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PubMed2002

Direct and rapid identification and genogrouping of meningococci and porA amplification by LightCycler PCR.

Invasive meningococcal infections are usually diagnosed by culture. This approach is far from optimal due to, e.g., treatment with precollection antibiotics. Molecular-genetics methods are therefore recognized as important tools for optimal laboratory confirmation of meningococcal infections as well as characterization of meningococci (Mc). The aims of the present study were to develop real-time PCRs for identification and genogrouping (A, B, C, Y, and W-135) of Mc and porA amplification that further can be used for subsequent genosubtyping. In a first run Mc were identified. In a second run they were genogrouped and porA genes were amplified. All the Mc isolates (n = 71) but one and cerebrospinal fluid samples (n = 11) tested gave the expected positive results. The specificity, inter- and intra-assay variations, and effects of different amounts of DNA on the melting temperatures were also explored. The LightCycler PCR system was found to effectively detect and characterize Mc in a few hours. This testing, including the DNA sequencing of the porA gene to reveal the genosubtype, does not take more than a working day, and the results can be compared to those from culturing with phenotypic analysis, which takes at least a few days.

Bacterial Typing Techniques↗

PubMed2001

[Clonal spread of Neisseria meningitidis W135].

OBJECTIVES: Efficient surveillance of communicable diseases involves dose collaboration between physicians, epidemiologist and bacteriologists. The characterization of meningococcal infections is a medical emergency due to their lethality and their epidemic behavior. The recent expansion of Neisseria meningitidis of serogroup W135 among pilgrims and their contacts underlines the need of a multidisciplinary procedure of alert. METHODS: Meningococcal strains are usually received by the National Reference Center for Meningococci (CNRM). They are identified and then typed to determine their antigenic formula (serogroup:serotype:serosubtype). For cluster analysis, the CNRM as well as the WHO collaborating center, perform molecular typing of isolated strains. Should an epidemic is suspected, the institut de Veille Sanitaire and the Direction Générale de la Santé are immediately informed. RESULTS: Between the 22th of March and the 20th of November 2000, 27 cases of systemic meningococcal infections due to N. meningitidis of the antigenic formula W135:2a:P1-2.5 were identified. Molecular typing of these strains showed that they were clonal and belonged to the complex ET-37. The dissemination of this clone among pilgrims who were vaccinated against serogroups A and C may suggest the selection of a new variant by an escape alteration in the capsule. However, such strains were detected in France as early as 1994. CONCLUSION: The global spread of N. meningitidis of serogroup W135 belonging to the ET-37 clonal complex should be kept under a close surveillance since epidemics may occur particularly in Africa. New vaccination procedures (quadrivalent vaccines and multivalent conjugate meningococcal vaccines) are therefore needed.

Clone Cells↗

PubMed2003

Serogroup C meningococcal conjugate vaccines: new preparations. Effective from age two months.

(1) Two unconjugated polyoside vaccines are available in France for the prevention of meningococcal infections: Vaccine meningococcique A+C from Pasteur Vaccines (against serogroups A and C) and Menomune from Aventis Pasteur MSD (against serogroups A, C, Y and W-135). Neither vaccine is effective in children under the age of two years. (2) 2002 saw the arrival of two conjugated vaccines directed solely against serogroup C meningococci and designed to protect infants from two months of age. Meningitec, marketed by Wyeth-Lederlé, is adsorbed to aluminium phosphate. The other conjugate vaccine is adsorbed to aluminium hydroxide and marketed under two names: Meninvact (Aventis Pasteur MSD) and Menjugate (Socopharm). (3) Immunogenicity studies have shown three advantages of conjugate vaccines over polyoside vaccines, namely a serologic response from as early as two months of age; a higher antibody titre 6 months after vaccination; and a larger increase in the antibody titre after booster injections. (4) Two-year follow-up data on a mass vaccination campaign launched in the United Kingdom in 1999 with Meningitec and Menjugate show that both vaccines have short-term efficacy in infants, children and adolescents. There was about an 80% fall in the number of invasive infections due to group C meningococci among vaccines, no such fall among unvaccinated subjects of the same age, and no major increase in the incidence of infections due to other serogroups. The number of deaths due to documented meningococcal infection showed a similar fall. (5) Most known adverse effects of these conjugate vaccines are mild and similar to those of other standard vaccines. They do not appear to be more frequent than with standard vaccines. Severe allergic reactions have occasionally been observed. A few deaths have followed vaccination with these products but appear to have been coincidental. There is no evidence that the two conjugate vaccines differ in terms of adverse effects. (6) Meningitec (suspension for injection) is more convenient to use than Meninvact and Menjugate (powders for injection). (7) Unlike the other companies concerned, Aventis Pasteur MSD failed to provide us with any documentation on their vaccine. (8) In practice, when specific vaccination against serogroup C meningococci is required (for case contacts or in areas of high incidence), Meningitec is currently the vaccine of choice. If Meningitec stocks are inadequate to deal with an outbreak, the second-line choice is Menjugate.

