Neisseria meningitidis
Overview
, 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. N. meningitidis is a major cause of morbidity and mortality in childhood in industrialized countries and is responsible for epidemics in Africa and in Asia. Anton Weichselbaum in 1887 was first reported the disease from patients infected with meningococci [2]. It is known that meningococci only infects human and never been reported from animals because the bacterium cannot get iron other than human source (transferrin and lactoferrin)[3] 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. 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.[4] 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.[5] 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.
Causes
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
Treatment
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. Six serogroups, A, B, C, Y, W135 and X 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. The occurrence of serogroup X was reported in North America, Europe, Australia, and West Africa[7] and the serogroups A,C,Y and W-135 Meningoccocal meningitis vaccine is not known to protect from serogroup X N. meningitidis disease. * 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 NmVac4-A/C/Y/W-135 (not has been licensed in the US) 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, NmVac4-A/C/Y/W-135 - DT). Menomune has a number of problems. The duration of action is short (3 years or less in children aged under 5),[8][9] 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.[10][11] 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.[12][13] 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).[14] 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.