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Meningococcal disease is an important medical emergency demanding early diagnosis and prompt treatment. This article provides an overview of meningococcal infection and discusses mode of transmission, risk factors, prevention of spread, vaccination and current recommendations for treatment.
Meningococcal antigen was measured by countercurrent immunoelectrophoresis in the blood and cerebrospinal fluid of 200 patients with group A meningococcal meningitis. Antigen was detected in the blood of 27 (13.5 per cent) patients. These patients had a worse prognosis and a higher incidence of allergic complications, such as arthritis and vasculitis, about 5 days after the start of antibiotic treatment. Antigen was found in the CSF of 129 (67.5 per cent) patients); antigen often persisted in the cerebrospinal fluid despite antibiotic treatment before admission. A combination of immunoelectrophoresis and routine bacteriologic study was used in the diagnosis of 162 (84.8 per cent) patients with meningococcal meningitis. High levels of antigen and a slow antigen disappearance were associated with neurologic damage. The antigen is stable and may be detected from specimens of cerebrospinal fluid dried on filter paper.
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Antigenic diversity among and within strains of Neisseria gonorrhoeae and Neisseria meningitidis has complicated studies of the pathogenesis of these strains and obstructed vaccine development. We previously described a distinct surface antigen (H.8) common to pathogenic Neisseria. We have now demonstrated in vivo expression of the H.8 antigen by detecting antibody responses to the antigen in 13 patients with disseminated neisserial infections. Each serum sample from a convalescent patient blocked the binding between the infecting meningococcal or gonococcal strain and a monoclonal antibody directed to the H.8 antigen, as demonstrated by binding-inhibition studies in enzyme-linked immunosorbent assays (P less than .005). Testing by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting demonstrated an IgG response in each convalescent serum to an antigen co-migrating with the H.8 antigen. Specificity of this antibody response was confirmed by probing recombinant bacteriophage that expressed the H.8 antigen. The commonality and the immunogenicity of the H.8 antigen indicate its possible role in the pathogenesis of, and its potential as a vaccine component for, gonococcal and meningococcal diseases.
BACKGROUND: Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis (N. meningitidis). The highest documented risk of disease is for household contacts during the first seven days of a case being detected. Prophylaxis is considered for those in close contact with people with a meningococcal infection and in populations with known high carriage rates as carriers are at increased risk of disease and may pose a risk of infection to others. OBJECTIVES: To study the effectiveness of different prophylactic treatment regimens in: (1) preventing secondary cases of meningococcal disease after contact with a case; (2) preventing cases of meningococcal disease in populations with a high rate of N. meningitidis carriers; (3) eradicating N. meningitidis from the pharynx in healthy carriers of N. meningitidis;This review also addresses the issues of adverse affects and development of drug resistance. SEARCH STRATEGY: Electronic searches on The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (January 1966 to July 2004), EMBASE (1980 to September 2004), LILACS (1982 to July 2004), and searches of references of all identified studies. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials addressing the effectiveness of different antibiotic treatments for (a) prophylaxis of/against meningococcal disease; (b) eradication of N. meningitidis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted data from the included trials. Dichotomous data were analysed by calculating the relative risk (RR) and 95% confidence interval for each trial. MAIN RESULTS: There were no cases of meningococcal disease during follow up in any of the trials, thus effectiveness regarding prevention of future disease cannot be directly assessed. Ciprofloxacin (relative risk (RR) 0.04; 95% CI 0.01 to 0.12), rifampin (RR 0.17; 95% CI 0.12 0.24), minocycline (RR = 0.30; 95% CI 0.19 to 0.45) and ampicillin (RR 0.41; 95% CI 0.25 0.66) proved effective at eradicating N. meningitidis one week after treatment, compared with placebo. However, after one to two weeks only rifampin (RR 0.20; 95% CI 0.14 to 0.29) and ciprofloxacin (RR 0.03; 95% CI 0.00 to 0.42) still proved effective. No trials evaluated ceftriaxone against placebo. Ceftriaxone was more effective than rifampin, after one to two weeks of follow up (RR 5.93; 95% CI 1.22 to 28.68). Rifampin continued to be effective compared to placebo until up to four weeks of post treatment follow up but resistant isolates were seen following prophylactic treatment. AUTHORS' CONCLUSIONS: Given the fact that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, use of ciprofloxacin or ceftriaxone should be considered.Placebo-controlled trials do not seem ethical as prophylactic treatment has been proven to reduce the risk of disease among household contacts. More trials comparing the effectiveness of ceftriaxone, ciprofloxacin and rifampin for eradicating N. meningitidis could provide important insights.
