Chemoprophylaxis of tuberculosis

Chemoprophylaxis is the use of anti-TB drugs to prevent the development of the disease in individuals. Who are most at risk of contracting tuberculosis. With the help of specific chemopreparations, it is possible to reduce the population of mycobacteria tuberculosis, penetrated into the human body, and create optimal conditions for the full interaction of immunocompetent cells. The use of anti-TB drugs for preventive purposes reduces the probability of tuberculosis by 5-7 times.

In some cases, chemoprophylaxis is administered to children, adolescents and adults. Not infected with mycobacteria tuberculosis, with a negative reaction to tuberculin, - primary chemoprophylaxis. Primary chemoprophylaxis is usually a short-term emergency for individuals. Located in regions with a high incidence of tuberculosis. Secondary chemoprophylaxis is prescribed to people infected with mycobacterium tuberculosis (with a positive reaction to tuberculin), who do not have clinical and radiological signs of tuberculosis, as well as patients with residual changes in organs after previous tuberculosis.

Chemoprophylaxis of tuberculosis is necessary:

• for the first time infected with mycobacteria of tuberculosis ("turn" of tuberculin test) to clinically healthy children, adolescents and persons under 30 years of age (the regimen is determined individually taking into account risk factors);
• children, adolescents and adults who are in domestic contact with patients with active tuberculosis (with bacilli):
• children and adolescents who were in contact with patients with active tuberculosis in children's institutions (regardless of the allocation of patients to the Office);
• Children and adolescents residing on the territory of institutions of the anti-tuberculosis service;
• children from families of livestock breeders working in regions that are unsuccessful for tuberculosis incidence, children from families that have cattle on the individual farm;
• for the first time identified persons with signs of transferred tuberculosis and persons who received treatment for tuberculosis:
• Persons with pronounced residual changes in organs after the transferred tuberculosis (courses of chemoprophylaxis are carried out taking into account the nature of residual changes);
• Newborns vaccinated in the maternity home with BCG vaccine. Born from tuberculosis of mothers with untimely detected disease (chemoprophylaxis is carried out 8 weeks after vaccination);
• Persons with traces of previously transferred tuberculosis, in the presence of adverse factors (acute diseases, surgeries, trauma, pregnancy) that can exacerbate the disease;
• persons who have received treatment for tuberculosis, with marked residual changes in the lungs, in a dangerous epidemiological environment;
• Persons with traces of previously transferred tuberculosis in the presence of their diseases. Treatment of which with various drugs (for example, glucocorticoids) can cause exacerbation of tuberculosis (diabetes, collagenosis, silicosis, sarcoidosis, peptic ulcer and duodenal ulcer, etc.).

When choosing drugs for chemoprophylaxis, particular importance is attached to the efficacy and specificity of their action on the mycobacterium tuberculosis, the most justified consider the use of preparations of hydrazide isonicotinic acid and its analogues. Usually, chemoprophylaxis is carried out by the most active drug of this group - isoniazid. Children, adolescents and people of young age (under 30 years) with a hyperergic reaction to the Mantoux test with 2 TE prevention are recommended to carry out two drugs - isoniazid and ethambutol. For adults and adolescents, the daily dose of isoniazid for daily intake is 0.3 g, for children 8-10 mg / kg. If isoniazid is intolerant, use fluorazide: adults 0.5 g 2 times a day, children 20-30 mg / kg per day in 2 divided doses. Both adults and children need to prescribe vitamins B ₆ and C.

Usually, chemoprophylaxis is carried out for 3-6 months. Taking into account risk factors and indications after 6 months, a second course is possible. The regime and method of chemoprophylaxis are determined individually.

In specific epidemiological conditions, chemoprophylaxis of tuberculosis can be prescribed to other groups of the population.

