[Non-type b Haemophilus influenzae: a rare cause of meningitis in an infant with a guarded prognosis]. / Méningite à Haemophilus influenzae de type non b chez un nourrisson: cause rare à pronostic réservé.

Non-Type b Haemophilus is a rare cause of invasive secondary localization in young children. We here report the case of a child aged 11 months old who had Meningitis due to Non-Type b Haemophilus, a gram -negative bacilli of polymorphous appearance still exceptionally described in the literature, whose origin was undetermined and whose evolution was fatal. Clinicians and microbiologists should suspect the presence of these infrequent serotypes, especially on a particular case.

Clinical findings and management of patients with meningitis with an emphasis on Haemophilus influenzae meningitis in rural Tanzania.

INTRODUCTION: The spectrum of meningitis pathogens differs depending on the age of patients and the geographic region, amongst other. Although meningitis vaccination programs have led to the reduction of incidence rates, an imbalance between low- and high-income countries still exists. METHODS: In a hospital-based study in rural northern Tanzania, we consecutively recruited patients with confirmed meningitis and described their clinical and laboratory characteristics. RESULTS: A total of 136 patients with meningitis were included. Fever (85%), meningism (63%) and impairment of consciousness (33%) were the most frequent clinical symptoms/signs. Nearly 10% of all patients tested were positive for malaria. The majority of the patients with bacterial meningitis (39%), especially those under 5years of age, were confirmed to be infected with Haemophilus influenzae (26%), Streptococcus pneumoniae (19%) and Neisseria meningitidis (15%). Haemophilus influenzae represented the dominant causative organism in children under 2years of age. CONCLUSION: Our study emphasizes the importance of recognizing warning symptoms like fever, meningism and impairment of consciousness, implementing laboratory tests to determine responsible pathogens and evaluating differential diagnoses in patients with meningitis in sub-Saharan Africa. It also shows that Haemophilus influenza meningitis is still an important cause for meningitis in the young, most probabaly due to lack of appropriate vaccination coverage.

Educational achievement and economic self-sufficiency in adults after childhood bacterial meningitis.

IMPORTANCE: To our knowledge, no previous study has examined functioning in adult life among persons who had bacterial meningitis in childhood. OBJECTIVE: To study educational achievement and economic self-sufficiency in adults diagnosed as having bacterial meningitis in childhood. DESIGN, SETTING, AND PARTICIPANTS: Nationwide population-based cohort study using national registries of Danish-born children diagnosed as having meningococcal, pneumococcal, or Haemophilus influenzae meningitis in the period 1977-2007 (n=2784 patients). Comparison cohorts from the same population individually matched on age and sex were identified, as were siblings of all study participants. End of study period was 2010. MAIN OUTCOMES AND MEASURES: Cumulative incidences of completed vocational education, high school education, higher education, time to first full year of economic self-sufficiency, and receipt of disability pension and differences in these outcomes at age 35 years among meningitis patients, comparison cohorts, and siblings. RESULTS: By age 35 years, among persons who had a history of childhood meningococcal (n=1338), pneumococcal (n=455), and H. influenzae (n=991) meningitis, an estimated 11.0% (41.5% vs 52.5%; 95% CI, 7.3%-14.7%), 10.2% (42.6% vs 52.8%; 95% CI, 3.8%-16.6%), and 5.5% (47.7% vs 53.2%; 95% CI, 1.9%-9.1%) fewer persons, respectively, had completed high school and 7.9% (29.3% vs 37.2%; 95% CI, 1.6%-14.2%), 8.9% (28.1% vs 37.0%; 95% CI, 0.6%-17.2%), and 6.5% (33.5% vs 40.0%; 95% CI, 1.4%-11.6%) fewer had attained a higher education compared with individuals from the comparison cohort. Siblings of meningococcal meningitis patients also had lower educational achievements, while educational achievements of siblings of pneumococcal and H. influenzae meningitis patients did not differ substantially from those in the general population. At end of follow-up, 3.8% (90.3% vs 94.1%; 95% CI, 1.1%-6.5%), 10.6% (84.0% vs 94.6%; 95% CI, 5.1%-16.1%), and 4.3% (90.6% vs 94.9%; 95% CI, 2.0%-6.6%) fewer meningococcal, pneumococcal, and H. influenzae meningitis patients were economically self-sufficient and 1.5% (3.7% vs 2.3%; 95% CI, -0.2% to 3.2%), 8.7% (10.0% vs 1.3%; 95% CI, 5.0%-12.4%), and 3.7% (6.2% vs 2.5%; 95% CI, 1.6%-5.8%) more received disability pension compared with individuals from the comparison cohort. CONCLUSIONS AND RELEVANCE: In a Danish population, bacterial meningitis in childhood was associated with lower educational achievement and economic self-sufficiency in adult life. This association may apply particularly to pneumococcal and H. influenzae meningitis, whereas for meningococcal meningitis the lower educational achievement may be family-related.

