Tuberculous Recombinant Allergen Research Articles

Screening for Tuberculosis Infection in Risk Groups in the Adult Population of Moscow

The objective: to evaluate the effectiveness of screening for tuberculosis infection in risk groups among adults using the skin test with tuberculous recombinant allergen (TRA) - Diaskintest®.Subjects and Methods. In 2019-2021, screening for tuberculosis infection in risk groups and in the population with an unknown risk was carried out covering 449,842 people. People aged 18 years and older were examined - patients of the Tuberculosis Control Center, polyclinics and hospitals of medical organizations of the Moscow Health Department. Questionable results were taken into account as positive results of the TRA test.Results. The frequency of positive results of the TRA test in healthy population was as follows: in those contacting pregnant women and newborns - 2.0% (95% CI 1,54-2,10); in decreed groups (workers in food industry, water supply organizations, utilities) - 2,68% (95% CI 2,54-2,82). The situation was different in social risk groups (foreign citizens and stateless persons) - they responded positively to the TRA test in 21,05% (95% CI 20,08-22,06). Most of them arrived to Moscow from states with a high burden of tuberculosis. High-risk groups also include those abusing alcohol and substances; they had positive results in 10,58% (95% CI 8,41-13,24). Among the medical risk groups, the highest rates were observed in those followed up by tuberculosis control services after tuberculosis treatment completion - 39,96% (95% CI 38,31-41,64).Conclusion. Screening in the groups facing the highest risk of developing tuberculosis had a positive effect and once again confirmed the need to screen both resident and migrating population. The immunological skin test with Diaskintest is a reliable tool for examining tuberculosis risk groups.

The Use of Rifapentine for Preventive Chemotherapy in Children from Risk Groups of Developing Tuberculosis

The objective: to compare efficacy of preventive treatment of children with latent tuberculosis infection using various regimens of anti-tuberculosis drugs and assess the risk of adverse events to these drugs.Subjects and Methods. 117 children of 2-17 years old with latent tuberculosis infection [a positive result of the test with tuberculous recombinant allergen (TRA)] were enrolled in the prospective study. They received preventive treatment with the regimen containing isoniazid and rifapentine. The comparison group included 84 children who received isoniazid and rifampicin.Results. In terms of safety and efficacy of chemotherapy regimens in the study, the best results were obtained when using the regimen containing isoniazid and rifapentine: the therapy was well tolerated, hepatotoxic reactions were registered in 1.7% of children. After a full course of preventive treatment in 24 months of follow-up, there was a statistically significant decrease in the proportion of hyperergic results of the skit test with TRA from 44 (41.9%) to 0 (0%) χ2 McNemar 43.00; p < 0.01; and conversion of the TRA test result from positive to negative was observed in 18.1% of children.

Possible Use of Tuberculous Recombinant Allergen Test in the Differential Diagnosis of Diseases in the Upper Lung Lobes in Adults

The objective of the study: to evaluate the possible use of the subcutaneous test with tuberculous recombinant allergen (TRA) in the differential diagnosis of pulmonary tuberculosis localized in the upper lobes.Subjects and Methods. Data of examinations with subcutaneous TRA and Mantoux tests with 2 units in 648 patients aged 18 to 90 years with various lung pathologies and HIV-negative status and 122 healthy individuals were retrospectively analyzed. Among these subjects, the following diseases were diagnosed: tuberculosis, pneumonia, cancer, post-tuberculosis changes, and sclerotic changes after nonspecific diseases.Results. The sensitivity of TRA test in adults with tuberculous lesions in the upper lobes was 59.87%; the rate of negative responses in those without active tuberculosis was 76.0%; the sensitivity of Mantoux test with 2 units was higher and made 83.6%, but the rate of negative responses in those without tuberculosis was lower – 44.1%. TRA test is most important in the differential diagnosis of tuberculosis and pneumonia in which positive and hyperergic reactions are observed in 59.87 and 13.95% of cases, respectively.The comparative analysis of the rates for tuberculosis and post-tuberculosis changes showed no statistically significant difference in both Mantoux test (83.6 and 78.4%, respectively, p > 0.05) and TRA test (59.87 and 50.77%, respectively, p > 0.05). This indicates that these tests cannot be used to assess the activity of tuberculosis localized in the upper lobes of the lungs in adults.

