Clinical Meningitis Research Articles

Situación de las Enfermedades de Declaración Obligatoria (EDO) en Navarra, 2004

Epidemiological surveillance in Navarre (584,734 inhabitants) covers 34 transmissible diseases, whose notification is compulsory, and epidemic outbreaks of any aetiology. Notification is carried out on a weekly basis by the doctors from paediatrics, primary care and specialised care. In 2004, 75.8% of all the possible notification reports (a weekly report for each doctor) were received, a percentage that has improved in the last five year period. Flu only reached 14.4 cases per 1,000 inhabitants (Epidemic Index, EI: 0.30), due to the advance of the epidemic peak for the 2003-2004 season to the month of November. The rate of respiratory tuberculosis fell to 11.6 cases per 100,000 inhabitants, and the rate of non-respiratory tuberculosis rose to 2.7 per 100,000. Ten cases of tuberculosis (11.9%) were grouped into four outbreaks that affected adolescents and young adults. Thirty percent of the cases were produced in immigrants and 4.8% in persons coinfected with HIV, proportions that are similar to those of the previous year. Eleven cases of meningococcal disease were reported, (1.9 cases per 100,000 inhabitants; EI 0.73), but only in 8 cases was the clinical form sepsis and/or meningitis. Neisseria meningitidis serogroup B was isolated in 8 cases, and serogroup C in 2 cases, the latter 2 were adults and were not vaccinated. The incidence of immunopreventable diseases continues to fall, and for the fifth consecutive year no case of measles has been reported. Legionnaire's disease, which is detected through the systematic determination of the antigen in urine, rose to 5.8 cases per 100,000 inhabitants (EI: 1.42), without any epidemiological relation between them. The incidence of imported diseases rose, with 12 cases of malaria, 8 of shigellosis, 5 of hepatitis A and 2 of legionnaire's disease acquired outside Spain.

Meningitis urliana: casuística en un servicio de Neurología

Parotiditis is a viral infection that produces a non-suppurative inflammation of the parotid glands, although it may affect other salivary glands, the testicles, meninges and the pancreas. Clinical meningitis appears in 1-10% of cases, normally between the 4th and the 10th day after infection of the parotid glands. In this study, we analyse the clinical and analytic characteristics of the patients admitted to our Neurology Department over the last 12 years. A retrospective study was conducted by analysing the hospital discharge reports. The eligibility criterion was the existence of an acute meningeal syndrome linked to the presence of positive IgM titres for the parotiditis virus. In all, 13 cases were found, with a mean age of 16.5 years, and most of them were males (92.3%). Parotiditis preceded meningitis in all our patients with an average of 8.3 days, while orchiepididymitis, when it occurred, appeared at the same time or after meningitis. Analysis of the cerebrospinal fluid showed a lymphocyte profile with glycorrhachia above 40%, except in two cases that showed a non-persistent neutrophilic profile. There was a transient 30.7% reduction in prothrombin time in the patients. No sequelae were observed. Vaccination campaigns have drastically reduced the number of cases of meningitis due to this germ since the second half of the 90s. This virus must be borne in mind in cases of meningitis in young males who come from underdeveloped countries.

The Many Faces of Meningococcal Disease

We present 3 cases of Neisseria meningitidis with varied clinical presentations, including meningococcemia, meningitis, and pneumonia. Our cases suggest an association between concomitant bacterial and viral infections, including group A streptococcus and adenovirus, and an increased risk of invasive Neisseria infections. PCR data are a useful adjunct to bacterial cultures for the diagnosis. Our case series exemplify the continued high mortality of N. meningitides and highlights the need for more immunogenic vaccines for prevention.

Differences in survival, brain damage, and cerebrospinal fluid cytokine kinetics due to meningitis caused by 3 different Streptococcus pneumoniae serotypes: evaluation in humans and in 2 experimental models.

