Neisseria meningitides: Clinical Features, Laboratory Diagnosis, and Medical Management
N. meningitidis , or meningococcus, is an aerobic, gram-negative diplococcus, closely related to N. gonorrhoeae, and to several nonpathogenic Neisseria species, such as N. lactamica. The organism has both an inner (cytoplasmic) and an outer membrane, separated by a cell wall. The outer membrane contains several protein structures that enable the bacteria to interact with the host cells as well as perform other functions.
The outer membrane is surrounded by a polysaccharide capsule that is necessary for pathogenicity because it helps the bacteria resist phagocytosis and complement-mediated lysis. The outer membrane proteins and the capsular polysaccharide make up the main surface antigens of the organism.
Meningococci are classified by using serologic methods based on the structure of the polysaccharide capsule. Thirteen antigenically and chemically distinct polysaccharide capsules have been described. Some strains, often those found to cause asymptomatic nasopharyngeal carriage, are not groupable and do not have a capsule. Almost all invasive disease is caused by one of five serogroups: A, B, C, W, andY. The relative importance of each serogroup depends on geographic location, as well as other factors, such as age. For instance, serogroup A has historically been a major cause of disease in sub-Saharan Africa but is rarely isolated in the United States.
Meningococci are further classified on the basis of certain outer membrane proteins. Molecular subtyping using specialized laboratory techniques (e.g., pulsed-field gel electrophoresis) can provide useful epidemiologic information.
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Pathogenesis
Meningococci are transmitted by droplet aerosol or secretions from the nasopharynx of colonized persons. The bacteria attach to and multiply on the mucosal cells of the nasopharynx. In a small proportion (less than 1%) of colonized persons, the organism penetrates the mucosal cells and enters the bloodstream. The bacteria spread by way of the blood to many organs. In about 50% of bacteremic persons, the organism crosses the blood–brain barrier into the cerebrospinal fluid and causes purulent meningitis. An antecedent upper respiratory infection (URI) may be a contributing factor.
Clinical Features
The incubation period of meningococcal disease is 3 to 4 days, with a range of 2 to 10 days.
Meningitis is the most common presentation of invasive meningococcal infection (meningococcal disease) and results from hematogenous dissemination of the organism. Meningeal infection is similar to other forms of acute purulent meningitis, with sudden onset of fever, headache, and stiff neck, often accompanied by other symptoms, such as nausea, vomiting, photophobia (eye sensitivity to light), and altered mental status. Meningococci can be isolated from the blood in up to 75% of persons with meningitis.
Meningococcal sepsis (bloodstream infection or meningococcemia) occurs without meningitis in 5% to 20% of invasive meningococcal infections. This condition is characterized by abrupt onset of fever and a petechial or purpuric rash, often associated with hypotension, shock, acute adrenal hemorrhage, and multiorgan failure.
Less common presentations of meningococcal disease include pneumonia (5% to 15% of cases), arthritis (2%), otitis media (1%), and epiglottitis (less than 1%).
The case-fatality ratio of meningococcal disease is 10% to 15%, even with appropriate antibiotic therapy. The case-fatality ratio of meningococcemia is up to 40%. As many as 20% of survivors have permanent sequelae, such as hearing loss, neurologic damage, or loss of a limb. Risk factors for the development of meningococcal disease include deficiencies in the terminal common complement pathway, functional or anatomic asplenia, and underlying chronic disease. Persons with HIV infection are probably at increased risk for meningococcal disease. Certain genetic factors (such as polymorphisms in the genes for mannose-binding lectin and tumor necrosis factor) may also be risk factors.
Household crowding, and both active and passive smoking are associated with increased risk. Persons with antecedent viral infection are also at increased risk. Early studies in the United States demonstrated that blacks and persons of low socioeconomic status were at higher risk for meningococcal disease than other persons; however, race and low socioeconomic status are likely markers for differences in factors such as smoking and household crowding rather than risk factors.
As disease incidence has decreased, differences by race have also decreased, and no difference in disease incidence exists now between blacks and whites. During outbreaks, bar or nightclub patronage and alcohol use have also been associated with higher risk for disease.
Cases of meningococcal disease, including at least two fatal cases, have been reported among microbiologists. These persons have worked with N. meningitidis isolates rather than patient specimens.
Laboratory Diagnosis
Meningococcal disease is typically diagnosed by isolation of N. meningitidis from a normally sterile site. However, sensitivity of bacterial culture may be low, particularly when performed after initiation of antibiotic therapy. A Gram stain of cerebrospinal fluid (CSF) showing gram-negative diplococci strongly suggests meningococcal meningitis. Real-time polymerase chain reaction (rt-PCR) detects DNA of meningococci in blood, cerebrospinal fluid, or other clinical specimens. Although culture remains the criterion standard for diagnosis of meningococcal disease in the
United States, PCR is useful for detection of N. meningitidis from clinical samples in which the organism could not be detected by culture methods, such as when a patient has been treated with antibiotics before obtaining a clinical specimen for culture.
Kits to detect polysaccharide antigen in cerebrospinal fluid are rapid and specific, but false-negative results are common, particularly in serogroup B disease. Antigen tests of urine or serum are unreliable.
Serologic testing (e.g., enzyme immunoassay) for antibodies to polysaccharide may be used as part of the evaluation if meningococcal disease is suspected, but should not be used to establish the diagnosis.
Medical Management
The clinical presentation of meningococcal meningitis is similar to other forms of bacterial meningitis. Consequently, empiric therapy with broad-spectrum antibiotics (e.g., third-generation cephalosporin, vancomycin) should be started promptly after appropriate cultures have been obtained.
Many antibiotics are effective for N. meningitidis infection, including penicillin. Few penicillin-resistant strains of meningococcus have been reported in the United States. Once N. meningitidis infection has been confirmed, penicillin alone is recommended.
Epidemiology
Occurrence
Meningococcal disease occurs worldwide in both endemic and epidemic form.
Reservoir
Humans are the only natural reservoir of meningococcus. As many as 10% of adolescents and adults are asymptomatic transient carriers of N. meningitidis, most strains of which are not pathogenic (i.e., strains that are not groupable).
Transmission
Primary mode is by respiratory droplet spread or by direct contact.
Temporal Pattern
Meningococcal disease occurs throughout the year, however, the incidence is highest in the late winter and early spring.
Communicability
The communicability of N. meningitidis is generally limited. In studies of households in which a case of meningococcal disease has occurred, only 3%–4% of households had secondary cases. Most households had only one secondary case. Estimates of the risk of secondary transmission are generally 2–4 cases per 1,000 household members at risk. However, this risk is 500–800 times that in the general population.
Neisseria meningitides: Clinical Features, Laboratory Diagnosis, and Medical Management,Neisseria meningitides: Clinical Features,Clinical Features, Laboratory Diagnosis,Neisseria meningitides, Clinical Features, Laboratory Diagnosis
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