P. Mirabilis and Enterobacter spp. were detected each in 1 patient. The causative organism was unknown in 21 patients and there was no double infection. H. influenzae were detected in 18 patients in 1981-1985 period (36.7%), in 56 in 1986-1990 (54.9%) and in 60 in 1991-1994 (63.8%) showing an increasing tendency, but S. pneumoniae exhibited neither an increasing nor decreasing tendency. There was a decreasing tendency with S. agalactiae and E. coli, but the details were not clear because there were few patients aged less than 3 months. Although the period of coexistence of 4 main bacterial species was not made clear in this study. Listeria is considered to develop mainly in the early childhood, and we believe that the conventional way of using a cephem preparation and ampicillin combined for patients under 6 years need not be altered. However, panipenem (phonetic) is likely to be effective for insensible S. pneumoniae for the time being.     

Acute bacterial meningitis in children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi in 1996-97

To design appropriate interventions, we collected clinical and demographic data prospectively on all children aged one day to 14 years admitted with a diagnosis of bacterial meningitis (BM) from April 1st 1996 to March 31st 1997 to the Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. During the study period 267 children (2.7% of all paediatric admissions) were found to have BM; 83% were under 5 years of age, 61% under one year and 23% under one month. The most common causative organisms in the post neonatal period (n=206) were Streptococcus pneumoniae (27%), Haemophilus influenzae type b (Hib) 21%, and Salmonella typhimurium (6%). In the neonatal group (< 1 month, n=61) the most common causes were Streptococcus agalactiae (23%), S. typhimurium (15%), S. pneumoniae (11.5%) and other Gram negative rods (11.5%). Nineteen of 21 salmonella infections were in children under one year of age and all S. agalactiae were in infants under three months. There was delay on presentation: the average length of fever was 4.6 days, 39.5% had convulsed prior to arrival and 57% had an altered level of consciousness. An initial diagnosis of malaria had probably contributed to the delay in 22.5% (42 of 186 tested). 48% were < 80% weight for age, with 18% < 60%) weight for age. The overall mortality was 40%. The outcome was worst in salmonella infections, particularly neonatal salmonella BM with a case fatality rate (CFR) of 89% (8 of 9 cases). Coma on presentation worsened prognosis (mortality 64% if Blantyre Coma Score < 3, 26% if > 3). 15% of survivors had sequelae on discharge. 20% of Hib isolates were resistant to chloramphenicol, but all salmonellae were sensitive. 5% of S. pneumoniae were resistant to penicillin and 8% to chloramphenicol. Earlier access to adequate health care and awareness of BM in a malaria-endemic area would reduce mortality and morbidity. Vaccination against Hib infection would have reduced death by 18 (17%) and prevented sequelae in 7 cases.     

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.     

Meningococcal disease: recognition, treatment, and prevention

Meningococcal disease is an infection caused by Neisseria meningitidis, a gram-negative diplococcus that is the leading cause of bacterial meningitis in children and young adults in the United States, with an estimated 2,600 cases reported each year. N. meningitidis infection rates are highest in children 3 to 12 months of age. Four distinct clinical situations are associated with meningococcal infection. The most common is asymptomatic nasopharyngeal colonization. Benign bacteremia is discovered in the absence of classical clinical findings of meningococcemia, but blood cultures are positive for N. meningitidis. Meningitis, the most common pathologic presentation, is associated with fever, headache, and nuchal rigidity. The mortality rate is about 5% in children and 10% to 15% in adults. Meningococcemia, the most severe form of infection, may involve petechial rash, hypotension, and disseminated intravascular coagulation. It is a fulminant condition that can, if untreated, progress from initial symptoms to coma and death in 12 to 48 hours. Spread of these endemic cases can be controlled by administering prophylactic antibiotics to close contacts of patients.     

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.     