Preventive Chemotherapy

At present, it has been proved expedient to conduct chemoprophylaxis in children and adolescents in the early period of primary tuberculosis infection. The effectiveness of chemoprophylaxis is influenced by various factors:

• presence of concomitant diseases and nonspecific reactivity of the organism;
• rate of inactivation of isoniazid (in slow acetylators, the efficacy is
  higher);
• age (effectiveness is lower in children younger than 7 years, since the ability to adapt to various environmental factors at this age is less);
• seasonality of courses (efficiency is lower in winter and summer);
• quality of vaccination and revaccination of BCG;
• the use of various (eg, hyposensitizing) medications.

The worsening of the epidemiological situation caused by socio-economic and demographic changes led to an increase in the number of people infected with tuberculosis. Infection of children with tuberculosis in Russia is 10 times higher than in developed countries. The number of newly infected children in the past decade has more than doubled, they constitute up to 2% of the total child population in a number of regions. This requires the implementation of preventive measures in the most vulnerable groups of the child population. Unfortunately, the traditional chemoprophylaxis that has existed since the 1970s is not always effective enough.

The main problems of chemoprophylaxis and preventive treatment of tuberculosis are selection of drugs for prevention, determination of the duration of their use, and evaluation of the effectiveness and risk of treatment.

Since 1971, chemoprophylaxis is necessarily prescribed to children and adolescents at risk for TB incidence. Apply isoniazid at a dose of 10 mg / kg for 3 months after the detection of a positive or hyperergic reaction to tuberculin, while maintaining a positive reaction appoint a second course of chemotherapy for 3 months with two drugs.

Taking drugs from the group of isonicotinic acid hydrazides and their analogs allows to obtain a satisfactory protective effect, but their hepatotoxicity and the likelihood of development of drug resistance in mycobacteria of tuberculosis with long-term isoniazid intake (6-12 months) determine the urgency of finding other possibilities.

Alternative treatment regimens:

• The use of rifampicin in combination with pyrazinamide (with or without isoniazid) can reduce the duration of treatment to 3 months,
• reception of rifampicin in monotherapy (comparable in effectiveness to that of isoniazid, but less toxic);
• use of less toxic analogues of isoniazid;
• use of rifampicin derivatives.

The growth of drug resistance in mycobacteria of tuberculosis and the decrease in the effectiveness of treatment of tuberculosis patients are largely due to irregular intake of drugs or failure to adhere to the optimal treatment regimen (doses and multiplicity of admission). In this regard, when conducting chemoprophylaxis, a clear organization and strict control are necessary. It is important to choose the optimal form of chemoprophylaxis: in tuberculosis sanatoriums, school and preschool institutions of sanatorium type, outpatient.

Many domestic authors believe that in the presence of risk factors, chemoprophylaxis is advisable to use two drugs. In foci with unfavorable epidemic conditions (contact with bacilli generators, especially those with fibrous-cavernous tuberculosis) to prevent the development of tuberculosis in children, it is necessary to individually select a chemoprophylaxis regimen and prescribe repeated courses.

In the conditions of widespread distribution of drug-resistant Mycobacterium tuberculosis, children are increasingly in contact with strains resistant to anti-tuberculosis drugs, especially isoniazid. In these conditions, the effectiveness of chemoprophylaxis with isoniazid in monotherapy is significantly reduced, therefore, it is necessary to use drugs of the reserve series for 3 months or more.

This justifies the need to review the drafts developed at the beginning of the 20th century. Regimes of chemoprophylaxis and application of a differentiated approach to preventive treatment taking into account the risk factors of the disease (medical, biological, epidemiological, social, clinical genealogical) that determine the probability of infection and tuberculosis, the nature of tuberculin sensitivity and the state of immunological reactivity of infected children.

Organization of preventive treatment of children and adolescents from risk groups

Preventive treatment for children and adolescents, the first time infected with tuberculosis mycobacteria ("turn", the early period of latent tuberculosis infection), as well as children from high-risk groups, is appointed by the phthisiopaediatrician.

