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PubMed2004

Prospective population-based incidence of Haemophilus influenzae type b meningitis in Thailand.

There are limited prospective data for Haemophilus influenzae type b (Hib) disease in Asia, where some countries are considering vaccine introduction. A prospective population-based study was conducted to measure the incidence of Hib meningitis in children in two northern provinces of Thailand. Children <5 years with symptoms consistent with bacterial meningitis were enrolled in the study if inclusion criteria were met. The study enrolled 598 children with clinical meningitis, 76% of whom received lumbar puncture. The rate of probable bacterial meningitis was 26.6/100,000 children <5 years per year. There were four cases of laboratory confirmed Hib meningitis (rate 3.8/100,000 children <5 years per year). These findings suggest a relatively low incidence of Hib meningitis. However, additional data from studies of pneumonia are needed to define the Hib disease burden in Thailand.

Child, Preschool↗
PubMed1995

Early disseminated Lyme disease: Lyme meningitis.

Lyme meningitis is the direct result of invasion of the nervous system by Borrelia burgdorferi. Occurring within the first few months of infection, it initially presents as a chronic basilar meningitis. Much about the pathogenesis of Lyme meningitis has been learned from animal models, the best being the adult Rhesus macaque. Injection of these animals with a highly infective strain of B. burgdorferi has led to a very predictable course of events: erythema migrans within the first few weeks after injection, development of anti-B. burgdorferi antibody, detection of spirochetemia in weeks 3 and 4, and central nervous system (CNS) invasion within 1 month with cerebrospinal fluid (CSF) pleocytosis. In humans, facial palsy is the earliest clinical indicator. Headache and meningismus are symptoms of inflammation of the subarachnoid space. Severe fatigue and arthralgia are common extra-CNS symptoms. Culture is not generally useful for detecting or confirming Lyme meningitis. False-positive serologic tests may occur in patients with other infections, inflammatory processes, or malignancies. Immunoblotting will differentiate true-from false-positive antibody reactivity. Lack of a consistently positive serum antibody titer should make the diagnosis of Lyme meningitis suspect. Positive CSF antibody is almost universal in patients with Lyme meningitis. Polymerase chain reaction is a direct test that is highly specific and sensitive. The antibiotic treatment of choice is intravenous (i.v.) cephalosporins or penicillin for 2-3 weeks. If the clinical picture is anything less than absolutely classic, a lumbar puncture and Western blot of serum should be obtained in a seropositive patient before initiating intravenous antibiotic therapy. There is no role at this time for long-term (> 1 month) intravenous antibiotics. Nonsteroidal antiinflammatory agents can also be of benefit.

Diagnosis, Differential↗
PubMed2001

Serum cleaved Tau protein and neurobehavioral battery of tests as markers of brain injury in experimental bacterial meningitis.

Brain injury due to bacterial meningitis affects multiple areas of the brain with a heterogeneous distribution generating a challenge to assess severity. Tau proteins are microtubular binding proteins localized in the axonal compartment of neurons. Brain injury releases cleaved Tau proteins (C-tau) into the extracellular space where they are transported to the cerebral spinal fluid. We hypothesized that C-tau crosses the blood-brain barrier during inflammation and that it can be detected in serum. The correlation between serum C-tau levels and the extent of the meningitic insult was examined. Furthermore, we studied whether the use of a subset of neurobehavioral tasks can assess the extent of brain injury after meningitis. The tests were chosen primarily for their ability to detect deficits in the acoustic system, low brain, reflexive responding, as well as for impaired motor coordination and the higher brain functions of learning and memory. A rat model of group B streptococcal meningitis with variable severity was utilized. At five days after bacterial inoculation followed by antibiotic therapy neurobehavioral tests were performed and serum C-tau and histologic samples of the brain were obtained. Our study shows that during meningitis C-tau appears in serum and reflects the extent of neurologic damage. Neurobehavioral performance was altered after bacterial meningitis and could be correlated with histologic and biochemical markers of neurologic sequelae. We conclude that serum C-tau and a composite of neurobehavioral tests could become useful markers for assessing the severity of neurological damage in experimental bacterial meningitis.

Animals↗
PubMed1988

Association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis in hospitalized infants with enterovirus infection.

