Chemoprophylaxis of tuberculosis

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

In some cases, chemoprophylaxis is administered to children, adolescents, and adults. Not infected with Mycobacterium tuberculosis, with a negative reaction to tuberculin - primary chemoprophylaxis. Primary chemoprophylaxis is usually a short-term emergency measure in 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 have no clinical or radiological signs of tuberculosis, as well as to patients with residual changes in organs after previously suffered tuberculosis.

Chemoprophylaxis of tuberculosis is necessary:

• for the first time infected with Mycobacterium tuberculosis (a “turnaround” of the tuberculin test) clinically healthy children, adolescents and individuals under 30 years of age (the regimen is determined individually, taking into account risk factors);
• children, adolescents and adults who are in household contact with patients with active tuberculosis (with bacteria excretors):
• children and adolescents who have been in contact with patients with active tuberculosis in children's institutions (regardless of whether the patient has been exposed to MBT);
• children and adolescents living on the territory of anti-tuberculosis service institutions;
• children from families of livestock breeders working in regions with high rates of tuberculosis, children from families keeping livestock affected by tuberculosis on their own farms;
• newly diagnosed individuals with signs of previous tuberculosis and individuals who have undergone treatment for tuberculosis:
• persons with pronounced residual changes in organs after tuberculosis (chemoprophylaxis courses are carried out taking into account the nature of the residual changes);
• newborns vaccinated with the BCG vaccine in the maternity hospital, born to mothers with tuberculosis whose disease was not detected in a timely manner (chemoprophylaxis is carried out 8 weeks after vaccination);
• persons with traces of previously suffered tuberculosis, in the presence of unfavorable factors (acute diseases, operations, injuries, pregnancy) that can cause an exacerbation of the disease;
• persons who have undergone treatment for tuberculosis, with pronounced residual changes in the lungs, and who are in a dangerous epidemiological environment;
• persons with traces of previously suffered tuberculosis if they have diseases, the treatment of which with various drugs (for example, glucocorticoids) can cause an exacerbation of tuberculosis (diabetes, collagenosis, silicosis, sarcoidosis, gastric ulcer and duodenal ulcer, etc.).

When choosing drugs for chemoprophylaxis, special attention is paid to the effectiveness and specificity of their action on mycobacterium tuberculosis; the most justified is the use of isonicotinic acid hydrazide and its analogues. Usually, chemoprophylaxis is carried out with the most active drug of this group - isoniazid. For children, adolescents and young people (under 30 years) with a hyperergic reaction to the Mantoux test with 2 TE, prophylaxis is recommended to be carried out with two drugs - isoniazid and ethambutol. For adults and adolescents, the daily dose of isoniazid for daily use is 0.3 g, for children - 8-10 mg / kg. In case of isoniazid intolerance, phthivazid is used: adults 0.5 g 2 times a day, children 20-30 mg / kg per day in 2 doses. Both adults and children need to be prescribed vitamins B ₆ and C.

Chemoprophylaxis is usually administered for 3-6 months. Taking into account risk factors and indications, a repeat course may be administered after 6 months. The regimen and method of chemoprophylaxis are determined individually.

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

Preventive chemotherapy

At present, the advisability of chemoprophylaxis in children and adolescents in the early period of primary tuberculosis infection has been proven. The effectiveness of chemoprophylaxis is influenced by various factors:

• the presence of concomitant diseases and non-specific reactivity of the body;
• the rate of isoniazid inactivation (slow acetylators have a
  higher efficiency);
• age (efficiency is lower in children under 7 years of age, since the ability to adapt to various environmental factors at this age is less);
• seasonality of courses (lower efficiency in winter and summer);
• quality of BCG vaccination and revaccination;
• the use of various (for example, hyposensitizing) medications.

The worsening epidemiological situation caused by socio-economic and demographic changes has led to an increase in the number of people infected with tuberculosis. The infection rate of children with tuberculosis in Russia is 10 times higher than in developed countries. The number of children infected for the first time has more than doubled over the past decade, and in some regions they make up to 2% of the entire child population. This requires preventive measures in the most vulnerable groups of the child population. Unfortunately, traditional chemoprophylaxis, which has existed since the 1970s, is not always effective enough.

