[Characteristics and causes of the torpid (lingering) course of intrathoracic tuberculosis in children, the specific features of chemotherapy and outcomes].

To study the causes of the torpid course of intrathoracic tuberculosis in children and to develop preventive measures and effective treatment options, the authors conducted clinical, X-ray, microbiological, immunological, and biochemical studies and treated 90 children with the torpid course of intrathoracic tuberculosis. The specific features of detection and the clinical, X-ray, and laboratory characteristics of a process were studied. A procedure of chemotherapy was devised, which could achieve recovery in 55.6% of the children with minimum residual changes being observed. Analysis of the specific features of the torpid course of intrathoracic tuberculosis has revealed the main causes of this course, which are imperfection of measures for its early detection among healthy and risk-group children, which results in the late diagnosis of the process and imperfection of preventive measures.

[The phenotypes of haptoglobin and the level of acute-phasic proteins in the sera of children with local form of intrathoracic tuberculosis]. / Fenotipy gaptoglobina i uroven' ostrofaznykh belkov v syvorotke krovi u detei s lokal'nymi formami vnutrigrudnogo tuberkuleza.

Seventy-seven children aged 4-12 years who had local forms of primary intrathoracic tuberculosis were examined. On admission to and discharge from hospital, haptoglobin (Hp) was phenotyped and the content of Hp was measured, and the activity of alpha1-antitrypsin (alpha1-AT) was determined. In all ill children, the distribution of Hp phenotypes did not differ from the normal level, but all patients with tuberculous pleurisy were found to be carriers of Hp1 gene (among them the phenotype Hp 2-2 was absent and the minor variant of Hp 1-1 was detectable in half the cases). In patients of this group, alpha1-AT acted as a typical acute phase reagent and remained moderately increased by the termination of treatment in the vast majority of the examinees. On the contrary, on admission the content of Hp was to be decreased. Its increase was natural only in patients with tuberculous pleurisy. The level of Hp was associated with its phenotype. Carriers of Hp1-1 had elevated levels of Hp in the overwhelming majority of cases whereas those of Hp 2-2 had its decreased levels. It is concluded that in children with primary tuberculosis, the serum level of Hp may not be used as an indicator of the activity of the process. Possible causes and the values of decreased levels of circulating Hp in children with primary tuberculosis are discussed in the paper.

[Diagnosis of latent primary intrathoracic tuberculosis of respiratory system in the phase of calcification in children]. / Diagnostika skrytoi aktivnosti pervichnogo vnutrigrudnogo tuberkuleza organov dykhaniia v faze kal'tsinatsii u detei.

The paper shows the latent activity of newly diagnosed intrathoracic tuberculosis in the phase of calcification in children: clinical and X-ray changes, tuberculin sensitivity (Manteaux test), the presence of Mycobacterium tuberculosis (MBT) in the sputum and blood (cultivation, bacterioscopy, polymerase chain reaction PCR), the blood levels of acute-phase reagents: haptoglobin and alpha 1-protease inhibitor (alpha 1-PI), immunological parameters, tuberculosis antibodies (TAb), and MBT antigen. Ninety children were examined before treatment. Twenty-five children (Group 1) were found to have single minor calcified masses in one group of intrathoracic lymph nodes or in the lung. Thirty-five children (Group 2) had multiple lymph nodes or foci in the lung in the phase of consolidation and calcification. Thirty children (Group 3, controls) were diagnosed as having intrathoracic tuberculosis in the phase of infiltration. The signs of the latent activity of tuberculosis were detected in all the children of all three groups, being more pronounced in Group 3. Thus, MBT and TAb were revealed in 90% of the children in Group 3 and in 52.9 and 76.0% in Groups 1 and 2, respectively. There were higher levels of alpha 1-PI in 96.6 and 75.0% in Groups 3 and 1, respectively. There were signs of intoxication in 80 and 88% and a hyperergic Mantoux reaction in 44.0 and 43.3%, respectively. The frequency of the signs of activity did not greatly differ. Thus, children with newly diagnosed respiratory tuberculosis in the phase of calcification should be regarded as having the signs of tuberculosis activity, followed up as Group I patients, and prescribed chemotherapy for 3-6 months or more, depending on the extent of the process.

