Causes of meningococcal infection

Causes of meningococcal infection

Meningococcal infection is caused by the meningococcus Neisseria meningitidis, genus Neisseria, family Neisseriaceae. It is a bean-shaped coccus, located in pairs (diplococcus). In cerebrospinal fluid smears in patients with meningococcal meningitis, it is localized mainly intracellularly in the cytoplasm of polymorphonuclear neutrophils. It is similarly located in blood smears, but in fulminant forms of meningococcemia - mainly extracellularly. Meningococcus is gram-negative, has a polysaccharide capsule and outgrowths - pili. Special media containing protein or a set of amino acids (Muller-Hinton medium, etc.) are used for cultivation.

Meningococci are heterogeneous in antigen structure: they differ in polysaccharide antigens of the capsule and protein antigens. In accordance with the antigen structure of the polysaccharides of the capsule, meningococci are divided into serogroups A, B, C, H. I, K, L, X, Y, Z, 29E, W-135.

Meningococcus is unstable in the environment. At 55 °C it dies in 5 minutes, at 100 °C - in 30 seconds. It does not tolerate low temperatures well. It can remain viable at 5-6 °C for a little longer, up to 5 days. Special experiments have shown that at a temperature of 18-20 °C meningococcus remains in a sprayed state for no more than 10 minutes, however, at a humidity of 70-80%, a 5-day survival rate was noted.

Under the influence of disinfectants (0.01% chloramine solution, 1% phenol, 0.1% hydrogen peroxide solution), meningococcus dies within 2-3 minutes.

In human pathology, the most important role is played by meningococci of serogroups A, B and C. The pathogenicity factors include the capsule, pili, LPS and IgA proteases. The toxic properties of meningococcal LPS (endotoxin) exceed those of enterobacteria, as it has a high content of polyunsaturated fatty acids, which initiate a cascade of biochemical processes in the human body. Meningococci of the same serogroup differ genetically, in particular, in the gene encoding IgA protease activity; epidemic strains have high protease activity.

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Pathogenesis of meningococcal infection

It is caused by the characteristics of the pathogen, the conditions of infection, and immunogenetic factors.

Meningococcus has a dual nature: on the one hand, it is a pyogenic coccus, causing purulent meningitis, arthritis; on the other hand, it contains (like other gram-negative microorganisms) LPS, i.e. endotoxin, causing the development of intoxication syndrome.

Defense mechanisms in meningococcal infection are associated with barrierfunctions of the nasopharyngeal epithelium, the action of secretory IgA, the complement system, the phagocytic activity of polymorphonuclear neutrophils, and specific bactericidal antibodies.

In the case of bacterial carriage, the parasitism of meningococcus on the mucous membrane of the nasopharynx is not accompanied by subjective health problems, but upon examination in most cases a picture of acute follicularpharyngitis (local inflammatory reaction) is detected.

In nasopharyngitis, similar local changes are accompanied by catarrhal phenomena, in some cases - a febrile reaction, which is caused by toxinemia. The mechanism of infection generalization has not been fully studied, but a number of factors contributing to generalization are known: high IgA protease activity of the epidemic strain, high infective dose during close contact. The condition of the nasopharyngeal mucosa is of great importance. A previous respiratory infection, especially influenza, contributes to the generalization of meningococcal infection. Age-related reactivity of the body is of great importance. In case of congenital deficiency of terminal components of the complement system (C7-C9), the incidence of generalized forms of the disease increases 100-fold.

The most important link in the pathogenesis of the generalized form of meningococcal infection is bacteremia. In this case, the course of the infectious process depends on the ratio of the pathogenic properties of the pathogen and the protective mechanisms. In optimal cases (mild forms of meningococcemia), the death of the meningococcus is accompanied by the release of small amounts of LPS, which has a powerful activating effect on all protective systems of the body, due to which the body quickly gets rid of the pathogen. However, more often, due to intense bacteremia, neutrophils produce their myeloperoxidase resource, and phagocytosis becomes incomplete. Neutrophils containing viable meningococci overcome histohematic barriers and bring the pathogen into the subarachnoid space and joint cavity, where purulent inflammation develops.

At higher levels of bacteremia and toxinemia, complement consumption increases, phagocytosis is suppressed, the bactericidal activity of the blood decreases, the pathogen reproduces and high doses of LPS accumulate, which suppress phagocytosis and the functional activity of platelets. Oxidation-reduction processes in cell membranes are disrupted. Unregulated release of biologically active substances (kinins, catecholamines, IL, early phase proteins) that initiate a generalized inflammatory reaction is clinically expressed in the picture of ISS. Shock develops at a concentration of LPS in the blood of more than 800-1000 ng in 1 μl, and at a concentration of over 8000 ng in 1 μl, as a rule, it becomes irreversible. Of the pathogenetic mechanisms of ISS development associated with the action of LPS, the most significant are:

• disruption of energy processes in cell membranes, primarily in the formed elements of the blood and the vascular endothelium;
• microcirculation disorders, intravascular blood coagulation, which already at the early stages of the development of ITS lead to the development of multiple organ disorders.

Central circulation is disrupted later. All this explains the high mortality rate in fulminant meningococcemia.