BACKGROUND: Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis (N. meningitidis). Household contacts have the highest documented risk of the disease during the first seven days of a case being detected. Prophylaxis is, therefore, considered for those in close contact with people with a meningococcal infection and in populations with known high carriage rates as carriers are at increased risk of disease and may pose a risk of infection to others. OBJECTIVES: To study the effectiveness of different prophylactic treatment regimens in: (1) preventing secondary cases of meningococcal disease after contact with someone with the disease; (2) preventing cases of meningococcal disease in populations with a high rate of N. meningitidis carriers; (3) eradicating N. meningitidis from the pharynx in healthy carriers of N. meningitidis. This review also addresses the issues of adverse effects of prophylaxis and development of drug resistance. SEARCH STRATEGY: Electronic searches on the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to June 2006), EMBASE (1980 to June 2006), LILACS (1982 to June 2006); and searching of references of all identified studies were performed. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials addressing the effectiveness of different antibiotic treatments for: (a) prophylaxis against meningococcal disease; (b) eradication of N. meningitidis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted data from the included trials. Dichotomous data were analysed by calculating the relative risk (RR) and 95% confidence interval for each trial. MAIN RESULTS: There were no cases of meningococcal disease during follow up in any of the trials, thus effectiveness regarding prevention of future disease cannot be directly assessed. Ciprofloxacin (RR 0.04; 95% CI 0.01 to 0.12), rifampin (rifampicin) (RR 0.17; 95% CI 0.12 to 0.24), minocycline (RR 0.30; 95% CI 0.19 to 0.45) and ampicillin (RR 0.41; 95% CI 0.25 to 0.66) proved effective at eradicating N. meningitidis one week after treatment when compared with placebo. However, only rifampin (RR 0.20; 95% CI 0.14 to 0.29) and ciprofloxacin (RR 0.03; 95% CI 0.00 to 0.42) still proved effective at one to two weeks. Rifampin continued to be effective compared to placebo for up to four weeks after treatment but resistant isolates were seen following prophylactic treatment. No trials evaluated ceftriaxone against placebo but ceftriaxone was more effective than rifampin after one to two weeks of follow up (RR 5.93; 95% CI 1.22 to 28.68). AUTHORS' CONCLUSIONS: Given the fact that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, use of ciprofloxacin or ceftriaxone should be considered. Evidence suggests that all three agents are effective with up to two weeks follow up. Placebo-controlled trials do not seem ethical as prophylactic treatment has been proven to reduce the risk of disease among household contacts. More trials comparing the effectiveness of ceftriaxone, ciprofloxacin and rifampin for eradicating N. meningitidis would provide important insights.
The hierarchical organization of human host defense systems against systemic bacterial infections is considered by using meningococcal disease as a model. The bactericidal action of the complement system is the most potent defense mechanism against meningococci. The antibody-independent alternative pathway of complement activation is more important in infancy. When the specific antibody level increases by natural immunization or vaccination, the antibody-dependent classical pathway of complement activation provides an additional protection. The bactericidal effect of human phagocytes, primarily neutrophils, is mediated partly by the receptors of complement components and immunoglobulins and serves as an additional mechanism of resistance. The relative risk of meningococcal disease may be approximately estimated as 1,000 for the individuals without blood complement bacteriolytic activity, as 80 for those without specific bactericidal antibodies, and as 3 for individuals with ineffective phagocytosis as compared to those with the normal complement system, high levels of bactericidal antibodies, and effective phagocytosis by neutrophils.
