Neisseria Meningitidis Meningitis Research Articles

Developing a Novel Murine Meningococcal Meningitis Model Using a Capsule-Null Bacterial Strain.

Neisseria meningitidis (meningococcus) is a Gram-negative bacterium that colonises the nasopharynx of about 10% of the healthy human population. Under certain conditions, it spreads into the body, causing infections with high morbidity and mortality rates. Although the capsule is the key virulence factor, unencapsulated strains have proved to possess significant clinical implications as well. Meningococcal meningitis is a primarily human infection, with limited animal models that are dependent on a variety of parameters such as bacterial virulence and mouse strain. In this study, we aimed to develop a murine Neisseria meningitidis meningitis model to be used in the study of various antimicrobial compounds. We used a capsule-deficient Neisseria meningitidis strain that was thoroughly analysed through various methods. The bacterial strain was incubated for 48 h in brain-heart infusion (BHI) broth before being concentrated and injected intracisternally to bypass the blood-brain barrier in CD-1 mice. This prolonged incubation time was a key factor in increasing the virulence of the bacterial strain. A total of three more differently prepared inoculums were tested to further solidify the importance of the protocol (a 24-h incubated inoculum, a diluted inoculum, and an inactivated inoculum). Antibiotic treatment groups were also established. The clinical parameters and number of deaths were recorded over a period of 5 days, and comatose mice with no chance of recovery were euthanised. The bacterial strain was confirmed to have no capsule but was found to harbour a total of 56 genes coding virulence factors, and its antibiotic susceptibility was established. Meningitis was confirmed through positive tissue culture and histological evaluation, where specific lesions were observed, such as perivascular sheaths with inflammatory infiltrate. In the treatment groups, survival rates were significantly higher (up to 81.25% in one of the treatment groups compared to 18.75% in the control group). We managed to successfully develop a cost-efficient murine (using simple CD-1 mice instead of expensive transgenic mice) meningococcal meningitis model using an unencapsulated strain with a novel method of preparation.

Neisseria meningitidis Meningitis in Burkina Faso: Review of the Literature

Introduction: Neisseria meningitidis meningitis is a permanent threat in Burkina Faso due to its epidemic potential.
 Objective: To study the epidemiological aspects of meningitis caused by Neisseria meningitidis and to identify the main current trends. 
 Patients and Methods: This was a descriptive cross-sectional study with retrospective collection of data from the literature on Neisseria meningitidis epidemics in Burkina Faso. 
 Results: Burkina Faso has experienced several epidemics of meningitis caused by Neisseria meningitidis serogroup A. Indeed, the country was hit by epidemics due to this serogroup in 1957, 1985, 1994, 1995, 1996, 1997, 2004, 2005, 2006, 2007, 2008 and 2009. The 1996 epidemic was particularly deadly with 4363 deaths recorded. Neisseria meningitidis serogroup W has also been responsible for several epidemics including those of 1992, 2001, 2002, 2003, and 2012. While Neisseria meningitidis serogroup X was responsible for the first major epidemic in 2010. As for Neisseria meningitidis serogroup C, after a first outbreak in 1979, it was in 2019 that this serogroup was again responsible for an outbreak in eastern Burkina Faso. In all these outbreaks, children were the most affected and case fatality was high (more than 14%). In addition to the therapeutic management of cases, a vaccine response was used to contain these epidemics. The vaccines used were initially polysaccharide vaccines (meningococcal A+C vaccine, tetravalent A+C+Y+W vaccine), and since 2010, the MenAfriVac® conjugate vaccine, which has eliminated epidemics due to meningococcus (Nm) A. However, it is noted that other Neisseria meningitidis serogroups (X,C,W) continue to circulate. Epidemiological surveillance data showed a clear decline in Neisseria meningitidis in week 48 of 2022, behind Streptococcus pneumoniae which has become the leading cause of bacterial meningitis in Burkina Faso. The same trend has been observed since the mass vaccination campaign with the MenAfriVac® conjugate vaccine.
 Conclusion: The persistent circulation of Neisseria meningitidis serogroups W, X, and C raises concerns about further meningitis epidemics. It is important to maintain a high level of epidemiological surveillance of Neisseria meningitidis in Burkina Faso.

Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017.

The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) ≤ 0.06mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. Retrospective study of all culture positive IMD in adult patients (age ≥ 15years) in the Auckland region from 2004 to 2017. One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.

Adjuvants Derived from <i>Neisseria meningitidis</i> Serogroup B Induce a Cross Reactive Response against <i>Neisseria gonorrhoeae</i> in Mice

Introduction: Neisseria is a large genus of bacteria that colonize mucosal surfaces. Of the 11 species that colonize humans, only two are pathogens, N. meningitidis and N. gonorrhoeae. Both are obligate human pathogens; the last is causal agent of gonorrhea disease. Although curable with timely antibiotic treatment, an annual incidence of more than 62 million cases is estimated by the World Health Organization and there are no successful vaccines available. In contrast, several prophylactic vaccine options for Neisseria meningitidis meningitis do exist. Of note, there is trace of cross parenteral response induced between N. meningitidis and N. gonorrhoeae, and Proteoliposome (PL, also named outer membrane vesicles, OMV) vaccine has shown high impact on this response. Objective: To determine effect of VAMENGOC-BC? and its derivates (AFPL1 and AFCo1) at mucosal and systemic level and possible cross response against Neisseria gonhorroeae in Balb/c and C57Bl/6 mice. Methods: We evaluated cross response against N. gonorrhoeae in mouse serum IgG and saliva IgA after mucosal immunization with VA-MENGOC-BC or its derivatives (AF, Adjuvant Finlay PL1 or AFCo (cochleate) 1). Results: Immunizations with AFPL1 or AFCo1 induce anti N. gonorrhoeae at saliva IgA and serum IgG responses similar to VA-MENGOC-BC? vaccine. Conclusions: Such data confirms a new possible window of prime-boost vaccination strategy against gonorrhea and extends our knowledge regarding the effect of PL vaccines on cross responses.

Long-term health and socioeconomic consequences of childhood and adolescent onset of meningococcal meningitis.

We estimated the long-term socioeconomic consequences and health care costs of Neisseria meningitidis meningitis (NM). The prospective cohort study included Danish individuals with onset of NM in childhood and adolescence, diagnosed between 1980 and 2009. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. Two thousand nine hundred two patients were compared with 11,610 controls matched for age, gender, and other sociodemographic characteristics. In the follow-up analysis at the age of 30years, 1028 patients were compared with 4452 controls. We found that (1) NM caused increased mortality at disease onset, but after adequate treatment, the mortality rate was similar to that of the general population; (2) neurological and eye diseases were more frequently observed in patients; (3) patients had significantly lower grade-point averages; (4) patients had lower income even when transfer payments were taken into account; and (5) patients' initial health care costs were elevated.Conclusion: NM has significant influence on mortality, morbidity, education, and income. We suggest that the management of patients with previous meningococcal meningitis should focus on early educational and social interventions to improve social and health outcomes. What is known: • Meningococcal meningitis is a severe infectious disease affecting children and adolescents with high rates of mortality and complications. What is new: • Meningococcal meningitis causes increased mortality at disease onset, but after adequate treatment the mortality rate is similar to that of the general population. • Meningococcal meningitis in childhood and adolescence has a major long-term effect on morbidity, health care costs, education, employment, and income.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection

ObjectivesScreening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. MethodsEligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. ResultsThe study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. ConclusionPID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.

Infections Revealing Complement Deficiency in Adults

Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.

