Causes, pathogenesis and epidemiology of diphtheria

Diphtheria is caused by Corynebacterium diphtheiiae (genus Corynebacterium, the family Corynebacteriaceae) - a non-spore-forming gram-positive stick of the clavate shape.

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

Diphtheria bacillus is stable in the environment: in diphtheria films, on household items, in corpses, about 2 weeks are retained; in water, milk - up to 3 weeks. Under the influence of disinfectants in normal concentrations, kills for 1-2 minutes, while boiling - instantly.

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

Pathogenesis of diphtheria

It is generally recognized that diphtheria exotoxin is the primary killer in diphtheria. Heavy forms of diphtheria in an individual develop only in the absence or low titre of antitoxic antibodies. The toxin that enters the blood interacts with the cell by binding to the cytoplasmic receptors.

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

In the experiment it was shown that exotoxin blocks the carnitine-shuttle mechanism, which has universal significance in the metabolic system. This concept was confirmed in clinical practice. There are data on the high effectiveness of the use of carnitine for the treatment and prevention of myocarditis in diphtheria. Due to the blockade of the carnitine-shuttle mechanism by toxin, the main pathways for the exchange of proteins (amino acids), fats and carbohydrates are violated due to the fact that acetyl-CoA can not pass through the cytoplasmic membrane of the mitochondria and enter the Krebs cycle. The cell begins to experience an energy "hunger", as a result of which the basic metabolic pathways change. As a result, with severe cell damage in the cytosol, an increase in the concentration of reduced forms of nicotinamide adenine dinucleotide, lactate and hydrogen ions is progressing, glycolysis is inhibited, which can lead to decompensated intracellular acidosis and cell death. Intracellular acidosis and a high content of fatty acids cause activation of lipid peroxidation. With pronounced intensification of lipid peroxidation, destructive changes in membrane structures lead to irreversible changes in homeostasis. This is one of the universal mechanisms of disorganization and cell death. Due to the defeat of 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 most important.
• Defeat of exotoxin of cardiomyocytes (in patients with severe diphtheria from the first days of the disease).
• The defeat of neurons occurs with all forms of diphtheria, but with severe diphtheria the nature of these changes is always massive and pronounced. In addition to cranial and somatic nerves, in case of severe diphtheria, the parasympathetic division of the autonomic nervous system is also affected.

The multifactoriality of the defeat of various organs and systems (toxin action, cytokine cascade, lipid peroxidation, 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, respiratory muscle paralysis, asphyxia in respiratory tract diphtheria, DIC syndrome with the development of acute renal failure and / or adult respiratory distress syndrome and secondary bacterial infection, pneumonia, sepsis).

Epidemiology of diphtheria

Source of the pathogen - patients with any clinical form of diphtheria,  as  well as bacterial carriers of toxigenic strains. The main way of transmission of the pathogen is airborne, it is possible to contact-everyday (for example, with diphtheria of the skin), in rare cases, alimentary (milk). The susceptibility to diphtheria is universal, but in some people the infectious process proceeds in the form of asymptomatic carriage.

Immunity in diphtheria is antitoxic, not antibacterial. Possible repeated diseases and diseases in vaccinated, occurring more often  in an  easy form.

The most active source of infection is sick people. The timing of infectiousness is individual, determined by the results of a bacteriological study. Carriers are dangerous in connection with their greater in comparison with sick number, absence of clinical symptoms, an active way of life. Especially 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 the foci of diphtheria, carriers can be up to 10% or more of apparently healthy individuals. Diphtheria is referred to as controlled infections, i.e. The incidence is high in the event that mass vaccination of the population has not been carried out. In the past and during the last epidemic, the autumn-winter seasonality was noted. Before the scheduled vaccination, diphtheria was characterized by a periodicity: the incidence of morbidity arose every 5-8 years and lasted 2-4 years. 90% of patients were children, during the last epidemic among the adults predominated.

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