[New technologies in the prevention, detection, diagnosis and treatment of tuberculosis in children]. / Novye tekhnologii pri profilaktike, vyiavlenii, diagnostike i lechenii tuberkuleza u detei.

If the epidemiological situation is tense, new technologies should be developed and put into practice to enhance the efficiency of specific prevention, early detection, diagnosis and treatment of tuberculosis in children. There is evidence for the high efficacy and low reactogenicity of lower antigenicity-loading BCG-M vaccine that causes a 15-fold decrease in infant morbidity, as compared with that among non-vaccinated children, and this vaccine shows a 5-fold reduction in postvaccination complications as compared with BGC vaccine. The 26-year use of tuberculin diagnosis via Mantoux test with 2TE PPD-L during mass vaccination of children and adolescents has proved itself in early identification of tuberculosis and risk groups. A new risk group has been identified. This includes children with increasing tuberculin reactions; three-month intermittent chemoprevention with isoniazid reduces tuberculin sensitivity in the children and prevents tuberculosis in them. The developed short-term (6-9 months) courses of chemotherapy in preschool and school children by using drugs (isoniazid + rifampicin + pyrazinamide) yield the best healing without residual changes of uncomplicated forms of tuberculosis in 83 and 60% of the children with complicated events, respectively. The chemotherapy regimens have been divided into 4 groups of different dosage schedules.

[Tuberculosis in children: diagnosis of and methods for the evaluation of chemotherapy]. / Diagnostika i metod opredeleniia éffektivnosti khimioterapii tuberkuleza u detei.

The authors propose to determine altered forms of Mycobacteria, including sputum and blood granular forms, and the level of tuberculosis antibodies and serum Mycobacterium antigens by enzyme immunoassay as additional criteria for diagnosis of active primary tuberculosis in children. The diagnostic value of these indices is accounted for by the fact that they are found significantly more frequently and their level is significantly higher than the similar indices in healthy, tuberculosis-infected children and tuberculin-negative, prior BCG-vaccinated ones. By taking into account an decrease in the detection rate of sputum and blood granular mycobacteria and a change in the level of tuberculosis antibodies during chemotherapy, which are observed along with positive clinical and X-ray changes of a process, these tests should be recommended for evaluation of the efficiency of primary a bacillary tuberculosis in children.

[Experience in chemotherapy of tuberculosis in children based on WHO recommendations]. / Opyt khimioterapii tuberkuleza u detei na osnove rekomendatsii VOZ.

WHO recommends that patients with primary intrathoracic tuberculosis fall into 4 categories by clinical symptoms, severity and spread of the process. They are to receive 2 staged treatment. The duration of each chemotherapy phase depends on the time of reverse development of the specific process regarding abacillarity of the primary tuberculosis by clinicoroentgenological dynamics. Therapy in children is completed after a full resolution of the pathological changes or upon stabilization of the process at the stage of residual changes when clinical laboratory evidence indicates absence of latent activity of the process. According to these WHO criteria 255 children aged 3 to 12 years were treated in the Central Research Institute of Tuberculosis for the last 10 years.

[Improvement of diagnostics and methods of determining effectiveness of chemotherapy against tuberculosis in children]. / Sovershenstvovanie diagnostikik i metodov opredelneniia éffektivnosti khimioterapii tuberkuleza u detei.

