Tuberculin diagnosis in children

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

Tuberculin is a preparation obtained from culture filtrates or microbial bodies of MBT. Tuberculin is an incomplete antigen-hapten, i.e. when administered, it does not sensitize the human body, but only causes a specific delayed-type hypersensitivity response. Tuberculin PPD-L preparations are administered to the human body cutaneously, intradermally and subcutaneously. The route of administration depends on the type of tuberculin test. If the human body is pre-sensitized to MBT (by spontaneous infection or as a result of BCG vaccination), then a specific response reaction develops in response to the administration of tuberculin. It begins to develop 6-8 hours after the administration of tuberculin in the form of an inflammatory infiltrate of varying severity, the cellular basis of which is lymphocytes, monocytes, macrophages, epithelioid and giant cells. The trigger mechanism of the delayed-type hypersensitivity reaction is the interaction of the antigen (tuberculin) with receptors on the surface of effector lymphocytes, resulting in the release of mediators of cellular immunity, involving macrophages in the process of antigen destruction. Some cells die, releasing proteolytic enzymes that have a damaging effect on tissues. Other cells accumulate around the foci of specific damage. The inflammatory reaction occurs not only at the site of tuberculin application, but also around tuberculous foci. When sensitized cells are destroyed, active substances with pyrogenic properties are released. The time of development and morphology of reactions with any method of tuberculin application do not differ fundamentally from those with intradermal administration. The peak of the delayed-type hypersensitivity reaction occurs at 48-72 hours, when its nonspecific component is reduced to a minimum, and the specific reaches a maximum.

Indications for the procedure

Tuberculin diagnostics are divided into mass and individual.

Mass tuberculin diagnostics is used for mass screening of the population for tuberculosis. For mass tuberculin diagnostics, only one tuberculin test is used - the Mantoux test with 2 tuberculin units.

The Mantoux test with 2 TE is carried out for all children and adolescents vaccinated with BCG, regardless of the previous result, once a year. The child should receive the first Mantoux test at the age of 12 months. For children not vaccinated with BCG, the Mantoux test is carried out from the age of 6 months once every six months until the child receives the BCG vaccination, then according to the generally accepted method once a year.

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

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

In addition, there are groups of children and adolescents who are subject to the Mantoux test with 2 TE 2 times a year in the general health care network:

• patients with diabetes mellitus, gastric ulcer and duodenal ulcer, blood diseases, systemic diseases, HIV-infected patients receiving long-term hormonal therapy (more than 1 month);
• patients with chronic non-specific diseases (pneumonia, bronchitis, tonsillitis), subfebrile temperature of unknown etiology;
• not vaccinated against tuberculosis, regardless of the child's age;
• Children and adolescents from social risk groups located in specialized institutions (shelters, centers, reception and distribution centers), who do not have medical documentation, are examined using the Mantoux test with 2 TE upon admission to the institution, then 2 times a year for 2 years.

Contraindications to the Mantoux test with 2 TE

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

The Mantoux test is performed 1 month after the disappearance of clinical symptoms or immediately after the quarantine is lifted.

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

The results of mass tuberculin diagnostics in dynamics allow us to identify the following groups among children and adolescents:

• children and adolescents not infected with MBT - children and adolescents who have annual negative Mantoux tests with 2 TE, children and adolescents who have PVA;
• children and adolescents infected with MBT.

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Individual tuberculin diagnostics

When conducting individual tuberculin diagnostics, various tuberculin tests are used with cutaneous, intradermal and subcutaneous administration of tuberculin. For various tuberculin tests, bacterial allergens are used: both purified tuberculin in standard dilution (purified tuberculosis allergen for cutaneous, subcutaneous and intradermal use in standard dilution) and purified dry tuberculin (purified tuberculosis allergen for cutaneous, subcutaneous and intradermal use dry). Purified tuberculin in standard dilution can be used in anti-tuberculosis institutions, children's clinics, somatic and infectious disease hospitals. Purified dry tuberculin is allowed to be used only in anti-tuberculosis institutions (anti-tuberculosis dispensary, tuberculosis hospital and sanatorium).

Evaluation of tuberculin reaction

The intensity of the tuberculin reaction depends on many factors (specific sensitization of the organism, its reactivity, etc.). In practically healthy children infected with MBT, tuberculin reactions are usually less pronounced than in patients with active forms of tuberculosis. In children with tuberculosis, sensitivity to tuberculin is higher than in adults with tuberculosis. In severe forms of tuberculosis (meningitis, miliary tuberculosis, caseous pneumonia), low sensitivity to tuberculin is often noted due to pronounced suppression of the organism's reactivity. Some forms of tuberculosis (eye and skin tuberculosis), on the contrary, are often accompanied by high sensitivity to tuberculin.

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

• A local reaction is formed at the site of tuberculin administration and may manifest itself as hyperemia, papules (infiltrates), vesicles, bullae, lymphangitis, and necrosis. A local reaction has diagnostic value in the case of cutaneous 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, arthralgia, changes in blood tests (monocytopenia, dysproteinemia, slight acceleration of ESR, etc.). The general reaction most often develops with subcutaneous administration of tuberculin.
• Focal reaction develops in patients in the focus of a specific lesion - in tuberculosis foci of various localizations. Focal reaction is manifested clinically (in pulmonary tuberculosis, hemoptysis, increased cough, increased amount of sputum, chest pain, increased catarrhal phenomena may appear; in extrapulmonary tuberculosis - increased inflammatory changes in the zone of tuberculosis lesion) and radiologically (increased perifocal inflammation around tuberculosis foci). Focal reaction is more pronounced with subcutaneous administration of tuberculin.

