Pathogen-immune system interaction
The properties of the pathogen determine the specific approach to disease prevention. For active immunization, diphtheria toxoid is used (introduced into routine practice in the early 1930s). A crucial characteristic of pathogenesis lies in the mechanism of action of this vaccine: it stimulates the production of antitoxic immunity only.
This means that vaccination reliably protects a person from developing severe, life-threatening toxic forms of the disease, but does not affect the development of antibacterial immunity. Consequently, even a fully vaccinated person can become infected with Corynebacterium diphtheriae and become a bacterial carrier, shedding the pathogen into the environment and maintaining its circulation in the population.
Historical and epidemiological features
In the pre-vaccination era, the infection was characterized by mass epidemics with extremely high mortality rates across all age groups. Thanks to mass immunization by the 1970s in European and North American countries, toxic forms had virtually disappeared, and by 1990 most countries worldwide declared themselves free from severe diphtheria.
However, with a decline in population immunity, the pathogen is capable of rapidly causing new outbreaks. A striking example is the epidemic in the Russian Federation in the 1990s:
- Onset: A sharp increase in the number of cases was recorded in 1990.
- Peak: In 1994, over 17,000 cases were registered.
- Causes: Socio-economic crisis, active migration processes, a decline in the quality of medical care, and most importantly, widespread violations of mandatory vaccination and re-vaccination schedules.
- Consequences: The immune layer in major cities dropped to 45%. The disease affected predominantly the adult population, causing severe combined and toxic forms with a mortality rate of up to 5%.
The epidemic was halted only by intensifying the vaccination campaign, which achieved 90% population coverage and proved the efficacy of the toxoid.
Clinical manifestations of toxic action
The action of diphtheria toxin leads to the development of pronounced intoxication syndrome and specific local reactions. The classic picture of a severe toxic form includes an acute onset with high fever, severe weakness, and odynophagia.
Key objective signs of diphtheritic oropharyngeal inflammation:
- Specific plaques: Dense fibrinous films form (often confluent, white or grayish in color). They extend far beyond the tonsils, covering the palatine arches, uvula, and soft palate.
- Bleeding: The plaques are extremely difficult to separate with a spatula. When attempting to remove them, the bleeding surface of the mucous membrane is exposed.
- Tissue edema: Significant enlargement of the tonsils and marked edema of the oropharyngeal mucosa are observed.
- Cellular involvement: Regional lymphadenitis develops, accompanied by massive edema of the subcutaneous adipose tissue of the neck. The spread of this edema serves as the primary clinical marker of the severity of the toxic form.
The systemic impact of the toxin manifests as cardiovascular system damage (muffled heart sounds, tachycardia, arterial hypotension), as well as the risk of myocarditis, polyneuropathy, respiratory, and renal failure.
Physician's tactics upon infection detection
Suspecting diphtheria (especially in unvaccinated individuals with an aggravated epidemiological or social history), the physician must immediately identify the leading syndromes and perform differential diagnosis with tonsillitis (including Vincent's angina), peritonsillar abscess, and infectious mononucleosis.
Upon detecting signs of toxic diphtheria, the medical worker is obliged to:
- Ensure strict isolation of the patient.
- Issue an emergency referral for hospitalization in an infectious diseases hospital.
- Initiate a set of anti-epidemic measures.
Hospitalization is vital for administering specific therapy, finalizing the diagnosis, and maintaining continuous dynamic monitoring due to the high risk of life-threatening conditions.
Briefly: answers to topical questions
What are the morphological and tintorial properties of Corynebacterium diphtheriae?
Corynebacterium diphtheriae is a Gram-positive pleomorphic rod with thickened ends, non-spore-forming. It possesses the following properties:
- Morphology — thin, straight or curved non-motile rods multiplying by a "snapping" mechanism (in smears, they are arranged at an angle in the form of V, X, Y, L letters). Toxigenic strains have a microcapsule with cord factor.
- Tintorial properties — stain unevenly (beaded appearance). Metachromatic volutin granules (Babes–Ernst granules) are localized at the poles of the cell and are detected by special staining with Loeffler, Neisser, or by fluorescence microscopy with coriphosphine.
What are the main biovars the diphtheria pathogen is subdivided into?
The diphtheria pathogen is subdivided into biovars based on a complex of morphological, cultural, biochemical, and antigenic properties.
There are 3 main biovars of Corynebacterium diphtheriae:
- gravis — on liquid media, it is characterized by surface growth forming a film and crumbly sediment; in the current epidemiological situation, it is the predominant biovar.
- mitis — produces uniform turbidity of the medium and fine-grained sediment.
- intermedius.
Also, the belfanti biovar is distinguished within the species.
What elective nutrient media are used for the cultivation of Corynebacterium diphtheriae?
For the cultivation of Corynebacterium diphtheriae, complex nutrient media supplemented with blood or serum are used, since the pathogen does not grow on simple media.
The following media are used:
- Roux's elective medium — coagulated horse serum.
- Klauber medium II is a differential diagnostic blood-tellurite medium.
- Tinsdale medium — serum agar with potassium tellurite and cystine.
The role of potassium tellurite in these media is to inhibit the growth of concomitant microflora, to which the diphtheria bacillus is resistant.
What is the molecular mechanism of action of diphtheria exotoxin?
The mechanism of action of diphtheria exotoxin is the irreversible disruption of translation on ribosomes, leading to the cessation of protein synthesis and cell death.
The toxin consists of two fragments. The B-fragment binds to target cell receptors and forms a transport channel. The A-fragment penetrates the cytosol and exhibits enzymatic activity. It performs ADP-ribosylation of elongation factor EF-2, blocking its function. As a result, the exotoxin acts as a cytotoxin, causing necrosis of sensitive eukaryotic cells (primarily of the myocardium, nervous system, kidneys, and adrenal glands).
What methods exist for determining the toxigenicity of Corynebacterium diphtheriae?
To determine the toxigenicity of Corynebacterium diphtheriae, a molecular genetic method (PCR) is used.
This method aims directly at detecting the toxigenicity gene of the diphtheria bacillus. Determining toxigenicity is a mandatory step in identifying isolated corynebacteria by bacteriological methods, since the disease is caused exclusively by toxigenic strains of the pathogen.
To memorize the classic local symptoms of oropharyngeal diphtheria, use the acronym PLOT: P — Plaques (fibrinous, dense, extending beyond the tonsils). L — Lymphadenitis (enlargement of submandibular nodes). O — Edema (of the mucosa and subcutaneous tissue of the neck). T — Tissues bleed (when attempting to remove the plaque with a spatula).
Class and exam questions
Why can a vaccinated person still contract diphtheria?
Diphtheria toxoid vaccination induces only antitoxic immunity. It protects against severe forms of the disease but does not create an antibacterial barrier; therefore, infection and bacterial carriage remain possible.
How to distinguish diphtheritic tonsillar plaque from regular tonsillitis (strep throat)?
In diphtheria, the plaque has a dense fibrinous structure, often extending beyond the tonsils to the uvula and arches. When attempting to remove it with a spatula, the plaque separates with difficulty, and the underlying tissue begins to bleed.
What is the main external sign of the toxic form of diphtheria?
A key marker of the toxic form is the presence and extent of subcutaneous adipose tissue edema in the neck, which can extend down to the clavicles and below.
What else to study on this topic
- Criteria for assessing the severity of toxic forms of diphtheria
- Algorithm for laboratory diagnosis and confirmation of diagnosis
- Differential diagnosis with infectious mononucleosis
- Pathogenesis of diphtheria myocarditis and polyneuropathy
- Rules for hospitalization and discharge of convalescents
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