Tuberculosis vaccine (BCG)

In childhood, the main method of tuberculosis prevention is vaccination with BCG and BCG-M vaccines. Primary vaccination with BCG vaccine is carried out on all healthy newborns on the 3rd-7th day of life. Revaccination is subject to children aged 7 and 14 years who have a persistently negative RM with 2 TE, children infected with MBT are not subject to revaccination. Upon reaching the age of 15, regardless of the results of tuberculin diagnostics, vaccination against tuberculosis is not carried out. All vaccination activities are carried out according to the calendar of vaccination prevention of childhood infections.

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Vaccination aimed at forming artificial immunity to various infectious diseases has become the most widespread preventive measure in medicine in the 20th century. Depending on the virulence of microorganisms, the role of the immune system in the pathogenesis of infectious diseases caused by them and specificity, in some cases vaccination prevents the occurrence of the disease (smallpox, tetanus, poliomyelitis), in others it mainly affects its course. The main criterion in determining the method of mass immunization against any disease is its biological feasibility in specific epidemiological conditions. The lower the specific effectiveness of the vaccine, the more importance is attached to the negative consequences of its use (complications). As a result, the improvement of the epidemiological situation naturally leads to a revision of vaccination tactics.

The most controversial issue in the literature is the protective role of BCG in tuberculosis. In foreign literature, the spectrum of opinions on BCG vaccination has wide boundaries - from doubts about its individual qualities to a complete denial of the effectiveness of further use of anti-tuberculosis immunization.

According to research data, the effectiveness of currently used vaccines is 60-90% in terms of protection against generalized forms of tuberculosis for up to 15-20 years. Despite various approaches to assessing the effectiveness of BCG, published materials mainly reflect the tendency in developed countries with low tuberculosis incidence to abandon mass vaccination and switch to selective vaccination of children from high-risk groups for tuberculosis, i.e. immigrants, foreign workers, and people arriving from countries with a high prevalence of tuberculosis infection. At the same time, most authors prove the great protective role of BCG against generalized forms of tuberculosis and the lack of influence of immunization on the prevalence of infection, i.e. infection with Mycobacterium tuberculosis. Therefore, vaccination is most indicated for young children in countries where tuberculosis is endemic. In these cases, WHO recommends vaccinating newborns.

Among the studies conducted in our country, unlike foreign authors, there are almost no facts that cast doubt on the effectiveness of anti-tuberculosis vaccinations. All authors show the high effectiveness of BCG, reducing the incidence of disease among vaccinated people compared to unvaccinated people. And at present, BCG vaccination continues to have a positive effect on the epidemiology of tuberculosis. Improving the quality of vaccinations and increasing population coverage are still relevant. Since early administration of the BCG vaccine provides protection against the most dangerous clinical forms of tuberculosis (in particular, miliary tuberculosis and tuberculous meningitis), it is believed that efforts should be aimed at wide coverage of vaccinations of children at an early age.

Methodology for vaccination against tuberculosis

In Russia, mass vaccination of newborns against tuberculosis is carried out with two preparations - tuberculosis vaccine (BCG) and tuberculosis vaccine for gentle primary immunization (BCG-M) - lyophilisates for the preparation of suspensions for intradermal administration. The BCG and BCG-M vaccines are live mycobacteria of the BCG-1 vaccine strain, lyophilized in a 1.5% sodium glutamate solution: a porous powdery hygroscopic mass or tablets of white or cream color. The BCG-M vaccine is a preparation with a halved weight content of BCG mycobacteria in the vaccination dose, mainly due to killed cells. Vaccinations against tuberculosis should be carried out by specially trained medical personnel of the maternity hospital, the department for nursing premature babies, the children's clinic and the feldsher-obstetric station. Primary vaccination is performed on healthy full-term newborns on the 3rd-7th day of life. Revaccination is subject to children aged 7 and 14 years who have a negative reaction to the Mantoux test with 2 TE PPD-L.

• The first revaccination of children (vaccinated at birth) is performed at the age of 6-7 years (1st grade students).
• The second revaccination of children is carried out at the age of 14-15 years (9th grade students and teenagers of secondary specialized educational institutions in the first year of study).

Vaccinations at home are prohibited. In polyclinics, the selection of children to be vaccinated is carried out in advance by a doctor (paramedic) with mandatory thermometry on the day of vaccination, taking into account medical contraindications and anamnesis data with mandatory clinical blood and urine tests. In order to avoid contamination, it is unacceptable to combine tuberculosis vaccination with other parenteral manipulations on the same day, including blood sampling for phenylketonuria and congenital hypothyroidism. Failure to comply with the requirements for vaccination increases the risk of post-vaccination complications. Children who have not been vaccinated in the first days of life are vaccinated during the first 2 months in a children's polyclinic or other preventive institution without preliminary tuberculin diagnostics. Children over 2 months of age must first undergo a Mantoux test with 2 TE of purified tuberculin in a standard dilution before immunization. Children with a negative reaction to tuberculin are vaccinated.