Adolescent↗

PubMedDate not supplied

[Practical approach according to the Federal Infection Legislation in meningococcal diseases in community facilities from the viewpoint of Public Health physicians in Offenburg].

Within the area for which the Public Health Office Offenburg is in charge, numerous meningococcal diseases in childhood occurred in 1988. As a result there of, a new strategy for the control of meningococcal diseases in day-care centers has been developed. In this respect priority has been given to rapid mutual information among the persons involved together with the strict control and supervision of all contact persons. This strategy led to an acceptable compromise for all persons involved; the strategy aims at achieving scientific accuracy and legal correctness, it is transparent and reproducible, and is easily implemented from an organisational point of view.

Child↗

PubMed2004

[Acceptance of the new conjugate vaccines. Meningococcal and pneumococcal vaccines, in the cohort born in 1999, in the North Region of Portugal].

The new conjugate vaccines against group C meningococcal infection and pneumococcal infection were introduced in Portugal in 2001. In 2001/2002, the media published several alarming news on meningococcal disease and there was an increased demand of those vaccines, not included in the Portuguese National Vaccination Programme. In order to assess the coverage with these new vaccines against Neisseria meningitidis and Streptococcus pneumoniae, we conducted a descriptive study of the cohort born in 1999, using a convenience sample, from eight health centres in the North of Portugal. Data was collected from the vaccination records of 1877 children born in 1999: 37.2% had received the group C meningococcal conjugate vaccine and 33.3% the pneumococcal conjugate vaccine, while 21,2% had received both. Most vaccinations with pneumococcal conjugate vaccine were performed after 23 months of age, above the recommended age range. The biggest number of group C meningococcal conjugate vaccines given in a month, was recorded in February of 2002, when the maximum number of reported cases of meningococcal disease was also observed. Correlation of both distributions over time was very high (R(2)=0.95). In February 2002 the number of pneumococcal conjugate vaccine doses given rose again, after having been decreasing since October 2001. This study suggested research hypothesis for the future.

Child, Preschool↗

PubMed1995

Vaccination of patients deficient in a late complement component with tetravalent meningococcal capsular polysaccharide vaccine.

Eighteen patients with late complement component deficiency (LCCD) were immunized with meningococcal capsular polysaccharide vaccine. The LCCD patients had experienced one-to-five meningococcal infections before vaccination, but their immunological and clinical status was normal at the time of immunization. Serum samples from vaccinated complement-sufficient relatives of the LCCD patients and healthy Russian male adults were used as controls. Total and immunoglobulin-specific concentrations of antibodies to group A, C, W135, and Y capsular polysaccharides were determined by enzyme immunoassay in serum samples taken before and 1-108 weeks after immunization. The individual preimmunization and post-immunization antibody concentrations varied greatly. The median antibody concentrations of the LCCD patients increased significantly after vaccination, and were not significantly different from those of the control groups. The antibody concentrations remained elevated for at least 1 year after vaccination. The post-immunization antibody concentrations correlated with the number of meningococcal infections within 10 years before vaccination. In spite of the vaccination two LCCD patients experienced a meningococcal disease 9 and 12 months, respectively, after vaccination.