Acute bacterial meningitis as the cause of a traffic accident.

This is a report about a traffic accident without an apparent external cause. The driver responsible for the accident was diagnosed with acute bacterial meningitis. From a forensic aspect the meningitis was determined as the underlying reason for the accident, but it could not be assumed that the driver should have recognized the danger in time.

Bacterial profile and clinical outcome of childhood meningitis in rural Yemen: a 2-year hospital-based study.

BACKGROUND: Childhood acute bacterial meningitis (ABM) is an important cause of death and long-term neurological disability in Yemen, the only low income-high mortality country in the Arabian Peninsula. The objective of this study was to document the microbial characteristics, the antibacterial sensitivity pattern, and the outcome for children hospitalized with ABM, prior to the introduction of Haemophilus influenzae type b (Hib) vaccine in Yemen. PATIENTS AND METHODS: The study was retrospective, conducted at a rural district hospital, serving the rural population of the northern parts of Yemen. All patients aged 1 month-15 years admitted between May 1999 and June 2001, with clinical evidence of meningitis and cerebrospinal fluid (CSF) cultured, were included in the study. Clinical information from case notes, including CSF result and the outcome on discharge, were obtained. Analysis of extracted data was performed using Epi Info software. RESULTS: During the 2-year study period, 160 study patients met the inclusion criteria, and 7 (4.4%) were negative for bacterial growth. In the 153 positive cultures there were 46 (30.1%) Streptococcus pneumoniae (SP), 23 (15%) H. influenzae (HI), 81 (52.9) Neisseria meningitidis (NM), 2 (1.3%) Staphylococcus aureus (S. aureus), and 1 (0.7%) Escherichia coli. Sixteen study patients died (overall case fatality rate (CFR) 10%), 7 aged under 12 months, 6 aged 12-60 months, and 3 more than 60 months. Ten deaths were due to SP meningitis, 2 HI meningitis, 3 NM meningitis, and 1 had S. aureus. Of the 144 survivors, 28 (19.4%) developed permanent neurological complications, 17 aged less than 12 months, 6 aged 12-60 months, and 5 more than 60 months. SP meningitis accounted for 57.1% (16/28), and 6 (21.4%) had HI meningitis. Among the 89 aged 1-60 months, 13 died (CFR 14.6%), and 23 (30.3%) of the 76 survivors developed permanent complications. Of those tested 20% and 35% of the 20 HI tested isolates and 9.5% and 14.3% of the 42 SP isolates, were resistant to ampicillin and penicillin G, respectively, and the majority of the 81 NM isolates were sensitive to both. The 3 pathogens were largely resistant to gentamicin, and almost all were susceptible to chloramphenicol and cefotaxime. CONCLUSION: In contrast to the studies from the low-mortality countries of the region, our study showed that the predominant pathogens of childhood ABM were SP and NM. SP meningitis was associated with increased mortality and permanent disability.

Identification of a haem-utilization protein (Hup) in Haemophilus influenzae.

Haemophilus influenzae has an absolute growth requirement for a porphyrin source. This growth requirement can be satisfied in vitro by haem, haemoglobin or the haemoglobin-haptoglobin, haem-haemopexin and haem-albumin complexes. A family of proteins, termed the Hgp proteins, which are essential for utilization of the haemoglobin-haptoglobin complex, has previously been identified. A strain lacking the Hgp proteins also has a residual ability to utilize haemoglobin, indicating that additional moieties contribute to haemoglobin utilization. Using a haemoglobin affinity method an approximately 105 kDa protein was isolated. Mutation of the identified gene in an Hgp null background reduced the ability of the mutant strain to utilize haemoglobin in vitro. The mutation also resulted in a reduced ability to utilize haem, haem-haemopexin, haem-albumin and haemoglobin-haptoglobin, thus identifying a general haem-utilization protein (Hup) in Haemophilus influenzae.