Experimental meningitis with Streptococcus pneumoniae serotypes 1, 3, and 9 has resulted in pronounced differences in disease severity, but clinical meningitis studies addressing serotype-related differences in case-fatality rates are lacking. Study subjects were Danish patients with pneumococcal meningitis due to serotype 1 (n=38), 3 (n=69), or 9V (n=59) during 1990-2002 for whom clinical information was available. The 3 serotypes were tested for brain damage and cerebrospinal fluid (CSF) inflammatory kinetics in 2 experimental models of meningitis. Patients with serotype 1 had a significantly lower case-fatality rate (3%), compared with patients with serotypes 3 (23%) and 9V (32%) (P=.0047, log-rank test). Age and serotype were independent prognostic factors for fatal outcome. In experimental meningitis, the median number of areas per brain slide with brain damage was significantly lower in rats infected with serotype 1 than in rats infected with serotypes 3 and 9V. Three distinct patterns of brain damage were observed: serotype 1, cortical hemorrhage; serotype 3, cortical necrosis and abscess formation; and serotype 9V, subcortical (callosal) abscess formation. Serotype 1 caused the poorest bacterial growth and lowest CSF levels of white blood cells, tumor necrosis factor- alpha, and interleukin-8 (P<.05). Case-fatality rates of patients with pneumococcal meningitis, the degree and pattern of brain damage, and CSF cytochemical alterations in experimental pneumococcal meningitis differ according to serotype.

Investigation of Listeria monocytogenes contamination pattern in local Chinese food market and the tracing of two clinical isolates by RAPD analysis

This study was undertaken to investigate the contamination pattern of Listeria monocytogenes in local Chinese food markets and to trace two clinical isolates. Random amplification polymorphic DNA (RAPD) was developed to track the source of L. monocytogenes in ready-to-eat (RTE) food products and from clinical origin. Three random primers, PB1, PB4 and HLWL74, were used to subtype all the L. monocytogenes strains isolated from RTE food products, fresh food products, environmental sewages in the markets and two clinical meningitis patients. It was shown that all the 49 isolates could be classified into 5, 4 and 4 types using these three random primers, PB1, PB4, and HLWL74, respectively. Twenty-seven composite profiles were identified by a combination of the three primers. The same composite profiles of L. monocytogenes could be found both in the fresh food products, environmental sewages and RTE food products, suggesting that the L. monocytogenes in the RTE food products may come from those in the fresh food products or sewage in the same market. The composite profiles of the two clinical isolates were the same as those of strains isolated from RTE food products, indicating that the disease might have resulted from the consumption of the RTE food products contaminated with L. monocytogenes. The results show that RAPD could be a powerful tool for the investigation of contamination pattern of L. monocytogenes in Chinese food markets and also for tracking the source of L. monocytogenes in clinical patients.

Improving the bacteriological diagnosis of tuberculous meningitis.

We made a bacteriological diagnosis of tuberculous meningitis in 107 of 132 (81%) adults with clinical tuberculous meningitis: acid-fast bacilli were seen in 77 of 132 (58%) and cultured from 94 of 132 (71%). Volume of cerebrospinal fluid, duration of symptoms, cerebrospinal fluid neutrophils, lactate, and glucose were all independently associated with bacteriological confirmation.

Variation in Toll-like receptor 4 and susceptibility to group A meningococcal meningitis in Gambian children.

Meningitis is an important cause of childhood mortality in sub-Saharan Africa. A case-control study investigating the role of the Toll-like receptor 4 gene in host susceptibility to Group A Neisseria meningitidis meningitis was conducted in 524 Gambian children. There was no association between a functional Toll-like receptor 4 gene polymorphism and meningitis, suggesting that this variant is not a major determinant of disease in this population.

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.

An outbreak of echovirus 13 meningitis in central Israel.

Until recently, echovirus 13 has been a very rare cause of aseptic meningitis. We investigated an outbreak of echovirus 13 in central Israel during the summer of 2000 using a prospective case control study and a retrospective study. Echovirus 13 was isolated from 79 cerebrospinal fluid (CSF) specimens from different medical centres in central Israel. Patients' ages ranged from 10 days to 41 years (95% < 15 years, M/F ratio 62/38). A total of 128 patients with clinical aseptic meningitis were admitted to the Department of Pediatrics during the outbreak (aged 10 days to 18 years, mean 5.4 years), and 58 CSF samples were processed for viral cultures. Thirty of them did not grow any virus, 26 samples yielded echovirus 13, and 2 samples echovirus 7. The clinical features of patients with echovirus 13 in the CSF were similar to those in whom no virus was isolated or those infected with other enteroviral strains except for higher rate of fever on admission, and prolonged time with fever following the diagnosis in the echovirus 13 patients. CSF cell count varied from 4 to 2,333 cells/mm3 with polymorphonuclears (PMN) predominant in 90% of our patients. In a case-control study there was no significant difference between patients and matched controls with regard to parameters such as: day care attendance, recreation in summer camp, swimming pools and at the beach, and consumption of tap water. All the patients in our series recovered fully with no neurological abnormalities. The illness caused by echovirus 13 was benign and involved mainly patients younger than 15 year of age. Several features that characterized this outbreak include relatively high WBC in the blood and a minent CSF PMN response.

