• Mantoux reaction in children - Causes, symptoms and treatment. MF.

    Mantoux test( Pirke test, tuberculin test, tuberculin diagnostics) is a method of investigating the intensity( severity) of immunity to the causative agent of tuberculosis by evaluating the skin reaction to a special preparation of mycobacteria, tuberculin.

    What is tuberculin?

    The meaning of tuberculin is to "designate" the presence of a tubercle bacillus in the body so that the body's response( qualitatively and quantitatively) to this "presence" can be assessed. In this sense, tuberculin copes well with its task - it is for this reason that the drug has not been radically processed and for more than 100 years, to date it is one of the main means of diagnosing tuberculosis.

    Tuberculin( the exact name of "alttuberculin", AT) of Koch is "extract", lysate from mycobacterium tuberculosis, inactivated( killed) by heating. The classical drug, in addition to the tuberculin itself, contained many impurities - the remains of the nutrient medium on which the bacteria, salts and other substances influenced the purity of the reaction and made it difficult to assess the result of the samples. Since the late 60s of the 20th century, cleaner tuberculin preparations have been developed, the so-called PPD( Purified Protein Derivate), which are still used today. In Russia, the drug PPD-L is used, i.e.purified tuberculin, obtained by the Russian scientist Linnikova in 1965.The modern tuberculin preparation, in addition to tuberculin itself, contains salts of a phosphate buffer solution, sodium chloride, a stabilizer of Tween-80, and phenol as a preservative. Basically, the drug is free from ballast impurities, but it can contain them in trace amounts, which can affect the result of the reaction.

    However, the mechanism of interaction of tuberculin with the immune system is still unknown until the end. On the one hand, the protein lysate( peptides, amino acids) can not be a complete antigen. Indeed, tuberculin does not cause the formation of immunity. But this point of view does not explain the amplification, as with vaccination, of the reaction with frequent staging of the sample - the so-called."Booster effect" of the Mantoux test. So what is tuberculin? Most likely, tuberculin can be characterized as a heterogeneous mixture of organic substances of varying degrees of complexity, derived from mycobacteria.

    What is the Mantoux reaction?

    Mantoux reaction is the body's reaction to the introduction of tuberculin. At the site where the drug is injected into the skin, a specific inflammation arises( a tuberculous process is simulated), caused by infiltration of T-lymphocytes-specific blood cells responsible for cellular immunity. Fragments of mycobacteria, as it were, attract lymphocytes from nearby blood vessels of the skin. But not all T-lymphocytes enter the game, but only those that are already fully or partially "familiar" with the causative agent of tuberculosis. If the body is already "acquainted" with the real mycobacterium tuberculosis, then there will be more such lymphocytes, the inflammation is more intense, and the reaction will be "positive"( there is infection with a tubercle bacillus).Naturally, a positive reaction means that the inflammation is greater than that caused by the injection itself and a certain diagnostic threshold. By measuring the diameter of the papule( pushkin), you can estimate the intensity of immunity to a tubercle bacillus. The reaction of the body to tuberculin is one of the varieties of allergy( tuberculin itself is an allergen).

    The results of the Mantoux test are influenced by: immunodeficiency( real), chemotherapy of tumors and hemodialysis, as well as various violations in the method of its carrying out: transportation and storage of tuberculin, using non-standard and poor-quality tools, with errors in the technique of setting and reading Mantoux reactions. In view of the above factors, in isolation, the positive Mantoux reaction in itself is not 100% evidence of tuberculosis infection. To confirm the diagnosis, it is required to conduct a number of other studies - excluding the connection with BCG vaccination, chest fluorography, microbiological sputum culture and a number of others. In turn, a negative result does not give a 100% guarantee of the absence of mycobacterium tuberculosis in the body.

    Why do we need a Mantoux reaction?

    Rather so, but do you need a Mantoux test at all? In this regard, WHO answers in the affirmative - yes, for countries with high relevance of tuberculosis( such are Russia and most of the CIS countries at the moment), this trial is one of the effective measures of infection control. Even in countries where the relevance of tuberculosis is low, for example in the US and France, the Mantoux test is used quite actively - to identify those infected with tuberculosis in high-risk groups.

    Mantoux reaction is needed for:

    - the detection of primary infected, that is, those who first discovered the fact of infection with a tubercle bacillus;

    - detection of those infected for more than one year with hyperergic reactions to tuberculin;

    - infected more than one year with an increase in infiltration by 6 mm or more;

    - diagnosis of tuberculosis in individuals who are infected with Koch's bacillus, but do not show symptoms at this time;

    - confirmation of the diagnosis of tuberculosis;

    - selection of contingents of children subject to revaccination against tuberculosis.

