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PubMed2001

Risk factors for meningococcal disease in college students.

CONTEXT: Elevated rates of meningococcal disease were noted among 18- to 22-year-olds in the mid-1990s. However, national data on rates of meningococcal disease in US college students were not collected until 1998. OBJECTIVES: To determine rates of meningococcal disease in US college students and to identify risk factors for meningococcal disease in this population. DESIGN, SETTING, AND PATIENTS: Prospective surveillance study with nested case-control study of US college students with meningococcal infection from September 1, 1998, to August 31, 1999. Fifty state health departments and 231 college health centers participated. MAIN OUTCOME MEASURES: Incidence of and risk factors for meningococcal disease in US college students. RESULTS: Ninety-six cases of meningococcal disease were identified. The incidence rate for undergraduates was 0.7 per 100 000 persons vs 1.4 per 100 000 for the general population of 18- to 23-year-old nonstudents (P<.001). Freshmen living in dormitories had the highest incidence rate at 5.1 per 100 000. Of the 79 case-patients for whom information was available, 54 (68%) had illness due to vaccine-preventable meningococcal serogroups. On multivariable analysis of case-control study data, freshmen who lived in dormitories had an elevated risk of meningococcal disease (matched odds ratio, 3.6; 95% confidence interval, 1.6-8.5; P =.003) compared with other college students. CONCLUSIONS: Freshmen who live in dormitories have an independent, elevated risk of meningococcal disease compared with other college students. Use of the currently available quadrivalent polysaccharide vaccine among college students could substantially decrease their risk of meningococcal disease.

Adolescent↗

PubMed2004

Dosage escalation, safety and immunogenicity study of four dosages of a tetravalent meninogococcal polysaccharide diphtheria toxoid conjugate vaccine in infants.

BACKGROUND: Young children have the highest incidence of meningococcal infection. Approximately 50% of disease in United States children less than 2 years of age is caused by serogroups C and Y. In the developing world, serogroups A and W-135 cause outbreaks and epidemics of infection. METHODS: Three groups of 30 infants were enrolled. The first group of infants was given 3 doses of a quadrivalent (group A, C, Y, W-135) polysaccharide meningococcal vaccine conjugated to diphtheria toxoid (MCV-4) at a dosage of 1 microg of each serogroup polysaccharide. The second group of infants was given MCV-4 at a dosage of 4 microg, and the last group of children received a 10-microg dosage. Vaccinations were given at 2, 4 and 6 months of age.A subset of these children was vaccinated at 15 to 18 months of age with licensed meningococcal polysaccharide (A, C, Y, W-135) vaccine. Serum bactericidal antibody (SBA) titers were measured with baby rabbit complement. RESULTS: The proportion of infants with local reactions increased significantly with increasing dosages after Injection 1 and 3. Approximately 1 month after completion of the primary series, the proportion of infants with an SBA titer > or = 1/8 ranged from 54 to 92%, depending on the serogroup and dose of polysaccharide contained in the vaccine. The SBA geometric mean titer varied from 17.4 to 101.6. There was no statistically significant difference between the SBA responses among the 3 dosage groups. After vaccination with polysaccharide vaccine at 15 to 18 months of age, mean fold increases in SBA of 4.9 to 170.3 were observed, suggesting an anamnestic response. CONCLUSIONS: MCV-4 appears to have a reactogenicity profile acceptable to parents and health care providers. It was only modestly immunogenic in infants, but it appeared to prime the immune system of the majority of infants given three doses in infancy. There is no statistically significant immunologic advantage conferred by increasing the dosage beyond 4 microg/ml, and local reactions are more frequent after the 10-microg/ml dosage.

Antibodies, Bacterial↗

PubMed1976

Serotypes of group B meningococci.

Strains of group B meningococci isolated from cases of sporadic infection, epidemic infection, and from patients unassociated with clinical meningococcal infection have been examined by a serological typing technique. The majority of group B meningococci from clinical infections in the UK have serotype 2 antigen. Such strains were relatively uncommon among carriers who had no association with meningococcal disease.