Adolescent↗

PubMedDate not supplied

Timeliness of notification in infectious disease cases.

Records of notification in cases of eight infectious diseases in the "Servei Territorial de Salut Publica" of the Province of Barcelona, Spain, between 1982 and 1986 were reviewed. Time from onset of symptoms to notification, time from notification to completion of data collection, and time from onset to completion of the case investigation were analyzed. For the period from onset to notification, the shortest mean was registered for meningococcal infection (6.31 days) and the longest was for pulmonary tuberculosis (54.79 days). For time from notification to complete investigation, the shortest value was for pulmonary tuberculosis (12.20 days) and the longest for rickettsioses (35.79 days). Time from onset to completion of data collection was 22.87 days for meningococcal infection and 72.34 days for tuberculosis of other organs (probably because of the long period of time that elapses between the onset of the first symptoms and notification). It would appear that both physicians and the general population must be educated so that lay-men can identify early signs and symptoms of disease and physicians can realize that statutory notification of infectious diseases is strongly linked to community health care.

Communicable Disease Control↗

PubMed1986

[Subacute septicemia caused by Meningococcus of serogroup Y and acquired deficiency of complement C3 fraction].

The high frequency of meningococcal infections in patients with congenital deficiency of a component of the complement terminal pathway emphasizes the critical role of this system in host resistance against Neisseriaceae. We report the observation of a subacute septicaemia due to N. meningitidis serogroup Y. This girl had an acquired deficit of the C3 fraction of complement due to a high titre of C3 nephritic factor (C3NeF). There was no evidence of partial lipodystrophy or biological symptoms of glomerular disease. The meningococcal infection revealed this biological abnormality.

Child↗

PubMed1999

Enhanced surveillance of meningococcal disease in the West Midlands: 1996 to 1998.

Surveillance of meningococcal disease is vital if we are to respond to a changing burden of disease, but current sources of routine data suggest different trends. A scheme for enhanced surveillance of meningococcal disease began in the West Midlands in January 1996 using several data sources, including case reporting from consultants in communicable disease control, data from the PHLS Meningococcal Reference Unit, and monitoring of statutory notifications and laboratory reports. One thousand two hundred and twenty-eight cases of probable meningococcal infection were identified in three years (1996-1998), 594 of which were laboratory confirmed. Routine data for the same period yielded smaller totals--920 notifications and 412 laboratory reports--suggesting that these sources underestimate incidence by 25% to 30%. Diagnosis by polymerase chain reaction became increasingly important, and accounted for 38% of confirmed cases in 1998. A significant excess of male cases was observed (p < 0.01), most obvious in children under 5 years of age. There was no increase in N. meningitidis C2a strains, which had been identified as a threat nationally. A national system of enhanced surveillance has now been set up to inform programmes that aim to reduce the burden of meningococcal infection.

Adolescent↗

PubMed1985

[Acute myocardial dysfunction in meningococcal septicemia].

A progressive myocardial dysfunction is known to occur in prolonged septic shock. The cases of two patients with acute meningococcal infection and Waterhouse-Friderichsen syndrome are reported. Hemodynamic measurements showed, in the early stage, the classical picture of hyperdynamic septic shock, with increased cardiac output and low systemic vascular resistances. However, rapidly progressive cardiac failure then occurred, with high filling pressures and low cardiac output. One patient went into irreversible shock. In the other the administration of inotropic agents was beneficial, with a slow but progressive improvement in left ventricular function over several weeks. Acute myocarditis has been frequently observed in patients with meningococcal infections. It is suggested that the acute myocardial failure observed in those circumstances is caused by the myocarditis.

Acute Disease↗

PubMed1981

[Serologic studies of patients with meningococcal nasopharyngitis].

