Incorporation of Real-Time PCR into Routine Public Health Surveillance of Culture Negative Bacterial Meningitis in Sao Paulo, Brazil

Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. We validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%-100%) for N. meningitidis, 97.8% (85.5%-99.9%) for S. pneumoniae, and 66.7% (9.4%-99.2%) for H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to routine microbiologic methods increased the yield for detection of S. pneumoniae, N. meningitidis, and H. influenzae cases by 52%, 85%, and 20%, respectively. The main risk factor for being culture negative and RT-PCR positive was presence of antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly sensitive and specific and substantially added to measures of meningitis disease burden when incorporated into routine public health surveillance in Brazil.

Epidemiology of bacterial meningitis among children in Brazil, 1997-1998

OBJECTIVE: To document the incidence and the descriptive epidemiology of bacterial meningitis among individuals under age 20 in a geographically defined region in Brazil during the two-year period immediately preceding the introduction of Haemophilus influenzae type b (Hib) vaccines into the national immunization program of Brazil. METHODS: Population-based epidemiological study of all cases of bacterial meningitis reported among residents of Campinas, Brazil, under age 20 (n=316,570) during the period of 1997-98, using comprehensive surveillance records compiled by the Campinas Health Department from cases reported among hospital inpatients, outpatients, emergency room visits, death certificates, and autopsy reports. RESULTS: The incidence of bacterial meningitis (n=274) was 334.9, 115 and 43.5 cases/10(5) person-years (pys) for residents of Campinas under age 1, 5 and 20, respectively. All cases were hospitalized, with an average length of stay of 12 days. Documented prior antibiotic use was 4.0%. The case-fatality rate of bacterial meningitis in individuals under age 20 was 9% (24/274) with 75% of deaths occurring in children under the age of five. The incidence of Hib meningitis (n=26) was 62.8 and 17 cases/10(5) pys in children age <1 and <5, respectively. CONCLUSIONS: The incidence of Hib meningitis in children under the age of 5 in Campinas during 1997-98 was similar to that reported in the US, Western Europe, and Israel prior to widespread Hib vaccine use in those regions. This study provides a baseline for later studies to evaluate changes in the etiology and incidence of bacterial meningitis in children after introduction of routine Hib vaccination in Brazil.

Epidemiological profile of acute bacterial meningitis in the state of Rio Grande do Norte, Brazil

INTRODUCTION: Acute bacterial meningitis (ABM) remains a public health problem in Brazil. To evaluate the epidemiology of ABM cases at Giselda Trigueiro Hospital, Rio Grande do Norte, a descriptive retrospective survey was conducted covering 2005 to 2008. METHODS: Clinical and laboratory data were collected from the epidemiology department of the hospital and analyzed. RESULTS: Out of 168 ABM cases, 24.4%, 10.7%, and 2.4% were, respectively, caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenza b, and 5.4% by other bacteria. The mean age was 22.48 ± 18.7 years old. CONCLUSIONS: Streptococcus pneumoniae was the main causative pathogen in the young urban population.

Bacterial meningitis and living conditions

INTRODUCTION: Bacterial meningitis has great social relevance due to its ability to produce sequelae and cause death. It is most frequently found in developing countries, especially among children. Meningococcal meningitis occurs at a high frequency in populations with poor living conditions. This study describes the temporal evolution of bacterial meningitis in Salvador, Brazil, 1995-2009, and verifies the association between its spatial variation and the living conditions of the population. METHODS: This was an ecological study in which the areas of information were classified by an index of living conditions. It examined fluctuations using a trend curve, and the relationship between this index and the spatial distribution of meningitis was verified using simple linear regression. RESULTS: From 1995-2009, there were 3,456 confirmed cases of bacterial meningitis in Salvador. We observed a downward trend during this period, with a yearly incidence of 9.1 cases/100,000 population and fatality of 16.7%. Children aged <5 years old and male were more affected. There was no significant spatial autocorrelation or pattern in the spatial distribution of the disease. The areas with the worst living conditions had higher fatality from meningococcal disease (β = 0.0078117, p < 0.005). CONCLUSIONS: Bacterial meningitis reaches all social strata; however, areas with poor living conditions have a greater proportion of cases that progress to death. This finding reflects the difficulties for ready access and poor quality of medical care faced by these populations.

Report of the Working Group on Bacterial Meningitis and Related Conditions

Meningococcal disease is a serious condition with high morbidity and significant mortality. The Department of Health and Children’s Working Group on Bacterial Meningitis and Related Conditions has monitored the epidemiology of Meningococcal disease and in 1997, in its first report, proposed strategies to prevent this infection and its complications. This report has been reviewed and updated and a second report issued in July 1999. This Report describes the epidemiology of Meningococcal disease and includes practical guidance in relation to the management of clusters and chemoprophylaxis. The Report also includes guidelines in relation to the hospital based management of suspected Meningococcal Sepsis/Meningitis and which can be adapted depending on local circumstances Download the Report here

The utility of the polymerase chain reaction assay for aetiologic definition of unspecified bacterial meningitis cases

