Tuberculin Diagnosis in Children

Tuberculin diagnostics is a set of diagnostic tests to determine the specific sensitization of the body to the MBT using tuberculin. Since the establishment of tuberculin to the present day, tuberculin diagnostics has not lost its importance and remains an important method of examination of children, adolescents and young people. When meeting with mycobacteria (infection or vaccination of BCG) the body responds with a certain immunological reaction and becomes sensitive to the subsequent administration of antigens from mycobacteria, that is, sensitized to them. This sensitivity, which is delayed in nature (that is, a specific reaction manifests itself after a certain time - 24-72 hours), was called delayed-type hypersensitivity. Tuberculin has a high specificity, acting even in very large dilutions. Intradermal administration of tuberculin to a person whose body is previously sensitized by both spontaneous infection and as a result of BCG vaccination causes a response-specific reaction that is of diagnostic significance.

Tuberculin is a drug obtained from culture filtrates or microbial bodies of MBT. Tuberculin is an incomplete antigen-hapten, that is, upon administration it does not sensitize the human body, but only causes a specific delayed-type hypersensitivity response. Drugs of tuberculin PPD-L are injected into the human body skin, intradermally and subcutaneously. The route of administration depends on the type of tuberculin test. If the human body is pre-sensitized with MBT (spontaneous infection or as a result of BCG vaccination), then a response-specific response develops in response to the introduction of tuberculin. It begins to develop 6-8 hours after the introduction of tuberculin in the form of different manifestations of an inflammatory infiltrate, the cellular basis of which is formed by lymphocytes, monocytes, macrophages, epithelioid and giant cells. The triggering mechanism of delayed type hypersensitivity reaction is the interaction of the antigen (tuberculin) with receptors on the surface of the effector lymphocytes, resulting in the release of mediators of cellular immunity that involve macrophages in the process of antigen destruction. Some cells die, secreting proteolytic enzymes, which have a damaging effect on the tissue. Other cells accumulate around the foci of specific lesions. Inflammatory reaction occurs not only in the place of application of tuberculin, but also around tuberculosis foci. When the sensitized cells are destroyed, active substances with pyrogenic properties are released. The time of development and the morphology of the reactions in any method of application of tuberculin do not differ fundamentally from those in intradermal administration. The peak of hypersensitivity reaction of the delayed type occurs on 48-72 hours, when its non-specific component is reduced to a minimum, and the specific reaches a maximum.

Indications for conduction

Tubercular diagnostics is divided into mass and individual.

Mass tuberculin diagnostics is used for mass population screening for tuberculosis. To conduct mass tuberculin diagnostics use only one tuberculin test - a Mantoux test with 2 tuberculin units.

The Mantoux test with 2 TE is administered to all children and adolescents vaccinated with BCG regardless of the previous result 1 time per year. The child should receive the first Mantoux test at 12 months of age. For children not vaccinated with BCG, the Mantoux test is carried out 6 months of age 1 time every six months before the child receives BCG vaccination, then by the standard method once a year.

Individual tuberculin diagnostics are used for individual examinations. The goals of individual tuberculin diagnostics are as follows:

• differential diagnosis of postvaccinal and infectious allergies (delayed-type hypersensitivity);
• Diagnosis and differential diagnosis of tuberculosis and other diseases;
• the threshold of individual sensitivity to tuberculin;
• determination of tuberculosis activity;
• evaluation of treatment effectiveness.

In addition, there are groups of children and adolescents who are required to put Mantoux test with 2 TE 2 times a year under the conditions of the general treatment network:

• patients with diabetes mellitus, peptic ulcer of the stomach and duodenum, blood diseases, systemic diseases, HIV-infected, receiving long-term hormone therapy (more than 1 month);
• patients with chronic nonspecific diseases (pneumonia, bronchitis, tonsillitis), subfebrile condition of unclear etiology;
• Not vaccinated against tuberculosis, regardless of the child's age;
• children and adolescents from social risk groups who are in specialized institutions (shelters, centers, receivers-distributors) who do not have medical documentation are examined using Mantoux test with 2 TE at admission to the institution, then 2 times a year for 2 years .

Contraindications to Mantoux test with 2 TE

• skin diseases, acute and chronic infectious and somatic diseases (including epilepsy) during the period of exacerbation;
• allergic conditions, rheumatism in acute and subacute phases, bronchial asthma, idiosyncrasy with severe cutaneous manifestations during exacerbation;
• It is not permissible to conduct tuberculin tests in children's groups where quarantine for childhood infections is declared;
• Mantoux test is not performed within 1 month after other preventive vaccinations (DTP, measles vaccinations, etc.).