The main problems of chemoprophylaxis and preventive treatment of tuberculosis are the selection of drugs for prophylaxis, determining the duration of their administration and assessing the effectiveness and risk of treatment.

Since 1971, chemoprophylaxis has been mandatory for children and adolescents from risk groups for tuberculosis. Isoniazid is used at a dose of 10 mg/kg for 3 months after a positive or hyperergic reaction to tuberculin is detected; if the positive reaction persists, a second course of chemoprophylaxis is prescribed for 3 months with two drugs.

Taking drugs from the group of isonicotinic acid hydrazides and their analogues allows for a satisfactory protective effect, but their hepatotoxicity and the likelihood of developing drug resistance in Mycobacterium tuberculosis with long-term use of isoniazid (6-12 months) determine the relevance of searching for other options.

Alternative treatment regimens:

• taking rifampicin in combination with pyrazinamide (with or without isoniazid) allows to reduce the duration of treatment to 3 months,
• taking rifampicin as monotherapy (its effectiveness is comparable to that of isoniazid, but it is less toxic);
• use of less toxic analogues of isoniazid;
• use of rifampicin derivatives.

The growth of drug resistance of Mycobacterium tuberculosis and the decrease in the effectiveness of treatment of patients with tuberculosis are largely due to irregular drug intake or failure to comply with the optimal treatment regimen (doses and frequency of administration). In this regard, when conducting chemoprophylaxis, clear organization and strict control are necessary. The choice of the optimal form of chemoprophylaxis is important: in tuberculosis sanatoriums, school and preschool institutions of sanatorium type, on an outpatient basis.

Many domestic authors believe that in the presence of risk factors, chemoprophylaxis should be carried out with two drugs. In foci with unfavorable epidemic conditions (contact with bacteria excretors, especially with patients 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 context of widespread drug-resistant tuberculosis mycobacteria, children are increasingly exposed to strains resistant to anti-TB drugs, especially isoniazid. In these circumstances, the effectiveness of isoniazid monotherapy chemoprophylaxis is significantly reduced, so it is necessary to use reserve drugs for 3 months or more.

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

Organization of preventive treatment for children and adolescents from risk groups

Preventive treatment for children and adolescents infected with Mycobacterium tuberculosis for the first time (“virage”, early period of latent tuberculosis infection), as well as for children from high-risk groups, is prescribed by a phthisiopediatrician.

Risk factors contributing to the development of tuberculosis in children and adolescents: epidemiological, medical-biological, age-related, gender-related and social.

Epidemiological (specific) factors:

• contact with people sick with tuberculosis (family or casual contact);
• contact with animals sick with tuberculosis. Medical and biological (specific) factors:
• ineffective BCG vaccination (the effectiveness of BCG vaccination is assessed by the size of the post-vaccination mark: if the size of the vaccination scar is less than 4 mm or if it is absent, immune protection is considered insufficient);
• hyperergic sensitivity to tuberculin (according to the Mantoux test with 2 TE).

Medical and biological (non-specific) factors:

• concomitant chronic diseases (urinary tract infections, chronic bronchitis, bronchial asthma, allergic dermatitis, chronic hepatitis, diabetes mellitus, anemia, psychoneurological pathology);
• frequent acute respiratory viral infections in the anamnesis (the group of “frequently ill children”).

Age and gender (non-specific) factors:

• age up to 3 years;
• prepuberty and adolescence (13 to 17 years);
• female gender (during adolescence, girls are more likely to get sick).

Social (non-specific) factors:

• alcoholism, drug addiction in parents;
• parents' stay in places of imprisonment, unemployment;
• living in orphanages, children's homes, social centers, deprivation of parental rights, homelessness;
• large family, single-parent family;
• living in a migrant environment.