    The selection of children and adolescents for revaccination is based on Mantoux test results at 6-7 and at 14-15 years. In areas where the epidemiological situation of tuberculosis is unsuccessful, revaccination is carried out at 6-7, 11-12 and 16-17 years. Revaccination of BCG is subject to healthy individuals with only a negative reaction to tuberculin.

    Contraindications to the formulation of Mantoux test.

    It should be specially emphasized that the Mantoux test is harmless both for healthy children and adolescents, and for children with various physical illnesses. Tuberculin does not contain living microorganisms, and in the applied dosage of 2 TE( 0.1 ml) does not affect either the body's immune system or the whole organism.

    Sample setting does not make sense in children under 12 months, because the result of the sample will be unreliable or inaccurate, due to the age-related features of the development of the immune system - the reaction may be false-negative. Children under 6 months are not able to respond adequately to the Mantoux test.

    Contraindications to tuberculin test are:

    - skin diseases,

    - acute and chronic infectious and somatic diseases at the stage of exacerbation( Mantoux test is made 1 month after disappearance of all clinical symptoms or immediately after removal of quarantine),

    - allergic conditions,

    - Epilepsy.

    It is not allowed to carry out a sample in those collectives where there is a quarantine for children's infections. The Mantoux test is made 1 month after all clinical symptoms have disappeared or immediately after quarantining.

    Mantoux reaction and grafting

    Because the immunity produced by immunizations can affect the result of the Mantoux test, its formulation should not be performed on one day with any kind of vaccination. Otherwise, the risk of false positive reactions increases. At the same time, immediately after evaluating the results of the test, on the same day or later, vaccinations can be carried out without restrictions.

    If vaccinations are carried out prior to the sample, then to avoid interference, the interval between the introduction of inactivated( killed) vaccines, such as against influenza, diphtheria and tetanus, etc., and the Mantoux reaction should be at least 4 weeks. This applies equally to the introduction of sera and immunoglobulins. In the case of vaccination with live vaccines( measles, mumps, rubella, OPV, etc.), this interval should be increased to 6 weeks.

    How is the Mantoux test done?

    In accordance with the Order of the Ministry of Health of the Russian Federation of 22.11.95 № 324 in Russia Mantoux test is carried out once a year, starting from the age of 12 months, regardless of the results of the previous test.

    A special tuberculin syringe is intradermally( middle third of the inner surface of the forearm) injected with tuberculin in terms of 2 tuberculosis units( TE).The volume of the administered dose is 0.1 ml. The needle is inserted by a cut upwards, to a depth sufficient to ensure that the outlet hole is completely immersed in the skin. In order to make sure that the needle does not penetrate the skin and provide the intradermal injection itself, the needle is slightly raised, stretching the skin. After the introduction of tuberculin, a specific bulging of the upper layer of the skin is formed, more commonly known as the "button".

    How to care for the "button"?

    The simplest answer is no. In any case, until the evaluation of the results. Do not smear the place of staging a sample of green, peroxide. No need to seal the wound with adhesive tapes - under it the skin can sweat. Do not allow the child to comb the "button".Remember that improper care of the place of introduction of tuberculin can affect the result of the test, and this is not necessary neither for the patient, nor for the doctor.

    After evaluating the results, if there is an abscess or sore, it can be treated like any other wound, using all the traditional means.

    How are results evaluated?

    The most important thing in the Mantoux sample is not the production, but the evaluation of its results, and even more important, the conclusions from the evaluation result of the sample. After the introduction of tuberculin, a specific skin firming is formed on day 2-3."Papule"( infiltration, compaction).In appearance, it is a slightly rounded skin area above the skin. If you press it lightly with a transparent ruler( or if you press and release it with your finger), it should lighten slightly. Unlike simple redness, to the touch( although it is not always possible to catch with fingers), the papule differs from the surrounding skin with its consistency - it is more dense. From the point of view of anatomy, this papule is the result of a kind of saturation of the skin with cells, namely lymphocytes, sensitized( ie sensitive) to Koch's stick. Naturally, the more "knowing" about the mycobacterium of lymphocytes in the body, the more infiltrate( papule) will be.

