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PubMed1969

Human immunity to the meningococcus. II. Development of natural immunity.

Results of the present study suggest that natural immunity to meningococcal disease is initiated, reinforced, and broadened by intermittent carriage of different strains of meningococci throughout life. In young adults, carriage of meningococci in the nasopharynx is an efficient process of immune sensitization. 92% of carriers of serogroup B, C, or Bo meningococci were found to develop increased titers of serum bactericidal activity to their own meningococcal isolate, and 87% developed bactericidal activity to heterologous strains of pathogenic meningococci. The rise in bactericidal titer occurred within 2 wk of onset of the carrier state, and was accompanied by an increase in titer of specific IgG, IgM, and IgA antibodies to meningococci. In early childhood, when few children have antibodies to pathogenic meningococci, active immunization seems to occur as a result of carriage of atypical, nonpathogenic strains. Immunity to systemic meningococcal infection among infants in the neonatal period is associated with the passive transfer of IgG antibodies from mother to fetus. The antigenic determinants which initiate the immune response to meningococci include the group-specific C polysaccharide, cross-reactive antigens, and type-specific antigens.

Adolescent↗

PubMed2000

Molecular and biological analysis of eight genetic islands that distinguish Neisseria meningitidis from the closely related pathogen Neisseria gonorrhoeae.

The pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae cause dramatically different diseases despite strong relatedness at the genetic and biochemical levels. N. meningitidis can cross the blood-brain barrier to cause meningitis and has a propensity for toxic septicemia unlike N. gonorrhoeae. We previously used subtractive hybridization to identify DNA sequences which might encode functions specific to bacteremia and invasion of the meninges because they are specific to N. meningitidis and absent from N. gonorrhoeae. In this report we show that these sequences mark eight genetic islands that range in size from 1.8 to 40 kb and whose chromosomal location is constant. Five of these genetic islands were conserved within a representative set of strains and/or carried genes with homologies to known virulence factors in other species. These were deleted, and the mutants were tested for correlates of virulence in vitro and in vivo. This strategy identified one island, region 8, which is needed to induce bacteremia in an infant rat model of meningococcal infection. Region 8 encodes a putative siderophore receptor and a disulfide oxidoreductase. None of the deleted mutants was modified in its resistance to the bactericidal effect of serum. Neither were the mutant strains altered in their ability to interact with endothelial cells, suggesting that such interactions are not encoded by large genetic islands in N. meningitidis.

Animals↗

PubMed2001

Risk-factors for meningococcal disease in Victoria, Australia, in 1997.

In Victoria between 1990 and 1996, meningococcal infections occurred in 1-2/100,000 people each year, with sometimes devastating outcome. In 1997, a typical year, we conducted a case-control study of all cases notified to the State Disease Control Unit, to investigate personal, environmental and lifestyle risk factors. In bivariate analysis many exposures were statistically significantly different (at P = 0.01) in cases and controls. The level of risk, and specific risks, differed between children (under 16) and adults (16 years and over). In multivariate analysis few exposures remained significant (at P = 0.05). However, these included having a smoker amongst close contacts, exposure to construction dust, recent illness, a history of snoring and speech problems, and sharing a bedroom. Besides confirming some previously identified risk factors, this is the first time that snoring and speech problems have been identified as risk factors for meningococcal disease.

Adolescent↗

PubMed1984

Malumfashi Endemic Diseases Research Project, XXI. Pointers to causes of death in the Malumfashi area, northern Nigeria.

For 228 of 425 deaths (54%) occurring among 26 100 people of known age in the Malumfashi area of northern Nigeria, data were collected on symptoms present prior to death. Information was obtained on monthly registration visits, as part of demographic investigations, and data for the period November 1977-October 1978 have been analysed. Enumerators used a carefully prepared list of 25 symptoms to elicit information from relatives of the deceased. Pyrexia, diarrhoea and measles accounted for 77% of all deaths. Epidemiological determinants were responsible for all cases of meningococcal infections in the dry season and most cases of diarrhoea in the wet season. Most deaths attributed to measles occurred in the late dry season and early wet season. Epidemics of measles seemed to be localized at any one time in certain villages and the micro-epidemiology of this feature is considered. Malaria does not appear to be responsible for all deaths from pyrexia in the nought to four age group.