Reaction to the introduction of the vaccine

At the site of intradermal administration of the BCG or BCG-M vaccine, a specific reaction develops in the form of an infiltrate 5-10 mm in diameter with a small nodule in the center and the formation of a smallpox-type crust; in some cases, a pustule is noted. Sometimes, a small necrosis with a slight serous discharge appears in the center of the infiltrate. In newborns, a normal vaccination reaction appears after 4-6 weeks. In revaccinated patients, a local vaccination reaction develops after 1-2 weeks. The reaction site should be protected from mechanical irritation, especially during water procedures. Do not apply bandages or treat the reaction site, and parents should be warned about this. The reaction is subject to reverse development within 2-3 months, sometimes in a longer period. In 90-95% of vaccinated people, a superficial scar up to 10 mm in diameter should form at the vaccination site. Monitoring of vaccinated children is carried out by doctors and nurses of the general health care network; they must check the vaccination reaction 1, 3 and 12 months after immunization, recording the size and nature of the local reaction:

• papule;
• pustule with crust formation (with or without discharge);
• scar;
• pigmentation, etc.

Contraindications to BCG and BCG-M vaccination

There are certain contraindications to BCG and BCG-M vaccination.

• Acute diseases:
  • intrauterine infection;
  • purulent-septic diseases;
  • moderate to severe hemolytic disease of the newborn;
  • severe damage to the nervous system with pronounced neurological symptoms;
  • generalized skin lesions.
• Primary immunodeficiency state, malignant neoplasms.
• Generalized BCG infection detected in other children in the family.
• HIV infection:
  • in a child with clinical manifestations of secondary diseases;
  • in the mother of the newborn, if she did not receive antiretroviral therapy during pregnancy.

Newborns are given a gentle vaccination with BCG-M. When immunosuppressants and radiation therapy are prescribed, the vaccination is given 12 months after the end of treatment.

Persons temporarily exempted from vaccinations should be taken under observation and registration and vaccinated after full recovery or removal of contraindications. If necessary, appropriate clinical and laboratory examinations are carried out. In each individual case not included in this list, immunization against tuberculosis is carried out with the permission of the relevant specialist doctor. In case of contact with infectious patients in the family, child care facility and other institutions, vaccinations are carried out after the quarantine period.

Complications after vaccination and revaccination against tuberculosis

The anti-tuberculosis vaccine is a preparation of live attenuated BCG bacteria, so it is not possible to avoid post-vaccination complications.

Complications associated with BCG vaccination have been known for a long time and have accompanied it since the beginning of its widespread use.

According to the classification proposed by the International Union Against Tuberculosis (WHO) in 1984, complications arising from BCG vaccination are divided into four categories:

• local lesions (subcutaneous infiltrates, cold abscesses, ulcers) and regional lymphadenitis;
• persistent and disseminated BCG infection without a fatal outcome (lupus, ostitis);
• disseminated BCG infection, a generalized lesion with a fatal outcome that develops in congenital immunodeficiency;
• post-BCG syndrome (erythema nodosum, granuloma annulare, rashes).

The doctor's action algorithm includes the following stages of examining the child

After he was given the anti-tuberculosis vaccine.

• When examining a child in a children's clinic, a pediatrician must remember that each child vaccinated intradermally with a tuberculosis vaccine must be examined at the age of 1, 3, and 6 months until the local vaccination reaction has healed.
• During the examination, the pediatrician pays attention to the injection site and the condition of the regional (cervical, axillary, supra- and subclavian) lymph nodes.
• Significant (more than 10 mm) ulceration at the site of vaccine administration, an increase of more than 10 mm in one of the specified peripheral lymph nodes, and prolonged (more than 6 months) non-healing of the local vaccination reaction are indications for referring the child for consultation with a pediatric phthisiatrician.

Clinical manifestations

An analysis of the main clinical signs and the nature of the course of all complications identified in children showed that they mostly developed in the form of inflammatory changes at the site of the vaccination reaction or in regional lymph nodes. Complications in the form of keloid scars arose as a result of pathological healing of the local vaccination reaction. Severe complications caused by BCG are extremely rare, their risk is much lower.

Inflammatory complications usually appear during the development of a local vaccination reaction. Much less often they occur at a later date - 1-2 years later, extremely rarely - 3-4 years after vaccination. In order to promptly identify complications, the pediatrician informs the mother about the normal reaction to the introduction of the vaccine, and also periodically examines the child.