Role of leukocytes in cerebral autoregulation and hyperemia in bacterial meningitis in rabbits.

The effect of leukocytes on regional cerebral blood flow (rCBF) and cerebrovascular autoregulation in experimental meningitis was determined in rabbits. Four groups of animals were studied. Cerebrospinal fluid (CSF) leukocyte migration was prevented in two groups by pretreatment with 1.5 mg/kg of IB4, a monoclonal antibody directed against CD11/18 leukocyte adhesion receptors. Intracisternal inoculation was performed with saline (control and control-IB4 groups) or Haemophilus influenzae type b (Hib and Hib-IB4 groups). Eighteen hours later, rCBF was determined with radiolabeled microspheres. Autoregulation was assessed by graded hemorrhagic hypotension. Compared with untreated meningitis (Hib group), IB4-pretreated meningitis (Hib-IB4 group) was associated with a reduced CSF leukocyte count (1,980 +/- 880 vs. 200 +/- 110 cells/microliter; P < 0.05) and an elevated CSF colony count (2.87 +/- 0.08 vs. 5.63 +/- 0.72 log10colony-forming units/ml; P < 0.05). Compared with control, baseline CBF was elevated in both untreated and IB4-pretreated meningitis (51 +/- 2, 54 +/- 2, 66 +/- 5, and 102 +/- 17 ml.100 g-1.min-1 in control, control-IB4, Hib, and Hib-IB4 groups, respectively). The degree of hyperemia in meningitis was related to the CSF colony count, with a high CBF occurring in animals with high colony counts. During hypotension, CBF remained at or above baseline in the Hib group and both control groups, indicating preservation of cerebrovascular autoregulation in untreated Hib meningitis. In the Hib-IB4 group, the elevated baseline CBF was not maintained during hypotension, falling to 51% of baseline at a cerebral perfusion pressure of 30 mmHg and indicating impairment of cerebrovascular autoregulation. These results suggest that CSF leukocytes are not primarily responsible for the hyperemic response in Hib meningitis. Cerebral hyperemia may be induced either directly by bacterial components or indirectly by components of the inflammatory cascade that precede CSF leukocyte migration.

Audiovestibular and neuropsychological outcome of adults who had recovered from childhood bacterial meningitis.

A sample of 22 subjects was studied from a population of adults who had suffered from bacterial meningitis in childhood. Audiovestibular, oculomotor and neuropsychological investigations were performed and quality of life was assessed. An age-matched control group of 20 subjects was recruited. In the meningitis group, nine subjects had abnormal pure tone audiograms. One was previously undiagnosed and a progression was found in four. There was an overrepresentation of subclinical vestibular pathology (6 out of 9 (67%)) in this group. Audiovestibular test results showed a peripheral pattern and oculomotor tests were normal. The quality of life scores of those with hearing loss were significantly higher than those in the control group. Neuropsychological tests of brain dysfunction were abnormal in six out of 22 (27%) who had recovered from meningitis. The prevalence of such dysfunctions was not related to audiovestibular disorder. The quality of life scores of those with brain dysfunctions were similar to those of the control group. The findings of reduced auditory memory and tone level perception in four out of 22 (18%), suggest that lesions of central auditory pathways may follow from bacterial meningitis. The results support the idea that inner ear damage is the major cause of hearing loss after bacterial meningitis. Despite the absence of brainstem involvement, central nervous system lesions with disturbed auditory processing and language functions can be of significance. The high frequency of discrete brain dysfunctions indicate that a thorough neuropsychological investigation is required after bacterial meningitis.

Hemophilus influenzae type b meningitis: pediatric overview.

The authors valued the incidence and clinical therapeutic aspects of Haemophilus influenzae type b (Hib) meningitis in children. They report a retrospective study, in children, with diagnosis of acute purulent meningitis, from January 1982 to December 1994, aged between 1 month and 14 years. Particular attention was direct to Haemophilus influenzae type b meningitis (20 cases). The incidence rate of Hib meningitis in the overall cases (89) was 22.47% (20), while among children younger than 5 years Hib was the most frequently pathogen isolated (20/58-34.47%). In 1/4 of cases, particularly in children younger than 1 years, exordium was aspecific and unclear. At admission culture and examination of Cerebrospinal Fluid (CFS) have been done. CFS was cultured on blood agar and chocolate plates. A latex agglutination test was used for rapid detection of the bacterial antigens. In some cases we looked for bacterial antigens in urine. 20% of children had complications and 10% had sequelae (1 years of follow-up). We didn't have any dead. Antibiotic treatment was principally with Ampicillin, Cephalosporin and Chloramphenicol. The results of this study confirm the Hib gravity and suggest that the administration of conjugate vaccine against Hib to all living in Italy is justified.