Altogether 258 serum samples obtained from 102 patients with generalized meningococcal infection were studied by means of the immune bacteriolysis test and the indirect hemagglutination test. This study revealed a pronounced increase in the titer of bactericidal and hemagglutinating antibodies to group A meningococcus in the process of the disease. The dynamics and intensity of antibody formation, revealed by means of the two tests, were found to be in complete correspondence. Antibody formation was most intensive in meningitis accompanied by meningococcemia. In most cases these antibodies were found to belong to the class of IgM on account of their physico-chemical nature. The highest bactericidal activity was found in the sera with high hemagglutinin titers; the summary titers of these sera were 4-64 times higher than the titers of cystein-resistant antibodies.
The authors present experimental-epidemiological data permitting to give an objective quantitative characteristics of the hazard of infection in meningococcus infection (including the carrier state and nasopharyngitis). In 70% of cases meningococcus infection occurred at a distance of less than 0.5 meters. With increase of the distance and reduction of the time of contact the risk of meningococcus infection in a collective body falls to the zero (no such phenomenon is observed in other droplet infections).
The generalized meningococcal infection in infants in frequently associated with changes (mostly with an increase) in neutrophil reactivity, which can be identified with the aid of spontaneous luminol-dependent chemiluminescence (CL) of diluted blood. The changes in the functional activity of neutrophils mirror the adequacy of the reaction to the meningococcal infection, which turns out maximal in the patterns of medium gravity. The low indicators of CL serve as a prognostic criterion for an unfavourable course of the meningococcal infection, which requires early immunocorrective treatment.
Patients with meningococcal infection, meningitis and with a mixed form of the disease were demonstrated to have unbalance in the redox system of glutathione during the all disease periods till the clinical recovery. Activation of glutathione peroxidases to hydrogen peroxide and tertiary butyl hydroperoxide in erythrocytes was coupled, during the whole disease, with unbalance of the time-course of changes in the interrelated enzymes--superoxide dismutase and glutathione peroxidase to hydrogen peroxide, while in neutrophils, the balance of those enzymes remained unimpaired. Glutathione transferase activity appeared reduced both in erythrocytes and neutrophils. Potential mechanisms by which the redox system of glutathione and superoxide dismutase may be deranged in meningococcal infection are under discussion.
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CONTEXT: The number of meningococcal outbreaks on college campuses have been increasing in the past few years. However, no published studies have documented the incidence of invasive meningococcal infection in college students or whether the incidence is higher than in the general population of the same age. OBJECTIVE: To compare the incidence of invasive meningococcal infection in Maryland college students with that of the general population of the same age. DESIGN: Retrospective cohort study. SETTING AND PATIENTS: Maryland residents with meningococcal infection from 1992-1997 identified from active, laboratory-based, statewide surveillance for invasive meningococcal disease. MAIN OUTCOME MEASURES: Incidence of invasive meningococcal infection. RESULTS: Of 228 patients with invasive meningococcal infection, 67 were aged 16 to 30 years; 11 and 3 of these attended Maryland 4- and 2-year colleges, respectively. Of these, 12 (86%) had infection caused by Neisseria meningitidis serogroups included in the current meningococcal vaccine. The average annual incidence was 1.74 per 100000 among students in 4-year schools vs 1.44 per 100000 for the general population of the same age (P=.60). Among students in 4-year schools, the incidence was 3.24 per 100000 in on-campus residents vs 0.96 per 100000 in off-campus residents (relative risk, 3.4; 95% confidence interval, 1.0-11.6; P=.05). CONCLUSIONS: The incidence of meningococcal infection in college students is similar to the incidence in the general population of the same age, but college students residing on campus appear to be at higher risk than those residing off campus.