Lymphadenitis. In inflammatory complications, the lymph nodes of the axillary region are most often affected, detected mainly in young children. Axillary lymphadenitis is the most severe type of complication. Their appearance varies in time, most often - during the development of a local vaccination reaction, that is, from 1 to 4 months after the vaccine is administered. There may also be a later enlargement and suppuration of the lymph nodes. The disease begins gradually. When bathing the child, the mother pays attention to the enlargement of the lymph node in the left axillary region, sometimes in the supra- or subclavian region. Gradually, the lymph node continues to enlarge. By the time you see a doctor, the node reaches the size of a bean or a hazelnut. The consistency of the affected lymph node is initially soft, elastic, later - dense. Palpation of the lymph node is painless, the skin above it is unchanged or slightly pinkish, the local temperature is normal. These signs allow the doctor, especially in the case of late-onset complications, to correctly determine the etiology of the disease.

The smaller the child, the faster the clinical manifestations develop: after 1-2 months the size of the lymph node reaches a walnut. In the absence of treatment, softening occurs in the center of the node, quickly leading to total caseation of the lymph node, breakthrough of caseous masses, formation of a fistula with moderate or abundant purulent discharge. As a rule, even with fistulous forms, especially in the first month of the disease, the child has no complaints, later, in the absence of treatment, symptoms of intoxication may develop (subfebrile body temperature, loss of appetite, lethargy, irritability, poor weight gain, anemia, liver enlargement). When treatment is prescribed, complaints disappear quickly: after 2-2.5 weeks.

To exclude diagnostic errors, despite the characteristic clinical picture of post-vaccination lymphadenitis, laboratory research methods are used. In the center of the pathological focus, that is, in the place of the most pronounced softening of the lymph node, a puncture is performed, its contents are extracted. The prepared smears are necessary for cytological and bacterioscopic studies. In addition, the punctate in a sterile test tube is examined bacteriologically (sowing for non-specific flora and tuberculosis mycobacteria).

• During cytological examination of the puncture, leukocytes, destroyed neutrophils and caseous lumps are detected in the field of vision. The latter confirm the correctness of the diagnosis. Epithelioid cells are rarely encountered.
• Bacterioscopic examination of a smear by fluorescent microscopy often reveals a few acid-fast mycobacteria (BCG) in the field of vision. Sowing for non-specific flora after 5-6 days gives a negative result.
• MBT culture after 2-3 months is accompanied by growth of mycobacteria. Typing confirms their belonging to BCG.

An infiltrate is formed at the site of vaccine administration with suppuration in the center or its absence, the size of the formation is from 15 to 30 mm. Larger infiltrates are extremely rare. The appearance of an infiltrate may be combined with a reaction of regional lymph nodes: they increase to 10 mm, their consistency is soft elastic. With a favorable course, after 2 weeks from the start of treatment, the reaction of the lymph nodes subsides: they either cease to be determined or decrease in size. Diagnosis is not difficult, since infiltrates occur within 1 or 2 months after vaccination.

Cold abscess (scrofuloderma) is a tumor-like formation, the skin above it is unchanged or has a pale pink color, the local temperature is not elevated, palpation is painless, fluctuation (softening) is determined in the center. Cold abscess is often combined with a reaction of the axillary lymph nodes on the left: they increase to 10 mm, become doughy consistency. Along with clinical manifestations, the correctness of the diagnosis is confirmed by laboratory methods of studying the punctate obtained from the place of greatest softening of the abscess.

According to our data, in children with complications after vaccination in the maternity hospital, lymphadenitis was registered in 77.1% of cases, and cold abscesses - in 19.1%. In children with complications after vaccination in the clinic, cold abscesses were found in 63% of cases, and lymphadenitis - in 37%. Thus, it was found that complications in the form of cold abscesses in children vaccinated in the clinic, compared to those vaccinated in maternity hospitals, are encountered 3.3 times more often. Speaking about cold abscesses, we mean a violation of the technique of administering the vaccine, which indicates a lower level of training of medical personnel in clinics.

If a cold abscess is not diagnosed in a timely manner, it will spontaneously open and an ulcer will form in its place.

An ulcer as a type of complication is characterized by significant dimensions (from 10 to 20-30 mm in diameter), its edges are undermined, the infiltration around is weakly expressed, which distinguishes it from an infiltrate with ulceration in the center, the bottom is covered with abundant purulent discharge. And in this case, diagnostics does not cause difficulties. Studies according to the above scheme confirm the connection between the occurrence of an ulcer and the introduction of a vaccine. Sowing the contents of the ulcer for non-specific flora often gives a negative result, also confirming the etiology of the disease.

