by Gabrielle Ménard and Gabrielle Rappaport

Introduction

Neisseria meningitidis, also referred to as meningococcus, is the causative agent of meningococcal diseases, such as meningitis. The first description of the disease was by Vieusseux in 1805, during an epidemic in Geneva, Switzerland. Later, in 1887, Weichselbaum provided the first identification of the Neisseria meningitidis bacterium, from the cerebrospinal fluid of a patient suffering from meningitis. The only natural reservoir for N. meningitidis is humans; there is no confirmed animal reservoir.

Disease

N. meningitidis is transmitted from person to person through respiratory droplets or direct secretions. Close contact with an infected person, such as living with them or exchanging fluids through kissing, puts one at high risk of infection. N. meningitidis first settles in the nasopharyngeal (nose and throat) cells of an individual, where it can colonize and multiply. In some cases, it will cross the mucosal layer and enter the bloodstream, evading the immune system by expressing specialized virulent structure. (Figure 1). Another severe case is when N. meningitidis crosses the blood-brain barrier (a structure separating the circulating blood from the brain and spinal cord) and enters the cerebrospinal (brain and spinal) fluid.

Furthermore, there are both pathogenic and non-pathogenic serotypes of N. meningitidis. Serotypes are subdivisions of a species that contain bacteria that are closely related and distinguishable by their surface proteins. Pathogenic serotypes can cause meningococcal meningitis, when N. meningitidis crosses the BBB to the meninges, causing headaches and fever, sensitivity to light, muscular rigidity, confusion, and possibly death. If the bacterium is in the blood, meningococcal septicemia can occur, which can lead to purpura fulminans, a non-blanching purple-blue rash. This form of disease can also induce septic shock, consisting of low blood pressure, organ failure and potentially death.

Epidemiology

Meningococcal disease has been found to vary around the world from very rare (0.5 cases per 100 000 a year in North America, <1/100 000 in Europe) to around 1000 cases per 100 000 population a year (in Africa). People living in the African “meningitis belt”, ranging from Ethiopia to Senegal, are at highest risk of contracting the disease. In this specific area, outbreaks occur every 5-10 years. N. meningitidis carriage happens in 8-25% of the human population, a major portion of which are young children, adolescents and young adults. Carriage can be and is usually asymptomatic, not causing infection in the carrier. Before proper treatment was available, the mortality rate of systemic meningococcal disease was 70-90%. Currently, it is reduced a lot in comparison, but is still considered to be high, at 10-15%. In the largest meningococcal epidemic outbreak recorded in 1996-1997 in Africa, 300,000 cases of serotype A infection resulted in 30,000 deaths.

Virulence systems:

Neisseria meningitidis is an extracellular pathogen, meaning that it colonizes and proliferates in the extracellular fluid and blood. To escape the body’s defences, the major asset of N. meningitidis is the biosynthesis of a capsule made of sialic acid that covers the bacteria and protects it from the host’s immune system. Following its entry in the host, the capsule will prevent the antimicrobial peptides (AMPs) present in the mucus layers of the throat from degrading and killing the invading bacteria. The capsule will also hide the bacteria from professional eating cells of the immune system called phagocytes. They will not be able to recognize it as a foreign invader, and therefore it will not be eaten and degraded by phagocytosis. Finally, encapsulated bacteria are further protected because the polysaccharide coating has low affinity for complement proteins. The complement system is formed by the association and binding of several host proteins on the surface of extracellular bacterial pathogens, leading to the formation of the MAC complex which perforates the surface of the bacteria and kills it.

Neisseria meningitidis will reach the blood stream where it will proliferate, still protected by its capsule. To be able to cross the blood brain barrier, a structure called the Tfp pili (type IV pili) must be expressed. Pili are rope-like projections on the surface of bacteria made of several assembled subunits called pilin. (Figure 2) They allow bacteria to adhere to host cells through adhesion molecules present at their tip. In this case, it is responsible for adhesion to endothelial cells of the brain, which triggers an intracellular signalling pathway in the host cells. This signalling leads to the disruption of the junctions between the hosts cells, allowing Neisseria meningitidis to cross the endothelial layer and reach the cells of the central nervous system and the meninges. The retraction of the pili also provides motility to the bacteria, allowing it to move across surfaces.

Treatment:

Antibiotic treatment must be started as soon as a Neisseria meningitidis infection is suspected, as the damage it causes can be very severe and irreversible. A sample of blood or cerebrospinal fluid is also usually taken and analysed to confirm the diagnosis. A variety of different antibiotics can be effective against N. meningitidis, penicillin being the most widely used. It fights the infection by disrupting the bacterial cell wall and creating small holes in it. The cell’s content will then leak out, which causes its death. Some strains are now becoming resistant to penicillin, so ceftriaxone is also used. However, even with antibiotic treatment, patients can be left with severe disabilities like lost limbs or brain damage. Vaccination is therefore the most effective way to prevent such consequences.

References:

Center for Disease Control and Prevention. (2015). Meningococcal disease. Retrieved from: http://www.cdc.gov/meningococcal/about/diagnosis-treatment.html

Coureuil, M., Join-Lambert, O., Lécuyer, H., Bourdoulous, S., Marullo, S., & Nassif, X. (2012). Mechanism of meningeal invasion by Neisseria meningitidis. Virulence, 3(2), 164–172.

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Halperin, S. A., Bettinger, J. A., Greenwood, B., Harrison, L. H., Jelfs, J., et al. (2012). The changing and dynamic epidemiology of meningococcal disease. Vaccine, 30, 26-36.

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Stephens, D. S., Greenwood, B., & Brandtzaeg, P. (2007). Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. The Lancet, 369, 9580, 2196-2210.