Neisseria Meningitidis Overview

Neisseria Meningitidis

• Humans are the only natural hosts for meningococci.
• Transmitted by airborne droplets
• Colonizes the membranes of the nasopharynx
• Part of the transient flora of the upper respiratory tract
• Carriers are usually asymptomatic.
• Can enter the bloodstream and spread to specific sites, such as the meninges or joints.
• May be disseminated throughout the body (meningococcemia).
• About 5% of people become chronic carriers.
• Carriage rate can be as high as 35% in people who live in close quarters. This explains high frequency of meningitis outbreaks in the armed forces before the use of the vaccine.
• Carriage rate is also high in patients’ close (family) contacts.
• Outbreaks of meningococcal disease also have occurred in college students living in dormitories.

Virulence Factors

• A polysaccharide capsule enables the organism to resist phagocytosis by polymorphonuclear leukocytes (PMNs).
• Endotoxin, which causes fever, shock, and other pathophysiologic changes (in purified form, endotoxin can reproduce many of the clinical manifestations of meningococcemia).
• An immunoglobulin A (IgA) protease that helps the bacteria attach to the membranes of the upper respiratory tract by cleaving secretory IgA.

Clinical Findings

• The two most important manifestations of disease are meningococcemia and meningitis.
• Waterhouse-Friderichsen syndrome is the most severe form of meningococcemia. It is characterized by high fever, shock, widespread purpura, disseminated intravascular coagulation, thrombocytopenia, and adrenal insufficiency.
• Bacteremia can result in the seeding of many organs, especially the meninges.
• Meningococcal meningitis symptoms: fever, headache, stiff neck, and an increased level of PMNs in spinal fluid.

Laboratory Diagnosis

• The principal laboratory procedures are smear and culture of blood and spinal fluid samples.
• A presumptive diagnosis of meningococcal meningitis can be made if gram-negative cocci are seen in a smear of spinal fluid.
• The organism grows best on chocolate agar incubated at 37°C in a 5% CO2 atmosphere.
• A 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 on the basis of sugar fermentation: meningococci ferment maltose, whereas gonococci do not (both organisms ferment glucose).
• Immunofluorescence can also be used to identify these species.
• Tests for serum antibodies are not useful for clinical diagnosis.
• The latex agglutination test detects capsular polysaccharides in the spinal fluid. This test can be used to rapidly diagnose meningococcal meningitis.

Neisseria Gonorrhoeae

• Gonococci, like meningococci, cause disease only in humans.
• The organism is usually transmitted sexually; newborns can be infected during birth.
• Because gonococcus is quite sensitive to dehydration and cool conditions, sexual transmission favors its survival.
• Gonorrhea is usually symptomatic in men but often asymptomatic in women.
• Genital tract infections are the most common source of the organism, but anorectal and pharyngeal infections are important sources as well.

Virulence Factors

• Pili mediate attachment to mucosal cell surfaces and are antiphagocytic. Piliated gonococci are usually virulent, whereas nonpiliated strains are avirulent.
• Two virulence factors in the cell wall are endotoxin (Lipopolysaccharide, LOS) and the outer membrane proteins.
• The organism's IgA protease can hydrolyze secretory lgA, which could otherwise block attachment to the mucosa.
• Gonococci have no capsules.

Host Defenses

• 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, primarily as a result of antigenic changes of pili and the outer membrane proteins.

Clinical Findings

• Gonococci infect primarily the mucosal surfaces (e.g., the urethra and vagina), but dissemination occurs.
• Certain strains of gonococci cause disseminated infections more frequently than others.
• The most important feature of these strains is their resistance to being killed by antibodies and complement.
• The mechanism of this "serum resistance" is uncertain, but the presence of a porin protein (porin A) in the cell wall, which inactivates the C3b component of complement, appears to play an important role.
• Gonococci cause both localized infections, usually in the genital tract, and disseminated infections with seeding of various organs.
• Gonococci reach these organs via the bloodstream (gonococcal bacteremia).
• Gonorrhea in men is characterized primarily by urethritis accompanied by dysuria and a purulent discharge. Epididymitis can occur.
• In women, infection is located primarily in the endocervix, causing a purulent vaginal discharge and intermenstrual bleeding (cervicitis).
• The most frequent complication in women is an ascending infection of the uterine tubes (salpingitis, PID). PID can result in sterility or ectopic pregnancy as a result of scarring of the tubes.
• Disseminated gonococcal infections (DGI) commonly manifest as arthritis, tenosynovitis, or pustules in the skin.
• Disseminated infection is the most common cause of septic arthritis in sexually active adults.
• The clinical diagnosis of DGI is often difficult to confirm using laboratory tests because the organism is not cultured in more than 50% of cases.