Altered Mycobacterial forms, particularly granular forms, in the sputum and blood, as well as the serum level of tuberculosis antibodies and mycobacterial antigens by enzyme immunoassay are proposed to be determined as additional criteria for diagnosing active primary tuberculosis in children. The diagnostic value of these indices is accounted for by that they are more frequently detected and their levels are significantly higher than the similar ones in healthy, tuberculosis-infected children, and tuberculin-negative, earlier BCG vaccinated children. By taking into account a reduction in the detection rate of granular forms of Mycobacteria in the sputum and blood and altered levels of tuberculosis antibodies during chemotherapy, which were observed in parallel to the positive clinical and X-ray changes, these tests may be recommended for evaluation of the efficiency of treatment for primary abacillary tuberculosis in children.

[Immunity parameters in children with prior intrathoracic tuberculosis]. / Pokazateli immuniteta u detei, perenesshikh vnutrigrudnoi tuberkulez.

Fifty-four children who had experienced intrathoracic tuberculosis were clinically and immunologically studied 3-10 years following chemotherapy. The count of T cells and their functional activity were found to be normal in 90.7% of children. Tuberculosis antibodies were identified in 62% of children, which suggests only long preserved specific sensitization. The tuberculosis antigen titer 1:16 was detected in 5.5% of children with residual changes, which generates the necessity of examining such children for a latent active process.

[Liver in children with prior intrathoracic tuberculosis during long-term observation period after chemotherapy]. / Sostoianie pecheni u detei, perenesshikh vnutrigrudnoi tuberkulez, v otdalennye sroki nabliudeniia posle okonchaniia khimioterapii.

Ultrasonography of the liver and biliary tract revealed both nonspecific (chronic persistent hepatitis) and paraspecific changes in 93.8% of children with local forms of primary tuberculosis in the phase of infiltration, including 17.3% in whom the changes appeared as biliary dyskinesia. Late outcomes indicated that antituberculous chemotherapy had no negative effect on the liver. The ultrasonographic studies detected abnormal changes of the hepatic parenchyma only in 7.8%, mainly in those with chronic persistent hepatitis.

[The detection of mycobacteria in children and adolescents by using the polymerase chain reaction]. / Vyiavlenie mikobakterii s pomoshch'iu polimerazno-tsepnoi reaktsii u detei i podrostkov.

A polymerase chain reaction (PCR) was used for determination of mycobacterial DNA in clinical samples from children and adolescents. The results were positive in 23 and 53% of cases, respectively, while standard microbiological methods failed to show presence of any bacteria in the samples. Case histories contained information on high incidence of positive Mantoux test. Microbiologically the diagnosis was confirmed only in 7 adolescents. In children mycobacteria were not found.

[Tuberculosis risk groups among children and principles of approach to chemoprophylaxis]. / Gruppy riska zabolevaniia tuberkulezom u detei i printsipy podkhoda k naznacheniiu khimioprofilaktiki.

The trends in tuberculin reactions of Mantoux test (2 TU) performed annually before and after the diagnosis of tuberculosis shows that the risk groups consist of subjects with increasing tuberculin sensitivity and those susceptible to acute respiratory virus infections. An individual approach to prescription of chemoprophylaxis considering the number of risk factors (epidemiological, age-sex, biomedical, social) is advisable. Sanatorium chemoprophylaxis is needed in the presence of at least 2 factors. A 3-month isoniazid chemoprophylaxis prevents the disease and normalizes sensitivity to tuberculin.

[Characteristics of the course and treatment of pulmonary tuberculosis associated with nonspecific respiratory diseases in children]. / Osobennosti techeniia i lecheniia tuberkuleza legkikh u detei pri sochetanii ego s nespetsificheskimi zabolevaniiami organov dykhaniia.