One hundred eight hospitalized infants with enteroviral infections were studied to determine the association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis. Of 108 infants, 55 (51%) had meningitis. Clinical manifestations on admission did not distinguish between infants with and those without meningitis. Echoviruses 30 and 11 and coxsackie virus B were frequently associated with meningitis (34/38; 90%) whereas echoviruses 18, 24, and 25 were not (5/35; 4%). The virus isolation rate was directly proportional to the number of leukocytes in cerebrospinal fluid: 5 of 58 (9%) when up to 9 cells/mm3 were found, 10 of 21 (48%) when 10 to 99/mm3 cells were found, and 25 of 29 (86%) when greater than equal to 100 cells/mm3 were found. Meningitis is often unsuspected in children hospitalized with enterovirus infection. The frequency of meningitis among hospitalized infants is serotype dependent and is most frequently, but not exclusively, found with pleocytosis of the cerebrospinal fluid.

Cerebrospinal Fluid↗
PubMed2001

Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa.

BACKGROUND: The diagnosis of acute bacterial meningitis in children is difficult in sub-Saharan Africa, because the clinical features overlap with those of other common diseases, and laboratory facilities are inadequate in many areas. We have assessed the value of non-laboratory tests and incomplete laboratory data in diagnosing childhood acute bacterial meningitis in this setting. METHODS: We prospectively studied 905 children undergoing lumbar puncture at a rural district hospital in Kenya over 1 year. We related microbiological findings and cerebrospinal-fluid (CSF) laboratory measurements to tests that would typically be available at such a hospital. FINDINGS: Acute bacterial meningitis was proven in 45 children (5.0% [95% CI 3.7-6.6]) and probable in 26 (2.9% [1.9-4.2]). 21 of the 71 cases of proven or probable acute bacterial meningitis had neither neck stiffness nor turbid CSF. In eight of 45 children with proven disease the CSF leucocyte count was less than 10x10(6)/L or leucocyte counting was not possible because of blood-staining. The presence of either a leucocyte count of 50x10(6)/L or more or a CSF/blood glucose ratio of 0.10 or less detected all but two of the 45 children with proven acute bacterial meningitis; these two samples were grossly blood-stained. INTERPRETATION: The diagnosis of childhood acute bacterial meningitis is likely to be missed in a third of cases at district hospitals in sub-Saharan Africa without adequate and reliable laboratory resources. CSF culture facilities are expensive and difficult to maintain, and greater gains could be achieved with facilities for accurate leucocyte counting and glucose measurement.

Acute Disease↗
PubMed1995

Cleaved L-selectin concentrations in meningeal leukaemia.

Involvement of the central nervous system has important therapeutic implications in acute leukaemia. Because the identification of blast cells in cerebrospinal fluid (CSF) is often difficult, there is a need for sensitive markers of leukaemic infiltration. Since the shed form of L-selectin (sL-selectin) is frequently increased in acute leukaemia (sL-selectin+ leukaemia), we examined whether assay of sL-selectin in CSF could improve our ability to detect such meningeal involvement. CSF sL-selectin was significantly (p < 0.001) higher in 15 patients with sL-selectin+ meningeal leukaemia (median 60 ng/mL, range 34-150) than in 20 patients with acute leukaemia without meningeal involvement (12 ng/mL, 1-39) or 88 control patients (14 ng/mL, 0-37). Serial measurements of sL-selectin in patients with sL-selectin+ leukaemic meningitis showed increased CSF concentrations of the cleaved receptor in 4 patients with therapy-resistant meningeal leukaemia and sustained normal concentrations in 9 patients in remission. Our results suggest that CSF sL-selectin may be a useful marker in the detection of meningeal involvement by blast cells in patients with sL-selectin+ leukaemia.

Adult↗
PubMed1997

Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants.

BACKGROUND: In developing countries, pneumonia and meningitis due to Haemophilus influenzae type b (Hib) are common in children under age 12 months and the mortality from meningitis is high. Protein-polysaccharide conjugate vaccines have brought Hib disease under control in industrialised countries. We did a double-blind randomised trial in The Gambia to assess the efficacy of a Hib conjugate vaccine for the prevention of meningitis, pneumonia, and other invasive diseases due to Hib. METHODS: Between March, 1993, and October, 1995, 42,848 infants were randomly allocated the conjugate vaccine Hib polysaccharide tetanus protein (PRP-T) mixed with diphtheria-tetanus-pertussis vaccine (DTP), or DTP alone at age 2 months, 3 months, and 4 months. Children who presented with signs of invasive Hib were investigated by blood culture and, where appropriate, by lumbar puncture, chest radiograph, or percutaneous lung aspirate. Children were followed up for between 5 and 36 months. FINDINGS: The median ages at which children received the study vaccine were 11 weeks, 18 weeks, and 24 weeks. 83% of children enrolled received all three doses of vaccine. 17 cases of culture-positive Hib pneumonia, 28 of Hib meningitis, and five of other forms of invasive Hib disease were detected amongst the study children. The efficacy of the vaccine for the prevention of all invasive disease after three doses was 95% (PRP-T vaccinees 1, controls 19 [95% CI 67-100]), for the prevention of Hib pneumonia after two or three doses, 100% (vaccinees 0, controls 10 [55-100]), and for the prevention of radiologically defined pneumonia at any time after enrollment, 21.1% (PRP-T vaccinees 198, controls 251 [4.6-34.9]). INTERPRETATION: PRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants. The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib. The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis.