Other Infected Sites

• Other infected sites include the anorectal area, throat, and eyes.
• Anorectal infections occur chiefly in women and homosexual men. They are frequently asymptomatic, but a bloody or purulent discharge (proctitis) can occur.
• In the throat, pharyngitis occurs, but many patients are asymptomatic.
• In newborn infants, purulent conjunctivitis (ophthalmia neonatorum) is the result of gonococcal infection acquired from the mother during passage through the birth canal.
• The incidence of gonococcal ophthalmia has declined greatly in recent years because of the widespread use of prophylactic erythromycin eye ointment (or silver nitrate) applied shortly after birth.
• Gonococcal conjunctivitis also occurs in adults as a result of the transfer of organisms from the genitals to the eye.
• Other sexually transmitted infections (e.g., syphilis and non-gonococcal urethritis caused by Chlamydia trachomatis) can coexist with gonorrhea; therefore, appropriate diagnostic and therapeutic measures must be taken.

Laboratory Diagnosis

• The diagnosis of urogenital infections depends on Gram staining and culture of the discharge. However, nucleic acid amplification tests are widely used as screening tests.
• In men, the finding of gram-negative diplococci within PMNs in a urethral discharge specimen is sufficient for diagnosis.
• In women, the use of the Gram stain alone can be difficult to interpret; therefore, cultures should be done.
• Gram stains on cervical specimens can be falsely positive because of the presence of gram-negative diplococci in the normal flora and can be falsely negative because of the inability to see small numbers of gonococci when using the oil immersion lens.
• Cultures must also be used in diagnosing suspected pharyngitis or anorectal infections.
• Specimens from mucosal sites, such as the urethra and cervix, are cultured on Thayer-Martin medium, which is 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 either by its fermentation of glucose (but not maltose) or by fluorescent-antibody staining.

Neisseria Meningitidis

• Humans are the only hosts for Neisseria meningitidis.
• Transmission occurs via airborne droplets.
• Colonizes nasopharynx and becomes part of the transient flora.
• Carriers are usually asymptomatic.
• Can enter the bloodstream and spread to meninges, joints, or throughout the body (meningococcemia).
• Roughly 5% of people become chronic carriers, serving as infection sources.
• High carriage rates observed in close quarters (e.g., military recruits, college dorms).
• A major cause of bacterial meningitis in infants over 2 months.
• Particularly group A is associated with epidemics.
• Group B meningococci common in developed countries.
• Second most common cause of meningitis overall, but most common in 2-18 year olds.

Meningococci Virulence Factors

• Polysaccharide capsule: resists phagocytosis by PMNs.
• Endotoxin: causes fever, shock, and other pathophysiologic changes.
• IgA protease: helps bacteria attach to upper respiratory tract membranes.

Clinical Findings

• Meningococcemia and meningitis are the major manifestations.
• Waterhouse-Friderichsen syndrome is the most severe form of meningococcemia, characterized by fever, shock, purpura, disseminated intravascular coagulation, thrombocytopenia, and adrenal insufficiency.
• Symptoms of meningococcal meningitis include fever, headache, stiff neck, and increased PMNs in spinal fluid.

Laboratory Diagnosis

• Smear and culture of blood and spinal fluid samples are crucial.
• Presumptive diagnosis of meningococcal meningitis can be made if gram-negative cocci are observed in a spinal fluid smear.
• Grows best on chocolate agar incubated at 37°C in a 5% CO2 atmosphere.
• Presumptive diagnosis of Neisseria can be made with oxidase-positive colonies of gram-negative diplococci.
• Differentiate between N. meningitidis and N. gonorrhoeae by sugar fermentation (meningococci ferment maltose, gonococci do not, both ferment glucose).
• Immunofluorescence can also identify these species.
• Serum antibody tests are not useful for clinical diagnosis.
• Latex agglutination test detects capsular polysaccharides in spinal fluid, facilitating rapid diagnosis.

