Neisseria meningitidis

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

Neisseria meningitidis is a heterotrophic gram-negative diplococcal bacterium best known for its role in meningitis[1] and other forms of meningococcal disease such as meningococcemia. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries and is responsible for epidemics in Africa and in Asia.[2]

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.[3]

Anton Weichselbaum in 1887 first discovered the disease in patients infected with meningococci [4].

Meningococci only infect humans and have never been isolated from animals because the bacterium cannot get iron other than from human sources (transferrin and lactoferrin).[5]

It exists as normal flora in the nasopharynx of up to 5-15% of adults. [6] It causes the only form of bacterial meningitis known to occur epidemically.

Meningococcus is spread through the exchange of saliva and other respiratory secretions during activities like coughing, kissing, and chewing on toys. Though it initially produces general symptoms like fatigue, it can rapidly progress from fever, headache and neck stiffness to coma and death. The symptoms are easily confused with those of meningitis due to other organisms such as Hemophilus influenzae and Streptococcus pneumoniae.[3] Death occurs in approximately 10% of cases.[7] 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).

Suspicion of meningitis is a medical emergency and immediate medical assessment is recommended. Current guidance in the United Kingdom is that any doctor who suspects a case of meningococcal meningitis or septicaemia (infection of the blood) should give intravenous antibiotics (benzylpenicillin or Cefotaxime) and admit the ill person to the hospital.[8] 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. [9] Meningococcal septicaemia typically causes a purpuric rash that does not lose its colour 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 emergency room as soon as possible. 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 [3].

Contents

Virulence

Lipooligosaccharide (LOS) is a component of the outer membrane of N. meningitidis which acts as an endotoxin which is responsible for fever, septic shock, hemorrhage due to the destructions of RBC.[10] 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.[11][12]

Recently a hypervirulent strain was discovered in China. Its impact is yet to be determined.[3]

Mechanisms of cellular invasion

N. meningitidis is an extracellular human-specific pathogen responsible for septicemia and meningitis. Like most bacterial pathogens, N. meningitidis exploits host cell signaling pathways to promote its uptake by host cells. N.meningitidis does not have a type III nor a type IV secretion system.[13] The signaling leading to bacterial internalization is induced by the type IV pili, which are the main means of bacterial adhesion onto cells. The signaling induced following Type IV pilus-mediated adhesion is responsible for the formation of microvilli-like structures at the site of the bacterial-cell interaction.[11] These microvilli trigger the internalization of the bacteria inside the cells. A major consequence of these signaling events is a reorganization of the actin cytoskeleton, which leads to the formation of membrane protrusion, engulfing bacterial pathogens into intracellular vacuoles. Efficient internalization of N. meningitidis also requires the activation of an alternative signaling pathway coupled with the activation of the tyrosine kinase receptor ErbB2. Beside Type IV pili, other outer membrane proteins may be involved in other mechanism of bacteria internalization inside cells.[14]

Diagnosis

The gold standard of diagnosis is isolation of N. meningitidis from sterile body fluid.[3] A 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 (all Neisseria show a positive reaction) and the carbohydrates maltose, sucrose, and glucose test in which N. meningitidis will oxidize (that is, utilize) the glucose and maltose. Serology determines the group of the isolated organism.

If the organism reaches the circulation, then blood cultures should be drawn and processed accordingly.

Quintain NS and RMIT University have developed a rapid diagnostic test for meningococcal disease, which will ultimately provide results in under 15 minutes.

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 cerebrospinal fluid (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.[3]

Quintain is working with Melbourne-based company Charlwood Design, to produce a prototype clinical device that will incorporate a mechanism for safe sample handling and delivery. It is expected that the diagnostic test will be available within 2-3 years, with the nanoparticulate gold diagnostic platform adapted for a range of other clinically important diseases shortly thereafter.

Treatment

Patients with documented N. meningitidis infection should be hospitalized immediately for treatment with antibiotics (penicillin G, ceftriaxone, and cefotaxime)and for PCN sensitive individual [chlorampenicol] is the drug of choice and supportive care. Studies supporting the use of corticosteroids are inconclusive.[3]

Prevention

All recent contacts of the infected patient over the 7 days before onset should receive medication (rifampin, ceftriaxone, or ciprofloxacin) 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 of 8 hours or longer, should also receive chemoprophylaxis.[3]

There are currently two vaccines available in the US to prevent meningococcal disease. Meningococcal conjugate vaccine (MCV4) was licensed in the U.S. in 2005. It is the preferred vaccine for people 2 through 55 years of age. Meningococcal polysaccharide vaccine (MPSV4) has been available since the 1970s. It may be used if MCV4 is not available, and is the only meningococcal vaccine licensed for people older than 55. Information about who should receive the meningococcal vaccine is available from the Centers for Disease Control and Prevention (CDC)[15].

See also

References

  1. ↑ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 329–333. ISBN 0838585299. 
  2. ↑ Genco, C; Wetzler, L (editors) (2010). Neisseria: Molecular Mechanisms of Pathogenesis. Caister Academic Press. ISBN 978-1-904455-51-6. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Mola SJ, Nield LS, and Weisse ME (February 27, 2008). "Treatment and Prevention of N. meningitidis Infection". Infections in Medicine. http://www.consultantlive.com/headache/article/1145625/1403886. 
  4. ↑ van Deuren, M., Brandtzaeg, P., and van der Meer, J .W. .M. (2000). Update on meningoccal disease with emphasis on pathogenesis and clinical management. Clinical Microbiological Reviews. 13, 144-166
  5. ↑ Meningococcal Disease (2001) Humana Press, Andrew J. Pollard and Martin C.J. Maiden
  6. ↑ "Neisseria meningitidis". http://www.brown.edu/Courses/Bio_160/Projects1999/bmenin/nmenin.html. Retrieved 22 October 2009. 
  7. ↑ Meningococcal Disease (2001) Humana Press, Andrew J. Pollard and Martin C.J. Maiden
  8. ↑ Health Protection Agency Meningococcus Forum (August 2006). Guidance for public health management of meningococcal disease in the UK. Available online at: http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1194947389261
  9. ↑ Meningococcal Vaccines (2001) Humana Press, Andrew J. Pollard and Martin C.J. Maiden
  10. ↑ "Lipooligosaccharides: the principal glycolipids of the neisserial outer membrane." Griffiss JM, et al. Rev Infect Dis. 1988 Jul-Aug;10 Suppl 2:S287-95. http://www.ncbi.nlm.nih.gov/pubmed/2460911
  11. ↑ 11.0 11.1 Jarrell, K (editor) (2009). Pili and Flagella: Current Research and Future Trends. Caister Academic Press. ISBN 978-1-904455-48-6. 
  12. ↑ Ullrich, M (editor) (2009). Bacterial Polysaccharides: Current Innovations and Future Trends. Caister Academic Press. ISBN 978-1-904455-45-5. 
  13. ↑ Wooldridge, K (editor) (2009). Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis. Caister Academic Press. ISBN 978-1-904455-42-4. 
  14. ↑ Carbonnelle E et al. (2010). "Mechanisms of Cellular Invasion of Neisseria meningitidis". Neisseria: Molecular Mechanisms of Pathogenesis. Caister Academic Press. ISBN 978-1-904455-51-6. 
  15. ↑ "Menningococcal Vaccines - What You Need to Know" (2008). Center for Disease Control and Prevention. http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-mening.pdf