[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.

[Adverse effects in children receiving short-term chemotherapy for intrathoracic tuberculosis]. / Pobochnye reaktsii u detei pri ukorochennykh kursakh khimioterapii vnutrigrudnogo tuberkuleza.

The incidence and pattern of adverse effects were analyzed in children receiving short-term chemotherapy for intrathoracic tuberculosis in relation to the course of a tuberculous process (complicated and uncomplicated). During chemotherapy, side effects of antituberculous agents were noted in 82 children of 255 examinees. The incidence of side effects was affected by concurrent diseases detected in 52.4% of children showing a poor tolerance, receiving antituberculosis therapy for up to 6 months. Adverse effects were found in 18.2% of children, and in 55.3% with over 12-month chemotherapy. Short-term chemotherapy in children with the uncomplicated course of tuberculosis significantly reduced the incidence of adverse responses as compared to long-term chemotherapy (20 versus 36%) by reducing allergic reactions by 3 times (6.7 versus 19.7%). In children with complicated tuberculosis, the use of 4 drugs in the intensive phase of chemotherapy failed to increase the incidence of side effects (35.5 versus 40.8%). In most children, adverse reactions are reversible and a complete intolerance of antituberculous agents (streptomycin and rifampicin) was observed only in 4% of cases.

[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.

[Effectiveness of chemotherapy of intrathoracic tuberculosis in children: late follow-up data]. / Effektivnost' khimioterapii vnutrigrudnogo tuberkuleza u detei po dannym otdalennykh nabliudenii.

Clinical and X-ray studies were made in 148 children 2-10 years after hospital treatment to evaluate the stability of clinical recovery by the frequency of relapses in relation to the use of different drug treatment regimens. Children from an experimental group (n = 75) received shorter chemotherapy with 3-4 drugs (isoniazid, rifampicin, pyrazinamide in uncomplicated tuberculosis plus streptomycin in complicated one) in the intensive phase of chemotherapy. Pyrazinamide was not used in the intensive phase in the control group (n = 73). Long-term follow-ups showed a high efficiency of shorter chemotherapy regimens in treating intrathoracic tuberculosis in children since they do not lead to the higher incidence of recurrences--2.7% in both groups. The latter occurred in adolescents who had severe residual changes, who had been irregularly followed up at the tuberculosis control dispensary after hospital discharge, who had not received seasonal preventive chemotherapy courses, and who had experienced complicated, generalized or acute tuberculosis.

[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.

[Efficiency of shorter chemotherapy courses for intrathoracic tuberculosis in children]. / Ukorochennyi kurs khimioterapii pri vnutrigrudnom tuberkuleze u detei.

To develop differential chemotherapy regimes for intrathoracic tuberculosis in children aged 3-12 years, 255 children with active tuberculosis underwent clinical and X-ray examination. Of them, 120 children received shorter chemotherapy in an early intensive phase by using three drugs (isoniazid, rifampicin, and pyrazinamide supplemented by streptomycin) in complicated tuberculosis. A control group (n = 135) had therapy without pyrazinamide. Shorter courses of therapy were shown not only to reduce total treatment duration on an average to 6.4 and 9.2 months in uncomplicated and complicated tuberculosis, respectively, but to contribute to more perfect healing processes and resolution of abnormal changes in 85.3 and 60.0% of children with uncomplicated and complicated forms, respectively. At the same time shorter treatment is well tolerated. It shows much fewer side effects than does longer treatment (20 and 36%). There are no increases in the incidence of recurrent tuberculosis late at follow-up (2.7 and 2.7%, respectively).

[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).

[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.

[BCG vaccination and increasing the effectiveness of treatment of post-vaccination complications by the use of rifampicin and dimexide]. / Vaktsinatsiia BTsZh i povyshenie éffektivnosti lecheniia postvaktsinal'nykh oslozhnenii s primeneniem applikatsii rifampitsina s dimeksidom.

The results of treatment for postvaccination complications were compared in 287 children (125 patients with regional lymphadenitis and 162 patients with cold abscesses). The treatment included local applications of rifampicin and dimexide solutions. Postvaccination lymphadenitis occurred significantly more frequently in children receiving BCG vaccine versus those receiving BCG-M vaccine with diminished antigenic load. Local applications of rifampicin+dimexide solution as an adjuvant treatment to isoniazid therapy of abscessed lymphadenitis permit the physician to reduce the number of puncture administration of 5% saluzid solution and decrease 2-fold the treatment duration. Similar results were obtained for cold abscess treatment. Rifampicin+dimexide applications to treat postvaccination complications in the form of lymphadenitis and cold abscesses in infiltration phase do not require local administration of saluzid, oral isoniazid. The complete resorption is reached within 1-2 months.

[Revaccination of schoolchildren with BCG-M vaccine and use of a new model of BI-19 jet injector]. / Revaktsinatsiia shkol'nikov vaktsinoi BTsZh-M i ispol'zovanie novoi modeli bezygol'nogo in"ektora BI-19.

A comparative analysis of the effectiveness of revaccination of 1595 schoolchildren with the BCG and BCG-M vaccine is given in relation to the method of vaccine administration and revaccination frequency (1st revaccination was given in the 1st and 2nd in the ninth form). Both vaccines were found to be equally effective both in the development of a postvaccination skin sign and postvaccination allergy. The method of BCG vaccine administration (with a jet injector and needle syringe) had no essential influence on the revaccination effect. The advantage of a new BI-19 jet injector used for tuberculin diagnosis consisted in that there was no need to adjust the results of tuberculin diagnosis as was the case with a previous BI-IM jet injector.

[New methods of prevention, diagnosis and treatment of tuberculosis in children]. / Novye metody profilaktiki, diagnostiki i lecheniia tuberkuleza u detei.

The follow-up included two groups of schoolchildren: 862 were repeatedly given BCG and 725, BCG-M vaccines. It was demonstrated that both vaccines had the same effectiveness and the latter could also be used. Upright tomographic findings in 70 children showed that it was highly informative for the diagnosis of intrathoracic tuberculosis in children, especially for that of bronchoadenitis. Monitoring of 315 children with destructive pulmonary processes (157 of them had lesions of tuberculous etiology) made it possible to define risk factors of destructive tuberculosis contamination (in particular, genetical predisposition), the diagnostic criteria and high diagnostic value of the enzyme-linked immunoassay (96%). Ultrasound examination of the liver in 121 tuberculosis children enabled one to diagnose the type and etiology of liver affection, to control its state during treatment, to specify the side effects of the drugs and to modulate the therapy. The course and outcomes of tuberculosis were found to be affected by liver affections. The parenteral administration of isoniazid in combination with other drugs was shown to be highly beneficial in disseminated form of tuberculosis in children.