Neisseria Gonorrhoeae

• Like meningococci, only infects humans.
• Usually transmitted sexually, with newborns susceptible during birth.
• Sensitive to dehydration and cool conditions, favoring sexual transmission.
• Often asymptomatic in women, but usually symptomatic in men.
• Genital tract infections are the primary source, but anorectal and pharyngeal infections are also significant.

Neisseria Gonorrhoeae Virulence Factors

• Pili: mediate attachment to mucosal cell surfaces and are antiphagocytic.
• Endotoxin (Lipopolysaccharide, LOS) and outer membrane proteins are virulence factors in the cell wall..
• IgA protease hydrolyzes secretory IgA.
• Gonococci do not have capsules.
• Main host defenses include antibodies (IgA and IgG), complement, and neutrophils.

Neisseria Gonorrhoeae Disease

• Primarily infects mucosal surfaces (urethra, vagina).
• Can cause disseminated infections via bloodstream (gonococcal bacteremia).
• In men, urethritis with dysuria and purulent discharge is common, with epididymitis possible.
• In women, endocervical infection causing purulent vaginal discharge and intermenstrual bleeding (cervicitis) is prevalent.
• Salpingitis (PID) is a common complication in women, potentially leading to sterility or ectopic pregnancy.
• Disseminated gonococcal infections (DGI) often present as arthritis, tenosynovitis, or skin pustules.
• DGI is a common cause of septic arthritis in sexually active adults.
• Diagnosis can be challenging due to low culture positivity rates in DGI.

Other Infected Sites

• Anorectal infections occur mainly in women and homosexual men, often asymptomatic but may cause proctitis.
• Pharyngitis can occur, though frequently asymptomatic.
• In newborns, purulent conjunctivitis (ophthalmia neonatorum) is caused by gonococcal infection acquired during birth.

Ophthalmia Neonatorum

• Incidence has declined due to widespread prophylactic erythromycin eye ointment or silver nitrate treatment at birth.
• Gonococcal conjunctivitis in adults can occur due to transference from genitals to the eye.

Coexisting Infections

• Other sexually transmitted infections (syphilis, chlamydia) can coexist with gonorrhea, necessitating appropriate testing and treatment.

Laboratory Diagnosis

• Diagnosis of urogenital infections relies on Gram staining and culture of discharge.
• Nucleic acid amplification tests are widely used for screening.
• In men, gram-negative diplococci within PMNs in urethral discharge warrant diagnosis.
• In women, Gram stains are more complex to interpret, necessitating cultures.
• Cultures are essential for suspected pharyngitis or anorectal infections.

Culture Techniques

• Specimens from mucosal sites (urethra, cervix) are cultured on Thayer-Martin medium (chocolate agar with antibiotics) to suppress normal flora.
• Oxidase-positive colonies of gram-negative diplococci indicate Neisseria.
• Specific identification of gonococci is achieved by glucose fermentation (but not maltose) or fluorescent-antibody staining.

Neisseria Meningitidis

• Humans are the primary host for meningococci - transmitted through airborne droplets.
• Meningococci colonize the nasopharynx and become part of the transient flora, often without symptoms.
• Carriers can become chronic and spread the infection, particularly in close proximity (military recruits, families).
• Meningococci are a common cause of meningitis, especially in children and young adults, second only to Streptococcus pneumoniae.
• Meningococci possess three crucial virulence factors:
  • Polysaccharide capsule: hinders phagocytosis by polymorphonuclear leukocytes (PMNs).
  • Endotoxin: responsible for fever, shock, and other systemic effects.
  • Immunoglobulin A (IgA) protease: helps bacteria attach to the respiratory tract by cleaving secretory IgA.
• Meningococcal disease manifests in two major forms:
  • Meningococcemia: bacteremia leading to complications like Waterhouse-Friderichsen syndrome (severe shock, purpura, disseminated intravascular coagulation, thrombocytopenia, adrenal insufficiency).
  • Meningitis: inflammation of the meninges with symptoms including fever, headache, stiff neck, and increased PMN count in spinal fluid.
• Laboratory diagnosis relies on smears and cultures of blood & spinal fluid.
  • Gram-negative cocci in spinal fluid smear suggest meningococcal meningitis.
  • Growth on chocolate agar at 37°C with 5% CO2.
  • Oxidase-positive colonies of gram-negative diplococci indicate Neisseria.
  • Meningococci differentiate from gonococci by fermenting maltose.
  • Immunofluorescence and latex agglutination tests (detecting capsular polysaccharides) are also used.