Age Factors↗
PubMed1997

Degeneration of Cajal-Retzius cells in the developing cerebral cortex of the mouse after ablation of meningeal cells by 6-hydroxydopamine.

In the central nervous system, the neurotoxic drug 6-hydroxydopamine (6-OHDA) selectively deletes central catecholaminergic neurons and meningeal cells. Meningeal cells are known to contribute to brain development and their specific degeneration leads to disorganized neuronal positioning. We have analyzed whether a particular population of cortical pioneer neurons, the Cajal-Retzius (CR) cells, which lie just below meningeal cells, is also affected by 6-OHDA treatment. We show that application of 6-OHDA to the cortical surface leads to a rapid degeneration of CR cells, without affecting other cortical neurons. The ablation of CR cells was prevented by normetanephrine, which blocks the 6-OHDA uptake into meningeal cells. These results indicate that the disappearance of CR cells after 6-OHDA treatment may be a result of the ablation of the meningeal cells and suggest a trophic dependence of CR cells upon meningeal cells.

Animals↗
PubMed2003

Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis.

To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of both pro- and mature IL-18 in brain tissue in WT mice. IL-18(-/-) and WT mice were equally susceptible to develop meningitis after intranasal infection, yet IL-18(-/-) mice showed a prolonged survival and a suppressed inflammatory response, as reflected by a less profound inflammatory infiltrate around the meninges and lower concentrations of cytokines and chemokines in brain tissue. These findings suggest that endogenous IL-18 contributes to a detrimental inflammatory response during pneumococcal meningitis and that elimination of IL-18 may improve the outcome of this disease.

Adjuvants, Immunologic↗
PubMed1985

Progressive hearing loss following Haemophilus influenzae meningitis.

Loss of hearing is a sequelae of meningitis. This hearing loss has been known to fluctuate for as long as one year following the acute infection. This paper presents a case of an 11-year documented downward fluctuating hearing loss following Haemophilus influenzae meningitis. The case indicates that patients should be followed audiologically for years following meningitis. A review of the literature of hearing loss in meningitis is presented with special emphasis on cases in which the hearing loss fluctuated. The cases in the literature were usually not followed for more than one year. In this case of acquired hearing loss secondary to Haemophilus influenzae meningitis, the patient's hearing fluctuated over 11 years, in a downward progression. It is not clear what type of mechanism is involved in the ongoing damage to the cochlea that could account for this gradual fluctuation. It is suggested that as the possibility of long-term fluctuation exists, patients with meningitis should be monitored audiologically for many years.

Auditory Threshold↗
PubMed1997

Meningeal cells are targets and inactivation sites for the neuropeptide somatostatin.

Transcripts of the somatostatin receptor subtypes sst3 and sst2 are expressed in meninges from rat brain as well as in immunocytochemical pure rat meningeal cells and rat fibroblasts in culture. mRNA of three other subtypes tested are absent or detected in trace amounts by reverse transcription-polymerase chain reaction. Presence of active receptors on the surface of meningeal cells and fibroblasts could be verified by direct visualisation of binding sites by affinity labelling with a somatostatin gold conjugate. The metabolically stable somatostatin agonist SMS 201-995 (octreotide) had a time-dependent effect on the [3H]thymidine incorporation by meningeal cells: after 2-5 h, the agonist inhibited cell proliferation to about 80% of controls, after 24 h proliferation was stimulated to about 150% of controls. Apart from being targets for somatostatin, meningeal cells had a high capacity to inactivate the peptide by proteolytic degradation. By analysis of cleavage sites and use of specific inhibitors, endopeptidase-24.11 ('enkephalinase', neutral endopeptidase, neprilysin, EC 3.4.24.11) was identified to be responsible for the initial catabolism of the peptide whereas aminopeptidase(s) truncated the fragments. Thus, meningeal cells express transcripts of multiple somatostatin receptor subtypes and produce peptidases that inactivate the neuropeptide somatostatin.

Animals↗
PubMed2000

Central origin of IL-1beta produced during peripheral inflammation: role of meninges.

