Microbiology & infectious diseases

• Colonizes mucosal surfaces, especially oropharynx and nasopharynx (Carroll: Manual of Clinical Microbiology, 12th Edition, 2019)
  • Colonization rates are highest among young adults (~16 - 23 years old)
  • Only found in humans
• Invasive meningococcal disease occurs in < 1/100,000 in the U.S. but has a case fatality rate of nearly 15% (Clin Infect Dis 2018;66:1276)
  • Risk factors for development of invasive disease include complement deficiencies, immunosuppression (e.g., eculizumab) and asplenia or functional asplenia
  • Disruption of mucosa such as by concomitant viral infection or smoking may increase risk of disease
• Outbreaks of invasive disease are associated with transmission of certain serogroups (Methods Mol Biol 2012;799:1)
  • Only 6 serogroups cause invasive meningococcal disease: A, B, C, W135, X, Y
  • Serogroups B, C and Y are the most common in the U.S.
  • Serogroup A is most common in sub-Saharan African countries (meningitis belt region), with attack rates that can exceed 1/1,000 (Ann Trop Med Parasitol 1997;91:777)
  • Hyperinvasive lineages identified in several large outbreaks (Clin Infect Dis 2003;36:679)

• Person to person transmission likely by inhalation of respiratory droplets
• Type IV pili, outer membrane proteins (Opa, Opc, PorA, PorB) and lipooligosaccharide (LOS) mediate adhesion and contribute to colonization of epithelial surfaces (Clin Sci (Lond) 2010;118:547)
  • Also mediate intracellular uptake and survival, allowing subepithelial spread and dissemination
• Most strains produce capsules, which are composed of variable polysaccharides that determine the serogroup
  • Capsules aid in immune evasion, especially of the complement system (Front Cell Infect Microbiol 2022;12:1020201)
  • Strains that do not produce capsules rarely cause disease

• Positive cultures should always be handled in a class II biological safety cabinet to avoid exposure and laboratory acquired infection
• Fastidious organism; avoid desiccation and limit transportation time of specimens to maximize recovery
• Culture (Carroll: Manual of Clinical Microbiology, 12th Edition, 2019)
  • Can be recovered on sheep blood and chocolate agar grown at 35 °C with 3 - 7% carbon dioxide
  • Does not grow on MacConkey agar
  • Growth in blood culture media may be inhibited by sodium polyanethole sulfonate (SPS), a common media additive
  • For nonsterile sources such as respiratory, can culture on selective media such as Thayer-Martin, New York City agar
• Identification
  • Gram stain: gram negative diplococci, coffee bean appearance; may appear intracellular
  • Colony morphology: smooth, gray, convex, nonhemolytic
  • Oxidase test positive
  • Identification of Neisseria species by matrix assisted laser desorption ionization time of flight (MALDI TOF) mass spectrometry should be confirmed by an additional identification method such as carbohydrate utilization test
  • Carbohydrate utilization tests (e.g., CarboFerm Neisseria Kit, Hardy Diagnostics) assess differential ability to oxidize glucose, maltose, sucrose, lactose
    • N. gonorrhea: glucose positive only
    • N. meningitidis: glucose and maltose positive
  • Serogrouping may be done by latex or slide agglutination
• Invasive meningococcal disease is a nationally reportable condition

• 2 year old boy with meningococcal meningitis (World J Clin Cases 2019;7:636)
• 26 year old man with urethritis (Sex Transm Dis 2011;38:439)
• 58 year old smoking woman with community acquired pneumonia (Chest 2017;152:e95)

Contributed by Elizabeth M. Garrett, Ph.D.

Contributed by Elizabeth M. Garrett, Ph.D.

A 19 year old man with functional asplenia presents to the emergency department with headache, nausea, fever and hypotension. Blood cultures are negative but a Gram stain on cerebrospinal fluid shows small, gram negative diplococci. Which of the following is a significant virulence factor of this organism?

1. Coagulase
2. Hemolysin
3. Peptidoglycan
4. Polysaccharide capsule

D. Polysaccharide capsule. This organism’s description is consistent with Neisseria meningitidis which are gram negative diplococci that may not grow in blood cultures in a patient with possible sepsis and meningitis. N. meningitidis may or may not produce capsule; however, capsule is produced by nearly all isolates that cause invasive disease and is a significant virulence trait that allows immune evasion.

Answers A and B are incorrect because N. meningitidis does not produce coagulase and is nonhemolytic. Answer C is incorrect because peptidoglycan is a component of bacterial cell walls and is not a virulence factor.

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Reference: Neisseria meningitidis

A 25 year old woman rapidly develops septic shock, including petechiae on her palate, conjunctiva and trunk. Blood cultures grow gram negative diplococci that appear encapsulated. On subculture, the organism grows on sheep’s blood agar and chocolate agar but does not grow on MacConkey plates. Which of the following is a significant risk factor for infection by this organism?

1. CARD9 deficiency
2. Chronic granulomatous disease
3. Terminal complement pathway deficiency
4. Thalassemia

C. Terminal complement pathway deficiency. This organism’s description is consistent with Neisseria meningitidis which are gram negative diplococci that may appear encapsulated, grows on sheep’s blood and chocolate but not MacConkey agar and may cause fulminant septic shock including petechiae. Defects in the terminal complement pathway, including congenital or as a result of immunosuppressive drugs such as eculizumab, increase the risk of infection by encapsulated bacteria including N. meningitidis, Haemophilus influenzae and Streptococcus pneumoniae.

CARD9 deficiency, chronic granulomatous disease and thalassemia can increase a patient’s risk for infection but have no specific association with N. meningitidis. Answer A is incorrect because CARD9 deficiency confers susceptibility to fungal infections such as candidiasis. Answer B is incorrect because chronic granulomatous disease can lead to recurrent infections most commonly in the lung by common pathogens including Staphyloccocus aureus, Serratia, Nocardia and Aspergillus. Answer D is incorrect because thalassemia can increase the overall risk of infection but not specifically N. meningitidis infection unless the patient has undergone a splenectomy.

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Reference: Neisseria meningitidis