Neisseria Gonorrhoeae

• Gonococci, like meningococci, infect only humans, primarily via sexual transmission.
• Gonococci are sensitive to dehydration and cool conditions, explaining their preference for sexual transmission.
• Gonorrhea commonly produces symptoms in men (urethritis, dysuria, purulent discharge), but often presents asymptomatically in women.
• Major virulence factors:
  • Pili: mediate attachment and antiphagocytic properties. Piliated strains are virulent, nonpiliated strains are avirulent.
  • Endotoxin (LOS): triggers inflammatory responses.
  • Outer membrane proteins: play various roles in infection.
  • IgA protease: breaks down secretory IgA, facilitating mucosal adherence.
• Gonococci do not possess capsules.
• Host defenses are antibodies (IgA, IgG), complement, and neutrophils.
• Gonococci can evade immune responses through antigenic variations of pili and outer membrane proteins.
• Gonococcal infections primarily target mucosal surfaces (urethra, vagina), but may spread systemically through bacteremia.
• Disseminated gonococcal infections (DGI) are associated with strains resistant to antibody and complement destruction.
• DGI commonly presents as arthritis, tenosynovitis, or skin pustules and often involves porin protein (porin A), which inactivates complement.
• Clinical manifestations:
  • Gonorrhea in men: urethritis with dysuria & purulent discharge, epididymitis.
  • Gonorrhea in women: endocervicitis with purulent vaginal discharge & intermenstrual bleeding, salpingitis (Pelvic inflammatory disease) leading to sterility or ectopic pregnancy.
  • DGI: arthritis, tenosynovitis, skin pustules.
• Other infection sites: anorectal area (proctitis), throat (pharyngitis), eyes (ophthalmia neonatorum, conjunctivitis in adults).
• Ophthalmia neonatorum occurs in newborns during birth; its incidence has decreased due to prophylactic erythromycin or silver nitrate at delivery.
• Co-infection with syphilis or Chlamydia trachomatis is possible; proper diagnosis and treatment are crucial.

Laboratory Diagnosis

• Urogenital infections are diagnosed through Gram staining and cultures.
• Nucleic acid amplification tests are widely used for screening.
• Gram-negative diplococci within PMNs in urethral discharge indicate gonorrhea in men.
• Gram stains in women are less reliable, so cultures are essential.
• Gram stains on cervical specimens are prone to false positives (normal flora) or false negatives (low gonococcal numbers).
• Cultures are also required for pharyngitis and anorectal infections.
• Mucosal samples are cultured on Thayer-Martin medium (chocolate agar with antibiotics) to suppress normal flora.
• Oxidase-positive, gram-negative diplococcal colonies indicate Neisseria.
• Gonococcal identification is confirmed through glucose fermentation (but not maltose) or fluorescent-antibody staining.

Neisseria Meningitidis

• Humans are the sole natural hosts for meningococci.
• Spread occurs through airborne droplets, colonizing the nasopharynx.
• Carriers are typically asymptomatic.
• Meningococci can enter the bloodstream and spread to various sites, including the meninges, joints, and cause meningococcemia.
• Approximately 5% of individuals become chronic carriers and serve as a source of infection.
• The carriage rate can rise to 35% in close-living environments, explaining meningitis outbreaks in military recruits prior to vaccination.
• Outbreaks have also occurred in college dormitories.
• Meningococci are a leading cause of bacterial meningitis in infants over 2 months old, alongside Streptococcus pneumoniae.
• Among these, N. meningitidis, particularly group A, is the most likely to cause meningitis epidemics.
• Group B meningococci are frequent causes of meningitis in developed countries.
• Overall, N. meningitidis is the second most common cause of meningitis, after S. pneumoniae, but the most prevalent in individuals aged 2-18 years.

Meningococci Virulence Factors

• Polysaccharide capsule: Resists phagocytosis by polymorphonuclear leukocytes (PMNs).
• Endotoxin: Causes fever, shock, and other pathophysiological changes; mimics clinical manifestations of meningococcemia in its purified form.
• IgA protease: Aids bacterial attachment to upper respiratory tract membranes by cleaving secretory IgA.