    The size of the papule is measured in sufficient light with a transparent( so that the maximum diameter of the infiltrate can be seen) by a ruler on Day 3( 48-72 hours) after the introduction of tuberculin. The ruler should be located transversely to the longitudinal axis of the forearm. It is not allowed to use a thermometer and other "improvised materials" like millimeter paper and homemade x-ray film rulers for measurement. Only the size of the seal is measured. Redness around the compaction is not a sign of immunity to tuberculosis or infection, but it is recorded when there is no papules.

    Classification of Mantoux test results

    The reaction is considered:

    - negative - with no infiltrate( compaction) or with a knock-off reaction( 0-1 mm);

    - doubtful - with infiltrate( papule) 2-4 mm in size with only hyperemia( reddening) of any size without infiltration( compaction);

    - positive - in the presence of a pronounced infiltrate( papule) with a diameter of 5 mm or more.

    Reactions with an infiltrate size of 5-9 mm in diameter are considered to be weakly positive;average intensity - 10-14 mm;expressed - 15-16 mm;

    - hyperergic( i.e., too pronounced) in children and adolescents is a reaction with an infiltrate diameter of 17 mm or more, in adults it is 21 mm or more, and also vesicle-necrotic( ie, with the formation of pustules and necrosis)reaction, regardless of the size of the infiltrate, lymphangitis, daughter screenings, regional lymphadenitis( enlarged lymph nodes).

    False-negative reactions - in some patients, the Mantoux test may be negative even if infected with a tubercle bacillus. Such reactions can be caused by:

    - Anergia - that is, the inability of the immune system to respond to "irritation" with tuberculin. Such a reaction can be observed in people with various immunodeficiencies, including AIDS.In this situation, a special test for anergy( a Mantoux test with a higher tuberculin content of 100 TE) is conducted, it is necessary to conduct an examination of the immune system of the child for defects;

    - Recent infection - within the last 10 weeks.

    - Too small age - children under 6 months are unable to "respond" to the introduction of tuberculin.

    False positive reactions - such reactions mean that the patient is not infected with a Koch stick, but the Mantoux test shows a positive result. One of the most frequent reasons for this reaction is infection with non-tuberculous mycobacteria. Other causes may be the patient's allergic disorders and a recent infection. At present, there are no ways to reliably differentiate the response to tuberculosis and nontuberculosis mycobacteria, but the following facts may speak in favor of tuberculosis infection:

    - a hyperergic or severe reaction;

    is a long period since BCG vaccination;

    - a recent finding in the region with increased circulation of tuberculosis;

    - contact with the carrier of a tubercle bacillus;

    - the presence in the family of a patient of relatives who have been ill or infected with tuberculosis.

    "Virage" of Mantoux sample

    "Virage" of Mantoux test - change( increase) in the result of a sample( diameter of a papule) compared to last year's result. It is a very valuable diagnostic feature. Criteria for the bend are:

    - the appearance of the first positive reaction( papule 5 mm or more) after a previously negative or questionable;

    - reinforcement of the previous reaction by 6 mm or more;

    - hyperergic reaction( more than 17 mm) irrespective of the duration of vaccination;

    - a reaction of more than 12 mm 3-4 years after vaccination with BCG.

    It is the turn that makes the doctor think about what happened during the last year of infection. For example, if the result of the trial for the last three years looked like 12, 12, 12, and in the fourth year the result was 17 mm, then with a high degree of probability we can talk about the infection. Naturally, all influencing factors - allergy to tuberculin components, allergy to other substances, recently transferred infection, the fact of recent vaccination with BCG or another vaccine, etc. should be excluded.

    "Booster" Mantoux effect

    "Booster" effect of Mantoux test - boost effect( boost).increasing the diameter of the papule with frequent( more often than once a year) setting of the sample. Despite the fact that tuberculin is not a full-fledged antigen and can not cause the formation of immunity, the effect appears to be associated with an increase in the sensitivity of lymphocytes to tuberculin. The booster effect also has the opposite side: people infected with a tubercle bacillus lose their ability to react to tuberculin over the years and eventually the result of the test becomes false-negative. Booster effect( in both its manifestations) occurs in adolescents and adults, which, apparently, is due to a higher degree of development of the immune system. In children, this effect is less pronounced, however, setting Mantoux test more often than once a year is not desirable.

    Positive Mantoux test: BCG vaccination and / or infection?

    As vaccination is mandatory in Russia and other CIS countries, it is necessary to be able to distinguish the positive result of the Mantoux test due to postvaccinal immunity and infection with tuberculosis. In order to differentiate one from the other, it is necessary to know the size of the cutaneous scab( post-vaccination sign) after BCG immunization, the time elapsed from the time of vaccination or revaccination, the results of previous tests and the current size of the papule.