The Mantoux test is carried out 1 month after the disappearance of clinical symptoms or immediately after quarantining.

In order to identify contraindications, the doctor (nurse) before conducting the test conducts the study of medical documentation, a survey, an examination of the persons subjected to the trial.

The results of mass tuberculin diagnostics in dynamics make it possible to allocate the following contingents among children and adolescents:

• children and adolescents not infected with the Office - children and adolescents who have an annual negative Mantoux test with 2 TE, children and adolescents with PVA;
• children and adolescents infected with the Office.

[1], [2], [3],

Individual tuberculin diagnostics

When carrying out individual tuberculin diagnostics, use various tuberculin tests with cutaneous, intradermal and subcutaneous injection of tuberculin. For various tuberculin samples, bacterial allergens are used: as purified tuberculin in standard dilution (the tubercle cleansed allergen for cutaneous, subcutaneous and intradermal application in standard dilution), and tuberculin purified (the allergen tubercle cleared for cutaneous, subcutaneous and intradermal application dry). Purified tuberculin in standard dilution can be used in anti-tuberculosis facilities, children's polyclinics, somatic and infectious hospitals. Tuberculin purified dry is allowed to use only in anti-tuberculosis facilities (TB dispensary, tuberculosis hospital and sanatorium).

Evaluation of tuberculin reaction

The intensity of tuberculin reaction depends on many factors (specific sensitization of the body, its reactivity, etc.). In practically healthy children, infected with MW, tuberculin reactions are usually less pronounced than in patients with active forms of tuberculosis. In patients with tuberculosis of children, the sensitivity to tuberculin is higher than in adults with tuberculosis. When severe forms of tuberculosis (meningitis, miliary tuberculosis, caseous pneumonia) often indicate a low sensitivity to tuberculin due to a pronounced inhibition of the reactivity of the body. Some forms of tuberculosis (tuberculosis of eyes, skin), on the contrary, are often accompanied by high sensitivity to tuberculin.

In response to the introduction of tuberculin in the body of a pre-sensitized person, a local, general and / or focal reaction develops.

• Local reaction is formed at the site of the introduction of tuberculin, can manifest itself as hyperemia, papula (infiltrate), vesicles, bulls, lymphangitis, necrosis. The local reaction is of diagnostic importance for the dermal and intradermal administration of tuberculin.
• The general reaction is characterized by general changes in the human body and can manifest itself in the form of deterioration of health, increased body temperature, headaches, arthralgias, changes in blood tests (monocytopenia, disproteinemia, slight acceleration of ESR, etc.). The general reaction often develops with subcutaneous injection of tuberculin.
• Focal reaction develops in patients in the focus of a specific lesion - in tuberculosis foci of different localization. There is a focal reaction clinically (with pulmonary tuberculosis may appear hemoptysis, increased cough, increased sputum discharge, the appearance of pain in the chest, increased catarrhal phenomena, with extrapulmonary tuberculosis - increased inflammation in the area of tuberculosis) and radiological (increased perifocal inflammation around tubercular foci). Focal reaction is more pronounced with subcutaneous injection of tuberculin.

[4], [5], [6], [7], [8],

Evaluation of tuberculin diagnostics

The results of the sample can be evaluated as follows:

• negative reaction - complete absence of infiltrate (papules) and hyperemia, it is permissible to have a knock-off reaction of 0-1 mm;
• doubtful reaction - infiltrate (papule) of 2-4 mm size or presence of hyperemia of any size without infiltration;
• positive reaction - infiltrate (papule) of 5 mm or more, here include the presence of vesicles, lymphangitis. Screenings (around the papule at the injection site of tuberculin a few more papules of any size are formed).

Among the positive reactions are the following:

• weakly positive - the size of the papule is 5-9 mm;
• medium intensity - the size of the papule is 10-14 mm;
• expressed - the size of the papule is 15-16 mm;
• hyperergic - in children and adolescents, the size of the papule is 17 mm and above, in adults it is 21 mm or more, and vesicle-necrotic reactions, presence of lymphangitis, and screenings, regardless of the size of the papule, are also referred to as hyperergic reactions.