Accidents↗

PubMed2002

Surveillance for meningococcal carriage by Muslims returning from the Hajj to Hat Yai Airport, Thailand.

This study had three objectives: firstly, it aimed to examine an appropriate model for preventing and controlling the risk of meningococcal disease as a result of an epidemic carrying by returning pilgrims at Hat Yai International Airport; secondly, it aimed to establish the number of meningococcal carriers among pilgrims returning from Saudi Arabia; thirdly, it considered the health problems that arose during the Hajj pilgrimage. A structured questionnaire was used to collect data from 374 pilgrims at the Hat Yai airport checkpoint between March 15th and April 2nd, 2001. Each subject provided a naso-pharyngeal swab and reported on their health status by postcard once they had reached their homes 7-10 days later. It was found that most of the pilgrims were from Satun Province (23%). The average age was 50.5 years (range 20 to 86; SD 12.8). More than half of the pilgrims had some knowledge of meningococcal meningitis. Most, about 80.7%, knew that vaccination against meningococcal infection is required before traveling to Saudi Arabia. About 77.8% were vaccinated at the Provincial Health Office (PHO) in their hometown. Nearly 19% had underlying diseases such as chronic cough, asthma, diabetes, hypertension, headache and rheumatism. During their pilgrimage some were troubled by symptoms of respiratory tract disease, fever and headache. All had negative laboratory results. Only 16.6% returned postcards describing their self-assessed health status. About 30.6% described themselves as healthy. Among those who reported sick, coughs, sore throats and stomach aches were prevalent. Health education and public information about vaccine need to be strengthened. The best place to get the vaccination is their hometown PHO. Trained health personnel, instead of tour leaders or guides, should pay attention to the health of the pilgrims. The tour leaders are an important target group for improved health knowledge because most pilgrims will trust and follow them. Even though there were negative laboratory results, it is worth having a good surveillance system for meningococcal meningitis in order to prevent epidemics and reduce mortality among returning pilgrims.

Adult↗

PubMed1991

[Meningococcal sepsis in our area. Study of the disease severity factors and therapeutic management over a 10-year period].

Meningococcal sepsis with cardiovascular manifestations is one of the leading causes of pediatric intensive care admission (14.85%) in our area. We carried out a two phase study over period of 10 years from 1979 to 1988, involving a retrospective analysis of clinical and analytical manifestations in order to determine a prognostic score of the severity of meningococcal infections in our area. A total of 86 cases were studies over a two year period. After establishing the prognostic score, we applied a previously assayed therapeutic protocol, based on the number of criteria of severity, in 170 children selected as having the same criteria. The factors of seriousness considered were: Appearance of the first symptoms less than 12 h. previously, appearance of petechia less than 6 h. previously, hyperthermia, shock at admission, absence of meningitis, fulminating course of purpura and convulsions, leukopenia less than or equal to 5,000 mm3, prothrombin activity less than or equal to 45%, platelets less than or equal to 75,000 mm3, fibrinogen less than or equal to 250 mgrs% and FPD greater than 40 micrograms/ml (p less than or equal to 0.01 (CHI SQUARE]. In the first phase of study, overall mortality was associated with the presence of three criteria, and was highest when more than seven criteria were present. The results indicate that mortality from meningococcal sepsis is linked to fulminating deterioration of hemodynamics and DIC.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗

PubMed1991

Endotoxin liberation by strains of N. meningitidis isolated from patients and healthy carriers.

The main objective of this study was to assess whether the capacity of Neisseria meningitidis to release endotoxin depends upon the type of strain or upon bacterial mass. Endotoxin release was studied in 32 strains isolated from patients with meningococcal infections and in 49 from asymptomatic carriers, using a quantitative test (limulus test with a chromogenic substrate). The results show that the strains from patients release significantly higher amounts of endotoxin than strains from carriers regardless of serogroup and isolation site. No correlation was found between stage of bacterial growth and the amount of endotoxin liberated. These findings suggest that endotoxin liberation is a characteristic of certain strains of N. meningitidis and is not determined simply by bacterial mass.