Agglutination Tests↗

PubMed1998

Prognostic scores for use in African meningococcal epidemics.

Current WHO guidelines for the case management of meningococcal infections during epidemics in developing countries often cannot be applied, largely because of the limited health resources in such countries. Several scoring scales based on clinical and laboratory features in numerous combinations have been developed for the management of meningococcal infections in developed countries, and these have facilitated early identification of patients with fulminant disease and thus early intervention and reduction in mortality. Unfortunately such scoring scales are not appropriate for use in developing countries. We identified hypotension, tachycardia, tachypnoea, delay in capillary refill time, coma, absence of neck stiffness and petechiae and/or purpura as simple prognostic factors of meningococcal disease. Two scores were developed: score I, which includes all seven prognostic factors, had a sensitivity and specificity of 80% and 94%, respectively. Score II, which excluded hypotension, had a sensitivity and specificity of 73.3% and 89.7%, respectively. Quick and simple scoring scales are therefore not only applicable but useful for the case management of patients in meningococcal epidemics in developing countries.

Adolescent↗

PubMed1999

Ultrasound-enhanced latex immunoagglutination and PCR as complementary methods for non-culture-based confirmation of meningococcal disease.

Preadmission administration of antibiotics to patients with suspected meningococcal infection has decreased the likelihood of obtaining an isolate and has stimulated development of rapid and reliable non-culture-based diagnostic methods. The sensitivity of the conventional test card latex agglutination test (TCLAT) for detection of capsular polysaccharide has been reported to be suboptimal. In the United Kingdom meningococcal DNA detection by PCR has become readily available and is now used as a first-line investigation. Recently, the performance of latex antigen detection has been markedly improved by ultrasound enhancement. Three tests for laboratory confirmation of meningococcal infection, (i) PCR assays, (ii) TCLAT, and (iii) ultrasound-enhanced latex agglutination test (USELAT), were compared in a retrospective study of 125 specimens (serum, plasma, and cerebrospinal fluid specimens) from 90 patients in whom meningococcal disease was suspected on clinical grounds. Samples were from patients with (i) culture-confirmed meningococcal disease, (ii) culture-negative but PCR-confirmed meningococcal disease, and (iii) clinically suspected but non-laboratory-confirmed meningococcal disease. USELAT was found to be nearly five times more sensitive than TCLAT. Serogroup characterization was obtained by both PCR and USELAT for 44 samples; all results were concordant and agreed with the serogroups determined for the isolates when the serogroups were available. For 12 samples negative by USELAT, the serogroup was determined by PCR; however, for 12 other specimens for which PCR had failed to indicate the serogroup, USELAT gave a result. USELAT is a rapid, low-cost method which can confirm a diagnosis, identify serogroups, and guide appropriate management of meningococcal disease contacts. A complementary non-culture-based confirmation strategy of USELAT for local use supported by a centralized PCR assay service for detection of meningococci would give the benefits of timely information and improved epidemiological data.

Bacteremia↗

PubMed1984

Inflammation triggers hypoferremia and de novo synthesis of serum transferrin and ceruloplasmin in mice.

Oil of turpentine was used to induce an artificial inflammation so that we could study its effect on iron metabolism and on synthesis of serum transferrin and ceruloplasmin in mice. It was found that turpentine-induced inflammation triggered the establishment of a hypoferremic state characterized by low levels of serum iron, followed by recovery and a gradual return to normal plasma iron levels. This turpentine-induced hypoferremia and its subsequent recovery paralleled the hypoferremia obtained during meningococcal infection. Moreover, serum transferrin and ceruloplasmin activity levels increased drastically during the recovery from hypoferremia. [14C]leucine incorporation studies revealed a de novo synthesis of both transferrin and ceruloplasmin. Turpentine-induced hypoferremia was also found to provide a protective effect against meningococcal infection which could be partially reversed by exogenous iron. The results of this study suggest that transferrin and ceruloplasmin may be synthesized partly in response to the altered iron metabolism observed during hypoferremia.