Positive results for the Mantoux test with 2 TE are regarded as postvaccinal allergy in the following cases:

• the association of positive and questionable reactions to 2 TE with previous vaccination or revaccination of BCG (ie positive or questionable reactions appear in the first 2 years after vaccination or revaccination of BCG);
• there is a correlation of the sizes of the reactions (papules) to tuberculin and the size of the postvaccinal sign of BCG (scar): the papule up to 7 mm corresponds to the scars from BCG to 9 mm, and to 11 mm - to the scars more than 9 mm;
• the greatest size of the reaction to the Mantoux test is revealed in the first two years after vaccination or revaccination of BCG; after the next 5-7 years, the post-vaccination sensitivity to tuberculin extinction.

Reaction to 2 TE PPD-L is assessed as a result of infectious allergy (delayed-type hypersensitivity) in the following cases:

• transition of a negative reaction to 2 TE tuberculin in a positive, not associated with vaccination or revaccination of BCG; an increase in the size of the papule by 6 mm or more after the previous post-vaccination allergy - the early period of the primary tuberculosis infection, that is, the turn;
• a sharp increase in sensitivity to tuberculin (by 6 mm and more) for 1 year (in tuberculin-positive children and adolescents after a previous infectious allergy);
• Gradual, over several years, increased sensitivity to tuberculin with the formation of reactions to 2 TE of moderate intensity or pronounced reactions;
• 5-7 years after vaccination or revaccination, BCG is stable (for 3 years or more) the remaining sensitivity to tuberculin at the same level without the tendency to fade - monotonous sensitivity to tuberculin,
• the extinction of sensitivity to tuberculin after a previous infectious allergy (usually in children and adolescents, previously observed by a phthisiopathic and receiving a full course of preventive treatment).

The study of the results of tuberculin diagnostics performed by children and adolescents showed the dependence of the intensity of response reactions on 2 TE PPD-L on many factors, which should also be taken into account in the examination of patients.

It is known that the intensity of the reaction to 2 TE depends on the frequency and multiplicity of revaccinations against tuberculosis. Each subsequent revaccination leads to an increase in sensitivity to tuberculin. In turn, a decrease in the frequency of revaccinations of BCG leads to a decrease in the number of positive results for the Mantoux test in 2 times, hyperergic - in 7 times. Thus, revocation of revaccinations helps to reveal the true level of infection of children and adolescents in the Office, which, in turn, allows full coverage of the BCG with revaccination of adolescents at the required time. It is possible that it is advisable in epidemiologically favorable conditions to conduct only one revaccination - at 14 years, and in epidemiologically unfavorable conditions, two - at 7 and 14 years. It is shown that the average size of the papule by 2 TE at the bend is 12.3 ± 2.6 mm. According to E.B. Meve (1982), in unvaccinated healthy children, the size of the papule of 2 TE PPD-L does not exceed 10 mm.

The intensity of hypersensitivity reactions of delayed type on 2 TE is influenced by a number of factors. Many authors confirmed the dependence of the intensity of the Mantoux reaction on the magnitude of the postvaccinal sign of BCG. The more postvaccinal scar, the higher the sensitivity to tuberculin. With age, the frequency of positive reactions increases. In children born with a body weight of 4 kg or more, sensitivity to tuberculin is higher, ore-feeding for longer than 11 months also leads to high responses to 2 TE (possibly due to low iron content in milk). Glistovye invasions, food allergies, acute diseases of the respiratory organs increase the sensitivity to tuberculin. With high sensitivity to tuberculin, the II (A) blood group is more often found, which correlates with a predisposition to the exudative type of morphological reactions in patients with pulmonary tuberculosis with the same blood group.

In conditions of exogenous superinfection, with hyperthyroidism. Allergies, viral hepatitis, influenza, obesity, concomitant infectious diseases, chronic foci of infection, against the background of the introduction of certain protein preparations, the reception of thyroidin, tuberculin reactions are intensified.

The study of sensitivity to tuberculin in children of early and preschool age showed a decrease in the frequency of adverse reactions in children aged 3 and 7 years. These periods coincide with the carrying out of vaccinations against children's infections for children (DTP, DTP-M, ADS-M, measles, and parotoxin vaccines). Increased susceptibility to tuberculin is observed when Mantoux test is performed with 2 TE in the period from 1 day to 10 months after the above vaccinations. Previously, negative reactions become questionable and positive, and after 1-2 years again become negative. Therefore, the tuberculosis diagnosis is planned either before the prophylactic vaccination against childhood infections, or not earlier than 1 month after vaccination. When Mantoux test is performed before preventive vaccinations against childhood infections, they can be performed on the day of reacting to the Mantoux test, if the size of the response to tuberculin does not require specialist intervention.

[9], [10]