Neisseria meningitidis

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Neisseria meningitidis
Neisseria meningitidis (cropped).png
Photomicrograph of N. meningitidis
Scientific classification
Kingdom: Bacteria
Phylum: Proteobacteria
Class: Betaproteobacteria
Order: Neisseriales
Family: Neisseriaceae
Genus: Neisseria
Species: N. meningitidis
Binomial name
Neisseria meningitidis
Albrecht & Ghon 1901

Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis[1] and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. N. meningitidis is a major cause of illness and death during childhood in industrialized countries and has been responsible for epidemics in Africa and in Asia.[2] The bacteria are round and are often joined in pairs. They are Gram-negative since they have outer and inner membranes with a thin layer of peptidoglycan in between. Cultures of the bacteria test positive for the enzyme cytochrome c oxidase.[3]

It exists as normal flora (nonpathogenic) in the nasopharynx of up to 5–15% of adults.[4] It causes the only form of bacterial meningitis known to occur epidemically. It is the main cause of bacterial meningitis in children and young adults, whereas Streptococcus pneumoniae (aka pneumococcus) is the most common bacterial cause of meningitis in middle-age and older adults, together with Staphylococcus aureus. Meningococci is only known to infect humans and has never been isolated from other animals; this is thought to stem from the bacterium's inability to get iron other than from human sources (transferrin and lactoferrin).[5]

Meningococcus is spread through the exchange of saliva and other respiratory secretions during activities like coughing, sneezing, kissing, and chewing on toys. It infects the host cell by sticking to it mainly with long thin extensions called pili and the surface-exposed proteins Opa and Opc.[6] Though it initially produces general symptoms like fatigue, it can rapidly progress from fever, headache and neck stiffness to coma and death. The symptoms of meningitis are easily confused with those caused by other organisms such as Hemophilus influenzae and Streptococcus pneumoniae.[7] Death occurs in approximately 10% of cases.[5] Those with impaired immunity may be at particular risk of meningococcus (e.g. those with nephrotic syndrome or splenectomy; vaccines are given in cases of removed or non-functioning spleens).


The growth of Neisseria meningitidis colonies on New York City Medium Agar

In 1884 Ettore Marchiafava and Angelo Celli first observed the bacterium inside cells in the cerebral spinal fluid (CSF).[8] Anton Weichselbaum in 1887 isolated the bacterium from the CSF of patients with bacterial meningitis.[9] He named the bacterium Diplococcus intracellularis meningitidis.[8]


Disease-causing strains are classified according to the antigenic structure of their polysaccharide capsule.[citation needed] Serotype distribution varies markedly around the world,[10] with type A being most prevalent in Africa and Asia but practically absent in North America hindered development of a universal vaccine for meningococcal disease. Among the 13 capsular types of N. meningitidis that have been identified, six of these (A, B, C, W135, X, and Y) account for most disease cases worldwide.[11] In the United States, serogroup B is the predominant cause of disease and mortality, followed by serogroup C.


Approximately 2500 to 3500 cases of N. meningitidis infection occur annually in the United States, with a case rate of about 1 in 100,000. Children younger than 5 years are at greatest risk, followed by teenagers of high school age. Rates in sub-Saharan Africa can be as high as 1 in 1000 to 1 in 100.[7]

Transmission occurs via inhalation of respiratory droplets from a carrier/patient who is themselves in the early stages of disease. Contact with a carrier is the predominant risk factor. Other risk factors include recent upper respiratory infection, smoking, and complement deficiency. In susceptible individuals, N. meningitidis may invade the bloodstream and cause systemic infection, intravascular coagulation, circulatory collapse and shock. The incubation period is short, from 2 to 10 days.

The incidence of meningococcal disease in the United States is highest among infants younger than 1-year-old with a second peak of incidence in young adults.