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Evaluation of tuberculin diagnostic results

The test results can be assessed as follows:

• negative reaction - complete absence of infiltrate (papule) and hyperemia, the presence of a prick reaction of 0-1 mm is acceptable;
• questionable reaction - infiltrate (papule) measuring 2-4 mm or the presence of hyperemia of any size without infiltrate;
• a positive reaction is an infiltrate (papule) measuring 5 mm or more, this includes the presence of vesicles, lymphangitis, and seeding (several more papules of any size are formed around the papule at the site of tuberculin injection).

Among the positive reactions, the following are highlighted:

• weakly positive - papule size 5-9 mm;
• medium intensity - papule size 10-14 mm;
• pronounced - papule size 15-16 mm;
• hyperergic - in children and adolescents the papule size is 17 mm and above, in adults - 21 mm and above, also hyperergic reactions include vesicular-necrotic reactions, the presence of lymphangitis, and cysts, regardless of the size of the papule.

Positive results of the Mantoux test with 2 TE are considered as post-vaccination allergy in the following cases:

• a connection was noted between positive and questionable reactions to 2 TE with previous BCG vaccination or revaccination (i.e. positive or questionable reactions appear in the first 2 years after BCG vaccination or revaccination);
• there is a correlation between the sizes of reactions (papules) to tuberculin and the sizes of the post-vaccination BCG sign (scar): a papule up to 7 mm corresponds to scars from BCG up to 9 mm, and up to 11 mm - to scars more than 9 mm;
• The largest reaction to the Mantoux test is detected in the first two years after vaccination or revaccination with BCG; in the following 5-7 years, post-vaccination sensitivity to tuberculin fades.

The reaction to 2 TE PPD-L is considered to be the result of an infectious allergy (delayed-type hypersensitivity) in the following cases:

• transition of a negative reaction to 2 TE of tuberculin to a positive one, not associated with vaccination or revaccination with BCG; increase in the size of the papule by 6 mm or more after a previous post-vaccination allergy - the early period of primary tuberculosis infection, i.e. a turn;
• a sharp increase in sensitivity to tuberculin (by 6 mm or more) within 1 year (in tuberculin-positive children and adolescents after a previous infectious allergy);
• gradual, over several years, increase in sensitivity to tuberculin with the formation of reactions to 2 TE of moderate intensity or severe reactions;
• 5-7 years after vaccination or revaccination with BCG, persistent (for 3 years or more) sensitivity to tuberculin at the same level without a tendency to fade - monotonous sensitivity to tuberculin,
• fading of sensitivity to tuberculin after a previous infectious allergy (usually in children and adolescents previously observed by a phthisiopediatrician and who received a full course of preventive treatment).

A study of the results of tuberculin diagnostics performed on children and adolescents showed a dependence of the intensity of responses to 2 TE PPD-L on many factors, which should also be taken into account when examining 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 entails an increase in sensitivity to tuberculin. In turn, a decrease in the frequency of BCG revaccinations leads to a decrease in the number of positive results for the Mantoux test by 2 times, hyperergic - by 7 times. Thus, the cancellation of revaccinations helps to identify the true level of infection of children and adolescents with MBT, which, in turn, allows for full coverage of adolescents with BCG revaccination within the required time frame. It is possible that it is advisable to carry out only one revaccination in epidemiologically favorable conditions - at the age of 14, and two in epidemiologically unfavorable conditions - at 7 and 14 years. It has been shown that the average papule size for 2 TE with a turn is 12.3 ± 2.6 mm. According to E.B. Mewe (1982) found that in unvaccinated healthy children the size of the papule per 2 TE PPD-L does not exceed 10 mm.

The intensity of delayed-type hypersensitivity reactions to 2 TE is affected by a number of factors. Many authors have confirmed the dependence of the Mantoux reaction intensity on the size of the post-vaccination BCG mark. The larger the post-vaccination scar, the higher the sensitivity to tuberculin. The frequency of positive reactions increases with age. Children born with a body weight of 4 kg or more have a higher sensitivity to tuberculin, breastfeeding for more than 11 months also entails high reactions to 2 TE (possibly due to the low iron content in milk). Helminthic invasions, food allergies, and acute respiratory diseases increase sensitivity to tuberculin. With high sensitivity to tuberculin, blood group II (A) is more often detected, 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, hyperthyroidism, allergies, viral hepatitis, flu, obesity, concomitant infectious diseases, chronic foci of infection, against the background of the introduction of certain protein preparations, taking thyroidin, tuberculin reactions are enhanced.

A study of tuberculin sensitivity in young and preschool children showed a decrease in the frequency of negative reactions in children aged 3 and 7 years. These periods coincide with vaccinations against childhood infections (DPT, DPT-M, ADS-M, measles, mumps vaccines). Increased sensitivity to tuberculin is noted when the Mantoux test is administered with 2 TE within 1 day to 10 months after the above vaccinations. Previously negative reactions become doubtful and positive, and after 1-2 years they become negative again. Therefore, tuberculin diagnostics are planned either before preventive vaccinations against childhood infections, or not earlier than 1 month after vaccinations. When the Mantoux test is administered before preventive vaccinations against childhood infections, they can be administered on the day of recording the reaction to the Mantoux test, if the size of the tuberculin response does not require specialist intervention.

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