Latent tuberculosis infection among university students

Objective : to study the prevalence of latent tuberculosis infection (LTBI) among university students, to evaluate the effectiveness of preventive treatment in students with LTBI. Subjects and methods . In 2016-2019, the three-stage study was conducted that enrolled all university students in the city of Stavropol. In 2016-2017 during the first stage of the study, 4,139 students had tests with tuberculous recombinant allergen (TRA). At the second stage of the study, 141 medical files of students with positive results of TRA tests were retrospectively analyzed, all students were followed up and 133 of them underwent preventive treatment. In 2018-2019 at the third stage of the study, the long-term results of preventive treatment were evaluated. Results. Tests with TRA allowed detecting LTBI and defining indications for preventive treatment with anti-tuberculosis drugs. Among 133 students with LTBI who had preventive treatment, there were no cases of tuberculosis; sensitivity to TRA decreased, which manifested by a decreased induration size during the control test. Thus, in 36 months of follow-up over 83 patients with hyperergic reaction, it persisted only in 4 of them.

ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ПРИМЕНЕНИЯ КОЖНОЙ ПРОБЫ С АЛЛЕРГЕНОМ ТУБЕРКУЛЕЗНЫМ РЕКОМБИНАНТНЫМ ДЛЯ ВЫЯВЛЕНИЯ ТУБЕРКУЛЕЗА В СТАВРОПОЛЬСКОМ КРАЕ

The objective of the study: to evaluate the effectiveness of the introduction of screening for tuberculosis using the skin test with tuberculous recombinant allergen (TRA) in children and adolescents in Stavropol Region. Subjects and methods. The method of continuous sampling was used for retrospective analysis of files of 1,112 patients with respiratory tuberculosis in Stavropol Region. There were two time periods distinguished: 2009-2011 and 2016-2018. In 2009-2011, Mantoux test with 2 TU PPD-L was used for screening for tuberculosis in children and adolescents, and in those 15 years old and older, fluorography could be used. Among those of 18-24 years old, fluorography was the only method used. In 2016-2018, a skin test with TRA was used for screening for tuberculosis in children of 8-17 years old. Results. In the clinical structure of tuberculosis in children of 0-14 years old in both periods, the primary forms prevailed. During Period II, the primary tuberculosis complex was detected statistically significantly more often compared to Period I: 31/113 (27.4%) and 11/113 (9.7%) ( p < 0.01; χ2), which was associated with the additional examination of individuals selected based on results of the test with TRA, using spiral computed tomography of the chest, which provided good visualization of this form of tuberculosis. When tuberculosis was detected in adolescents (15-17 years old), the test with TRA demonstrated statistically significant higher efficacy – 46.9% (15/32 of all detected) compared to Mantoux test with 2 TU – 1.5% (1 / 65 of all detected), p < 0.01; χ2. In Period II, the structure of clinical forms of tuberculosis among adolescents improved due to increased incidence of focal tuberculosis from 16.7% (Period I) to 32.5% ( p < 0.05) and decrease in the frequency of lung destruction from 33/84 (39.2%) (Period I) to 3/40 (7.5%), p < 0.05; χ2. Bacillary excretion was registered in 21/84 (25.0%) of the adolescents (Period I) and in 3/40 (7.5%) of them (Period II), p < 0.05; χ2. Dispensary follow-up over preventive treatment in children with a positive and hyperergic reaction to the test with TRA provided a positive effect on the frequency of respiratory tuberculosis development in young people (18-24 years). In the period from 2009 to 2018, the incidence (per 100,000 population) decreased by 69.8%.