Lipooligosaccharide (LOS) is a component of the outer membrane of N. meningitidis which acts as an endotoxin which is responsible for septic shock and hemorrhage due to the destruction of red blood cells.[12] Other virulence factors include a polysaccharide capsule which prevents host phagocytosis and aids in evasion of the host immune response; and fimbriae which mediate attachment of the bacterium to the epithelial cells of the nasopharynx.[13][14] Further, meningococci make an IgA protease, an enzyme that cleaves IgA class antibodies and thus allows the bacteria to evade a subclass of the humoral immune system.

A hypervirulent strain was discovered in China. Its impact is yet to be determined.[7]

Signs and symptoms[edit]

Suspicion of meningitis is a medical emergency and immediate medical assessment is recommended. Current guidance in the United Kingdom is that if a case of meningococcal meningitis or septicaemia (infection of the blood) is suspected intravenous antibiotics should be given and the ill person admitted to the hospital.[15] This means that laboratory tests may be less likely to confirm the presence of Neisseria meningitidis as the antibiotics will dramatically lower the number of bacteria in the body. The UK guidance is based on the idea that the reduced ability to identify the bacteria is outweighed by reduced chance of death.

Septicaemia caused by Neisseria meningitidis has received much less public attention than meningococcal meningitis even though septicaemia has been linked to infant deaths.[16] Meningococcal septicaemia typically causes a purpuric rash that does not lose its color when pressed with a glass ("non-blanching") and does not cause the classical symptoms of meningitis. This means the condition may be ignored by those not aware of the significance of the rash. Septicaemia carries an approximate 50% mortality rate over a few hours from initial onset. Many health organizations advise anyone with a non-blanching rash to go to a hospital as soon as possible.[citation needed] Note that not all cases of a purpura-like rash are due to meningococcal septicaemia; however, other possible causes need prompt investigation as well (e.g. ITP a platelet disorder or Henoch-Schönlein purpura).

Other severe complications include Waterhouse-Friderichsen syndrome (a massive, usually bilateral, hemorrhage into the adrenal glands caused by fulminant meningococcemia), adrenal insufficiency, and disseminated intravascular coagulation.[7]


The gold standard of diagnosis is isolation of N. meningitidis from sterile body fluid.[7] A cerebrospinal fluid (CSF) specimen is sent to the laboratory immediately for identification of the organism. Diagnosis relies on culturing the organism on a chocolate agar plate. Further testing to differentiate the species includes testing for oxidase, catalase (all clinically relevant Neisseria show a positive reaction) and the carbohydrates maltose, sucrose, and glucose test in which N. meningitidis will ferment (that is, utilize) the glucose and maltose. Serology determines the subgroup of the organism.

If the bacteria reach the circulation, then blood cultures should be drawn and processed accordingly.

Clinical tests that are used currently for the diagnosis of meningococcal disease take between 2 and 48 hours and often rely on the culturing of bacteria from either blood or CSF samples. However, polymerase chain reaction tests can be used to identify the organism even after antibiotics have begun to reduce the infection. As the disease has a fatality risk approaching 15% within 12 hours of infection, it is crucial to initiate testing as quickly as possible but not to wait for the results before initiating antibiotic therapy.[7]


Persons with confirmed N. meningitidis infection should be hospitalized immediately for treatment with antibiotics. Indeed, because meningococcal disease can disseminate very rapidly, a single dose of intramuscular antibiotic is often given at the earliest possible opportunity, even before hospitalization, if disease symptoms look suspicious enough.[7] Third-generation cephalosporin antibiotics (i.e. cefotaxime, ceftriaxone) should be used to treat a suspected or culture-proven meningococcal infection before antibiotic susceptibility results are available.[17] Empirical treatment should also be considered if a lumbar puncture, to collect CSF for laboratory testing, cannot be done within 30 minutes of admission to hospital.[citation needed] Antibiotic treatment may affect the results of microbiology tests, but a diagnosis may be made on the basis of blood-cultures and clinical examination.[citation needed]