Rapidly progressive bilateral postmeningitic deafness in children: Diagnosis and management

ObjectivesTo determine the diagnostic approach to severe or profound bilateral postmeningitic deafness and to propose management guidelines. Material and methodsA retrospective review of five patients (two adolescents and three infants) with rapidly progressive severe bilateral deafness following an episode of meningitis managed between 2004 and 2010. ResultsThe two adolescents presented Neisseria meningitidis meningitis and the three infants presented Streptococcus pneumoniae meningitis. Acquired bilateral deafness was diagnosed by audiometry an average of 68.8 days (range: 9–210) after the episode of meningitis. Behavioural audiological testing, adapted to age and state of health, was performed in all patients. Deafness was confirmed by Auditory Brainstem Response tests. All five patients were assessed by computed tomography (CT) and magnetic resonance imaging (MRI) within ten days. T2-weighted MRI sequences showed endolymph changes in four patients. CT scan demonstrated ossification in only one patient. Bilateral cochlear implant was performed in all patients, with complete electrode array insertion for eight implants and partial insertion for two implants (20 and 21 out of 22 electrodes inserted). Good results were obtained with cochlear implants in four cases. ConclusionsBilateral deafness can occur immediately or several months after bacterial meningitis, regardless of the micro-organism responsible, justifying screening by behavioural audiological testing adapted to age for two years following bacterial meningitis. Auditory Brainstem Response testing can confirm audiometric findings. When severe or profound bilateral deafness is observed, MRI must be performed urgently to detect endolymph inflammation or ossification. Early bilateral cochlear implantation is recommended in the presence of ossification.

Meningitis resulting in hearing loss and labyrinthitis ossificans — does the causative organism matter?

Our aim was to demonstrate whether one causative agent of meningitis is more likely to cause profound hearing loss and labyrinthitis ossificans. We obtained data from the New South Wales health department for cases of meningitis between 1995 and 2005 (1568 cases) and the Sydney Cochlear Implant Centre for cochlear implant patients with hearing loss secondary to meningitis from 1984 to 2005 (70 ears in 59 patients). The aetiological agents were compared with regard to their ability to cause profound hearing loss and cochlear ossification. Neisseria meningitidis resulted in 56.9% of cases of meningitis and 11.4% of the cases of profound hearing loss resulting in cochlear implantation (incidence of profound hearing loss of 0.4%). Streptococcus pneumoniae, however, caused 41.1% of meningitis but 85.7% of cochlear implantation (incidence of 4.6%). Labyrinthitis ossificans was more common after infection with Streptococcus pneumoniae but there was no statistically significant difference between Streptococcus pneumoniae, Haemophilus influenzae or Neisseria meningitidis for labyrinthitis ossificans (p = 0.45, chi-squared test). In conclusion Neisseria meningitidis meningitis carries a very low risk of profound hearing loss but Streptococcus pneumoniae meningitis a significantly higher risk. Copyright © 2008 John Wiley & Sons, Ltd.

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

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. 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. 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. 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.

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.

Dexamethasone Therapy for Bacterial Meningitis in Infants and Children

BACKGROUND Bacterial meningitis affects an estimated 15 000 infants and children in the United States each year. The case-fatality rates for these patients are from 5% to 10%; as many as 20% to 30% of survivors have long-term sequelae, the most common of which is hearing impairment.1 The reported incidence of hearing loss after meningitis has ranged from 5% to 20% of patients, depending on the selection of patients, techniques used to assess hearing, and etiology.2-5 In 1972 to 1977, Dodge and co-workers2 documented hearing loss in 31% of patients with Streptococcus pneumoniae meningitis, 10% with Neisseria meningitidis meningitis, and 6% with Haemophilus influenzae meningitis. Bilateral sensorineural hearing impairment occurred in 14%, 10%, and 3%, respectively. Newer antimicrobial agents with superior bactericidal activity in cerebrospinal fluid have not reduced morbidity and case-fatality rates compared with conventional therapy. The pathophysiologic events believed to contribute to adverse outcome from bacterial meningitis include alteration of cerebral capillary endothelial cells that comprise the blood-brain barrier, cytotoxic and vasogenic cerebral edema, and increased intracranial pressure.6 These events can lead to decreased cerebral perfusion pressure with a resultant diminution in cerebral blood flow causing regional hypoxia and focal ischemia of brain tissue. Because of its anti-inflammatory effects, corticosteroid therapy has been evaluated in experimental meningitis and in infants and children with meningitis. Dexamethasone produced significant reductions in intracranial pressure, brain edema, and lactate concentrations in cerebrospinal fluid in experimental H influenzae and S pneumoniae meningitis.7,8 In addition, the administration of dexamethasone was associated with decreased concentrations of prostaglandin E2 in cerebrospinal fluid and lowered mortality and clinically evident neurologic sequelae in rabbits with experimental pneumococcal meningitis.9