ПРИМЕНЕНИЕ АЛЛЕРГЕНА ТУБЕРКУЛЕЗНОГО РЕКОМБИНАНТНОГО В КОМПЛЕКСНОМ ПРОФИЛАКТИЧЕСКОМ ОБСЛЕДОВАНИИ НА ТУБЕРКУЛЕЗ ПОСТОЯЛЬЦЕВ УЧРЕЖДЕНИЙ СОЦИАЛЬНОГО ОБСЛУЖИВАНИЯ С КРУГЛОСУТОЧНЫМ ПРЕБЫВАНИЕМ

The objective of the study : To assess the efficacy of comprehensive examination using the skin test with tuberculous recombinant allergen in standard dilution (TRA) and fluorography with the mobile X-ray unit in the patients living in social service institutions for a long period of time. Subjects and methods : 624 persons living in social service institutions were examined, of them 438 walking patients had fluorography tests by the mobile X-ray unit and a skin test with TRA. 186 immobile and partially mobile patients had sputum microscopy and the skin test with TRA. Results. It was found out that sputum microscopy for acid-fast mycobacteria was uninformative for early detection of tuberculosis in immobile and partially mobile patients of social service institutions and it should be used simultaneously with TRA test. Immunodiagnostics in the patients of these institutions allowed identifying risk groups facing high risk to develop active tuberculosis in 6.6% of cases and prescribing them with preventive treatment in a timely manner.

The skin test with tuberculous recombinant allergen AT successful treated patients with lung tuberculosis

38 patients with newly diagnosed tuberculosis, immediately after the end of the main course of treatment, when they were transferred to the third group of dispensary supervision (6-9 months) and when they were removed from the dispensary supervision (2-3 years later), a skin test with an allergen tuberculous recombinant was made. The positive skin test with tuberculosis recombinant allergen was defined at 20 patients - 13 mm. At the moment of removing to the III group only one skin test with tuberculosis allergen recombinant became negative, 19 (94,5%) patients had positive reactions - 13±2,3 mm. At the time of discharging from dispensary the positive reactions were determined at 16 (80%) cases - 10±2,3 mm, p0,05. In this group, 13 (65%) patients had normergic skin tests with tuberculosis allergen recombinant and 7 (35%) - hyperergic tests. At the time of removing to the III group at five from seven patients with hyperergic tests the results remained the same, median and at the moment of discharging from tuberculosis service only one patient had the hyperergic skin test with tuberculosis allergen recombinant - 18mm. Among patients with normergic skin tests with tuberculosis allergen recombinant at the time of group III removing median was 11±2,1 mm. At the last dynamic control the normergic results were determined at 15 (75%) patients and the tests median remained almost unchanged - 10±1,8 mm, the differences are reliable compared to the initial data (p0,05). In group which included 18 patients with negative skin tests with tuberculous allergen recombinant, the skin response stayed negative throughout all examination period except for one patient so patients of this group had not only clinical, radiological and bacteriological, but immunological signs of involution of the tuberculosis process. The study of the influence of clinical, epidemic and social factors to skin reaction showed that first group patients were significantly more likely to be unemployed (30% versus 5,5%; p0,05) whereas in second group married patients were reliably registered (61,1% versus 25%; p0,05). Other factors differed unreliably.