Animals↗

PubMed1992

Mesangiocapillary glomerulonephritis associated with meningococcal meningitis, C3 nephritic factor and persistently low complement C3 and C5.

We report two unusual cases in which mesangiocapillary glomerulonephritis occurred in association with meningococcal infection. C3 nephritic factor, an autoantibody to alternate pathway C3 convertase, was present. Low serum complement C3 and C5 levels were also noted. The depressed complement levels, in conjunction with terminal complement complexes at the upper limit of normal, suggest activation of the early and late complement cascade. We suggest that children presenting with meningococcal infection should have a regular urine examination, as well as full complement measurements performed, in view of the association with hypocomplementaemic mesangiocapillary glomerulonephritis. Similarly, prophylactic penicillin should be prescribed for patients with mesangiocapillary glomerulonephritis and persistently low C5 levels to prevent meningococcal complications.

Adolescent↗

PubMed2001

Health economics of a hexavalent meningococcal outer-membrane vesicle vaccine in children: potential impact of introduction in the Dutch vaccination program.

The cost-effectiveness of universal vaccination of infants with a new hexavalent meningococcal B outer-membrane vesicle vaccine is projected for The Netherlands by applying decision analysis. The societal perspective is taken and direct and productivity costs (friction costs method) are considered. Future costs and effects are discounted at 4% (base year 1998). In this simulation model, vaccination would prevent 19 deaths and eight cases with severe long-term sequelae per year, rendering 526 additional quality adjusted life years (QALYs) per year. Yearly costs of acute phase of illness due to meningococcal infections in children are estimated at 1,426,634, while the future costs due to sequelae are estimated at 3,801,121 per year. Of all these costs, the vaccination program could prevent 3,334,052 per year. The program costs of meningococcal vaccination are estimated at 11,601,356, resulting in a cost-effectiveness ratio (CER) of 15,721 per QALY. These results are sensitive to the vaccine dose price (conservatively estimated at 10), efficacy, and coverage of meningococcal sero-subtypes.

Bacterial Outer Membrane Proteins↗

PubMed1986

[Characteristics of the functional antigens of Neisseria meningitidis group B].

The work deals with the characterization of the functional antigens of N. meningitidis, group B. Analysis of the total extract of N. meningitidis strain B16B6 with the use of sera obtained from patients with meningococcal infection, nasopharyngitis, salmonellosis, as well as from meningococcus carriers and healthy donors, by immune blotting techniques and the affinity isolation of the functional antigens indicate that protein antigen with a molecular weight of 13-15 kd is the main common antigen inducing the formation of antibodies in patients with meningococcal infection.

Antibody Formation↗

PubMed2005

[Investigation concerning demand and vaccination applicants to traveler's vaccines (typhoid fever and meningococcal vaccines) not marketed in Japan].

In recent years, the number of Japanese traveling to foreign countries is increasing. Most of them travel to Asian regions where many infectious diseases that are rare or don't occur in Japan still remain endemic or epidemic. Of these infectious diseases typhoid fever and meningococcal infection are now preventable because safe and effective vaccines have been developed and now marketed. However, these vaccines are hardly available in Japan because the Japanese Government has not admitted them. To investigate the demand for the two vaccines, the author personally imported inactivated polysaccharide typhoid vaccine and groups A, C,Y and W135 combined polysaccharide meningococcal vaccine, both manufactured by Aventis-Pasteur. After obtaining approval of the ethical committee of our hospital, vaccination was started. From May 6, 2003 to September 30, 2004, 124 applicants received typhoid vaccine and 35 were injected with meningococcal vaccine. Of 124 vaccinees of typhoid vaccine, 46 went to Afghanistan, 15 to India, 8 to Thailand. Of 35 vaccinees of meningococcal vaccine 6 went to the USA, 5 to Guinea and 3 to England. In addition a total of 12 physicians and nurses having no international scheduled trip were also immunized with meningococcal vaccine. None of these vaccines are widely known in Japan now. Based on our results, however, the expansion of recognition and demand for these two vaccines is expected.

