Neisseria Meningitidis (Student notes)

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Neisseria Meningitidis, also known as meningococcus, is non-motile, gram-negative cocci that cluster in pairs. They are one of the most common causes of bacterial meningitis, a severe infection of the central nervous system that can result in death in a matter of hours.

The bacterium most commonly affects younger individuals, especially in crowded settings such as in schools, institutions, and festivals. Because of its potential to cause severe disease, prompt diagnosis, and aggressive treatment with antibiotics are essential.

Laboratory features

They are seen as 2 small, red-stained, paired cocci when viewed under the microscope. Because of this, they are known as diplococci.

Neisseria Meningitidis is an encapsulated bacterium as it posses an outer polysaccharide capsule, containing capsular antigens. These antigens enable us to group different strains into serogroups.

At least 13 different capsular antigens have been identified and the most virulent belongs to serogroups A, B, and C.

Neisseria Meningitidis is a fastidious bacterium that grows best on media containing 5-10% CO2. They are very sensitive to drying, heat, disinfectants, and antibiotics. They are able to grow on chocolate agars as well as the selective medium Thayer-martin medium.

Neisseria Meningitidis is oxidase-positive, which means that they possess cytochrome c oxidase enzymes. These are able to utilize both glucose and maltose as carbon and energy sources.

Virulence factors

Neisseria Meningitidis share many virulence factors with its family member Neisseria gonorrhea (causative agent of the STD Gonorrhea), which includes membrane proteins, enzymes, and adhesive proteins and structures.

First of all, the meningococci possess an outer polysaccharide capsule which protects the bacterium from phagocytosis by immune cells. It also expresses pili which aid the bacteria in adhering to mucosal surfaces, usually the epithelium of the nasopharynx. 

This is further aided by its ability to express an IgA protease enzyme which enables the bacterium to cleave and inactivate IgA antibodies present on mucosal surfaces.

Neisseria Meningitidis also express Opa proteins which facilitate binding and internalization into mucosal epithelial cells. Furthermore, they express the porin proteins PorB and PorA, which are able to inhibit activation of neutrophils as well as the maturation of phagosomes. 

This enables the bacterium to reside within immune cells like neutrophils, evading the immune system.

Finally, Neisseria Meningitidis also express lipooligosaccharides in their membrane which can have a toxic effect in the host organism if released due to cell lysis in patients with meningococcal infections, resulting in severe, disseminated meningococcal disease (more later).

Disease/infection

Meningococcus usually colonizes the nasopharynx of asymptomatic carriers and is transmitted by respiratory droplets from these carriers, or from sick individuals in the early stages of the disease. 

Neisseria Meningitidis is one of the leading causes of bacterial meningitis. Outbreaks most often occur in winter and early spring in crowded areas where there is close contact between individuals such as in schools, institutions, and festivals.

Once Neisseria Meningitidis colonizes the nasopharynx, it first results in a relatively asymptomatic meningococcal pharyngitis. However, in young children and in other susceptible individuals, the bacteria can cause disseminated disease by spreading through the blood, leading to meningitis and/or septicemia.

Meningitis

The epithelial lining of the nasopharynx normally serves as a barrier to bacteria, however, as a rare event, meningococci are able to penetrate this barrier and enter the bloodstream where they multiply rapidly, causing bacteremia (meningococcemia). 

This may not be very severe and some patients may only have a slight fever and other nonspecific symptoms. In some cases, the disseminated bacteria are able to cross the blood-brain barrier, infecting the meninges. Here it can multiply and induce an acute inflammatory response, accompanied by an influx of neutrophils, resulting in purulent meningitis.

Symptoms of meningitis include an initial fever that can develop into a severe headache accompanied by a stiff neck, vomiting, and sensitivity towards bright lights. The disease and symptoms can progress very rapidly, and After the onset of the severe symptoms, coma and death can occur within hours.

Other symptoms, such as joint symptoms and a petechial and/or purpuric rash are also commonly observed in meningococcal infections.

Meningococcal septicaemia

Up to 30% of patients with meningitis progress to fulminant septicemia, mainly due to the release of the bacterial endotoxin LOS (lipooligosaccharides). The condition is severe and is associated with symptoms such as the appearance of large, purple, blotchy skin hemorrhages (purpura), vomiting, diarrhea, and circulatory collapse.

The appearance of purpuric rashes in meningococcal septicemia is due to the release of the bacterial endotoxin LOS once infected cells are destroyed. Once, released, this toxin is able to activate clotting factor XII (Hageman factor), which initiates intravascular blood coagulation, known as disseminated intravascular coagulopathy (DIC).

DIC uses up most of the coagulation factors in the blood, resulting in many small microhemorrhages under the skin (purpura), which is basically leakage of blood due to a lack of coagulation factors.

Acute fulminant meningococcal septicemia is more prevalent among young children. These children are also prone to develop Waterhouse-Friedrichsen syndrome which is acute adrenal gland failure due to bleeding in the adrenal glands.

When patients with meningococcal septicemia experience circulatory collapse, the hypotension can result in gangrene as tissues don’t receive enough blood to maintain tissue integrity. This usually occurs in the extremities, in which case patients might require amputation in order to survive.

Overall, meningococcal infections is a very severe disease that tends to strike young, previously healthy individuals resulting in death in a matter of hours. Because of this, prompt diagnosis and aggressive treatment is essential.

Diagnosis

When suspecting a meningococcal infection, blood and cerebrospinal fluid (CSF) cultures should be drawn to be cultivated on chocolate agars in order to identify any bacteria present in these otherwise sterile solutions.

However, treatment can be not be delayed by laboratory diagnostics, especially cultivation, which can take days. Therefore, other rapid laboratory tests also exist.

When performing a lumbar puncture and taking samples of the CSF, gram staining can be performed immediately. If positive, the sample often shows contamination of neutrophils and meningococci.

In addition, latex agglutination tests with serogroup-specific anticapsular antibodies can be used to obtain rapid presumptive identification of the serogroup of the infecting meningococcus bacteria.

In the case of screening individuals for the carriage in the nasopharynx, swab samples are obtained in an effort to cultivate the bacteria. For this type of cultivation, the selective Thayer-Martin medium should be used.

Although this sample may be positive for Neisseria bacteria, it can be both Neisseria Gonorrhoeae and Neisseria Meningitidis. In this case observation of the bacterias, sugar utilization enables us to separate between the two, as Neisseria Meningitidis can utilize both glucose and maltose, but Neisseria Gonorrhoeae can only utilize glucose.

Treatment

As mentioned, laboratory tests should not delay the treatment of meningitis. If suspected, laboratory samples should be obtained immediately followed by treatment with antibiotics. 

Neisseria Meningitidis can be effectively treated with penicillin and ampicillin. The bacteria do not produce b-lactamases that can inactivate these antibacterial agents, and they can both readily pass the blood-brain barrier to fight the infection. 

Some patients may only present with septicemia, in which case the etiology of the infection can be unclear. In these cases, cefotaxime or ceftriaxone is recommended as it has a broader spectrum and is effective against several, potentially severe infections Including urinary tract infections and pneumonia, as well as meningitis.

Prevention

A conjugate meningococcal vaccine (MCV4) exists and is approved for use in adolescents and adults between 11 and 55 years of age. This vaccine is highly recommended to individuals traveling to countries with a high prevalence of meningococcal meningitis (e.g. meningitis belt in Africa).

Because Neisseria Meningitidis often causes outbreaks of meningitis in crowded areas where there is close contact between people. Individuals which have come into contact with an infected individual (friends, family, etc.) are usually treated with prophylactic rifampin or ciprofloxacin.