Long-term outcome of Haemophilus influenzae meningitis in Navajo Indian children.

OBJECTIVES: To determine the long-term neurologic, cognitive, and educational outcomes of Navajo children who survived Haemophilus influenzae type b meningitis. DESIGN: Retrospective cohort study, with 3.6- to 15.0-year follow-up. SETTING: Navajo Indian reservation. PARTICIPANTS: Population-based cohort of 76 Navajo children with Haemophilus meningitis at less than 5 years of age between 1975 and 1986, with 41 (54%) consenting to undergo follow-up in 1990. Each case was matched to one nearest-age sibling and one unrelated age-matched control. MAIN OUTCOME MEASURES: Standard intelligence test scores, neurologic abnormalities, and school performance. RESULTS: The mean IQ for cases was lower than that for siblings (79 vs 87, P = .006) or age-matched controls (79 vs 95, P < .001). Twenty-nine percent of cases had severe neurologic sequelae, including mental retardation (24%), severe hearing loss (5%), cerebral palsy (7%), and seizure disorder (12%). Eight percent of siblings (relative risk for cases vs siblings, 8.0; P = .05) and 2% of age-matched controls (relative risk vs cases, 10.0; P = .01) had mental retardation. No siblings or age-matched controls had any other severe neurologic sequela. Twenty-nine percent of cases, 23% of siblings (relative risk, 2.5; P = .45), and 0% of age-matched controls (P = .001) required special education services, while 42% of cases, 23% of siblings (relative risk, 3.3; P = .10), and 11% of age-matched controls (relative risk, 4.0; P = .005) had been retained in a grade in school. CONCLUSIONS: Navajo survivors of Haemophilus meningitis suffer more long-term neurologic, cognitive, and school-related disability than siblings or age-matched controls. They may also suffer higher morbidity than Haemophilus meningitis survivors in the general population.

Cerebrovascular responsiveness to CO2 in Haemophilus influenzae type b meningitis in rabbits.

The effect of experimental meningitis on regional cerebral blood flow (rCBF), cerebral metabolic rate for oxygen (CMRO2), and cerebrovascular responsiveness to CO2 was determined in pentobarbital-anesthetized rabbits. The animals were inoculated intracisternally with saline (control) or log-phase Haemophilus influenzae type b (Hib). Eighteen hours later rCBF was determined with radiolabeled microspheres at normocapnia, hypocapnia, and hypercapnia. Cerebrovascular responses to hypocapnia and hypercapnia were assessed by calculating the change in cerebrovascular resistance per millimeter mercury change in PaCO2. At all CO2 levels, meningitis (M) was associated with elevated CBF compared with control (C: 47.5 +/- 3.0, M: 60.9 +/- 4.5 ml.100 g-1.min-1 at normocapnia, P < 0.01). Regional differences were present. In forebrain, the hyperemia in meningitis was confined to the superficial cortical grey matter. When compared with control, meningitis was not associated with altered vasoreactivity during hypocapnia (C: -0.026 +/- 0.006, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g-1.min-1.mmHg PaCO2(-1)) or hypercapnia (C: -0.037 +/- 0.004, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g.min.mmHg PaCO2(-1)). CMRO2 in meningitis was not significantly different from control (C: 3.53 +/- 0.29, M: 3.51 +/- 0.22 ml O2.100 g-1.min-1). These findings indicate that cerebrovascular responsiveness to CO2 is preserved in experimental Hib meningitis. Furthermore, enhanced CBF together with unchanged CMRO2 indicates that "luxury" cerebral perfusion is present in this model of bacterial meningitis.

Brainstem auditory evoked potentials following meningitis in children.

