Neisseria Meningitidis Overview

Humans are the only natural hosts for meningococci
Transmitted by airborne droplets
Colonizes the nasopharynx and becomes part of the normal flora
Carriers are usually asymptomatic
From the nasopharynx, meningococci can enter the bloodstream and spread to specific sites (e.g., meninges or joints) or be disseminated throughout the body (meningococcemia)

About 5% of people become chronic carriers
Carriage rate can be high (35%) in people who live in close quarters (e.g., military recruits), explaining the high frequency of meningitis outbreaks in the armed forces
Carriage rate is also high in patients' close (family) contacts
Outbreaks of meningococcal disease also occur in college students living in dormitories
Meningococci are the second most common cause of meningitis
Most common cause of meningitis in persons between the ages of 2 and 18 years

Polysaccharide capsule: resists phagocytosis by polymorphonuclear leukocytes (PMNs)
Endotoxin: causes fever, shock, and other pathophysiologic changes
IgA protease: cleaves secretory IgA, helping the bacteria attach to the membranes of the upper respiratory tract

Meningococcemia and meningitis are the most important manifestations of disease
Most severe form of meningococcemia is the life-threatening Waterhouse-Friderichsen syndrome, characterized by high fever, shock, widespread purpura, disseminated intravascular coagulation, thrombocytopenia and adrenal insufficiency
Meningococcal meningitis symptoms include fever, headache, stiff neck, and increased levels of PMNs in spinal fluid

Smear and culture of blood and spinal fluid samples are the principal laboratory procedures
Presumptive diagnosis of meningococcal meningitis can be made if gram-negative cocci are seen in a smear of spinal fluid
Organism grows best on chocolate agar incubated at 37°C in a 5% CO2 atmosphere
Presumptive diagnosis of Neisseria can be made if oxidase-positive colonies of gram-negative diplococci are found
Differentiation between N. meningitidis and N. gonorrhoeae is made by sugar fermentation: meningitidis ferments maltose while gonococci do not (both ferment glucose)
Immunofluorescence can also be used to identify species
Serum antibody tests are not useful for clinical diagnosis
Latex agglutination test detects capsular polysaccharides in spinal fluid, assisting in rapid diagnosis of meningococcal meningitis

Gonococci, like meningococci, cause disease only in humans
Usually transmitted sexually; newborns can be infected during birth
Transmission favored by sexual activity, as gonococci are sensitive to dehydration and cool conditions
Gonorrhea is usually symptomatic in men but often asymptomatic in women
Genital tract infections are the most common infection source, but anorectal and pharyngeal infections are also important

Pili: mediate attachment to mucosal cell surfaces and are antiphagocytic. Piliated gonococci are usually virulent; nonpiliated strains are avirulent
Endotoxin (Lipopolysaccharide, LOS) and outer membrane proteins are virulence factors in the cell wall
IgA protease: hydrolyzes secretory IgA, which could otherwise block attachment to the mucosa
No capsules

Antibodies (IgA and IgG), complement, and neutrophils are the main host defenses against gonococci
Antibody-mediated opsonization and killing within phagocytes occur, but repeated gonococcal infections are common due to antigenic changes of pili and the outer membrane proteins

Gonococci primarily infect mucosal surfaces, but dissemination occurs
Certain strains of gonococci cause disseminated infections more frequently than others
These strains are resistant to being killed by antibodies and complement
The presence of a porin protein (porin A) in the cell wall, which inactivates the C3b component of complement, plays an important role in this "serum resistance"

Gonococci cause localized infections (usually in the genital tract) and disseminated infections with seeding of various organs.
Gonococci reach organs via the bloodstream (gonococcal bacteremia)
Gonorrhea in men is characterized by urethritis, accompanied by dysuria and a purulent discharge. Epididymitis can occur.
Infection in women is primarily located in the endocervix, causing purulent vaginal discharge and intermenstrual bleeding (cervicitis)
The most frequent complication in women is an ascending infection of the uterine tubes (salpingitis, PID: Pelvic Inflammatory Disease), which can result in sterility or ectopic pregnancy due to scarring of the tubes
Disseminated gonococcal infections (DGI) commonly manifest as arthritis, tenosynovitis, or pustules in the skin.
DGI is the most common cause of septic arthritis in sexually active adults.
Clinical diagnosis of DGI is difficult to confirm using laboratory tests as the organism is not cultured in more than 50% of cases.

Anorectal area, throat, and eyes can be infected
Anorectal infections are frequently asymptomatic in women and homosexual men, but a bloody or purulent discharge (proctitis) can occur
Pharyngitis occurs in the throat, but many patients are asymptomatic.
Purulent conjunctivitis (ophthalmia neonatorum) in newborn infants results from gonococcal infection acquired from the mother during passage through the birth canal
Gonococcal conjunctivitis also occurs in adults due to transfer of organisms from the genitals to the eye

The incidence of gonococcal ophthalmia has declined greatly due to the widespread use of prophylactic erythromycin eye ointment (or silver nitrate) shortly after birth

Other sexually transmitted infections (e.g., syphilis and non-gonococcal urethritis caused by Chlamydia trachomatis) can coexist with gonorrhea
Appropriate diagnostic and therapeutic measures must be taken

Diagnosis of urogenital infections depends on Gram staining and culture of the discharge
Nucleic acid amplification tests are widely used as screening tests
The finding of gram-negative diplococci within PMNs in a urethral discharge specimen is sufficient for diagnosis in men
The use of the Gram stain alone is difficult to interpret in women. Cultureshould be done.
Cervical Gram stains can be falsely positive due to the presence of gram-negative diplococci in the normal flora, and falsely negative due to the inability to see small numbers of gonococci with the oil immersion lens
Cultures must be used to diagnose suspected pharyngitis or anorectal infections

Specimens from mucosal sites (such as the urethra and cervix) are cultured on Thayer-Martin medium, a chocolate agar containing antibiotics (vancomycin, colistin, trimethoprim, and nystatin) to suppress the normal flora.
The finding of an oxidase-positive colony composed of gram-negative diplococci is sufficient to identify the isolate as a member of the genus Neisseria
Specific identification of the gonococcus can be made by its fermentation of glucose (but not maltose) or by fluorescent-antibody staining