Specific features of intrathoracic tuberculosis course, outcomes and treatment are outlined for 109 children. In 59 of them tuberculosis was associated with nonspecific respiratory diseases (NRD). 28.8%, 25.4%, 18.6, 27.2% of patients had cystic hypoplasia, chronic hypoplasia, recurrent pneumonia, recurrent bronchitis, respectively. Complicated course of tuberculosis occurred 2 times more frequently in its combination with NRD (71.2%). Destruction and discharge of bacteria were recorded in 49.2 and 47.5% of patients, respectively. Undulating running was 3.4 and side effects 1.6 times more frequent. Tuberculous children with NRD need longer antituberculous therapy using wide-spectrum antibiotics, symptomatic and exercise treatment, massage, surgical intervention if necessary. Complete resolution of lung lesions in NRD children were seen 4.8 times less frequently. In case of late diagnosis 54% of them retained residual changes in the form of lung tissues fibrosis, calcified foci in the lungs and lymph nodes.

[Detection of tuberculosis in children of new risk groups and efficacy of chemoprophylaxis]. / Vyiavlenie tuberkuleza u detei iz novykh grupp riska i effektivnost' khimioprofilaktiki.

109 children at risk of tuberculosis frequently suffering from acute respiratory diseases (ARD) and 87 children with rare ARD have undergone a 3-month course of isoniazide chemoprophylaxis. In 95.0% of the examinees the above chemoprophylaxis lowered ARD morbidity to 1-2 times a year, reduced and stabilized tuberculin sensitivity, prevented tuberculosis. Isoniazide treatment of 87 children whose parents worked with cattle that might be infected prevented tuberculosis in them, diminished tuberculin sensitivity. It is thought valid that chemoprophylaxis should be given in sanatoria primarily to children exposed to two and more risk factors (epidemiological, age-sex, medicobiological, social).

[Immune system in children with pulmonary tuberculosis]. / Sostoianie immuniteta u detei s vyrazhennymi formami vnutrigrudnogo tuberkulëza.

T- and B- cell immunity, levels of antituberculous antibodies, M. tuberculosis antigens and circulating immune complexes (CIC) were studied in 61 children with clinical manifestations of intrathoracic tuberculosis. T-cell immunity was subnormal in 39.5% of the examinees. Moderate inhibition of this immunity occurred in 14%. 46.5% of the examinees had normal T-cell immunity. B-lymphocyte count, IgG levels were normal, whereas IgA and IgM were low and elevated, respectively. T-cell immunity appeared the weakest in children with more advanced disease. Acute tuberculosis was associated with more frequent occurrence of CIC, antituberculous antibodies, tuberculous antigen. Administration of sodium nucleinate promoted normalization of T-cell immunity in the above patients. If they had antituberculous antibodies, antigens and CIC 2.5-12 months after chemotherapy, this indicated the persistence of the process activity and required continuation and perfection of chemotherapy.

[Effectiveness of isoniazid in tuberculosis chemoprophylaxis in children with rising tuberculin sensitivity]. / Effektivnost' khimioprofilaktiki tuberkuleza izoniazidom u detei s usilivaiushcheisia tuberkulinovoi chuvstvitel'nost'iu.

70 children aged 4-15 with growing tuberculin sensitivity received preventive treatment with isoniazid in children's sanatorium. The drug was taken for 2 or 3 months in a dose 10 mg/kg daily (19 and 51 children, respectively). Preventive isoniazid course proved effective as none of the children treated developed tuberculosis within 3 years. The 3-month course is preferable as it is more potent in relation to tuberculin sensitivity immediately after the treatment termination and 1, 2 years after it.

[Contemporary methods in the diagnosis and treatment of intrathoracic tuberculosis in children]. / Sovremennye metodiki diagnostiki i lecheniia vnutrigrudnogo tuberkulëza u detei.

Reduced chemotherapy courses (6-10 months) were studied for effectivity in 108 children with advanced intrathoracic tuberculosis. Intramuscular isoniazid, pyrazinamide+rifampicin produced a complete response in 87.9% of the cases who suffered side effects 2 times less frequently. The overall treatment course became shorter by 2-3 months. The treatment of 157 children with destructive pulmonary tuberculosis required long-term (12 months and more) treatment with employment of all the tuberculostatic armory and surgical intervention in 15.3% of the cases.