The results of the serological examination of 156 patients with bacteriologically confirmed meningococcal nasopharyngitis are presented. For control 221 patients with acute respiratory diseases and 345 healthy persons from groups having no registered cases of meningococcal infection were examined. The passive hemagglutination test with serogroup A and C polysaccharides revealed the presence of antibody titers between 1:20 and 1:640 in 67.3% of nasopharyngitis patients and antibody titers not exceeding 1:40 in 11.3-11.6% of persons in the control groups. The time course of antibody formation in nasopharyngitis was similar to that in generalized forms, but response was less pronounced: the maximum response was observed on days 5-10, and the decrease of the antibody level by day 20. In 47 foci of meningococcal infection the etiology of the disease was serologically confirmed on the first day of an epidemiologist's visit to the focus in 62.2% of 162 nasopharyngitis patients and in 36% of patients with acute respiratory diseases.

Adolescent↗

PubMed1986

[Epidemiological significance of carriers of hyaluronidase-active meningococci].

To find out the epidemiological role of the carriers of hyaluronidase-positive meningococcal strains, their spread in the foci of meningococcal infection, as well as outside these foci, was studied. For this purpose, altogether 5059 persons from 40 family foci of infection and 40 organized groups were examined. The number of carriers of hyaluronidase-active meningococci, detected among those of them who had contacts with sick persons, was 13 times greater than among the persons having no such contacts. In preschool institutions with unfavorable morbidity situation this number was 16 times greater than in those with favorable situation. In the family foci carriers of hyaluronidase-active meningococci constituted 80-88 %. The percentage of the carriers of hyaluronidase-active meningococci causing cases of the generalized form of meningococcal infection varied in different groups. According to the results obtained in this study, the threshold percentage of such carriers constituted 30 in preschool institutions, 36 in boarding schools and 50 in common school and in hostels for adults.

Adolescent↗

PubMedDate not supplied

[The Neisseria meningitidis serotypes and subtypes circulating among bacterial carriers in Moscow (1989-1991)].

N. meningitidis strains isolated from 218 healthy carriers in 1989-1991 in closed communities of adults, irrespective of cases of meningococcal infection registered in these communities, were characterized with a variety of different type and subtype antigens. Only in 139 strains (63.76%) their types and/or subtypes could be determined with the use of a set of 6 serotypes and 11 subtypes of monoclonal antibodies. 26 group B strains and 31 group C strains had multiple antigenic composition. 13 group A strains were found to be more homogeneous: 8 of them, isolated in one area, belonged, according to Dr. Achtman's data, to a definite clone VI-1, heretofore unknown. No prevailing serotype/subtype could be revealed, which reflected the wide heterogeneity of N. meningitidis at the period of the decrease of morbidity in meningococcal infection. The observed stability of serotype/subtype of strains, isolated from the same carriers and circulating in the same communities, suggests that the serotype/subtype of N. meningitidis is a valuable epidemiological marker.

Adult↗

PubMed1992

Intranasal infection of infant mice with Neisseria meningitidis.

In human meningococcal infection the mechanism of the transition from asymptomatic carriage to invasive disease is unknown, partly due to the lack of an effective animal model that mimics all stages of the human disease. Therefore, we have endeavoured to develop a model for the human infection by instilling a suspension of Neisseria meningitidis into the nostrils of infant mice and subsequently determining the numbers of organisms in the nasal passages, lungs, blood and brains. Intranasal (i.n.) instillation resulted in consistent nasal colonisation which usually developed into a lung infection. In many cases the lung infection preceded bacteraemia, which occasionally resulted in death of the mice. The severity of the infection and the transition to bacteraemia were enhanced by intraperitoneal (i.p.) treatment of the mice with iron dextran or human transferrin. A N. meningitidis strain that was avirulent in an i.p. infection was also avirulent following i.n. infection. The requirement for lung colonisation to precede bacteraemia and the need for i.p. injection of iron compounds limit the use of i.n. infection of the infant mouse as a model for human meningococcal disease. However, various aspects of meningococcal virulence can be examined using this model.

Animals↗

PubMed2000

Meningococcal pneumonia: characterization and review of cases seen over the past 25 years.

