Neisseria Meningitidis, also called meningococcus, is an aerobic gram-negative diplococcal bacterium and belongs to the Neisseriance family. There are 13 known serogroups of N. meningitidis, of which 6 serogroups can cause life-threatening diseases. These are the serogroups A, B, C, W-135 and Y. Infection with N. Meningitidis can cause the disease Meningococcosis. The incidence of meningococcosis is highest in countries in sub-Saharan Africa, in the so-called meningitis belt. During serious epidemics the incidence in these countries is 1,000 per 100,000 people.1 In these countries it is mainly serogroup A that causes the disease.3 In Europe and North America the incidence is 1-3 per 100,000. In these countries it is mainly subgroup B that causes disease. The other disease-causing subgroups occur worldwide.
Habitat
The human nasopharynx is the natural habitat of N. meningitidis; it is a commensal bacterium. The majority of people will carry the bacteria in their throat at some point, albeit asymptomatically. These people are then so-called carriers who can infect others. The incidence of carriage is highly dependent on age and is particularly high in adolescents and young adults. Studies have shown that in the absence of an epidemic, approximately 10% of healthy people carry N. Meningitidis in the upper part of the body. the respiratory tract.3 Only a few carriers become ill.
People at increased risk of developing meningococcosis after infection with N. Meningitidis are: children under 5 years of age, teenagers, young adults, smokers, people with influenza or an infection with a mycoplasma bacterium, carriers of a strain that is not yet protected against immunity has been built up, persons with a complement deficiency of C3, C5-C8 and properdin and persons with a deficiency in bactericidal antibodies.
Virulence factors
The virulence factors of the bacterium are: the presence of a capsule, endotoxins and membrane proteins, such as pili, Opa and Opc and porA and porB that promote the attachment of the bacterium to the host cell. Other factors that influence virulence are rapid multiplication and phase and antigenic variation through genetic switches.
Spread
Infection and therefore the spread of the bacteria takes place aerogenously via droplets from the nasopharyngeal cavity (speaking, singing, coughing, sneezing) or via direct contact (kissing). Infection and prevalence are therefore especially high in populations that live close together, such as in a student house or on a military base. N. Meningitis enters the human body through inhalation and can enter the bloodstream through the mucous membrane of the nasopharynx. The bacteria that are able to survive and multiply in the bloodstream can then cross the blood-brain barrier. The most characteristic syndromes associated with Meningococcosis are therefore meningitis (meningitis) and sepsis (blood poisoning). Infection with N. Meningitidis can cause an acute and a chronic infection. Both phases will be explained below.
The acute phase
Infection with the bacterium N. Meningitidis occurs through inhalation or through direct contact with respiratory secretions from the mouth or nose. Upon entering the body, the bacterium moves to the epithelial cells in the nasopharynx, the part of the pharynx located behind the nasal cavity. Pili on the membrane surface of the bacterium allows it to penetrate through the mucus layer and facilitates adhesion to cells of the epithelial tissue.
The bacteria can spread via the nasopharynx to nearby epithelial cells and can thus cause a local infection, such as pneumonia. In addition to the aforementioned colonization in the upper respiratory tract, the bacteria can also move to the lower respiratory tract and eventually penetrate the bloodstream to cause systemic and local infections. Upon entering the bloodstream, the three main cascade pathways are activated: the complement system, coagulation + fibrinolysis pathway and the inflammatory response.
The bacterium N. Meningitidis can invade the epithelial cells of the nasopharynx by endocytosis and subsequently multiply in the phagocytic vacuoles. In this way, they can evade the human immune system. Once the bacteria enter the bloodstream, they can cross the blood-brain barrier and enter the cerebrospinal fluid. This can cause an infection at this location.
After the bacteria have entered the body, the next barrier must be overcome, namely the host’s defense mechanism. The primary, non-specific defense against bacterial invasion consists of complement and phagocytic cells.N. Menigitidis works according to a so-called stealth attack, which means that the incubation period of the infection is difficult to determine, or that asymptomatic carriage occurs. In addition, the adaptive immune system is evaded during an infection.
The key elements in the pathogenesis during the acute phase of meningococcal disease are inflammatory cytokines and chemokines, which are produced by dendritic cells. The most important cytokines and chemokines in this phase are IL-1, IL-6, IL-8 and TNF-α. These may also play a role in the permeability of the blood-brain barrier. Furthermore, Toll-like receptors play an important role during the body’s innate immune response. Toll-like receptors are special receptors that recognize so-called pathogen-associated molecular patterns. They thereby activate the antigen-presenting dendritic cells. The receptors TLR2 and TLR4 in particular are important for cytokine expression in N. Meningitidis.
Lipo-oligosaccharide (LOS) and lipopolysaccharide (LPS) are responsible for activating the immune response. These are molecules that are located on the outer membrane of the bacterium N. Meningitidis. The structure of LOS is almost the same as that of LPS, the only difference is that the LOS does not contain O-antigens. LOS and LPS play a role in colonizing the bacteria and preventing phagocytosis.
The chronic phase
The chronic form of an infection with Neisseria meningitidis, either meningitis or meningococcemia (meningococcemia), is referred to in the literature as either chronic or subacute. A clear distinction is difficult to make and an unambiguous definition cannot be found in literature sources. In the Merck Manual, the definitions of subacute and chronic meningitis are given as follows: a subacute phase exists when a meningeal inflammation lasts more than 2 weeks and a chronic meningitis occurs when it lasts more than 1 month.(1 ) In another source, chronic meningitis is defined as: symptoms and signs of meningeal inflammation and persistent CSF (CerebroSpinal Fluid) abnormalities, such as elevated protein levels and pleocytosis (more cells than normal) for at least one month.(2) Yet another source defines chronic meningococcemia (CM) as meningococcal sepsis, without meningeal symptoms, lasting at least 1 week.(3) What the sources have in common, however, is that untreated CM can last several months and – although it is a self-limiting disease − it can also be fatal.
The signs and symptoms of chronic meningitis are similar to those of acute bacterial meningitis (except for stiff neck and altered state of mental consciousness) , but they develop more slowly (over weeks rather than days) and more gradually. In addition, symptoms can occur intermittently. The serotypes that occur in CM are – as in the acute form – mainly serogroups A, B, and C. And N. Meningitidis is again present intracellularly in the host and detectable in the skin, CSF and as in a case has been described in the tonsils.
The chronic form of meningococcemia is relatively rare (occurring in less than 10% of the total number of patients with meningitis and relatively malignant). Signs and symptoms that occur with this form of infection are intermittent fever and chills, the presence of meningococci in the blood (bacteraemia), skin rash, headache (due to high intracranial pressure) and joint pain. Chronic meningococcal septicemia involves persistent bacteriaaemia, which is also accompanied by rash, joint pain and fever. The complaints can last for several weeks and then worsen.
What makes the disease difficult to recognize and detect are the periods in which the patient – although ill – appears to be completely healthy and shows no symptoms and (during periods when the patient does show symptoms) the bacteria are not always detectable in blood cultures . is.