Causes, pathogenesis and epidemiology of diphtheria

Diphtheria is caused by Corynebacterium diphtheiiae (genus Corynebacterium, family Corynebacteriaceae), a non-spore-forming, gram-positive, club-shaped rod.

Corynebacterium diphtheriae grows only on special nutrient media (tellurite medium is the most common). According to their biological properties, diphtheria corynebacteria are divided into three biovars: mittis (40 serovars), gr avis (14 serovars) and closely related intermedius (4 serovars). The main factor of pathogenicity of the pathogen is toxin formation. Non-toxigenic strains do not cause disease. Diphtheria toxin has all the properties of an exotoxin: heat lability, high toxicity (second only to botulinum toxin and tetanus toxin), immunogenicity, neutralization by antitoxic serum.

The diphtheria bacillus is stable in the environment: in diphtheria films, on household items, in corpses it survives for about 2 weeks; in water, milk - up to 3 weeks. Under the influence of disinfectants in normal concentrations it dies within 1-2 minutes, when boiled - instantly.

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

Pathogenesis of diphtheria

It is generally accepted that diphtheria exotoxin is the primary damaging factor in diphtheria. Severe forms of diphtheria in an individual develop only in the absence or low titer of antitoxic antibodies. The toxin that has penetrated into the blood interacts with the cell by binding to cytoplasmic receptors.

Diphtheria toxin can damage any cells, especially at high concentrations, but most often affects target cells: cardiomyocytes, oligodendrogliocytes, and leukocytes.

The experiment showed that the exotoxin blocks the carnitine shuttle mechanism, which is of universal importance in the metabolic system. This concept has been confirmed in clinical practice. There is evidence of high efficiency of carnitine use for the treatment and prevention of myocarditis in diphtheria. Due to the blockade of the carnitine shuttle mechanism by the toxin, the main pathways of protein (amino acid), fat and carbohydrate metabolism are disrupted due to the fact that acetyl-CoA cannot pass through the cytoplasmic membrane of mitochondria and enter the Krebs cycle. The cell begins to experience energy "hunger", as a result of which the main metabolic pathways change. As a result, with severe cell damage, the concentration of reduced forms of nicotinamide adenine dinucleotide, lactate and hydrogen ions in the cytosol progresses, glycolysis is inhibited, which can lead to decompensated intracellular acidosis and cell death. Intracellular acidosis and high fatty acid content cause activation of lipid peroxidation. With pronounced intensification of lipid peroxidation, destructive changes in membrane structures entail irreversible shifts in homeostasis. This is one of the universal mechanisms of cell disorganization and death. As a result of damage to target cells in severe diphtheria, the following pathophysiological changes occur.

• In the first days of the disease, the development of hypovolemia and DIC syndrome is of greatest importance.
• Damage to cardiomyocytes by exotoxin (in patients with severe diphtheria, already from the first days of the disease).
• Neuronal damage occurs in all forms of diphtheria, but in severe diphtheria the nature of these changes is always massive and pronounced. In addition to the cranial and somatic nerves, severe diphtheria also affects the parasympathetic division of the autonomic nervous system.

The multifactorial nature of damage to various organs and systems (the action of toxins, the cytokine cascade, lipid peroxidation, the development of various types of hypoxia, autoimmune processes, etc.) in clinical practice is manifested by the development of a number of syndromes.

The main causes of death in diphtheria are heart damage, paralysis of the respiratory muscles, asphyxia in diphtheria of the respiratory tract, DIC syndrome with the development of acute renal failure and/or adult respiratory distress syndrome and secondary bacterial infection, pneumonia, sepsis).

Epidemiology of diphtheria

The source of the pathogen is patients with any clinical form of diphtheria, as well as carriers of toxigenic strains. The main route of transmission of the pathogen is airborne, contact-household is possible (for example, with diphtheria of the skin), in rare cases alimentary (milk). Susceptibility to diphtheria is universal, but in some people the infectious process occurs in the form of asymptomatic carriage.

Immunity to diphtheria is antitoxic, not antibacterial. Repeated diseases and diseases in vaccinated people are possible, often occurring in a mild form.

The most active source of infection is sick people. The period of infectivity is individual and is determined by the results of bacteriological examination. Carriers are dangerous due to their greater number compared to patients, the absence of clinical symptoms, and an active lifestyle. Particularly dangerous are carriers suffering from respiratory infections, in which the mechanism of transmission of the pathogen is activated. The average duration of carriage is about 50 days (sometimes more). The number of carriers of toxigenic corynebacteria is hundreds of times higher than the number of patients with diphtheria. In diphtheria foci, carriers can be up to 10% or more of outwardly healthy people. Diphtheria is classified as a controlled infection, i.e. the incidence is high if mass vaccination of the population has not been carried out. In the past and during the last epidemic, autumn-winter seasonality was noted. Before the start of scheduled vaccination, diphtheria was characterized by periodicity: increases in the incidence occurred every 5-8 years and lasted 2-4 years. 90% of patients were children; during the last epidemic, adults predominated among those infected.

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