ACTUAL ISSUES OF TUBERCULOSIS IN ADOLESCENTS EXPOSED TO TUBERCULOSIS INFECTION

The article characterizes respiratory tuberculosis in adolescents exposed to tuberculous infection. Exposure to tuberculosis in the family or when contacting close relatives makes the biggest contribution into development of the disease unless the patient is isolated from those exposed. Advanced and severe forms of tuberculosis with bacillary excretion are detected, compromising the life quality of adolescents. The main causes of late diagnostics are poor performance of TB services, primary medical units, low level of health education aimed at the increase of motivation to have planned medical examinations in the general population and to take relevant sanitary and hygienic measures in the sites of infection. Adolescents from the sites with bacillary excretion, and, first of all, if multiple or extensive drug resistant tuberculosis is detected, are to be considered a high priority group facing the risk to develop the disease with more frequent monitoring and deeper examination. In primary medical units, should any sings typical of tuberculosis be presented, it is sensible to add skin tests (Mantoux test and test with tuberculous recombinant allergen) to the minimum diagnostic procedures. Organizational, methodical and health education activities in the sites of infection are to be improved.

WAYS TO OPTIMIZE DETECTION OF TUBERCULOSIS IN A PULMONOLOGY UNIT

The objective: to optimize detection of tuberculosis in a pulmonology unit.Subjects and methods.In a pulmonology unit, patients suspected of having tuberculosis had a minimum number of diagnostic tests: a skin test with tuberculous recombinant allergen, three consecutive Ziel-Nelson microscopies of sputum and fluids of bronchoalveolar lavage, and in the laboratory of TB services they performed GeneXpert MTB/RIF, Bactec MGIT. Results of the diagnostics were analyzed in 70 patients with etiologic confirmation of diagnosis.Results.A targeted inquiry and taking the patient's history were informative in 4% of cases, skin test with TRA – in 27.1%, GeneXpert MTB/RIF – в in 100%, and Bactec MGIT – in 97.1%. Introduction of express diagnostic methods to a pulmonology unit reduced the average number of bed-days from admission to diagnostics of tuberculosis and transfer to a TB in-patient unit down to 9.80 ± 4.72 days. Molecular genetic methods can be recommended for introduction to general medical services as a diagnostic minimum when examining patients with a high risk of tuberculosis.

ВОЗМОЖНОСТИ ИММУНОДИАГНОСТИКИ ТУБЕРКУЛЕЗА У ПАЦИЕНТОВ НА ПОЗДНЕЙ СТАДИИ ВИЧ-ИНФЕКЦИИ

The significance of lipoarabinomannan (LAM) level in blood serum for the confirmation of tuberculosis was analyzed in 106 patients at the advanced stages of HIV infection. In 63 of 106 (59.4%) persons tuberculosis was diagnosed based on clinical signs. Patients with co-infection (HIV/TB) had confidently higher level of LAM in their blood serum versus HIV patients (13.75 ± 1.5 pg/ml; CI ± 2.97 and 7.49 ± 0.5 pg/ml; CI ± 0.96, respectively; Р = 0.000163). In general, sensitivity of the test of LAM level in blood serum of HIV patients made 85.7%, and specificity made 79.1%. It was found out that in TB/HIV patients, LAM level in blood serum was not influenced by such factors as extent of tuberculous lesions in respiratory organs (a positive result of LAM test in case of disseminated and local respiratory lesions was in 86% (37/43) and 85% of cases (17/20) respectively) and bacillary excretion (a positive result of LAM test in case of bacillary excretion and without was in 89.2% (33/37) and 76.9% (20/26) of cases respectively). The part of positive results when performing LAM test was in 87.5% of cases (54/63), while results of skin test with tuberculous recombinant allergen were positive only in 14.4% (9/63). The presented results allow concluding than it would be sensible to test LAM level in blood serum in the patients at the advanced stage of HIV infection. The informativeness of LAM test increases depending as the immune deficiency progresses and it becomes a valuable diagnostic tool at the level of CD4 < 200 cells per mcl.

АНАЛИЗ ПРИМЕНЕНИЯ КОЖНОЙ ПРОБЫ С ПРЕПАРАТОМ АЛЛЕРГЕНОМ ТУБЕРКУЛЕЗНЫМ РЕКОМБИНАНТНЫМ КАК СКРИНИНГОВОГО МЕТОДА ОБСЛЕДОВАНИЯ НА ТУБЕРКУЛЕЗНУЮ ИНФЕКЦИЮ У ДЕТЕЙ СТАРШЕ 7 ЛЕТ В ПЕНЗЕНСКОЙ ОБЛАСТИ В 2014-2016 гг.