Penetration of the pathogen into the subarachnoid space leads to the development of purulent meningitis. The earliest signs of increased permeability of the hematoliquor barrier and CSF production are detected, which is accompanied by an increase in LD and an increase in the glucose content in the cerebrospinal fluid to 3-4 μmol/l or more. Then, very quickly (within a few hours), a picture of diffuse purulent meningitis develops. The severity of the course and outcome of meningitis in the early stages is determined by the degree of expression of acute edema-swelling of the brain, and in the late stages, in the absence of adequate therapy, by the progression of the purulent-inflammatory process, the involvement of the substance and ventricles of the brain, a violation of cerebrospinal fluid dynamics and the development of hydrocephalus.

In the pathogenesis of acute cerebral edema-swelling, the leading role is played by two components - toxic and inflammatory. Toxic damage to the brain vessels, microcirculatory disorders, and the inflammatory process lead to brain hypoxia and increased BBB permeability. An increase in brain volume is associated with fluid penetration into the extracellular space and an increase in the volume of neurocytes and glial elements due to the failure of the ion pump and the entry of sodium and water into the cells. An increase in brain volume in a confined space leads to dislocation of the medulla oblongata with the descent of the cerebellar tonsils into the foramen magnum, which leads to compression, ischemia, and then to demyelination and death of brain stem cells and is accompanied by a violation of vital functions. In general, more than 90% of fatal outcomes in meningococcal infection are caused by ITS, acute cerebral edema-swelling, or a combination of the two. About 10% of deaths are associated with progressive meningoencephalitis.

Epidemiology of meningococcal infection

The reservoir and source of the pathogen is a sick person or a carrier of bacteria. There are three groups of infection sources, varying in their significance: carriers of meningococcus, patients with meningococcal nasopharyngitis and patients with a generalized form of meningococcal infection.

Carriage of meningococcus is widespread, is often acute and lasts no more than a month. Carriers lead an active lifestyle, but due to the absence of catarrhal manifestations, their significance as a source of infection is small.

Patients with meningococcal nasopharyngitis are the most important source of the causative agent of meningococcal infection and the epidemic process, since the mild course of the disease and an active lifestyle allow them to have many contacts. The presence of catarrhal symptoms activates the mechanism of transmission of the causative agent.

Patients with a generalized form of meningococcal infection are the most intensive source of highly virulent strains of meningococcus, however, they are immobilized, have little contact, and their number is tens and hundreds of times less than that of patients with nasopharyngitis.

The mechanism of transmission of the pathogen is aerosol, the route of transmission is airborne. However, compared to other airborne infections, this mechanism is "sluggish", since meningococcus is localized mainly on the mucous membrane of the nasopharynx, i.e. on the path of inhaled, not exhaled air. That is why duration, proximity (70% of infections occur with contact at a distance of less than 0.5 m), and contact conditions are of great importance for the transmission of the pathogen. Long-term close contacts in a closed warm room with high air humidity are especially dangerous.

Intense outbreaks of meningococcal infection among submarine crews even led to a complete loss of combat capability.

Susceptibility to meningococcus is universal. It is believed that during outbreaks in groups, all members become infected, but in the vast majority of cases the infectious process occurs in the form of carriage or nasopharyngitis. Newcomers to the group, as a rule, become infected and often develop generalized forms. This is clearly seen in military units: each reinforcement during conscription, especially in autumn, is accompanied by cases of generalized meningococcal infection among recruits.

The susceptibility of an individual depends on the presence of previous specific immunity, which is acquired by "pre-epidemic", i.e. repeated contacts with meningococcal carriers or patients with nasopharyngitis. The age structure of morbidity depends on demographic factors and social and living conditions. In developed countries with low birth rates and morbidity, up to 40% of those infected are adults. On the contrary, in countries with high birth rates and overcrowded populations, adults make up no more than 10% of patients.

The infection spreads ubiquitously. Sporadic, group and epidemic morbidity are recorded, mainly caused by meningococci of serogroups A, B and C.

The incidence rate varies in different regions of the world. In most European countries located in temperate latitudes, the incidence rates fluctuate from 0.01-0.02 to 3-5 per 100 thousand population, and this level is considered high. At the same time, in African countries (Benin, Burkina Faso, Northern Cameroon, Chad, Ethiopia, Gambia, Ghana, Mali, Niger, Northern Nigeria, Senegal and Sudan), which, according to L. Lapeysonnie, are part of the "meningitis belt" zone, which stretches 4,200 km south of the Sahara and north of the equator (has a width of 600 km), the endemic incidence rate fluctuates within 20-25 cases per 100 thousand population, and during periods of epidemic rises it can reach 200-800 cases per 100 thousand population.

An analysis of periodic increases in the incidence of meningococcal infection in various countries of the world has made it possible to identify three main types:

• frequent and irregular outbreaks of the disease, typical for African countries;
• increases with small amplitude, but with a clear tendency towards an increase in morbidity;
• periodic rises (every 8-30 years) - in developed countries.

In this case, the 30-year periodicity with a pronounced peak in incidence is associated with the spread of meningococcus serogroup A, and increases in incidence with a periodicity of about 8 years are associated with meningococcus serogroups B and C.

In countries with a moderate climate, the incidence rate begins to increase in the fall and reaches its peak in February-March, and during epidemics - in April-May, i.e. later than with other airborne infections. In megacities, an autumn rise is noted, associated with increased contact between children in preschool institutions, schools, boarding schools, etc. In military units, outbreaks are possible due to the arrival of conscripts.

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