Adult↗

PubMed2006

Changing epidemiology of bacterial meningitis among adults in England and Wales 1991-2002.

We examined the epidemiology of community-acquired bacterial meningitis among adults in England and Wales between 1991 and 2002. Among 3169 cases, meningococcal infection was predominant among young adults and pneumococcal meningitis among older adults. Whilst infection due to most causes decreased, the incidence of tuberculous (TB) meningitis doubled over the 12 years. The mortality rate among meningococcal and pneumococcal infections fell from 0.45/10(5) to 0.31/10(5) (P=0.0001). This study demonstrates important changes in the epidemiology of bacterial meningitis among UK adults. Improvements in clinical management, childhood vaccination programmes and the re-emergence of tuberculosis are likely to be drivers of these changes.

Adolescent↗

PubMed2001

Identification and characterization of App: an immunogenic autotransporter protein of Neisseria meningitidis.

In a search for immunogenic virulence factors in Neisseria meningitidis, we have identified a gene encoding a predicted 160 kDa protein with homology to the autotransporter family of proteins. Members of this family are secreted or surface exposed and are often associated with virulence in Gram-negative bacterial pathogens. We named the gene adhesion and penetration protein (app), because of its extensive homology to the hap gene of Haemophilus influenzae. We reconstructed the gene with reference to genomic sequence data and cloned and expressed the protein in Escherichia coli. Rabbit antiserum raised against recombinant App reacted with proteins in all meningococcal isolates examined, which represented clonal groups responsible for the majority of meningococcal invasive disease. Antibodies to the protein were detected in the sera of patients convalescing from meningococcal infection. Purified App had strong stimulating activity for T cells isolated from a number of healthy donors and from one convalescent patient. We confirmed that App is surface localized, cleaved and secreted by N. meningitidis. Importantly, the rabbit anti-App serum killed the organism in the presence of complement. Thus, App is conserved among meningococci, immunogenic in humans and potentially involved in virulence. It therefore merits further investigation as a component of a future multivalent vaccine.

Antigens, Bacterial↗

PubMed2005

Sensitivity of the Swedish statutory surveillance system for communicable diseases 1998-2002, assessed by the capture-recapture method.

To assess the sensitivity of the Swedish surveillance system, four notifiable communicable diseases in Sweden were examined during 1998-2002 with the two-sources capture-recapture method, based on parallel clinical and laboratory notifications. The sensitivity (proportion of diagnosed diseases actually being notified) was highest for salmonellosis (99.9%), followed by meningococcal infection (98.7%), and tularaemia (98.5%). For penicillin-resistant pneumococci, introduced as a notifiable disease in 1996, the overall sensitivity was 93.4%--increasing from 86.5% in 1998 to 98.5% in 2002. The system benefited from parallel reporting, with a sensitivity of clinical and laboratory notifications alone (all diseases combined) of 91.6% and 95.9% respectively. The sensitivity of both clinical and laboratory notifications was markedly higher in counties using the national electronic reporting system, SmiNet. Thus, sensitivity was higher for diseases with a long tradition of reporting, and there is a run-in period after a new disease becomes notifiable.

Communicable Disease Control↗

PubMed2007

Quality assessed nonculture techniques for detection and typing of meningococci.

PCR protocols are increasingly used in laboratories worldwide for the diagnosis and confirmation of invasive meningococcal infection. Protocols are now available for the identification of Neisseria meningitidis, for genogrouping, susceptibility to antibiotics and genotyping of the corresponding isolates. The implementation of quality assurance (QA) schemes and standardization of protocols are required. Diagnostic and confirmatory PCRs should perform consistently in clinical and reference microbiology laboratories. General QA schemes address the issues of sample preparation, PCR laboratory environment, equipment and validation of protocols. Moreover, external QA interlaboratory studies are essential. The European Monitoring Group on Meningococci has provided a good forum to conduct such studies through the development and distribution of samples and protocols for nonculture detection and typing of N. meningitidis.