All recent contacts of the infected patient over the 7 days before onset should receive medication to prevent them from contracting the infection. This especially includes young children and their child caregivers or nursery-school contacts, as well as anyone who had direct exposure to the patient through kissing, sharing utensils, or medical interventions such as mouth-to-mouth resuscitation. Anyone who frequently ate, slept or stayed at the patient's home during the 7 days before the onset of symptom, or those who sat beside the patient on an airplane flight or classroom for 8 hours or longer, should also receive chemoprophylaxis (the agent of choice is usually oral rifampicin for a few days).[7]


Main article: Meningococcal vaccine

There are currently three vaccines available in the U.S. to prevent meningococcal disease for people aged 2 or older. All three vaccines are effective against the same serogroups: A, C, Y, and W-135. Two meningococcal conjugate vaccines (MCV4) are licensed for use in the U.S. The first conjugate vaccine was licensed in 2005, the second in 2010. Conjugate vaccines are the preferred vaccine for people 2 through 55 years of age. A meningococcal polysaccharide vaccine (MPSV4) has been available since the 1970s and is the only meningococcal vaccine licensed for people older than 55. MPSV4 may be used in people 2–55 years old if the MCV4 vaccines are not available or contraindicated. Information about who should receive the meningococcal vaccine is available from the Centers for Disease Control and Prevention (CDC).[18]

On June 14, 2012, the U.S. Food and Drug Administration (FDA) approved a new combination vaccine against two types of meningococcal diseases and Hib disease for infants and children 6 weeks to 18 months old. The vaccine, Menhibrix, will prevent disease caused by Neisseria meningitidis serogroups C and Y, and Haemophilus influenzae type b. This is the first meningococcal vaccine that can be given to infants as young as six weeks old.[19]

On October 29, 2014 the U.S. Food and Drug Administration approved Trumenba, which is the first vaccine to be effective against serogroup B. for individuals 10 to 25 in age. Now there is coverage for groups A, B, C, W, and Y.[20]

Genetic transformation[edit]

Genetic transformation is the process by which a recipient bacterial cell takes up DNA from a neighboring cell and integrates this DNA into the recipient’s genome by recombination. In N. meningitidis, DNA transformation requires the presence of short DNA sequences (9-10 mers residing in coding regions) of the donor DNA. These sequences are called DNA uptake sequences (DUSs). Specific recognition of DUSs is mediated by a type IV pilin.[21] Davidsen et al.[22] reported that in N. meningitides DUSs occur at a significantly higher density in genes involved in DNA repair and recombination (as well as in restriction-modification and replication) than in other annotated gene groups. These authors proposed that the over-representation of DUS in DNA repair and recombination genes may reflect the benefit of maintaining the integrity of the DNA repair and recombination machinery by preferentially taking up genome maintenance genes that could replace their damaged counterparts in the recipient cell.

N. meningititis is an exclusively human pathogen that colonizes the nasopharyngeal mucosa, a region that is rich in macrophages. Upon activation, macrophages produce superoxide (O2¯) and hydrogen peroxide (H2O2). Thus N. meningitides is likely to encounter oxidative stress during its life cycle.[23] Consequently an important benefit of genetic transformation to N. meningitides may be the maintenance of the recombination and repair machinery of the cell that functions to remove oxidative DNA damages such as those caused by reactive oxygen. This is consistent with the more general idea that transformation substantially benefits bacterial pathogens by facilitating repair of DNA damages produced by the oxidative defenses of the host during infection.[24]

See also[edit]