Brain expression of Interleukin-1beta (IL-1beta) and its modulation have been extensively documented in different animal models. The majority of the studies were based on techniques such as RT-PCR, RIA and ELISA using global extracts. Meningeal tissue or choroid plexus both belong to the peripheral compartment. Thus, their presence in nervous tissue extracts may lead to erroneous interpretations. We measured IL-1beta mRNA in the cerebellum, hippocampus and cerebral cortex collected with meninges and in the same structures collected without meninges after a peripheral lipopolysaccharide (LPS) stimulation (0.5 microgram/g body weight), using RT-PCR. The presence of meninges in the extracts dramatically increased IL-1beta mRNA levels after LPS treatment while basal levels (before LPS injection) were not affected. Indeed, two-thirds of the response originated from the meningeal tissue and choroid plexus. Immunohistochemical studies showed that IL-1beta labelled cells, identified as macrophages, were exclusively localized in the ventricular and meningeal spaces, in our LPS condition treatment. These results point out the need of integrated analyses of data obtained with different techniques to demonstrate the presence in the nervous tissue of a molecule which is also widely expressed in the peripheral compartment.

Animals↗
PubMed1992

Pediatric bacterial meningitis: is prior antibiotic therapy associated with an altered clinical presentation?

STUDY HYPOTHESIS: The clinical features of children treated with oral antibiotics before the diagnosis of bacterial meningitis differ from those who receive no antibiotics. DESIGN: Retrospective case series. SETTING: University medical center. PARTICIPANTS: Two hundred fifty-eight children 24 months old or younger with bacterial meningitis hospitalized during a 12-year period. Eighty-three children were treated with oral antibiotics before the diagnosis of meningitis, and 175 children were not. INTERVENTIONS: None. METHODS: The emergency department chart and hospital records were reviewed for presenting demographic, historical, physical examination, and laboratory features. Clinical features of pretreated and untreated patients were compared. RESULTS: Pretreated children demonstrated less frequent temperature of 38.3 C or higher, altered mental status and a longer duration of symptoms before diagnosis, with more frequent vomiting; ear, nose, and throat infections; and physician visits in the week before detection of meningitis (P less than .05 for all comparisons). There was no difference in incidence of upper respiratory symptoms, seizures, nuchal rigidity, Kernig's and Brudzinski's signs, focal neurologic signs, mortality, and length of hospitalization between groups. CONCLUSION: Clinical features of children who have taken antibiotics before the detection of meningitis differ significantly from those who have not undergone antibiotic therapy. Physicians should be aware of these differences when evaluating young children on antibiotics for the possibility of meningitis.

Anti-Bacterial Agents↗
PubMed1998

Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis.

During meningitis, the host produces a plethora of signaling agents as part of a coordinated defense mechanism against invading pathogens. Nitric oxide (NO) and prostaglandin E2 (PGE2) are two such inflammatory mediators produced in response to bacterial endotoxins. Disruption of the blood-brain barrier (BBB) is one of many pathophysiological consequences of meningitis. The present objective was to examine the time-course of NO and PGE2 production in relationship to BBB permeability alterations during experimentally-induced meningitis. Meningeal inflammation was elicited by intracisternal administration of the bacterial endotoxin, lipopolysaccharides (LPS; 200 microg), and NO, PGE2, and BBB integrity were monitored over the next 24 h. Meningeal NO production was assessed by headspace chemiluminescence; cerebrospinal fluid PGE2 was determined by enzyme-linked immunosorbent assay (ELISA) immunoassay; and BBB integrity was determined by the brain accumulation of 14C-sucrose. Similar time-course profiles for NO and PGE2 were observed, with a peak effect for both inflammatory mediators observed within 6-8 h after intracisternal LPS dosing. Statistically significant (p < 0.05) disruption of the BBB was observed in various brain regions. Strikingly similar temporal relationships were observed for NO and PGE2 production and BBB disruption. These results suggest the hypothesis that NO and PGE2 may act in conjunction to disrupt the BBB during experimental meningitis.

Animals↗
PubMed1998

Haemophilus influenzae meningitis in adults.

Haemophilus influenzae meningitis is rare in adults. We reviewed the microbiological records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted to Chang Gung Memorial Hospital from January 1978 to May 1996. Haemophilus influenzae meningitis was found in six adult patients, accounting for 1.8% of 326 bacteriologically proven adult cases of meningitis diagnosed between January 1984 and May 1996. Predisposing conditions included head trauma and/or neurosurgical procedure in four patients and an extracranial extension of a pituitary adenoma in a diabetic patient. None of them had altered consciousness on the day of treatment. A CSF cell count less than 500 x 10(6) leukocytes/liter was noted in three patients. Antibiotic therapy was successful in all patients. Thus, predisposing conditions, particularly head trauma and/or neurosurgical procedure, are commonly present in adult patients with H. influenzae meningitis. Patients with the infection may have a low cellular count in the CSF that may be readily misinterpreted as meningitis caused by other pathogens.

