Neisseria meningitidis

Neisseria meningitidis

Although N. meningitidis can be found in the nasopharynx and oropharynx of 3% to 30% of asymptomatic

individuals, it is an etiologic agent of endemic and epidemic meningitis, meningococcemia, and rarely

pneumonia, purulent arthritis, or endophthalmitis. N. meningitidis has also been recovered from urogenital

and rectal sites as a result of oral-genital contact.

Virulence Factors

With few exceptions, N. meningitidis exhibits the same cellular structural characteristics as N. gonorrheoae:

the virulence factors pili, polysaccharide capsule, the cellular membrane proteins (Por, Opa, Rmp), and LOS

endotoxin. PorA and PorB are both produced in the meningococcus, whereas only PorB is expressed in

the gonococcus. Many virulent meningococcal strains produce IgAj protease, an enzyme that aids invasiveness.

Like the gonococcus, the outer membrane structures, or blebs, are seen during rapid growth. Of the 13 meningococcal serogroups, the encapsulated strains A, B, C, Y, and W-135 are most often associated with

epidemics. Group A strains are often incriminated in pandemics. Serogroups Band C are most common in

the United States, with group B frequently being involved in community-acquired disease. Serogroup Y

primarily causes meningococcal pneumonia, whereas W-135 is often responsible for invasive disease. Clinical



The primary sources of epidemic meningitis are oral secretions or respiratory droplets from asymptomatic carriers, especially among close contacts in closed populations such as college dormitories and military barracks. Epidemic meningitis most often occurs in young adults. It is characterized by abrupt onset of frontal headache, stiff neck (nuchal rigidity), and sometimes fever.

When N. meningitidis enters the bloodstream, two main diseases may occur: fulminant meningococcemia or meningitis. Meningococcemia, or sepsis, may occur with or without meningitis and carries a 25% mortality rate, even if treated. Purpura (hemorrhaging of blood into the skin and mucous membranes producing bruises) with petechial skin rash (pinpoint red spot caused by hemorrhage, Figure 18-10,A), tachycardia, and hypotension may develop during bacteremia, and

thrombosis is common. In some cases, the disease becomes fulminant and spreads rapidly, causing disseminated intravascular coagulation (DIC), septic shock, or hemorrhage in the adrenal glands (Waterhouse- Friderichsen syndrome; Figure 18-10, B). Death may occur in 12 to 48 hours from onset. Individuals with a deficiency in complement components C5 to C8 are at increased risk of meningococcemia. Meningococcal pneumonia usually affects older individuals with underlying

pulmonary problems.


Laboratory Diagnosis

Specimen Collection and Transport

Culture specimens for N. meningitidis may come from a wide variety of sterile and nonsterile sites. These include cerebrospinal fluid (CSF), blood, nasopharyngeal swabs and aspirates, and less commonly, sputum and urogenital sites. Collection and transport should be performed as specified by the laboratory for the various specimen types. When commercial blood culture systems are used, data from the manufacturer should be consulted to determine whether N. meningitidis can be routinely recovered or whether techniques such as blind subculture (subculture to CHOCfrom bottle with

no apparent visual growth) are required.


Direct Microscopic Examination

On Gram-stained smears from specimens such as CSF, the meningococci appear as intracellular and extracellular gram-negative diplococci (Figure 18-11). Encapsulated strains may have a halo around the organisms.

The highest yield of positive CSF Gram stains is obtained when specimens are concentrated. A number of investigators have reported that concentration by cytocentrifugation is superior to that by traditional centrifugation and has the potential to increase Gram stain detection by 10-to lOa-fold. In a patient with disseminated meningococcemia who has petechiae from hemorrhage of surface blood vessels, an impression Gram stain smear is often positive for gram-negative diplococci. Culture

