Causes of meningococcal infection

Causes of meningococcal infection

Meningococcal infection is caused by meningococcal Neisseria meningitidis, the genus Neisseria family of Neisseriaceae. This is a bean-shaped coccus, arranged in pairs (diplococcus). In smears of cerebrospinal fluid in patients with meningococcal meningitis, it is localized primarily intracellularly in the cytoplasm of polymorphonuclear neutrophils. Similarly, it is located in blood smears, but with fulminant forms of meningococcemia - mainly extracellular. Meningokokk gram-negative, has a polysaccharide capsule and outgrowths - drank. For cultivation, special media containing a protein or a set of amino acids (Mueller-Hinton medium, etc.) are used.

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

Meningococcus is not very stable in the environment. At 55 ° C, it dies after 5 minutes, at 100 ° C - after 30 seconds. Poorly tolerates low temperatures. A little longer, up to 5 days, can remain viable at 5-6 ° C. Special experiments have shown that at a temperature of 18-20 ° C meningococcus is kept in the sprayed state for no more than 10 minutes, but at a humidity of 70-80% 5-day survival was noted.

Under the action of disinfectants (0.01% chloramine solution, 1% phenol, 0.1% hydrogen peroxide solution) meningococcus perishes in 2-3 minutes.

In men's pathology, meningococci of serogroups A, B and C play the most important role. Pathogenicity factors include capsule, saw, LPS and IgA proteases. LPS (endotoxin) meningococcus, in terms of its toxic properties, exceeds the LPS of enterobacteria, because it has a high content of polyunsaturated fatty acids that initiate a cascade of biochemical processes in the human body. Meningococci of one serogroup differ genetically, in particular, according to the gene that codes for the activity of IgA protease; epidemic strains have high protease activity.

[1], [2], [3], [4], [5],

Pathogenesis of meningococcal infection

Due to the characteristics of the pathogen, the conditions of infection, immunogenetic factors.

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

The protective mechanisms for meningococcal infection are associated with the barrier functions of the epithelium of the nasopharynx, the action of secretory IgA, the complement system, the phagocytic activity of polymorphonuclear neutrophils, specific bactericidal antibodies.

When bacteriocarrier parasitizing meningococcus on the mucous membrane of the nasopharynx is not accompanied by subjective health problems, but on examination in most cases, a picture of acute follicular pharyngitis (local inflammatory reaction) is revealed .

When nasopharyngitis, similar local changes are accompanied by catarrhal phenomena, in some cases - a febrile reaction, which is due to toxemia. The mechanism of infection generalization is not fully understood, but a number of factors contributing to generalization are known: high IgA-protease activity of the epidemic strain, a high infectious dose with close contact. Important is the condition of the mucous membrane of the nasopharynx. Prior respiratory infection, especially influenza, promotes the generalization of meningococcal infection. The age-related reactivity of the organism is of great importance. With congenital deficiency of the 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 pathogenic properties of the pathogen and protective mechanisms. In optimal cases (mild forms of meningococcus), the death of meningococcus is accompanied by the release of small amounts of LPS, which has a powerful activating effect on all the body's defense systems, so that the body is quickly released from the pathogen. However, more often, due to intensive bacteremia, neutrophils produce their myeloperoxidase resource, and phagocytosis becomes incomplete. Neutrophils containing viable meningococci overcome the histohematological barriers and introduce the causative agent into the subarachnoid space and the joint cavity where purulent inflammation develops.

At higher levels of bacteremia and toxemia, complement consumption is increased, phagocytosis is suppressed, bactericidal activity of the blood decreases, the pathogen multiplies and accumulates high doses of LPS that suppress phagocytosis and platelet function. Oxidation-reduction processes in cell membranes are disturbed. Unregulated release of biologically active substances (kinins, catecholamines, IL, proteins of the early phase), initiating a generalized inflammatory reaction, is clinically expressed in the ITH picture. The shock develops at a concentration of LPS in the blood of more than 800-1000 ng in 1 μl, and at concentrations above 8,000 ng in 1 μl, as a rule, becomes irreversible. Of the pathogenetic mechanisms of the development of ITS associated with the effect of LPS, the most significant are:

• disturbance of energy processes in cell membranes, primarily in blood cells and vascular endothelium;
• disorders of microcirculation, intravascular coagulation of blood, which already in the early stages of the development of ITS lead to the development of polyorganism disorders.