Adult↗
PubMed2000

[Meningitis and interferon-alpha in the cereprospinal fluid. What diagnostic and therapeutic approach? A case report].

BACKGROUND: In meningitis without germs, the existence of an inflammatory syndrome leads toward a bacterial etiology while the detection of interferon-alpha (IFN-alpha) in the cerebrospinal fluid (CSF) argues for a viral meningitis. The coexistence of the inflammatory syndrome and the presence of IFN-alpha in the CSF makes this differentiation difficult. The reported case yields the picture and begs the question on the diagnostic approach and the required therapeutic attitude. CASE REPORT: A six-week-old infant, exclusively breast-fed, was hospitalized for fever. The examination showed an important inflammatory syndrome and meningeal attempt with a cellularity at 94/mm3 with 53% polymorphonuclear neutrophils, contrasting with normal proteinorrhachia and glycorrhachia. The IFN-alpha in the CSF was present at 4 UI/mL while the bacteriological culture and the viral search by PCR were negative. The clinical and biological worsening within the first 36 hours, in spite of the parenteral dispensation of a triple antibiotic therapy (amoxicillin, ceftriaxone, netilmicin), then a favorable clinical and biological response after adjunction of vancomycin, led toward a pneumococcal meningitis with reduced sensitivity to beta-lactams. The maternal antibiotic therapy by amoxicillin and its presence in the maternal milk favored the hypothesis of a decapitated bacterial meningitis. CONCLUSION: In the presence of a meningitis without germs, the coexistence of a sizable inflammatory syndrome and the detection of IFN-alpha in the CSF must be considered as an unusual phenomenon and motivate the pursuit of antibiotic therapy until viral identification.

Amoxicillin↗
PubMed1997

[Role of corticoids in purulent meningitis in children: analysis of literature studies].

Steroid therapy, in combination with antibiotics for bacterial meningitis in paediatric patients remains controversial. Steroids, and primarily dexamethasone a very potent anti-inflammatory agent, regulate the liberation of various cytokines and inflammatory mediators such as prostaglandins, released during bacterial meningitis and leading to long term complications. Several clinical trials studying infants and children with bacterial meningitis due to Haemophilus influenzae have evaluated the beneficial effects of the administration of dexamethasone at the onset of antibiotherapy and demonstrated that dexamethasone reduced the risk of acquired sensorineural deafness (bilateral moderate or more severe hearing loss) and the incidence of neurological sequelae. Limited information is available for the other bacterial meningitis, although meningococcal meningitis will become more frequent with the use of effective anti-Haemophilus vaccines. In addition some Streptococcus pneumoniae are now resistant to third generation cephalosporins and the use of dexamethasone in that case may be at risk. Finally, no evidence is available for an effective role for dexamethasone in neonatal bacterial meningitis, although it is quite often administered in that age group.

Anti-Inflammatory Agents↗
PubMed2004

Etiology, antimicrobial susceptibility profiles, and mortality associated with bacterial meningitis among children in Egypt.

PURPOSE: Surveillance for patients with meningitis is a high priority in order to determine the etiology of disease and design prevention strategies. This study presents data on the causes of bacterial meningitis among children <6 years of age treated in a network of hospitals throughout Egypt. METHODS: Training was provided to standardize the collection of clinical information and optimize recovery of bacterial pathogens. Bacterial isolates were tested for antimicrobial resistance patterns using Kirby Bauer disk diffusion, E-test and/or Beta-lactamase (BL) testing methods. RESULTS: Patients with culture-confirmed bacterial meningitis (228 children<6 years) were identified including 89 (39%) patients with H. influenzae (HI), 68 (30%) with Streptococcus pneumoniae (SP), 30 (13%) with N. meningitidis (NM), 18 (8%) with Mycobacterium tuberculosis (MTB) and 23 (10%) with other bacteria. The overall case fatality ratio was high (24%) and increased among children with TB meningitis (56%). The susceptibility for HI to ampicillin (AMP), chloramphenicol (C) and ceftriaxone (CRO) was 21%, 13%, and 100% respectively. The susceptibility for SP to C and CRO was 79% and 100%, respectively. CONCLUSIONS: HI and SP are the leading causes of bacterial meningitis among children in Egypt. The majority of HI strains tested were resistant to AMP or C suggesting the need for routine use of CRO as first line therapy. Among older children TB emerges as a significant cause of bacterial meningitis in Egypt.

Age Factors↗