The article presents the analysis of efficiency of skin test with tuberculous recombinant allergen (TRA, diaskintest), as a screening method for tuberculous infection in children and adolescents above 8 years old using Penza Region as an example. In 2016, 112,808 persons were screened with TRA test, 97.5% of children were covered with this test. TRA test proved to be effective for detection of tuberculosis in children and adolescents. When TRA test is used, less than 1% respond positively to it among those screened on a regular basis (in 2015 – 0.97% and in 2016 – 0.86%). The differential approach to the prescription of preventive treatment in risk groups significantly increases the motivation of 92.0% of parents to have it. With a positive result of TRA test, the screening for tuberculosis with this test and multispiral computer tomography of the chest significantly improve the structure of clinical forms of tuberculosis in children and adolescents due to an increase of the number of limited lesions with minimal manifestations.

КРИТЕРИИ ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ ТУБЕРКУЛЕЗА У ДЕТЕЙ В СОВРЕМЕННЫХ УСЛОВИЯХ

The main objective of a phthisiologist following up and treating children and adolescents with local forms of tuberculosis is to achieve complete clinical cure with minimal remaining post-tuberculosis changes. Evaluation of treatment progress is important since it defines not only the duration of chemotherapy and follow-up but it also serves a prognostic criterion of stable clinical cure and prevention of relapse in the future. New criteria for evaluation of tuberculosis activity and clinical cure in children and adolescents were assessed. It was proved that Mantoux test could not be the criterion of the disease activity. While results of the test with tuberculous recombinant allergen (TRA) performed at the moment of clinical cure did not depend on the volume and severity of changes and allowed assessing the activity of the disease with any intensity of specific changes in chest lymph nodes and lung tissue, and TRA test served as a criterion of activity of mycobacterial population in the host.

ВЫЯВЛЕНИЕ И ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА ТУБЕРКУЛЕЗА У ДЕТЕЙ И ПОДРОСТКОВ

According to the data of screening with tuberculous recombinant allergen (Diaskintest), 2.2% of children and adolescents in 29 regions of the Russian Federation in 2012-2013 (n = 810,107) belonged to the group facing a higher risk to develop tuberculosis. The frequency of minor forms such as focal tuberculosis (58.3%) increased in adolescents, detected by the test with TRA compared to the other methods: by Mantoux test (16.7%), by fluorography (13.0%) and by self-referral for medical help (10.0%). Screening with TRA allows forming Group VI of dispensary follow-up with the maximum accuracy. Results of Mantoux test and the test with TRA in tuberculosis patients were equitable. However, the test with TRA is more specific versus Mantoux test when used for differential diagnostics of tuberculosis.