Indications for referral to a phthisiatrician

• early period of primary tuberculosis infection (“turnaround”), regardless of the level of the Mantoux reaction with 2 TE and the presence of risk factors;
• hyperergic Mantoux reactions with 2 TE, regardless of the presence of risk factors;
• an increase in the size of the Mantoux reaction papule with 2 TE by 6 mm or more, regardless of the level of the Mantoux reaction with 2 TE and the presence of risk factors;
• gradual increase in sensitivity to tuberculin over several years with an average intensity and severity of the Mantoux reaction with 2 TE, regardless of the presence of risk factors;
• persistent sensitivity to tuberculin of moderate intensity and severity of the Mantoux reaction with 2 TE, in the presence of two or more risk factors;
• severe reaction to tuberculin (papule 15 mm or more) in children and adolescents from social risk groups.

Information required for referring children and adolescents to a phthisiatrician

• dates of BCG vaccination and revaccination;
• data on annual Mantoux reactions with 2 TE from the moment of birth;
• data on the presence and duration of contact with tuberculosis patients;
• results of fluorographic examination of the child's close relatives;
• data on previous acute, chronic, allergic diseases:
• data from previous examinations by a phthisiatrician;
• results of clinical and laboratory examination (general blood test, general urine test);
• expert opinion (if there are concomitant diseases);
• social history of the child or adolescent (living conditions, financial security, migration history).

The phthisiatrician prescribes preventive treatment on a differentiated basis. In the presence of specific risk factors (lack of BCG vaccination, contact with a tuberculosis patient), treatment is carried out in a hospital or sanatorium; in other cases, the volume and location of preventive treatment are determined individually.

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

Specific prevention of tuberculosis with chemotherapy drugs is carried out for two categories of children and adolescents.

Primary prevention of tuberculosis - in uninfected children and adolescents who have contact with tuberculosis patients (IV GDU with a phthisiatrician).

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

Groups in which chemoprophylaxis should be prescribed

• Infected children and adolescents:
  • - in the early period of primary tuberculosis infection (“turnover of tuberculin tests”) without local changes;
  • in the early period of primary tuberculosis infection (“turning tuberculin tests”) with a hyperergic reaction to tuberculin;
  • with increasing sensitivity to tuberculin:
  • with hyperergic sensitivity to tuberculin;
  • with persistent sensitivity to tuberculin in combination with risk factors.
• Children and adolescents in contact with tuberculosis patients.

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

Chemoprophylaxis is administered to children for 3 months, preventive treatment is administered individually, depending on risk factors, for 3-6 months. The effectiveness of chemoprophylaxis (preventive treatment) is determined using clinical and laboratory parameters and the results of tuberculin tests. A decrease in sensitivity to tuberculin, satisfactory clinical and laboratory parameters, and the absence of the disease indicate the effectiveness of the preventive measures. An increase in sensitivity to tuberculin or negative dynamics of clinical and laboratory parameters require additional examination of the child.

Methodology for conducting chemoprophylaxis

Treatment is carried out after a comprehensive examination by a phthisiatrician. Preventive treatment of newly infected tuberculosis persons (PIIPA) who do not have risk factors, with unchanged clinical, laboratory and immunological parameters, is carried out with one drug from the group of nicotinic acid hydrazides and analogues (isoniazid or metazid at a dose of 10 mg/kg, phthivazid at a dose of 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 to children in the presence of risk factors, with altered clinical, laboratory and immunological indicators of the body's reactivity. Sensitivity to tuberculin in the Mantoux reaction with 2 TE PPD-L is pronounced, hyperergic, the sensitivity threshold is at the 6th dilution and more, positive reactions are at 3 dilutions and more of the graduated Pirquet reaction. Treatment is carried out for 6 months - depending on the dynamics of tuberculin sensitivity in an intermittent mode, in a hospital or in a sanatorium.

Increased sensitivity to tuberculin (GDU VIB) in patients previously infected with tuberculosis after examination (GDU 0) and sanitation of foci of non-specific infection in the absence of risk factors for the disease requires the appointment of prophylactic treatment with one anti-tuberculosis drug for 6 months in an 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 is carried out with two antibacterial drugs (intermittent administration is possible). Sensitivity to tuberculin in the Mantoux reaction with 2 TE PPD-L is pronounced, hyperergic, the sensitivity threshold is at the 6th dilution and higher, positive reactions are at 3 dilutions and higher of the graduated Pirquet reaction. Treatment is carried out for 6 months - depending on the dynamics of tuberculin sensitivity, on an outpatient basis or in a sanatorium.