The report concerns findings for brainstem auditory evoked potentials (BAEPs) recorded in 116 children, aged between a few days and 7 years, having suffered from bacterial meningitis. 26% of cases occurred between birth and 6 months, 55% between 6 months and 2 years, and 19% after 2 years of age. Hemophilus was the most common bacteria (49%), followed by Pneumococcus (22%) and Meningococcus (15%). Neurological complications were found in 30% of the meningitis cases and accounted for 85% of all complications found. 29% of BAEPs were abnormal, of which 47% revealed transmission, 32% endocochlear and 21% retrocochlear impairment. Transmission impairment mainly occurred before the age of 2 years (88%), most frequently in meningococcus meningitis cases (44%), and independently of neurological complications. Retrocochlear impairment was found in association with neurological complications in 71% of cases. Endocochlear BAEP damage was found in 9.5% of cases, half of which were bilateral and total, representing cophosis: it was found at all ages, and without any particular associated neurological complication. Hemophilus was the commonest bacterial agent in endocochlear cases overall, with Pneumococcus underlying 50% of cophosis cases. The study shows BAEP recording in association with a clinical ear examination is useful following childhood bacterial meningitis, screening for definitive endocochlear and deafness, distinguishing total from partial hearing-loss and indicating suitable treatment.

[Value of dexamethasone therapy in bacterial meningitis]. / Stellenwert der Dexamethasontherapie bei der bakteriellen Meningitis.

Due to growing understanding of pathophysiological mechanisms in acute inflammation new strategies for treatment of bacterial meningitis have been developed. The use of dexamethasone as adjunctive therapy for bacterial meningitis during the first 4 days (0.15 mg per kilogram body weight every six hours 30 min before antibiotic treatment for four days) showed a significantly reduce of neurologic sequelae in four clinical studies. A reduction of case fatality rate in more severe cases down to 50% was observed. In regard of these results the American academy of infectious diseases recommends since 1991 for children from the age of 3 month with Haemophilus influenzae meningitis a therapy regime as above.

Haemophilus influenzae type B impairment of pial vessel autoregulation in rats.

To examine the mechanisms of autoregulatory impairment in meningitis, we studied the effects of Haemophilus influenzae type b (Hib) on pial vessels during hemorrhagic hypotension in rats, using a cranial window technique. We prepared cranial windows in barbiturate-anesthetized, mechanically ventilated rats. Artificial cerebrospinal fluid or 10(5) Hib in cerebrospinal fluid (n = 7 each group) was suffused over the pial surface. Pial arteriolar diameter was measured hourly for 4 h. Autoregulation was assessed as the ability of pial arterioles to dilate in response to graded hemorrhagic hypotension at 2 and 4 h. Pial arterioles exposed to Hib dilated progressively to 149 +/- 27% of baseline at 4 h. Vessel diameter in the Hib group was significantly greater than in the control group beginning at 2 h. Autoregulation was progressively impaired in Hib-exposed rats compared with control rats [-5.85 +/- 1.38 versus -8.02 +/- 2.02 and -3.82 +/- 1.57 versus -8.53 +/- 1.72% dilation/kPa fall in mean arterial blood pressure at 2 and 4 h, respectively (p < 0.05)]. These data suggest that autoregulation is impaired in pial arterioles exposed to Hib because involved vessels have a finite dilatory capacity and are close to maximal dilation before hypotensive challenge.

Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat.

In an attempt to understand the role of TNF in the central nervous system (CNS) pathophysiologic events associated with bacterial meningitis, we examined the effect of intravenous vs. intracisternal administration of TNF alpha on penetration of circulating 125I-labeled albumin into cerebrospinal fluid (CSF) and CSF white blood cell (WBC) counts in rats. Intracisternal administration of tumor necrosis factor alpha (TNF-alpha) resulted in dose- and time-dependent alterations of the CSF penetration and CSF WBCs, while intravenous administration of TNF-alpha did not induce any changes. These changes by intracisternal TNF were abolished by heat treatment of TNF or coadministration of MAb to TNF-alpha. Mab to TNF-alpha also significantly reduced the CSF penetration of circulating albumin in experimental hematogenous Haemophilus influenzae type b meningitis in infant rats but this salutary effect required both intravenous and intracisternal administration. However, MAb to TNF-alpha failed to affect CSF pleocytosis in experimental hematogenous meningitis. These findings suggest that some of CNS pathophysiologic changes in bacterial meningitis may be a result of the local production of TNF but other host inflammatory responses may also participate in CNS inflammation in hematogenous bacterial meningitis.