DNA, Bacterial↗

PubMedDate not supplied

Skeletal and cutaneous sequelae to meningococcal purpura.

Meningococcal infection can produce symptoms that have severe morbid or even fatal effects. The survival rate has increased over the last 20 years and health care workers are now faced with managing the sequelae of cutaneous and skeletal necroses. It is important for nurses to recognize symptoms of the disease as well as associated complications. A multidisciplinary approach is needed to manage all phases of the illness. This phenomenon occurs most commonly in children but may be seen in adolescents and young adults as well. Despite extensive alteration in body image and the need for long-term rehabilitation, with proper management, a full recovery may be expected.

Adolescent↗

PubMed2000

Acute meningococcaemia complicated by late onset gastrointestinal vasculitis.

Extra-meningeal and non-cutaneous manifestations of meningococcal infection are well recognized but rare. Herein we report a little recognized complication of meningococcaemia, namely late-onset gastrointestinal vasculitis. In the case presented, the prostacycline analogue iloprost was used in an attempt to minimize incipient digital gangrene ina patient with evidence of protracted immunological phenomena. In addition, diclofenac was used to treat severe arthralgia. Withdrawal of iloprost on day 19 was associated with abdominal pain and peritonism. Laparotomy demonstrated ischaemia and ulceration in the caecum, and histology revealed full thickness mucosal ulceration with a prominent vasculitic process. It is postulated that these findings were immunologically mediated, with possible rebound vasoconstriction following withdrawal of iloprost. It is also possible that NSAID use contributed to the findings via cyto-toxicity to mucosal cells.

Adolescent↗

PubMed2002

Outbreak of serogroup W135 meningococcal disease after the Hajj pilgrimage, Europe, 2000.

The 2000 Hajj (March 15-18) was followed by an outbreak of Neisseria meningitidis W135 2a: P1.2,5 in Europe. From March 18 to July 31, 2000, some 90 cases of meningococcal infection were reported from nine countries, mostly the United Kingdom (UK) and France; 14 cases were fatal. Although most early cases were in pilgrims, the outbreak spread to their contacts and then to those with no known pilgrim contact. In France and the UK, the outbreak case-fatality rate was compared with the rate reported from national surveillance. The risk of dying during this outbreak was higher in France and the UK, although the difference was not statistically significant. Prophylaxis for all pilgrims and their household contacts was offered in France; in the UK and other European countries, prophylaxis was recommended only for close contacts. No difference in transmission rates following intervention was detected between France and the UK.

Adolescent↗

PubMed1991

Adult overwhelming meningococcal purpura. A study of 35 cases, 1977-1989.

The study objective was to describe the clinical, biologic, and hemodynamic features of adult overwhelming meningococcal purpura and to examine the prognostic factors by multivariate analysis at the time of admission to the intensive care unit. Thirty-five patients (greater than or equal to 13 years of age) with meningococcal infection, circulatory shock, and generalized purpuric lesions of abrupt onset were recorded in eight intensive care units from 1977 to 1989. The patients were young (mean age, 26.6 years; range, 13 to 68 years) and had been previously healthy. The female-to-male ratio was 3:1. Mortality was 54.3%, with most deaths occurring within the first 48 hours, usually secondary to irreversible shock with multiple organ failure. Ischemic complications (eight cases), prolonged heart failure (seven cases), and secondary septicemia (five cases) were the chief complications among survivors. Initial hemodynamic study after volume loading showed low stroke volume index (mean +/- SD, 29.4 +/- 13 mL/m2) and tachycardia (mean +/- SD, 138 +/- 16 beats per minute), a profile suggesting a greater myocardial depression than usually observed in gram-negative bacillary septic shock. Univariate prognostic analysis showed that four variables at the time of admission were associated with fatal outcome: a plasma fibrinogen level of 1.5 g/L or less, a factor V concentration of 0.20 or less, a platelet count lower than 80 x 10(9)/L, and a cerebrospinal fluid leukocyte count of 20 x 10(6)/L or less. Stepwise regression analysis showed that low fibrinogen level (less than or equal to 1.5 g/L) was the sole adverse prognostic variable (odds ratio = 2, 95% confidence interval, 1.5 to 2.7). Adult overwhelming meningococcal purpura is still associated with high mortality and morbidity. Low fibrinogen level at time of admission may permit early recognition of the most severely ill patients.