Fifty-eight cases of meningococcal pneumonia were included in this review. Fifty cases previously described in the literature from 1974 through 1998 and 8 new cases were included in this series. The median age of patients was 57.5 years, and pleuritic chest pain was described in 21 (53.9%) of 39 cases. Blood cultures were positive in 42 (79.3%) of 53 cases for which results were mentioned. Despite the presence of bacteremia, patients did not develop the syndrome of meningococcemia with its associated complications. Serogroup Y meningococci were most commonly recovered and accounted for 44.2% of identified isolates. Therapy has dramatically changed over the past 25 years; prior to 1991, penicillin antibiotics were most often used. Since 1991, 12 (80%) of 15 patients received cephalosporin antibiotics. Only 5 (8.62%) of 58 patients died. Secondary cases of meningococcal infections following exposure to patients with meningococcal pneumonia were noted in 2 instances.

Age Distribution↗

PubMed1985

[Specific latex preparations in the etiological diagnosis of suppurative bacterial meningitis].

The results of the evaluation of the diagnostic latex preparations Bactigen, manufactured by Wampole Laboratories (USA) and intended for the detection of meningococcal antigens, serogropus A, B, C, Y, pneumococcal polyantigens and type b Haemophilus influenzae antigens in the spinal fluid and blood of patients with meningococcal infection and purulent bacterial meningitides, are presented. The pathological material was studied by traditional methods and by the latex agglutination (LAG) test. 522 LAG tests were made, including 414 tests for meningococcal infection, 60 tests for pneumococcal infection and 48 tests for type b H. influenzae. The results of this study revealed that the latex preparations were highly specific with respect to type b H. influenzae antigens and meningococcal antigens (false positive reactions constituted 0.96%). The simplicity of the test and the rapid techniques making it possible to obtain results within 30-40 minutes indicate good prospects of using the LAG test in laboratory practice.

Antigens, Bacterial↗

PubMed1998

Evaluation of scoring systems in acute meningococcaemia.

Patients expected to develop life-threatening complications in acute meningococcal infections require early recognition and appropriate monitoring. Different prognostic scoring systems have been developed. Three of them, chosen according to their bedside availability, were compared with our clinical observations. Twenty consecutive cases of proven meningococcal infection were admitted to the paediatric intensive care unit (PICU) of the Free University of Brussels (AZ-VUB). Biological and clinical features required for prognostic scoring were evaluated as soon as possible after admission. Glasgow meningococcal sepsis prognostic score (GMSPS), Neisseria sepsis index (NESI) and Algren criteria were retrospectively calculated and evaluated for their prognostic significance. Neisseria meningitidis was cultured from blood and cerebrospinal fluid in 11 patients and from blood in only nine patients. The age of the patients was between 1 and 15 years (mean 4.1 years). All patients received the same therapy on admission. Four patients died with a multiorgan failure within 18 hours. The three scoring systems in these four patients predicted death. Overall, the GMSPS score, the NESI score and the Algren criteria predicted death in respectively 10, nine and five patients. Death was falsely predicted in six patients by the GMSPS score, in five patients by the NESI score and in one patient by the Algren criteria. The Algren criteria predicted the severity of the clinical process more accurately than did the GMSPS and NESI scores. However, such predictability should be cautiously used even when 100% mortality is predicted. It might be used in decision-making in regard to the following issues: patient transfer to tertiary centres and mode of transportation, monitoring of patients in intensive care units, early insertion of invasive cardiovascular monitoring catheters and consideration of new or even experimental therapy. However, one should be extremely cautious of taking any therapeutically or ethical decision on the basis of one or more of the described scoring system, since we showed the lack of precision concerning the outcome of paediatric patients with meningococcaemia.

Acute Disease↗

PubMedDate not supplied

[The diagnostic specificity of the antigen-binding lymphocyte test in Neisseria-induced infections].

Neisseria-induce different infections, but many representatives of this genus are saprophytes. In this connection it is important to evaluate the species, and for N. meningitidis also group specificity of the immunological diagnostics of meningococcal infection and gonorrhea. In this work the specificity of the antigen-binding lymphocyte test was studied in experiments with the immunization of rabbits and the examination of patients. In the tests of indirect rosette-formation and its inhibition the role of antigenic relationships between different pathogenic and nonpathogenic Neisseria was excluded and the species and group specificity of our Neisseria immunoreagents, used in the diagnostics of meningococcal infection and gonorrhea, was proved.

Animals↗