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, also simply known as meningococcus, is a heterotrophic gram-negative diplococcal bacterium best known for its role in meningitis^[1] and other forms of meningococcal disease such as meningococcemia.

It only infects humans; there is no animal reservoir, and it exists as normal flora in the nasopharynx of up to 40% of adults. It causes the only form of bacterial meningitis known to cause epidemics.

Contents 1 Strains 2 Infection 3 Virulence 4 Diagnosis 5 Vaccines 6 References

Strains

There are many strains of meningococcus, which are differentiated based on the chemical composition of their polysaccharide capsule. The most clinically important are A, B, C, X, Y and W135:

• A occurs most often in sub-saharan Africa and vaccination is recommended prior to travel with the Men A&C vaccine.
• B is the most lethal form, comprising 40% of UK cases. The changing nature of the B group has prevented formation of a general B vaccine in the UK. However there has been developed the vaccine MeNZB against a specific strain of group B meningococcus, currently being used to control an epidemic in New Zealand. Previously, an earlier neisseria meningitidis vaccine against subtype B was not effective because the sialic acid residues of the capsule are similar to humans.
• C caused approximately 60% of UK cases before the introduction of successful vaccination program for infants. Previously the unconjugated C component of Men A&C was ineffective in those under 2 years. The development of a conjugated form (Men C conj) was needed to provoke infant immunity.
• W135 is particularly a problem for those undergoing annual pilgrimage to Mecca. It is a requirement of Saudi Arabia that all those intending to go on Hajj have a certificate of Men W135 vaccination.
• X: A broad outbreak of meningitis caused by serogroup X was reported in Niger in 2006.^[2] This outbreak is particularly worrying because there is not currently any vaccine against this strain.
• Y: In the last decade serogroup Y has emerged as a cause of disease in Northern America

Other strains include 29-E, H, I, K, L, and Z.

Infection

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 with general symptoms like fatigue, it can rapidly progress from fever, headache and neck stiffness to coma and death. Death occurs in approximately 10% of cases. 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.^[3] 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. Meningococcal septicaemia typically causes a purpuric rash that does not turn white 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).

Waterhouse-Friderichsen syndrome is a massive, usually bilateral, hemorrhage into the adrenal glands caused by fulminant meningococcemia.

Virulence

Lipooligosaccharide (LOS) is a component of the cell wall of N. meningitidis which acts as an endotoxin. 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.

Diagnosis

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. As the disease has a fatality risk approaching 15% within 12 hours of infection, early diagnosis and antibiotic treatment is crucial.

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.

Vaccines

There are currently two vaccines available in the US to prevent meningococcal disease. Menactra is licensed for use in people aged 11 to 55, while Menomune is used for people outside of this age group and for travellers.

Neisseria meningitidis has 13 clinically significant serogroups. These are classified according to the antigenic structure of their polysaccharide capsule. Five serogroups, A, B, C, Y and W135 are responsible for virtually all cases of the disease in humans. There is currently no effective vaccine for serogroup B, although a putative vaccine is currently undergoing clinical trials in Malta.

• Polysaccharide vaccines
• Conjugate vaccines

The two quadrivalent (i.e., targeting serogroups A, C, W-135 and Y) meningococcal vaccines available in the US are MCV-4 (a conjugate vaccine Menactra introduced in January 2005) and MPSV-4 (a polysaccharide vaccine marketed as Menomune), both produced by Sanofi Pasteur; Mencevax of GlaxoSmithKline and NmVac of JN-International Medical Corporation are also commonly used. Unfortunately, there is currently no evidence that any of the current vaccines offer significant protection beyond 18 months (plain polysaccharide vaccine Menomune, Mencevax and NmVac-4) to three years (polysaccharide protein conjugate vaccine Menactra, NmVac-4 DT).

Menomune has a number of problems. The duration of action is short (3 years or less in children aged under 5),^[4][5] because it does not generate memory T-cells. Attempting to overcome this problem by repeated immunisation results in a diminished, not increased antibody response, so boosters are not indicated with this vaccine.^[6][7] In common with all polysaccharide vaccines, Menomune does not produce mucosal immunity, so people can still become colonised with virulent strains of meningococcus, and no herd immunity develops.^[8][9] For this reason, Menomune is suitable for travellers requiring only short term protection, but not in national public health programmes.

Menactra contains the same antigens as Menomune, but the antigens are conjugated to diphtheria toxoid. It is hoped that this formulation will overcome the limitations of Menomune. Menactra is currently licensed only for use in people aged 11 to 55, therefore people outside of this age group can only be offered Menomune.

A study published in March 2006 comparing the two vaccines found that 76% of subjects still had passive protection three years after receiving MCV-4 (63% protective compared with controls), but only 49% has passive protection after receiving MSPV-4 (31% protective compared with controls).^[10] This has implications for the timing of recommendations for when meningococcal vaccines should be given, because there is currently no evidence that any of the current vaccines offer continued protection beyond three years.

References