    Scar remains after vaccination BCG is on the left shoulder, at the border of the upper and middle third. As a rule, it has a rounded shape, its dimensions vary from 2 to 10 mm, the average size - 4-6 mm. There is a relationship between the size of the hem and the duration of post-vaccination immunity. So, with a hem size of 5-8 mm, the duration of immunity in most children is 5-7 years, and with a diameter of 2-4 mm - 3-4 years.

    If there is no scar, if the result of the Mantoux test is 10 mm in the first 2 years of life, this indicates infection. To determine the first positive reactions in these children and adolescents do not interfere with postvaccinal immunity, and with systematic repetition of the Mantoux test, it is easy to identify the transition of the negative to a positive reaction( papule 5 mm or more).

    After 1-1,5 years after BCG vaccination, the reaction in the majority( about 60%) of children will be positive, in others - the questionable or negative. The maximum immunity, that is, the maximum size of positive Mantoux probes, is recorded 2 years after vaccination. Dimensions of the papule in the first two years of life can reach 16 mm. The average figures range from 5-11 mm. The index of 12-16 mm is recorded in children with a diameter of postvaccinal scars of 6-10 mm.

    However, over time, postvaccinal immunity dies out and 3-5 years after vaccination( or BCG revaccination), the Mantoux reaction, with an infiltrate of 12 mm, will already be talking about infection. After 6-7 years, most children( in the absence of infection) will already register doubtful and negative reactions.

    An important feature that makes it possible to distinguish between postvaccinal immunity and infection as the cause of a positive reaction is the presence of pigmentation( brownish staining of the place where the papule was) 1-2 weeks after the Mantoux test. Papula, which appears after vaccination, usually does not have clear contours, pale pink and does not leave pigmentation. The post-infection papule is more intensely colored, has clear contours and leaves pigmentation, which lasts about 2 weeks.

    When differentiating, in favor of primary infection with tuberculous mycobacteria, the following symptoms are said:

    - the papules 5 mm or more, first revealed after doubtful and negative reactions;

    - an increase in the result compared to last year's 6 mm if it was positive and caused by BCG vaccination;

    - persistent( for 3-5 years) persistent reaction with an infiltrate of 10 mm or more;

    - a hyperergic reaction regardless of the timing of vaccination;

    - infiltrate more than 12 mm and more after 3-4 years from the moment of vaccination.

    Presence of predisposing factors: presence in the family of sick( or sick) tuberculosis, extra-family contact with tubinfected persons, being in an endemic region, low socioeconomic status, low level of education of parents.

    In case of suspected infection, the child or adolescent is immediately sent for consultation to the TB doctor.

    If it was not possible to determine whether the positive result of the test is the result of vaccination or infection, a preliminary conclusion is made about the unclear etiology of the positive result of the sample, and six months later the sample is reintroduced. If the result is again positive when the sample is repeated, or if the result is increased, an infection report is made. With a decrease in the size of the papule, a conclusion is made about the postvaccinal nature of the positive result of the previous test.

    Positive Mantoux test, what should I do?

    So, the Mantoux test showed a positive result, all the influencing factors - vaccination with BCG and other vaccines, a recent infection, an allergy to tuberculin components, were excluded. Since the Mantoux test is an important but not 100% reliable means of diagnosing tuberculosis, additional examinations are carried out - chest fluorography, microbiological sputum culture, examination of family members.

    Children and adolescents with newly diagnosed tuberculosis infection have an increased risk of developing clinically significant tuberculosis - it is believed that 7-10% of these children can develop primary tuberculosis with all the inherent symptoms. Therefore, such children are to be monitored in the TB dispensary during the year. Within three months chemoprophylaxis with isoniazid is carried out. At the end of this period, the child is referred to a district pediatrician as "infected for more than one year".

    If such a child after a year does not show signs of increased sensitivity to tuberculin and a hyperergic reaction, then it is observed by a pediatrician on "general grounds".These children carefully monitor the result of the annual Mantoux test. The increase in such children's reaction to 6 mm or more indicates activation of the infection.

    Infected for more than one year with a hyperergic reaction to tuberculin and an increase in response to 6 mm or more are observed in the TB dispensary. Chemoprophylaxis is carried out within 3 months.

    If the child's test result is positive, but the previous test was conducted not one, but two or more years ago, the child is considered "infected with an unidentified limitation period".It is recommended to conduct a repeat test after 6 months. Based on the results of the second test, the question of the need for observation in the TB dispensary and chemoprophylaxis is being solved.