Adolescent↗

PubMedDate not supplied

Chronic meningococcemia in childhood: case report and review of the literature.

Chronic meningococcemia is a rare form of meningococcal infection. Most reported cases occur in adults. Only about 10% of reported patients are under 18 years of age. We herein report chronic meningococcemia in a 17-month-old immunocompetent child and review the literature. Our patient had a 4-month history of several episodes of intermittent fever accompanied by widespread erythematous and purpuric, crusted papules and pustules with necrotic centers. Blood cultures were positive for group C Neisseria meningitidis. Histopathology of a skin biopsy specimen revealed leukocytoclastic vasculitis. Because the disease is uncommon and can be confused with other conditions including other infectious processes, vasculitis, and collagen vascular diseases, it is important to have a high degree of suspicion for chronic meningococcemia. This will help avoid a delayed diagnosis and/or inappropriate treatment. The positive blood culture remains the diagnostic sine qua non. Treatment with ceftriaxone was rapidly successful in our patient.

Biopsy↗

PubMed1996

New serotype candidate of Neisseria meningitidis.

In spite of a large collection of MAbs used for the whole-cell ELISA (WCE) in the National Reference Laboratory for Meningococcal Infections in Prague 50-80% of N.meningitidis strains isolated in the Czech Republic remained non-typable (NT) and/or non-subtypable (NST). A project focused on the problem of NT/NST N.meningitidis was started and the new serotype candidate designated "22" resulted from this research. This paper presents the method of preparing and testing of the monoclonal antibody (MAb) specific for this new serotype and the first experience acquired from using it. The new serotype-specific MAb is of IgG3 class, does not react with any serotype/subtype reference strains and reacts in WCE with the strain used for its production and with some other NT/NST strains in the dilution 1:1,000. A collection of 97 N.meningitidis B:NT strains isolated from cerebrospinal fluid and/or blood of patients with invasive disease in the Czech Republic since 1973 to 1995 was serotyped using the new serotype "22"-specific MAb and 37 of these strains (38.2%) gave positive WCE result. The total number of 59 N.meningitidis B:NT strains isolated in 1995 from various clinical situations were serotyped and 26 of them (44.1%) were positive with the new serotype "22"-specific MAb. Seven of these N.meningitidis B:NT strains isolated in 1995 from various clinical situations were serotyped and 26 of them (44.1%) were positive with the new serotype "22"-specific MAb. Seven of these N.meningitidis B: "22" strains were isolated from cerebrospinal fluid or blood of patients with invasive meningococcal disease and prevailed in the age group of 0-4 years (5 cases). The significance of the new serotype candidate was underlined recently, when this serotype "22" was recognized in N.meningitidis B strain isolated from a died 10 months old boy. These results indicate the epidemiological and clinical significance of the new serotype candidate "22" in the Czech Republic.

Animals↗

PubMed2000

Non-Q wave acute myocardial infarction in acute meningococcemia in a 10-year-old girl.

INTRODUCTION: Children with acute meningococcemia may have impaired myocardial function resulting in low cardiac output despite normal intravascular volume. Severe meningococcal infection has been associated with acute interstitial myocarditis, endocarditis, and pericarditis, but not with myocardial infarction. CASE: We present the case of a 10-year-old girl with positive family history for premature myocardial infarction who sustained an acute myocardial infarction temporally related to meningococcemia. DISCUSSION: This is the first pediatric case of non-Q wave acute myocardial infarction associated with purpura fulminans in meningococcemia. Similarly, the association of high troponin I levels and meningococcemia has not been described previously. Although, the patient's genetic predisposition for myocardial infarction might have been a potential contributing factor, there was no angiographic evidence of coronary artery disease in this patient. Thereby, other factors related to shock, endotoxin, microthrombi of meningococcemia, and their treatment might have been also contributing. We propose possible mechanisms for this rare but serious complication of meningococcemia and review the literature.

Acute Disease↗