Risk factors that contribute to the development of the tuberculosis process in children and adolescents: epidemiological, medico-biological, age-sex and social.

Epidemiological (specific) factors:

• contact with people with tuberculosis (family or casual contact);
• contact with tuberculosis patients with animals. Medical-biological (specific) factors:
• ineffective BCG vaccination (the effectiveness of BCG vaccination is assessed by the size of the post-vaccination sign: if the size of the vaccine scars is less than 4 mm or its absence, immune protection is regarded as insufficient);
• hyperergic sensitivity to tuberculin (according to the Mantoux sample with 2 TE).

Medical-biological (nonspecific) factors:

• associated chronic diseases (urinary tract infections, chronic bronchitis, bronchial asthma, allergic dermatitis, chronic hepatitis, diabetes mellitus, anemia, neuropsychiatric pathology);
• frequent ARVI in the anamnesis (group of "often ill children").

Age-sex (nonspecific) factors:

• age up to 3 years;
• prepubertal and adolescence (13 to 17 years);
• female sex (teenage girls are more likely to get sick).

Social (nonspecific) factors:

• alcoholism, drug addiction among parents;
• stay of parents in places of deprivation of liberty, unemployment;
• living in orphanages, orphanages, social centers, depriving parents of parental rights, homelessness;
• large families, single parent family;
• residence among migrants.

Indications for referral to phthisiatricians

• early period of primary tuberculosis infection ("turn"), regardless of the Mantoux reaction level with 2 TE and the presence of risk factors;
• Hyperergic Mantoux reactions with 2 TE, regardless of the presence of risk factors;
• increase the size of the Mantoux papule with 2 TE for 6 mm or more, regardless of the Mantoux reaction level with 2 TE and the presence of risk factors;
• a gradual increase in sensitivity to tuberculin for several years with an average intensity and severity of the Mantoux reaction with 2 TE, regardless of the presence of risk factors;
• constant sensitivity to tuberculin of medium intensity and severity of the Mantoux reaction with 2 TE, in the presence of two or more risk factors;
• expressed reaction to tuberculin (papule 15 mm and more) in children and adolescents from social risk groups.

Information necessary for referring children and adolescents to the phthisiatrician

• date of vaccination and revaccination of BCG;
• data of annual Mantoux reactions with 2 TE from the moment of birth;
• data on the presence and duration of contact with patients with tuberculosis;
• results of a fluorographic examination of close relatives of the child;
• data on the transferred acute, chronic, allergic diseases:
• data from previous phthisiatric examinations;
• results of clinical and laboratory examination (general blood test, general urine analysis);
• the conclusion of specialists (in the presence of concomitant diseases);
• a social anamnesis of a child or adolescent (living conditions, material support, migratory anamnesis).

Preventive treatment phthisiatrician appoints differentially. In the presence of specific risk factors (lack of BCG vaccination, contact with a sick tuberculosis) treatment is performed in a hospital or sanatorium, in other cases the volume and location of preventive treatment is determined individually.

After additional examination at the phthisiatrician and exclusion of the local process, the child is prescribed chemoprophylaxis or preventive treatment.

Two types of children and adolescents carry out specific prophylaxis of tuberculosis with chemotherapy drugs.

Primary prophylaxis of tuberculosis is for uninfected children and adolescents who have contact with tuberculosis patients (IV TBD at a phthisiatrician).

Secondary prevention of tuberculosis - in infected children and adolescents, is carried out after positive results of screening tuberculin diagnostics (VI GDU at the phthisiatrician).

Groups in which it is necessary to prescribe chemoprophylaxis

• Infected children and adolescents:
  • - in the early period of primary tuberculosis infection ("circulation of tuberculin samples") without local changes;
  • in the early period of primary tuberculosis infection (the "turn of tuberculin samples") with hyperergic reaction to tuberculin;
  • with an increase in sensitivity to tuberculin:
  • with hyperergic sensitivity to tuberculin;
  • with a constant sensitivity to tuberculin in combination with risk factors.
• Children and adolescents in contact with patients with tuberculosis.