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

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

In the pathogenesis of acute edema-swelling of the brain, two components play a leading role - toxic and inflammatory. Toxic damage of the brain vessels, microcirculatory disorders, inflammatory process lead to brain hypoxia, increase of the BBB permeability. The increase in brain volume is associated with the penetration of fluid 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 the volume of the brain in an enclosed space leads to the dislocation of the medulla oblongata with the descent of the cerebellar tonsils into the large occipital foramen, which leads to compression, ischemia, and then to demyelination and death of brain stem cells and is accompanied by disruption of vital functions. In general, more than 90% of deaths associated with meningococcal infections are caused by ITH, acute edema-swelling of the brain or a combination of these. 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. There are three groups of sources of infection, different in importance: meningococcal carriers, meningococcal nasopharyngitis patients and patients with generalized form of meningococcal infection.

The carrier of meningococcus is widespread, 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 low.

Patients with meningococcal nasopharyngitis are the most important source of the causative agent of meningococcal infection and the epidemic process, because the easy 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 pathogen.

Patients with generalized form of meningococcal infection are the most intensive source of highly virulent strains of meningococcus, however they are immobilized, they do not contact much, and their number is tens and hundreds times less compared to patients with nasopharyngitis.

The mechanism of transmission of the pathogen is aerosol, the transmission path 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 the duration, proximity (70% of infections occurs at contact at a distance of less than 0.5 m), as well as the contact conditions, are of great importance for the transmission of the pathogen. Especially dangerous are long close contacts in a closed warm room with high humidity.

Intensive outbreaks of meningococcal infection, found among the crews of submarines, even led to a complete loss of combat capability.

Susceptibility to meningococcus is universal. It is believed that during outbreaks in the collectives all of its members become infected, but in the overwhelming majority of cases, the infectious process proceeds in the form of carrier or nasopharyngitis. Newcomers to the team, as a rule, become infected and often become ill with generalized forms. This is well traced in military units: every replenishment during calls, especially in autumn, is accompanied by cases of generalized form of meningococcal infection among recruits.

The susceptibility of an individual depends on the presence of a previous specific immunity, which is acquired by "pro-epidemic", i.e. Repeated contacts with meningococcal carriers or patients with nasopharyngitis. The age structure of morbidity depends on demographic factors. Social and living conditions. In developed countries with a low birth rate and incidence of up to 40% of cases are adults. On the contrary, in countries with high birth rates, population crowding, adults make up no more than 10% of patients.

The spread of the infection is ubiquitous. Record sporadic. Group and epidemic morbidity, mainly caused by meningococcus serogroups A, B and C.

The incidence rate in certain regions of the world varies. In most European countries located in temperate latitudes, incidence rates range from 0.01-0.02 to 3-5 per 100,000 population, and this level is considered high. At the same time, in the countries of Africa (Benin, Burkina Faso, Northern Cameroon, Chad, Ethiopia, Gambia, Ghana, Mali, Niger, Northern Nigeria, Senegal and Sudan), entering the zone of the meningitis belt ", Which stretches to 4200 km south of the Sahara and north of the equator (has a width of 600 km), the endemic level of incidence varies between 20-25 cases per 100 thousand population, and during periods of epidemic upsurge can reach 200-800 cases per 100 thousand of the population.

The analysis of periodic morbidity upsurge in meningococcal infection in different countries of the world has made it possible to distinguish three main types:

• frequent and irregular morbidity upsets, characteristic of African countries;
• ups with a small amplitude, but with a clear tendency to increase morbidity;
• periodic upsurge (in 8-30 years) - in developed countries.

At the same time, a 30-year periodicity with a pronounced peak of morbidity is associated with the spread of meningococcus serogroup A. And the incidence of morbidity with a periodicity of about 8 years - with meningococci of serogroups B and C.

In countries with a temperate climate, the incidence increases in the autumn and peaks in February-March, and during epidemics in April-May, ie in the period from February to March. Later than with other airborne infections. In megacities, an autumnal upswing is noted, connected with the strengthening of contacts between children in pre-school institutions, schools, boarding schools, etc. In military units, outbreaks associated with the recruitment of conscripts are possible.

[6], [7], [8], [9], [10], [11], [12], [13]