Most patients with acute suppurative meningitis are otherwise healthy individuals with regard to immune mechanisms against invasive bacterial disease. This medical emergency is among the most dramatic and potentially ravaging diseases that affect humans, particularly young children. The illness often strikes suddenly, and can either result in death or leave the survivors with significant neurological dysfunctions. The demonstration of a bacterial aetiology is necessary for decisions regarding treatment and prophylaxis. Conventional bacteriological methods frequently fail to identify an agent, as a result of administration of antibiotics or delayed lumbar punctures. We investigated the major aetiologic sources of unspecified bacterial meningitis cases (G00.9, ISCD-10) by polymerase chain reaction (PCR)-based identification of Neisseria meningitidis (crgA), Streptococcus pneumoniae (ply) and Haemophilus influenzae (bexA) in cerebrospinal fluid samples. The multiplex PCR detected N. meningitidis in 92%, S. pneumoniae in 4% and H. influenzae in 1% of the 192 clinical samples assayed; 3% were negative for all three DNA targets. Bacterial DNA detection was found to be a valuable adjunct to enhance bacterial meningitis surveillance when the yield of specimens by culture is reduced. The implementation of PCR assays as a diagnostic procedure in Public Health Laboratories is perceived to be a significant advance in the investigation of bacterial meningitis.

CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

Effectiveness of the association of dexamethasone with antibiotic therapy in pediatric patients with bacterial meningitis

Effectiveness of the association of dexamethasone with antibiotic therapy in pediatric patients with bacterial meningitis Objective: To evaluate the efficacy of the association of corticosteroids and the standard treatment of bacterial meningitis in pediatric patients. Methods: A systematic review of the literature was conducted through the MEDLINE database. Only randomized controlled trials comparing dexamethasone with placebo in the treatment of pediatric patients with bacterial meningitis were included. Results: Eight articles met the inclusion criteria and were selected for analysis. There were no difference in mortality (p = 0.86), and incidence of neurological (p = 0.41) and auditory (p = 0.48) sequelae between the groups. Conclusion: There are no benefits in associating corticosteroids with the standard treatment of bacterial meningitis in pediatric patients.

Bacterial meningitis: current therapy and possible future treatment options

Despite targeted therapy, case-fatality rates and neurologic sequelae of bacterial meningitis remain unacceptably high. The poor outcome is mainly due to secondary systemic and intracranial complications. These complications seem to be both a consequence of the inflammatory response to the invading pathogen and release of bacterial components by the pathogen itself. Therefore, within the last decades, research has focused on the mechanism underlying immune regulation and the inhibition of bacterial lysis in order to identify new targets for adjuvant therapy. The scope of this article is to give an overview on current treatment strategies of bacterial meningitis, to summarize new insights on the pathophysiology of bacterial meningitis, and to give an outlook on new treatment strategies derived from experimental models.

Bacterial meningitis impairs hippocampal neurogenesis

Bacterial meningitis causes persisting neurofunctional sequelae. Theoccurrence of apoptotic cell death in the hippocampal subgranular zone of the dentate gyrus characterizes the disease in patients and relates to deficits in learning and memory in corresponding experimental models. Here, we investigated why neurogenesis fails to regenerate the damage in the hippocampus associated with the persistence of neurofunctional deficits. In an infant rat model of bacterial meningitis, the capacity of hippocampal-derived cells to multiply and form neurospheres was significantly impaired comparedto that in uninfected littermates. In an in vitro model of differentiating hippocampal cells, challenges characteristic of bacterial meningitis (i.e. bacterial components, tumor necrosis factor [20 ng/mL], or growth factor deprivation) caused significantly more apoptosis in stem/progenitor cells and immature neurons than in mature neurons. These results demonstrate that bacterial meningitis injures hippocampal stem and progenitor cells, a finding that may explain the persistence of neurofunctional deficits after bacterial meningitis.

The formyl peptide receptor like-1 and scavenger receptor MARCO are involved in glial cell activation in bacterial meningitis

Recent studies have suggested that the scavenger receptor MARCO (macrophage receptor with collagenous structure) mediates activation of the immune response in bacterial infection of the central nervous system (CNS). The chemotactic G-protein-coupled receptor (GPCR) formyl-peptide-receptor like-1 (FPRL1) plays an essential role in the inflammatory responses of host defence mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the antimicrobial peptide cathelicidin CRAMP/LL-37 is up-regulated in bacterial meningitis, but the mechanisms underlying CRAMP expression are far from clear.

Determinants of timely management of acute bacterial meningitis in the ED

PURPOSE: The purpose was to study the emergency management of patients with suspected meningitis to identify potential areas for improvement. METHODS: All patients who underwent cerebrospinal fluid puncture at the emergency department of the University Hospital of Bern from January 31, 2004, to October 30, 2008, were included. A total of 396 patients were included in the study. For each patient, we analyzed the sequence and timing for the following management steps: first contact with medical staff, administration of the first antibiotic dose, lumbar puncture (LP), head imaging, and blood cultures. The results were analyzed in relation to clinical characteristics and the referral diagnosis on admission. RESULTS: Of the 396 patient analyzed, 15 (3.7%) had a discharge diagnosis of bacterial meningitis, 119 (30%) had nonbacterial meningitis, and 262 (66.3%) had no evidence of meningitis. Suspicion of meningitis led to earlier antibiotic therapy than suspicion of an acute cerebral event or nonacute cerebral event (P < .0001). In patients with bacterial meningitis, the average time to antibiotics was 136 minutes, with a range of 0 to 340 minutes. Most patients (60.1%) had brain imaging studies performed before LP. On the other hand, half of the patients with a referral diagnosis of meningitis (50%) received antibiotics before performance of an LP. CONCLUSIONS: Few patients with suspected meningitis received antimicrobial therapy within the first 30 minutes after arrival, but most patients with pneumococcal meningitis and typical symptoms were treated early; patients with bacterial meningitis who received treatment late had complex medical histories or atypical presentations.