114 patients with meningococcal infection were studied; 72 had group C infection and 42 group A infection. 14 patients had acute meningococcaemia, all of whom had group C infection and 9 of whom died. Clinical and laboratory findings were similar in patients with meningitis due to a group A and C organisms, but arthritis and cutaneous vasculitis were more common in patients with group C infection. The overall mortality was 22% in patients with group C infection, and 12% in patients with group A infection, but was the same in both groups when cases of acute meningococcaemia are excluded.
26 children with meningococcal infections were studied to find out the relationaship between plasma and cerebrospinal fluid levels of endotoxin, the clinical outcome, the level of antigen in plasma and cerebrospinal fluid, and indices of complement activation and disseminated intravascular coagulation. No association was found between endotoxin levels and the other factors. A high cerebrospinal fluid antigen level in patients with meningitis was associated with a poor prognosis.
A series of patients with meningococcal infections have been studied and divided in two groups: Group I patients with meningococcal sepsis and group II, those with meningococcal meningitis. Patients in group I presented with more severe encephalopathy, shock, DIC and acute systemic complications. Both groups showed a marked hypoaminoacidemia compared with normal controls (other than for the sulfur containing amino acids and phenylalanine). The concentration of aromatic and basic amino acids, the phenylalanine/tyrosine ratio, the transaminase levels and the negative nitrogen balance were higher in group I patients. The ratio of branched chain to aromatic amino acids was lower in group I. All these differences were statistically significant. The close association between the metabolic derangements and clinical manifestations may help in the understanding of several physiopathological aspects of meningococcal infections.
A prognostic score for evaluating meningococcal infections in patients consists of the following five features that indicate a poor prognosis: onset of petechiae within 12 hours of presentation; shock; normal or low peripheral leukocyte count; normal or low erythrocyte sedimentation rate; and absence of meningitis. Based on our experience and some published data, we suspected that the score may no longer be reliable. We reviewed the charts of 73 children with meningococcal infection from December 19, 1979 to December 19, 1987 and applied the prognostic score mentioned previously. Our findings indicate that although a low score is generally associated with a good outcome, a higher score is less predictive of poor outcome than previously suggested. A rash with petechiae or purpura, the presence of shock, and a normal or low peripheral leukocyte count continue to be predictors of poor outcome. Erythrocyte sedimentation rate was not evaluated owing to a limited amount of data. The absence of meningitis did not correlate with a worse outcome in our patients. Most patients who died had evidence of meningeal involvement at the time of presentation. Instead, altered mental status at presentation, particularly obtundation or coma, was an ominous sign. We conclude that absence of meningitis is not a good predictor of outcome, as was previously thought. Altered mental status at the time of presentation may prove to be a stronger indicator of poor outcome.
The incidence of meningococcal infections undergoes secular variations with modifications in the distribution of identified serotypes. Rhinopharyngeal carriage of meningococci, common in the community, is the natural means of immunization. Prevalence of this carriage varies across age groups and communities, as well as according to whether or not cases are present in the community under study. Identified factors that promote transmission of the bacteria include crowded living conditions, poor socioeconomic conditions, and, more controversially, respiratory tract viral infections. Development of meningococcal infection usually occurs within seven days of onset of carriage. Secondary cases account for approximately 3% of meningococcal infections in France. The risk of development of secondary cases is increased in subjects sharing the patient's home or exposed to his or her rhinopharyngeal secretions. Prevention of these secondary cases rests on chemoprophylaxis and immunization. The qualities of antimicrobial agents proposed for chemoprophylaxis are discussed, with special emphasis on spiramycin and rifampin which are the most widely used. This study, which rests on French epidemiologic surveillance findings and data from a review of the literature, forms the basis for new French guidelines.