Selective and nonselective media for the isolation of N meningitidis should, like cultures for N gonorrhoeae,

be incubated under carbon dioxide. N meningitides and the commensal Neisseria spp. will grow on sheep

blood agar (SBA) and CHOC. N meningitidis grown on SBA under CO2 produce bluish-gray colonies. N

meningitidis will grow on gonococcal selective agars and produce small, gray, sometimes mucoid, convex

colonies on sheep blood or CHOC agars (Figure 18-12). N lactamica. generally a nonpathogenic species that may mimic N meningitidis, can also grow on selective media. The lactose-positive characteristic of

N lactamica may be delayed or nonexistent. A rapid o-nitrophenyl-f)-d-galactopyranoside (ONPG) test, which

detects lactose utilization, is usually positive in :30minutes for N lactamica. See Chapter 9 for a description

of the ONPG test.



The oxidase and catalase tests should be performed on all isolates. Any of the carbohydrate utilization tests

described earlier can be used to speciate N meningitidis. Optimal results in these tests are obtained when

a fresh subculture of the organism is used. Serogrouping of the meningococci is most commonly done by

slide agglutination.

Although rare, glucose negative, maltose negative, asaccharolytic strains of N meningitidis have been

isolated. Maltose-negative strains could be misidentified as N gonorrhoeae, especially from genital or

other unusual sites. Maltose negative strains may lack the maltose phosphorylase pathway; this occurs mainly in serogroup B but also rarely in groups C and y. To avoid misidentification of maltose-negative

strains, other means of identification in addition to carbohydrate utilization should be used. These include the use of chromogenic substrate confirmation tests and serogrouping. One useful test included in some

identification systems is gamma glutamyl aminopeptidase, which is usually positive in N meningitides and negative in N gonorrhoeae, N lactam, ica and M. catarrhalis. Immunologic methods such as latex agglutination are commercially available in kits and are used to detect the group-specific surface antigens of N meningitidis. These bacterial antigen tests, when performed on CSF, blood, or urine, often allow more rapid detection of a causative organism, but due to lack of sensitivity, they should not replace culture and Gram stain.


Laboratory-Acquired Disease

In 2000, two cases of fatal laboratory-acquired meningococcal disease were reported to the CDC. Both clinical

microbiologists had examined plates, performed Gram stains, subcultured, and/or performed slide agglutination serogrouping on patient isolates on the open bench. Isolates recovered from the clinical laboratory scientists were identical to patient organisms. A retrospective survey identified 16 probable laboratoryacquired

meningococcal infections worldwide from 1996 to 2001. Because exposure to N meningitides aerosols increases risk of infection, the CDC recommends use of a biosafety level-2 cabinet for manipulation of suspected isolates of N meningitidis from sterile sites.



The drug of choice for treatment of confirmed N meningitidis meningitis is penicillin, but rifampin or a

sulfonamide is recommended as prophylaxis for close contacts. Patients with meningococcemia are best treated with third-generation cephalosporins.



In January 2005, the U.S. Food and Drug Administration (FDA) approved Menactra, a new meningococcal

vaccine for use in people 11 to 55 years of age. This vaccine, like the previous quadrivalent vaccine,

contains polysaccharide antigens to serogroups A, C, Y, and W-135. In Menactra, however, these antigens are

conjugated to diphtheria toxoid protein; this conjugate vaccine is expected to provide long-term immunity.

This vaccine, like its predecessor, does not protect against meningitis caused by serogroup B, one of the

most common serotypes causing infection in the United States, because group B polysaccharide is a

very poor immunogen in humans. The Advisory Committee on Immunization Practices recommends the vaccine be administered to students 11 to 12 years of age, those entering high school (15 years of age), and college freshmen living in dormitories.

Meningococcal vaccine is also recommended for military recruits, asplenic patients more than 2 years of age, and travelers to areas with epidemic disease. In October 2005, the FDA and the CDC issued a health advisory for Menactra. Five cases of Guillain- Barre syndrome (GBS), a serious neurologic syndrome, were reported following vaccination. It is unknown whether the GBS was associated with the vaccine or was just coincidental.

figure 18-11 figure 18-12 figure 18-12 table 18-6 figure 18-10

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