Preventive treatment of children from risk groups for tuberculosis should be individual, taking into account epidemiological and social risk factors. Chemoprophylaxis with a single anti-tuberculosis drug (isoniazid, phtivazide or metazide) in outpatient settings can be performed only in children from the IV, VIA, VIB groups in the absence of additional (specific or nonspecific) risk factors. Contact with patients with tuberculosis and the presence of other risk factors are threatening indicators that contribute to the development of tuberculosis. Preventive therapy for such children is carried out with two anti-tuberculosis drugs in children's specialized institutions. In the presence of allergic diseases in patients, preventive treatment is performed against the background of desensitizing therapy.

Chemoprophylaxis for children is carried out for 3 months, preventive treatment is carried out individually, depending on the risk factors for 3-6 months. The effectiveness of chemoprophylaxis (preventive treatment) is determined with the help of clinical and laboratory indicators and the results of tuberculin samples. The decrease in susceptibility to tuberculin, satisfactory clinical and laboratory indicators and absence of disease testify to the effectiveness of preventive measures. The increase in sensitivity to tuberculin or the negative dynamics of clinical and laboratory indicators require an additional examination of the child.

Methods of chemoprophylaxis

Treatment is carried out after a comprehensive examination at the phthisiatrician. Preventive treatment for the first time of people with tuberculosis (VIA) without risk factors, with unchanged clinical and laboratory and immunological indicators, is carried out with one drug from the group of nicotinic acid hydrazides and analogues (isoniazid or metazide 10 mg / kg, ftivazid 20 mg / kg, once a day, in the morning, in combination with pyridoxine) for 6 months. Treatment is carried out on an outpatient basis or in a sanatorium.

For preventive treatment, two antibacterial drugs are used. Isoniazid at a dose of 10 mg / kg, once a day, in the morning in combination with pyridoxine and ethambutol 20 mg / kg or pyrazinamide 25 mg / kg, once a day, is prescribed for children in the presence of risk factors, with changed clinical and laboratory and immunological indicators of the organism's reactivity. Sensitivity to tuberculin in the Mantoux reaction with 2 TE PPD-L expressed, hyperergic, sensitivity threshold - by the 6th dilution and more, positive reactions - by 3 dilutions and more graded reaction Pirke. Treatment is carried out for 6 months - depending on the dynamics of tuberculin sensitivity in the intermittent mode, in a hospital or in a sanatorium.

Increased susceptibility to tuberculin (GIB VIB) in patients previously infected with tuberculosis after the examination (GDN 0) and sanation of foci of nonspecific infection in the absence of risk factors of the disease requires the appointment of preventive treatment with one anti-tuberculosis drug for 6 months in intermittent mode on an outpatient basis or in a sanatorium. In the presence of risk factors, changes in clinical-laboratory and immunological indicators of the body's reactivity, preventive treatment with two antibacterial drugs is carried out (intermittent reception is possible). Sensitivity to tuberculin in the Mantoux reaction with 2 TE PPD-L expressed, hyperergic, sensitivity threshold - by the 6th dilution and more, positive reactions - by 3 dilutions and more graded reaction Pirke. Treatment is carried out for 6 months - depending on the dynamics of tuberculin sensitivity, outpatient or in a sanatorium.

Hyperergic sensitivity to tuberculin (GIB VIB) in the absence of risk factors and changes in clinical and laboratory and immunological indicators requires the appointment of preventive treatment with one anti-tuberculosis drug for 3 months. Outpatient or in a sanatorium, in combination with antihistamines. If sensitivity to tuberculin is reduced to the norm (with the exception of primary infection), treatment can be stopped. With preservation of hyperergic sensitivity to tuberculin, treatment is continued for 6 months with two anti-tuberculosis drugs, and an X-ray tomographic examination of the thoracic organs is necessary. Ultrasound of the abdominal organs, urinalysis on the BK.