Severe meningococcal disease in childhood

Severe meningococcal disease in childhood

Incidence of invasive Haemophilus influenzae type b infections in Filipino children.

Incidence of invasive Haemophilus influenzae type b infections in Filipino children.

Viral meningitis in child care center staff and parents: an outbreak of echovirus 30 infections.

A report of five cases of viral meningitis among adults with children enrolled in a child care center prompted an investigation of risk factors for viral transmission from children to adult household members. To determine recent echovirus 30 (E30) infections, the authors conducted a serologic survey. To determine risk factors for infection among adult household members, they conducted a retrospective cohort study using written questionnaires. Recent E30 infections were found in 84% of children tested, 57% of adult household members tested, and 47% of staff members tested. Infected adults were more likely than infected children to have clinical meningitis. Among adult household members, changing diapers was a risk factor for recent infection. Women who changed > or = 90 diapers per month had a higher infection rate than women who changed fewer diapers; in contrast, men who changed > or = 90 diapers per month had a lower infection rate than men who changed fewer diapers. Handwashing was protective: there was a negative correlation between handwashing after diaper changes and E30 infection among adults with infected children in diapers. Because child care centers can be a source of enteroviral infections among adult household members, adults with viral meningitis should be questioned about their children's day care or preschool attendance. The importance of handwashing should be stressed to adults with children in day care.

Evaluation of the Neurovirulence Test for Mumps Vaccines

Neurovirulence tests in Macaca fascicularis using commercial preparations of different vaccine bulks and a wild-type strain revealed that the test was unable to distinguish mixed from pure populations or a suitable vaccine from a related strain which has been shown to be associated with clinical meningitis. However, the test was able to distinguish a wild-type strain from the vaccine strains successfully. The ability of the test to discriminate between acceptable and unacceptable seeds requires further examination.

Aetiology and clinical signs of bacterial meningitis in children admitted to Goroka Base Hospital, Papua New Guinea, 1989-1992.

Children aged 1-59 months admitted to Goroka Base Hospital with signs suggestive of meningitis were recruited to determine what proportion of such children have clinical or bacterial meningitis and to investigate the bacterial aetiology. A laboratory classification of definite, probable, possible, indeterminate and no meningitis was established. Thirty per cent of 697 children had a final clinical diagnosis of meningitis, 12% had culture-proven bacterial meningitis (case fatality rate 34%) and 10% had probable or possible meningitis. Inability to feed, vomiting, drowsiness, "staring eyes" and haemoglobin < 9 g/dl in addition to the classical signs of meningitis were associated with increased mortality. Isolates from cerebrospinal fluid were 62 pneumococci, 22 Haemophilus influenzae type b (Hib) and one Neisseria meningitidis. Including blood culture-proven and antigen-proven Hib disease, Hib and pneumococci accounted for 44% and 46% of bacterial meningitis, respectively, and 23% of pneumococci were intermediately resistant to penicillin. Inability to feed, bulging fontanelle, convulsions in young children, neck stiffness, fever and "staring eyes" were all independently associated with bacterial meningitis. Conjugate Hib vaccine must be given to infants as early as possible. Conjugate pneumococcal vaccines, maternal immunization with 23-valent vaccine and pneumococcal protein vaccines are under investigation for prevention of pneumococcal disease.

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.

Haemophilus influenzae meningitis in Malaysia

To determine the pattern of postneonatal childhood meningitis in Malaysia. Retrospective cross-sectional study involving five pediatric departments in Malaysia. There were 435 cases of clinical meningitis admitted to the five centers. More than 90% of the patients were <5 years old, and one-half were <6 months of age. The estimated overall incidence of childhood meningitis in the first 5 years of life was 76.7 per 100000 per year. However, of the 435 cases only 71 (16.3%) fulfilled laboratory diagnostic criteria and in only 58 of these was an organism isolated. Nearly one-half (48%) of all bacteriologically proved cases were caused by Haemophilus influenzae type b (Hib). The mortality rate was 12.5% and 21 patients (30%) suffered neurologic sequelae. More than one-half of all cases of culture-positive childhood bacterial meningitis were caused by Hib, although successful isolation of a pathogen occurred in only a small proportion of cases. For this reason the true incidence of Hib meningitis in Malaysia remains unknown. These findings are consistent with previous studies in Malaysia.

Streptococcus pneumoniae bacteremia in children infected with HIV: presentation, course, and outcome.