Effects of aspirin treatment on survival in non-insulin-dependent diabetic patients with coronary artery disease. Israeli Bezafibrate Infarction Prevention Study Group

We studied seizures that occur during the acute phase of aseptic and bacterial meningitis in childhood. Of the 108 children with aseptic meningitis, five had seizures (4.7%). Four patients developed them within 24 hours of the onset of the initial symptom (fever in 3 cases), and three had repeated seizures on the first day. One case had SIADH complication, but another neurologic abnormalities were not observed. On the 18 children with bacterial meningitis, three cases (16.7%) had seizure, which occurred on the second day of illness. Disturbance of consciousness and cerebral hypertension were observed in 2 cases each, and abnormal cerebral CT findings in all the three. The NSE level in the cerebrospinal fluid was elevated in 2 cases. Thus, seizures occurring in the acute phase of aseptic meningitis may reflect transient cerebral functional abnormality accompanying fever or SIADH, whereas those in bacterial meningitis may result from neural tissue damage due to encephalopathy or angitis. In aseptic and bacterial meningitis, the presence of seizures in the acute phase was not correlated with the neurological outcome.     

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.     

Acute encephalitis and bacterial meningitis in children in Aichi Prefecture (1984-1993)

A survey was performed of acute encephalitis and bacterial meningitis in infancy and childhood from 1984 to 1993 using a questionnaire directed to departments of pediatrics in large hospitals in Aichi prefecture. The case records for 391 patients with acute encephalitis including related diseases and 328 patients with bacterial meningitis were obtained from 63 hospitals. Of 391 patients with acute encephalitis, 224 were male and 167 were female. Of 328 patients with bacterial meningitis, 200 were male and 128 were female. Sex ratio were 1.3, 1.6 respectively. Of the patients, 52.4% of encephalitis and 84.8% of meningitis were under 4 years of age and 0 year olds made up 53.7% of the latter. The causes of these diseases were confirmed in 38.7% and 82.9% of the encephalitis and meningitis patients, respectively, etiologically. In encephalitis, rubella virus was the most frequent with 29 cases, followed by measles virus (27 cases), herpes simplex virus (24) and varicella-zostervirus (19). In meningitis H. influenzae (95 cases), S. pneumoniae (56), Group B streptococcus (41) and E. coli (27) were frequently diagnosed. These diseases showed respective patterns of age distribution and clinical course, and moreover, the increases in their onset were clearly related to the prevalence of causal infections. Therefore, the results of this study should be utilized in the development of administrative measures for prevention of these diseases.     

Basic fibroblast growth factor in experimental and clinical bacterial meningitis

Basic fibroblast growth factor (bFGF), a neurotrophic factor in the CNS, is expressed at high levels in response to seizures or strokes. We examined the expression of bFGF during experimental bacterial meningitis and the levels of bFGF in the cerebrospinal fluid (CSF) of children with bacterial meningitis. For the experimental study, a mouse model of meningitis was established by intracranial injection of Streptococcus pneumoniae. Twenty-four hours after induced meningitis, the brains were sectioned and stained immunohistochemically for bFGF. Neutrophils and macrophages infiltrating the leptomeninges and the ventricles exhibited strong bFGF immunoreactivity. The neurons in the areas adjacent to the inflamed ventricles also showed enhanced bFGF expression. For the clinical study, we used an enzyme immunoassay to measure bFGF in CSF in 18 children with bacterial meningitis, 12 with aseptic meningitis, and 18 controls. The CSF levels of bFGF were twice as high in children with bacterial meningitis (medians 6.75-7.21 pg/mL) compared with those who had aseptic meningitis (2.9 pg/mL) or in control subjects (2.65 pg/mL, p < 0.0001, respectively). In patients with bacterial meningitis who survived, CSF bFGF decreased significantly after 24-50 h of antibiotic therapy (p < 0.0005). Patients who developed major sequelae or died had much higher levels of CSF bFGF than those without (134.9 pg/mL versus 7.38 pg/mL, p < 0.05). These findings of enhanced immunoreactivity of bFGF in experimental bacterial meningitis and an association of CSF levels of bFGF with disease severity in childhood bacterial meningitis suggest a biologic role for this neurotrophic factor in the pathophysiology of bacterial meningitis.