Keloid scar (from the Greek words keleis - tumor, eidos - type, similarity). In terms of morphological and histochemical properties, a keloid scar that develops after BCG is no different from keloid tissue that has developed spontaneously or for other reasons (usually after trauma). The leading cellular form in the connective tissue of keloid scars is functionally active fibroblasts with a well-developed granular endoplasmic reticulum and lamellar complex. The causes of keloid tissue development in general and at the site of a post-vaccination scar in particular are still unknown. However, there are factors predisposing to the development of a keloid scar: the period of prepubertal and pubertal development of a child, hereditary predisposition (insufficient development of connective tissue), trauma, a local non-healing vaccination reaction. The influence of the BCG vaccine itself, re-administered during revaccinations, cannot be ruled out.

As a rule, keloid scars are found in school-age children after revaccination, and also (extremely rarely) after primary vaccination. A keloid scar is a tumor-like formation of varying size, rising above the skin level, dense, sometimes of cartilaginous consistency. The main sign is the presence of capillaries in the thickness of the keloid, which are clearly visible during its examination. The shape of the scar is round, elliptical, sometimes stellate. The surface of the scar is smooth (glossy). The color varies: from pale pink, intense pink with a bluish tint to brownish. When diagnosing keloid scars, they should be differentiated from hypertrophic scars. The latter almost do not rise above the skin level, are white or slightly pinkish in color, their surface is uneven, and a network of capillaries is never visible in the thickness. In addition, the dynamics of development helps in correct diagnosis.

• A keloid scar usually grows slowly but continuously, accompanied by itching in its surroundings.
• A hypertrophic scar does not cause itching and gradually dissolves.

During the observation, the doctor should find out whether the keloid scar is growing or not, since in 2-5% of cases, the growth of keloids stops on its own. The size of these scars does not exceed 10 mm in diameter. The answer to this question can only be given by observing the child and teenager for 2 years after BCG revaccination. If a non-growing keloid scar is diagnosed, the patient is removed from the dispensary register no earlier than 2 years after detection. Keloids grow slowly. Over the course of a year, the scar increases by 2-5 mm. Gradually, a feeling of itching appears in its area. The longer the keloid scar exists without being diagnosed in time, the more pronounced the feeling of itching is. Later, unpleasant pain sensations, spreading to the shoulder, join the itching.

BCG ostitis. Lameness and reluctance to walk are the earliest manifestations of the disease. Acute onset is associated with a breakthrough of an asymptomatic bone lesion into the joint cavity. When the joint is affected, swelling, smoothing of contours, local increase in skin temperature without hyperemia ("white tumor") with rigidity and atrophy of the limb muscles, increasing local pain during palpation and axial load, limitation of range of motion are detected. Effusion into the joint cavity is possible (determined by the presence of fluctuation, ballottement of the patella, forced position of the limb), as well as gait disturbance. With advanced damage, joint contracture, septic abscesses, and fistulas develop. The general condition worsens, a moderate increase in body temperature is noted.

If BCG osteitis is suspected, additionally, survey radiographs of the affected area in two projections or CT examination are performed, which allows identifying characteristic signs of pathology: regional osteoporosis, bone atrophy, foci of destruction in the epimetaphyseal areas of long tubular bones with shadows of dense inclusions, sequesters, contact destruction of articular surfaces, narrowing of the joint space, compaction of the shadows of soft tissues of the joints. It is also necessary to conduct an X-ray examination of all family members, including not only the patient's mother and father, but also grandparents and other relatives who have been in contact with the child.

Generalized BCG-itis is the most severe complication of BCG vaccination, occurring in newborns with immunodeficiency states. Foreign authors cite the frequency of generalized BCG-itis as 0.06-1.56 per 1 million vaccinated. These rare post-vaccination complications associated with the dissemination and generalization of BCG infection and accompanied by damage to various groups of lymph nodes, skin, and the musculoskeletal system, occur as a severe general disease with polymorphic clinical symptoms caused by tuberculous damage to various organs and systems. Autopsy reveals miliary tubercles and foci of caseous necrosis, from which it is possible to isolate mycobacteria of the BCG vaccine strain, as well as purulent foci in the liver and other organs. It has been proven that such complications occur in children with immunodeficiency states.

Treatment of post-vaccination complications (except for generalized ones) is recommended to be carried out on an outpatient basis under the supervision of a phthisiatrician. Hospitalization of a child in either a tuberculosis or general hospital is undesirable. In the absence of a pediatric phthisiatrician (the child is from a village or district where there is no specialist), the child can be hospitalized, preferably in a box at a general hospital. Regardless of the type of complication identified, the doctor must prescribe anti-tuberculosis antibacterial drugs. However, the number of drugs, their dose, combination, duration of administration can be individual and depend on the severity of the manifestation of the type of complication, the age of the child, taking into account the tolerance of the drugs. All children with complications after vaccination against tuberculosis are observed in the dispensary according to the V registration group.