To examine the presentation, course, and outcome of pneumococcal bacteremia in children infected with human immunodeficiency virus (HIV). A retrospective series of HIV-infected children less than 18 years of age with Streptococcus pneumoniae bacteremia from four urban, tertiary care hospitals was evaluated. The main outcome measures included persistent bacteremia, the development of a focal infection, and death. Seventy-two episodes of pneumococcal bacteremia were identified in 59 patients. Fifty-four first episodes were included; 26/54 were occult. Mean temperature was 39.8 degrees C. In patients with bacteremia, white blood cells (WBCs) > or = 15,000 and > or = 10,000 had sensitivities of 40% and 75%, respectively. At the time of bacteremia, age >3 years old was associated with a lower mean WBC count compared with episodes occurring in patients <3 years old (11.2 vs 16.1, P < 0.05). Patients with occult bacteremia who were discharged with antibiotics (12 i.m., 7 p.o.) were less likely than patients without antibiotic treatment to have persistent bacteremia at a return visit within 72 hours (0/19 vs 2/5, P < 0.05). No patient with occult bacteremia died, progressed to clinical meningitis, or had other sequelae. Two of fifty-four patients died as a result of their first episode of invasive pneumococcal disease. Both patients who died had meningitis and appeared ill on initial presentation. Neither a WBC count > or = 15,000 nor > or = 10,000 is a sensitive indicator of pneumococcal bacteremia in HIV-infected children. Empiric antibiotics are useful to decrease the risk of persistent bacteremia. Children infected with HIV who have occult pneumococcal bacteremia appear to do well with appropriate antibiotics. Patients who are afebrile and well appearing on reevaluation may be safely treated as outpatients.

Epidemiology of invasive pneumococcal infections in infants and young children in Metropolitan Santiago, Chile, a newly industrializing country.

To study the epidemiology of invasive pneumococcal infections in infants and young children in Santiago, Chile, as a representative pediatric population in a newly industrializing country where pneumococcal conjugate vaccines may be used in the future. A 5-year retrospective laboratory-based review (1989 to 1993) was followed by a 3-year prospective laboratory and hospital surveillance study in two of the six health administrative areas of Santiago to detect all hospitalized cases of invasive pneumococcal disease (defined as Streptococcus pneumoniae isolated from blood, cerebrospinal fluid or another normally sterile site) among infants and children (0 to 23 months of age in the retrospective and 0 to 59 months of age in the prospective study). During the 5-year retrospective survey the incidence of invasive pneumococcal disease was 90.6 cases per 10(5) infants 0 to 11 months old and 18.5 cases per 10(5) toddlers 12 to 23 months old. Similar rates (60.2 per 10(5) infants and 18.1 per 10(5) toddlers) were recorded during the 3 years of prospective surveillance. Among the 110 cases in children 0 to 59 months of age detected during the 3-year prospective surveillance, 2 clinical forms, pneumonia and meningitis, accounted for 87.2% of all cases; 13 of the 49 pneumonia patients (26%) had empyema as a complication. Notably 40 of the 110 cases (36.4%) occurred before 6 months of age (63.4% of the 63 infant cases). Serotypes 1, 14, 5 and 6B were the most prevalent. Overall 76 and 69%, respectively, of S. pneumoniae isolates were antigenic types that would be covered by the 11- or 9-valent conjugate vaccines under development. Invasive pneumococcal infections in Santiago, Chile, exhibit an epidemiologic pattern intermediate between that of developing and industrialized countries. The high burden of disease in early infancy dictates that an accelerated immunization schedule (beginning in the perinatal period) or maternal immunization with pneumococcal vaccines should be explored.

Etiology of bacterial meningitis in a cohort from Salvador, Bahia

Bacterial meningitis remains a very important disease world-wide, mainly during childhood. In order to describe the etiology of bacterial meningitis among some children in Salvador, Bahia-Brazil, we retrospectively reviewed 7000 cerebrospinal fluid exams, performed within the period of September 1988 up to August 1995, at the CSF Laboratory, José Silveira Foundation; 892(12.7%) exams met the inclusion criteria; patients less than 16 years of age and clinical meningitis diagnosis. Among 139 cases of bacterial meningitis, H. influenzae type b (Hib) was the most frequent cause (26.0%), all of the cases in children under 5 years. We have been questioning whether the declining Hib disease trend since 1992 has been associated with the use of Hib conjugate vaccines among those children.

Epidemiología de la meningitis producida por Haemophilus influenzae tipo b, Neisseria meningitidis y Streptococcus pneumoniae en niños de la Comunidad Valenciana, España

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. 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. 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. 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.