  1. ^ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 329–333. ISBN 0-8385-8529-9. 
  2. ^ Genco, C; Wetzler, L (editors) (2010). Neisseria: Molecular Mechanisms of Pathogenesis. Caister Academic Press. ISBN 978-1-904455-51-6. 
  3. ^ Neisseria meningitidis at Centers for Disease Control and Prevention. Page last reviewed: October 24, 2008
  4. ^ "Neisseria meningitidis". Brown University. Retrieved 22 October 2009. 
  5. ^ a b Meningococcal Disease (2001) Humana Press, Andrew J. Pollard and Martin C.J. Maiden
  6. ^ Hall, DJ; Griffiths, NJ; Borodina, E; Mumtaz, V (2010). "Cellular and molecular biology of Neisseria meningitidis colonization and invasive disease". Clinical Science 118 (9): 547–564. 
  7. ^ a b c d e f g h Mola SJ, Nield LS, and Weisse ME (February 27, 2008). "Treatment and Prevention of N. meningitidis Infection". Infections in Medicine. 
  8. ^ a b Stephens, David S. (2009). "Biology and pathogenesis of the evolutionarily successful, obligate human bacterium Neisseria meningitidis". Vaccine 27: B71–B77. doi:10.1016/j.vaccine.2009.04.070. ISSN 0264-410X. 
  9. ^ Bhalla, P; Manchanda, V; Gupta, S (2006). "Meningococcal disease: History, epidemiology, pathogenesis, clinical manifestations, diagnosis, antimicrobial susceptibility and prevention". Indian Journal of Medical Microbiology 24 (1): 7. doi:10.4103/0255-0857.19888. ISSN 0255-0857. 
  10. ^ [1]
  11. ^ Harrison, Lee H. (2010). "Epidemiological Profile of Meningococcal Disease in the United States". Clinical Infectious Diseases 50 (s2): S37–S44. doi:10.1086/648963. ISSN 1058-4838. 
  12. ^ Griffiss JM, Schneider H, Mandrell RE, Yamasaki R, Jarvis GA, Kim JJ, Gibson BW, Hamadeh R, Apicella MA. (1988). "Lipooligosaccharides: the principal glycolipids of the neisserial outer membrane". Rev Infect Dis. 10 Suppl 2: S287–95. doi:10.1093/cid/10.supplement_2.s287. PMID 2460911. 
  13. ^ Jarrell, K (editor) (2009). Pili and Flagella: Current Research and Future Trends. Caister Academic Press. ISBN 978-1-904455-48-6. 
  14. ^ Ullrich, M (editor) (2009). Bacterial Polysaccharides: Current Innovations and Future Trends. Caister Academic Press. ISBN 978-1-904455-45-5. 
  15. ^ Health Protection Agency Meningococcus Forum (August 2006). Guidance for public health management of meningococcal disease in the UK. Available online at:
  16. ^ Meningococcal Vaccines (2001) Humana Press, Andrew J. Pollard and Martin C.J. Maiden
  17. ^ Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ (November 2004). "Practice guidelines for the management of bacterial meningitis". Clin Infect Dis 39 (9): 1267–84. doi:10.1086/425368. PMID 15494903. 
  18. ^ "Menningococcal Vaccines – What You Need to Know" (2008). Center for Disease Control and Prevention.
  19. ^ FDA approves new combination vaccine that protects children against two bacterial diseases, FDA Press Release, June 14, 2012
  20. ^ First vaccine approved by FDA to prevent serogroup B Meningococcal disease, FDA Press Release, October 29, 2014
  21. ^ Cehovin A, Simpson PJ, McDowell MA, Brown DR, Noschese R, Pallett M, Brady J, Baldwin GS, Lea SM, Matthews SJ, Pelicic V (February 2013). "Specific DNA recognition mediated by a type IV pilin". Proc. Natl. Acad. Sci. U.S.A. 110 (8): 3065–70. doi:10.1073/pnas.1218832110. PMC 3581936. PMID 23386723. 
  22. ^ Davidsen T, Rødland EA, Lagesen K, Seeberg E, Rognes T, Tønjum T (2004). "Biased distribution of DNA uptake sequences towards genome maintenance genes". Nucleic Acids Res. 32 (3): 1050–8. doi:10.1093/nar/gkh255. PMC 373393. PMID 14960717. 
  23. ^ Dyet K, Moir J (February 2006). "Effect of combined oxidative and nitrosative stress on Neisseria meningitidis". Biochem. Soc. Trans. 34 (Pt 1): 197–9. doi:10.1042/BST0340197. PMID 16417521. 
  24. ^ Michod RE, Bernstein H, Nedelcu AM (May 2008). "Adaptive value of sex in microbial pathogens". Infect. Genet. Evol. 8 (3): 267–85. doi:10.1016/j.meegid.2008.01.002. PMID 18295550.