РЕЗУЛЬТАТЫ ПРИМЕНЕНИЯ ИММУНОЛОГИЧЕСКИХ ТЕСТОВ НОВОГО ПОКОЛЕНИЯ У ДЕТЕЙ В УСЛОВИЯХ МАССОВОЙ ВАКЦИНАЦИИ ПРОТИВ ТУБЕРКУЛЕЗА

Development of new methods of immune diagnostics of tuberculous infection and their introduction into tuberculosis control practice have changed approaches to diagnostics of tuberculosis in Russia. Along with world recognized IGRA-tests the test with tuberculous recombinant allergen (TRA) developed by Russian researchers is also widely used. High diagnostic value of each of the methods is proved by multiple national and international trials however there is no research comparing results of these methods in the diagnostics of tuberculous infection in children, including those with concurrent conditions. During the study data of testing in 654 children in the age from 0 to 14 years old with positive sensitivity to tuberculin as per Mantoux test with 2 TU were analyzed. All patients had modern immunological tests done: TRA and IGRA-tests (QuantifeRON® Gold ELISA (QFT) and T-SPOT.TB). The study confirmed the low value of Mantoux test with 2 TU as a method of early tuberculosis detection in children; it detected underdiagnosis (10-50%) and overdiagnosis (78%) of latent tuberculous infection in the children with different sensitivity level as per data of Mantoux test with 2 TU. Comparing the results of TRA and IGRA tests it is possible to state that they are compatible for 76-81% of cases. The group of children was detected who had allergic and endocrine disorders (obesity), for whom IGRA tests were recommended to exclude chances of false-positive results of TRA tests.

ВОЗМОЖНОСТИ ДИАГНОСТИКИ АКТИВНОСТИ ТУБЕРКУЛЕЗНОГО ПРОЦЕССА У ПАЦИЕНТОВ С КЛИНИЧЕСКИ ИЗЛЕЧЕННЫМ ТУБЕРКУЛЕЗОМ ОРГАНОВ ДЫХАНИЯ

Goal of the study : to evaluate the test with tuberculous recombinant allergen (TRA) in the patients with effective treatment course due to tuberculosis, to investigate the impact of clinical, epidemiological and social factors on persistence of active tuberculosis. Materials and methods . Patients were divided into 2 groups basing on time period after completion of the main treatment course. Group I – 32 patients (up to 6 months), group II – 63 patients (more than 6 months). Results of the study . Results of TRA tests in Group I remained positive in 34.4% of patients and in Group II - 23.8%. The average size of the induration in Group I made 10 mm(95% CI 6.5-13.3), in Group II – 13 mm (95% CI 8.4-19.7) Patients from Group I had positive results of TRA test more often in case of initial infiltrate form of pulmonary tuberculosis and bacillary excretion. In patients from Group II the positive TRA results correlated with presence of concurrent conditions and exposure to a tuberculosis case in the past. Positive results were confidently more often observed in lonely patients in both groups. TRA test can be a valuable tool to evaluate the risk of tuberculosis relapse after completion of the main treatment course.

PMD56 - Cost-Effectiveness Analysis of Diagnostics of Tuberculosis Infection in The Russian Federation with The Use of Tuberculous Recombinant Allergen

PMD56 - Cost-Effectiveness Analysis of Diagnostics of Tuberculosis Infection in The Russian Federation with The Use of Tuberculous Recombinant Allergen

ЭФФЕКТИВНОСТЬ ИСПОЛЬЗОВАНИЯ АЛЛЕРГЕНА ТУБЕРКУЛЕЗНОГО РЕКОМБИНАНТНОГО В СКРИНИНГ-ДИАГНОСТИКЕ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ У ДЕТЕЙ И ПОДРОСТКОВ В СТАВРОПОЛЬСКОМ КРАЕ

Goal of the study: to define efficiency ofthe screening with the tuberculous recombinant allergen (TRA) in children and adolescents with the purpose of tuberculosis detection and defining the groups of the advanced risk of developing tuberculosis. Materials and methods. Efficiency ofscreening fortuberculosis was compared upon the results ofskin tests withTRA in 72,601 children and Mantoux test with 2 TU PPD-L in 99,448 children in the age from 1 to 14 years old. Results. The frequency of tuberculosis detection in the mass screening with TRA among children made 0.4 per 1000 of those examined, among adolescents it made 0.7 per 1000 of those examined which was significantly and confidently higher compared to the screening with Mantoux test. The use of TRA test allowed reducing more than 5 times the number of candidates for preventive chemotherapy under direct observation ofthe drug intake.

Эффективность кожного теста с аллергеном туберкулезным рекомбинантным при выявлении туберкулеза у детей и подростков Москвы в 2013 г.

Эффективность кожного теста с аллергеном туберкулезным рекомбинантным при выявлении туберкулеза у детей и подростков Москвы в 2013 г.