Adult↗

PubMed2000

Mathematical modelling of infection and disease due to Neisseria meningitidis and Neisseria lactamica.

BACKGROUND: Invasive meningococcal disease, due to Neisseria meningitidis, is an important cause of morbidity and mortality in young children and adolescents. Nasopharyngeal carriage of meningococci (MC), is most prevalent in young adults whereas carriage of Neisseria lactamica (LC), a related non-pathogenic organism, is most prevalent in young children. The objective of this study was to use modelling techniques to test hypotheses on the processes that govern the incidence of meningococcal disease (MD). METHODS: Deterministic compartmental models were fitted to age structured data sets of MC, LC and MD. RESULTS: The model most consistent with the available data sets is one where LC inhibits MC, an inhibition that lasts for a mean of 4.7 years. The hypothesis that LC also acts as a natural immunogen against MD was consistent with this model. The second peak of MD observed among adolescents could be due to the peak in the acquisition of MC in this age group. CONCLUSIONS: The role of LC as a natural immunogen against asymptomatic and symptomatic meningococcal infection was consistent with available field data. If the introduction of novel meningococcal vaccines into a population changes the prevalence of MC or LC, this could have a substantial impact on the effectiveness of immunization programmes. This paper demonstrates the potential utility of modelling to estimate these effects.

Adolescent↗

PubMed2004

Timeliness of case reporting in the Swedish statutory surveillance of communicable diseases 1998--2002.

To prepare for a new communicable disease act in Sweden, we performed an in-depth analysis of the performance of the present notification system (1998--2002). Four diseases were selected for analysis (meningococcal infection, salmonellosis, infection with penicillin-resistant pneumococci and tularaemia). Each step in the double notification flow (clinical and laboratory notifications) was studied and paper-based and electronic notifications compared. More than 15 possible single dates in the notification flows were analysed for 27,000 cases. The shortest notification flows (from date of sample collection to when the first notification was received at SMI--clinical or laboratory notification) were seen for meningococcal infections and salmonellosis (median 7 d) and the longest for tularaemia (11 d). Laboratory notifications were faster than clinical notifications, and electronic reporting 1.5-1.7 times faster than paper notifications. Further gains should be expected from the new electronic reporting system (SmiNet2), which will allow also clinical reporting electronically over the internet.

Communicable Diseases↗

PubMed1992

[Comparative effectiveness of various antibiotics in the treatment of patients with meningococcal meningitis].

The results of treating 322 patients with various forms of meningococcal infection accepted to a hospital within a year are presented. The patients were divided into 3 groups by the character of etiotropic therapy. The patients of group I were treated with benzylpenicillin and those of group 2 were treated with levomycetin sodium succinate. Group 3 included the patients, the therapy of whom with the above two antibiotics failed and they were subjected to treatment with cefazolin, cefotaxime, amikacin and other broad spectrum antibiotics. Benzylpenicillin generally proved to be the drug of choice in the antibacterial therapy of meningococcal infection. In comparison to levomycetin (chloramphenicol) it provide more rapid clinical recovery of the patients and normalization of the indices of the cerebrospinal fluid. Only failure of benzylpenicillin therapy was considered as an indication to the broad-spectrum antibiotics to be in the complex treatment of the patients. As additional methods for estimating the efficacy of antibacterial therapy it was recommended to employ calculation of the integral indices of hemograms (the leukocyte index of intoxication and the hematologic index of intoxication).

Adolescent↗

PubMed1991

[The drug sensitivity of meningococci and the characteristics of its determination].