In the presence of risk factors, changes in clinical and laboratory and immunological parameters of the organism's reactivity and hyperergic sensitivity with the threshold of sensitivity to tuberculin at the 6th dilution and more, with positive reactions for 3 dilutions and a more graded reaction, Pirke is given preventive treatment for 6 months - in dependence on the dynamics of tuberculin sensitivity, in a hospital or in a sanatorium.

Children and adolescents in tuberculosis foci (GDU IV), who are not infected with tuberculosis and infected for a year or more without additional medical and social risk factors, receive a three-month course of treatment with a single anti-tuberculosis drug. At the end of the course of treatment, if a negative reaction to tuberculin (2 TE PPD-L) is maintained, persons not infected with tuberculosis come under the supervision of the dispensary phthisiatrician.

In case of detection of a "bend" of tuberculin samples or hyperergic sensitivity to tuberculin, treatment should be continued up to 6 months with two anti-tuberculosis drugs (taking into account the drug resistance of mycobacteria tuberculosis) with an X-ray tomographic examination of the chest. Ultrasound of the abdominal organs, urine analysis on mycobacterium tuberculosis. Children infected with tuberculosis, with a low sensitivity to tuberculin after a three-month course of treatment, come under the supervision of a phthisiatrician. With the increase of sensitivity to tuberculin in the course of observation, a second course of treatment with two antituberculosis drugs is prescribed for 3 months.

Children and adolescents with hyperergic reaction to tuberculin or with a "bend" of tuberculin samples or with an increase in sensitivity to tuberculin of more than 6 mm. Who are in contact with a sick tuberculosis that secretes mycobacteria, receive controlled preventive therapy with two anti-tuberculosis drugs taking into account the drug sensitivity of mycobacteria. In the presence of additional medical and social risk factors, treatment is performed in a sanatorium or in a hospital.

Chemoprophylaxis of tuberculosis in HIV-infected children and adolescents

Chemoprophylaxis in HIV-infected individuals reduces the likelihood of tuberculosis and prolongs the life of patients. Indications for chemoprophylaxis are associated with the prevalence of tuberculosis infection among HIV-infected patients. An important criterion for resolving the issue of chemoprophylaxis and its duration is the number of persons infected with tuberculosis from an HIV-infected person with tuberculosis. This indicator depends on the survival of the patient during and without therapy. The timing of the survival of HIV-positive tuberculosis patients that secrete mycobacteria is short, the survival rate of AIDS patients does not reach a year.

One of the criteria for selecting patients for prophylactic treatment is the size of the papule that appears in response to intradermal introduction of tuberculin in standard dilution (2 TE), but no direct correlation between this indicator and the number of CD4 ⁺ Lymphocytes in the blood of HIV-infected patients has been detected. The effectiveness of chemoprophylaxis is the same as in people with depressed, and in persons with preserved immunity. Indirect advantages of chemoprophylaxis depend on the nature of the contact of the HIV-infected person with the patient with tuberculosis and the survival time of such persons during and without therapy. Belonging to a high-risk group (HIV-positive drug users with positive reactions to 2 TE PPD-L or lack of response to tuberculin) is a direct indication for chemoprophylaxis. With proper specific chemotherapy, the incidence decreases from 5.7 to 1.4 per 100 cases per year.

The timing of chemoprophylaxis and the priority of taking medications have not been determined. The most reasonable are 6-month courses of taking isoniazid by HIV-infected patients with a CD4 ⁺ lymphocyte count of 200 in mm ³ or less. Therapy allows to increase the life expectancy of patients on average by 6-8 months and in 19-26% it allows to prevent the development of clinical forms of tuberculosis.

[1], [2], [3], [4], [5], [6], [7], [8], [9],