Hyperergic sensitivity to tuberculin (HTS VIB) in the absence of risk factors and changes in clinical, laboratory and immunological parameters requires prophylactic treatment with one anti-tuberculosis drug for 3 months on an outpatient basis or in a sanatorium, in combination with antihistamines. If sensitivity to tuberculin decreases to normal (except for primary infection), treatment can be stopped. If hyperergic sensitivity to tuberculin persists, treatment is continued for 6 months with two anti-tuberculosis drugs; X-ray tomography of the chest organs is necessary. Ultrasound of the abdominal organs, urine analysis for BK.

In the presence of risk factors, changes in clinical, laboratory and immunological indicators of the body's reactivity and hyperergic sensitivity with a sensitivity threshold to tuberculin of the 6th dilution or more, with positive reactions to 3 dilutions or more of the graded Pirquet reaction, preventive treatment is carried out for 6 months - depending on the dynamics of tuberculin sensitivity, in a hospital or in a sanatorium.

Children and adolescents in tuberculosis foci (GDU IV), uninfected with tuberculosis and infected for a year or more without additional medical and social risk factors, receive a three-month course of treatment with one anti-tuberculosis drug. Upon completion of the course of treatment, if a negative reaction to tuberculin (2 TE PPD-L) persists, individuals not infected with tuberculosis are placed under the supervision of a phthisiatrician at the dispensary.

If a "turn" in tuberculin tests or hyperergic sensitivity to tuberculin is detected, treatment should be continued for up to 6 months with two anti-tuberculosis drugs (taking into account the drug resistance of Mycobacterium tuberculosis) with an X-ray tomographic examination of the chest organs, ultrasound of the abdominal organs, and urine analysis for Mycobacterium tuberculosis. Children infected with tuberculosis with low sensitivity to tuberculin are placed under the supervision of a phthisiatrician after a three-month course of treatment. If sensitivity to tuberculin increases during observation, a repeated course of treatment with two anti-tuberculosis drugs is prescribed for 3 months.

Children and adolescents with a hyperergic reaction to tuberculin or with a "turn" in tuberculin tests or with an increase in sensitivity to tuberculin of more than 6 mm. who are in contact with a patient with tuberculosis excreting 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 carried out in sanatorium conditions or in a hospital.

Chemoprophylaxis of tuberculosis in HIV-infected children and adolescents

Chemoprophylaxis in HIV-infected individuals can reduce the risk of tuberculosis and prolong the life of patients. Indications for chemoprophylaxis are related to the prevalence of tuberculosis infection among HIV-infected patients. An important criterion for deciding on chemoprophylaxis and its duration is the number of people infected with tuberculosis from an HIV-infected patient with tuberculosis. This indicator depends on the survival time of the patient with and without therapy. The survival time of HIV-positive tuberculosis patients excreting 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 appearing in response to the intradermal administration of tuberculin in a standard dilution (2 TE), however, no direct correlation was found between this indicator and the number of CD4 ⁺ lymphocytes in the blood of HIV-infected patients. The effectiveness of chemoprophylaxis is the same in individuals with suppressed and preserved immunity. Indirect benefits of chemoprophylaxis depend on the nature of the contact of an HIV-infected person with a tuberculosis patient and the survival time of such individuals with and without therapy. Belonging to a high-risk group for a patient (HIV-infected drug addicts with positive reactions to 2 TE PPD-L or with no reaction to tuberculin) is a direct indication for chemoprophylaxis. With proper implementation of specific chemotherapy, the incidence rate decreases from 5.7 to 1.4 per 100 cases per year.

The timing of chemoprophylaxis and the order of taking the drugs are not defined. The most justified are considered to be 6-month courses of isoniazid for HIV-infected patients with a CD4 ⁺ lymphocyte count in the blood of 200 per mm ³ or less. The therapy allows to increase the life expectancy of patients by an average of 6-8 months and in 19-26% allows to prevent the development of clinical forms of tuberculosis.

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