The results obtained in the study of antibiotic and sulfamide sensitivity of 197 Neisseria meningitidis strains of groups A, B and C, isolated from the spinal fluid and blood of patients with meningococcal infection hospitalized in the 2nd Clinico-Infectious Hospital, Moscow, in 1984-1989 and studied with the use of the disc diffusion method and the method of serial dilutions of antibiotics in solid culture media, are presented. As revealed in this study, N. meningitidis strains retained their high sensitivity to penicillin and ampicillin (MIC50 = 0.016 and 0.032 micrograms/ml respectively). Sensitivity to tetracycline decreased (MIC50 = 0.5 micrograms/ml) and to rifampicin increased (MIC50 = 0.063 micrograms/ml). 48.5% of strains were resistant to streptomycin. In recent years the proportion of N. meningitidis, resistant to sulfanilamide preparations, significantly decreased and MIC50 was equal to 2.5 micrograms/ml in comparison with 5-10 micrograms/ml in the preceding period. The results of testing sensitivity to antibiotics by both methods coincided. Still the disc diffusion method can be used in epidemiological surveillance on meningococcal infection, while for more exact differentiation of N. meningitidis strains the use of the method of serial dilutions is necessary.

Anti-Bacterial Agents↗

PubMedDate not supplied

Primary meningococcal arthritis of the hip in an immunocompetent adolescent.

The clinical spectrum of meningococcal infection ranges from asymptomatic carriage to fulminant sepsis, with meningitis and septicemia being well-recognized clinical presentations. Meningococcal arthritis as a complication of Neisseria meningitidis infection occurs in about 2-10% of cases, whereas primary meningococcal arthritis (PMA) is a relatively rare phenomenon, even in children. We report here a case of meningococcal infection in an immunocompetent adolescent suffering from acute pain of the right hip as the only symptom upon presentation at the hospital. In such a situation, meningococci are not usually considered as a possible causative agent.

Adult↗

PubMed2004

[Meningococcal vaccination: which one? When? Why?].

Two kinds of meningococcal vaccines are available for invasive meningococcal infections (IMI) prevention, non conjugated polysaccharide vaccines anti A+C or anti A+C+W135+Y and conjugated polysaccharide vaccines anti-C. The last one have the advantage of being effective from 2 months of age. Vaccination should to be used in four circumstances: for subjects remaining in close contact with an IMI case; for pilgrims going to Mecca (A+C+W135+Y vaccine must be used); for travelers to a location with active transmission of IMI and close contacts with local population; in case of "mass" vaccination decided by health authorities. Generalised vaccination of all of one or more age groups has been done for serotype C in some European countries, because of high incidence. Effectiveness of this kind of intervention should be weighted with the risk of immunoselection of another serotype and with the possibility of a spontaneous decrease of the incidence.

Age Factors↗

PubMed1999

Cellular immune responses to Neisseria meningitidis in children.

There is an urgent need for effective vaccines against serogroup B Neisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-gamma), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a TH1 response (low IL-10/IFN-gamma ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-gamma ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of TH2 cytokine production.

Adult↗

PubMedDate not supplied

[Inflammation mediators in pathogenesis of infection-toxic shock of meningococcal etiology].

Up-to-date advances made in understanding of the events underlying meningococcal infection-toxic shock (ITS) are reviewed. Endotoxin properties, its interaction with transport protein and specific membrane receptors entailing activation of macrophages and secretion of cytokines TNF and IL-1 are described. Both of them are considered as major mediators of ITS. Recent information about activation of complement and coagulation cascades, changes of kinetic and functional properties of polymorphonuclear leukocytes are summarized. As to secondary mediators, the emphasis is placed on bioregulatory system L-arginine-NO. A scheme of pathogenesis of meningococcal ITS is provided. The latter is corresponding both clinically and morphologically to other endotoxin shocks and its peculiarities in excessive activation of coagulation system.

Humans↗