Poor performance of BACTEC NR 730 blood culture system in early detection of Neisseria meningitidis

During an 8-month period at Children's Hospital, Oakland, Calif., a 9% rate for positive blood culture for children with Neisseria meningitidis meningitis was identified. The blood culture system used in each case was the BACTEC NR 730. This rate seemed significantly lower than previous rates (33 to 55%) (P.R. Dodge and M.N. Swartz, N. Engl. J. Med. 272:1003-1010, 1965; A.L. Hoyne and R.H. Brown, Ann. Intern. Med. 28:248-259, 1948; S. Levin and M.B. Painter, Ann. Intern. Med. 64:1049-1057, 1966). The low rate prompted our study. With 14 test strains, anaerobic and aerobic BACTEC bottles were evaluated for their ability to support and detect the growth of N. meningitidis. Sodium polyanetholesufonate (SPS) and inoculum size, two factors thought to affect the growth of N. meningitidis, were controlled for by use of bottles with and without SPS and by inoculum sizes simulating the magnitudes of bacteremia previously described for children infected with N. meningitidis (L.J. La Scolea, Jr., D. Dryja, T.D. Sullivan, L. Mosovich, N. Ellerstein, and E. Neter, J. Clin. Microbiol. 13:478-482, 1981). BACTEC failed to detect growth in aerobic bottles after 6 h of incubation, while 76 of 80 bottles (95%) showed growth when subcultured. At 24 h, BACTEC detected growth in only 29 of 80 bottles (36%); when subcultured, all 80 cultures grew confluently. At 48 h, BACTEC detected growth in the remaining 53 bottles. BACTEC failed to detect growth in anaerobic bottles at 6 h and at 1, 2, 4, and 5 days of incubation despite growth in subculture. Subcultures from bottles with tryptic soy broth with and without SPS showed growth in 63 to 76 bottles in 6 h and in all bottles after 24 h. The presence of SPS in BACTEC bottles had no effect on growth detection. On the basis of these studies and our clinical experience, we find the NR 730 system to be insensitive and unsuitable for detection of N.meningitidis in </= 24h. However, all test strains were detected after 48h.

Blood-monocyte functions in acute bacterial meningitis.

The blood-monocyte chemotactic, phagocytic and microbicidal activities were studied in 20 patients with acute bacterial meningitis. The cell functions were measured on admission, during treatment and after clinical recovery. In general, monocyte functions were within normal range on admission. However, in 2/2 patients with Neisseria meningitidis meningitis, complicated by disseminated intravascular coagulation, defective chemotaxis was observed. Other patients had normal or enhanced monocyte chemotaxis. Two patients died: one had normal monocyte functions, one had initially defective chemotaxis and microbicidal activity. During treatment, cell functions normalized and after recovery all but one patient had a normal blood-monocyte function profile. In conclusion, acute bacterial meningitis is not due to, or followed by, abnormal nonspecific functions of blood monocytes. However, development of disseminated intravascular coagulation is associated with depressed chemotactic responsiveness.