Meningococci Clinical Manifestations

• Meningococcemia: The most severe form is Waterhouse-Friderichsen syndrome, characterized by high fever, shock, widespread purpura, disseminated intravascular coagulation, thrombocytopenia, and adrenal insufficiency.
• Meningitis: Symptoms include fever, headache, stiff neck, and elevated PMNs in spinal fluid.

Meningococci Laboratory Diagnosis

• Smear and Culture: Blood and spinal fluid samples are examined.
• Gram-Negative Cocci in Spinal Fluid: Suggestive of meningococcal meningitis.
• Growth on Chocolate Agar: Optimal growth at 37°C in a 5% CO2 atmosphere.
• Oxidase-Positive Colonies: Presumptive identification of Neisseria.
• Sugar Fermentation: Differentiation between N. meningitidis and N. gonorrhoeae is based on maltose fermentation (positive in N. meningitidis, negative in N. gonorrhoeae).
• Immunofluorescence: Used for species identification.
• Latex Agglutination Test: Rapid diagnosis detects capsular polysaccharides in spinal fluid.

Neisseria Gonorrhoeae

• Humans are the only known hosts for gonococci.
• Transmitted primarily through sexual contact.
• Newborns can acquire infection during birth.
• Gonococci are sensitive to dehydration and cool conditions, favoring sexual transmission.
• Infection is often symptomatic in males, but typically asymptomatic in females.
• Genital tract infections are the main source, with anorectal and pharyngeal infections also contributing.

Neisseria Gonorrhoeae Virulence Factors

• Pili: Mediate attachment to mucosal cell surfaces and are antiphagocytic. Piliated gonococci are virulent, while nonpiliated strains are avirulent.
• Endotoxin (Lipopolysaccharide): Found in the cell wall.
• Outer Membrane Proteins: Located in the cell wall.
• IgA Protease: Hydrolyzes secretory IgA, preventing its blockage of mucosal attachment.
• Absence of a Capsule: Gonococci lack capsules.
• Host Defenses: Antibodies (IgA and IgG), complement, and neutrophils provide resistance to gonococci.
• Antigenic Variation: Repeated infections are frequent, predominantly due to antigenic changes in pili and outer membrane proteins.

Neisseria Gonorrhoeae Clinical Manifestations

• Localized Infections: Primarily occur in the genital tract (urethra, vagina).

• Disseminated Infections: Gonococci can spread through the bloodstream (gonococcal bacteremia) to various organs.

• Gonorrhea in Men: Characterized by urethritis with dysuria and purulent discharge. Epididymitis can occur.

• Gonorrhea in Women: Infection typically affects the endocervix, causing a purulent vaginal discharge and intermenstrual bleeding (cervicitis).

Neisseria Gonorrhoeae Clinical Manifestations (Continued)

• Salpingitis (PID): Ascending infection of uterine tubes can lead to sterility or ectopic pregnancy due to tubal scarring.
• Disseminated Gonococcal Infections (DGI): Commonly present with arthritis, tenosynovitis, and skin pustules.
• DGI in Sexually Active Adults: The most common cause of septic arthritis.
• Other Sites of Infection: Anorectal area (proctitis), throat (pharyngitis), and eyes (ophthalmia neonatorum).
• Ophthalmia Neonatorum: Gonococcal conjunctivitis in newborns acquired from the mother during childbirth.
• Prophylactic Erythromycin Eye Ointment: Widely used to reduce the incidence of gonococcal ophthalmia.
• Adult Gonococcal Conjunctivitis: Results from transfer of organisms from genitals to the eye.
• Co-infection with other STIs: Gonorrhea can coexist with syphilis and Chlamydia trachomatis infections.
• Appropriate diagnostic and therapeutic measures are crucial.

Neisseria Gonorrhoeae Laboratory Diagnosis

• Urogenital Infections: Diagnose through Gram staining and culture of discharge. Nucleic acid amplification tests are used for screening.
• Gram-Negative Diplococci in Urethral Discharge: In men, sufficient for diagnosis.
• Interpretation of Gram Stains in Women: Can be difficult due to normal flora and small numbers of gonococci. Cultures are recommended.
• Culture for Pharyngitis and Anorectal Infections: Specimens from mucosal sites are cultured on Thayer-Martin medium (chocolate agar with antibiotics).
• Oxidase-Positive Colony: Sufficient to identify the isolate as a member of the Neisseria genus.
• Specific Identification: Gonococci are distinguished by glucose fermentation (but not maltose) or fluorescent-antibody staining.