TREATMENT EFFICIENCY OF DRUG SUSCEPTIBLE PULMONARY TUBERCULOSIS

The article describes the study of comparative efficiency of fenazid (isonicotinoilhydrazine-О,N’) ferrous dihydrate sulphate (II) and isoniazid in drug susceptible pulmonary tuberculosis patients.The high treatment efficiency namely significant improvement and improvement was observed in the patients of Group 1 – 84.1% which could be compared to the standard treatment regimen (85-7%) in Group 2. The total number of adverse reactions in the main group was confidently lower – 18.6% against 33.9%, p < 0.05. Hepatotoxic reactions with 2-3 fold increase of alaninetransferase level was registered significantly less (9.3%) in Group 1 compared to the Group treated with isoniazid

INFLUENCE OF HLA-DRB1* ALLELIC SETS ON THE DEVELOPMENT OF TUBERCULOSIS IN CHILDREN

According to the WHO data, tuberculosis still represents a serious public health problem worldwide. Deterioration of socio-economic conditions in the population complicates epidemic situation for tuberculosis inRussia, thus leading to increase in acute progressive and complicated forms of tuberculosis in children and, consequently, to worsening structure of its clinical forms. Objectives: to determine associations between certain HLA-DRB1 alleles and risk of tuberculosis development in children. We examined 188 children aged from 3 to 14 years with various manifestations of tuberculous infection. Along with thorough examination of the patients, including multi-spiral CT scans of chest, we undertook genotyping of HLA-DRB1 alleles. Activity of tuberculous infection was determined by a set of immunological tests, i.e., tuberculin skin test, DIASKINTEST® (recombinant allergen of tuberculosis DIASKINTEST®). X ray diagnostics was performed with multi-spiral «Aquilion-32» computed tomograph (Toshiba), according to standard procedures. Molecular genetic typing of HLA-DRB1 alleles was performed by polymerase chain reaction (PCR-SSP), using standard commercial kits PROTRANS Ceclerplate System Protrans HLA-DRB1*. The children were divided into two groups: I group, 90 healthy children, II group, 98 children with tuberculosis. A comparisons group consisted of healthy donors (n = 346). Statistical processing of genetic material included evauation and analysis of the following parameters: frequency distribution of the antigen (F), χ2 criterion for significance (chi-square), the relative risk ratio (RR), etiologic fraction (EF), preventive fraction (PF). Children of the II group had significantly higher *04 allele HLADRB1*, as compared with control group (36.7% vs. 21.1%, χ2 = 10.08; р < 0.01). This finding may suppose a predisposal of these allele carriers to development of tuberculosis. At the same time, the rates of *07 (14.3% vs. 27.5%, χ2 = 7.15, р < 0.01) and *15 (18.4% vs. 28.3%, χ2 = 3.92; р < 0.01) HLA-DRB1* alleles were significantly lower, thus suggesting a protective effect of this allele. *04 allele seems to be a predisposing factor, whereas *07 and *15 alleles are protective for development of tuberculosis in children

Immunological methods in diagnosis of sarcoidosis end tuberculosis of lung

Differential diagnosis disseminated diseases provides sarcoidosis and tuberculosis. Frequency of mistakes consists over 40% [Visel AA, 2013]. That’s why including of new diagnosis methods is weary important. Оbjective: to indicat diagnosis value of immunologic methods in differential diagnosis with sarcoidosis and tuberculosis. In the department of phthisiopulmonology were examined 66 patients with lung over 2013 to 2014. Complex of examination included: examination of the respiratory excretion material (sputum) for detection of MBT using laboratory methods, X-ray examination (computed tomography), histological examination after transbronchial biopsy of lung tissue. All of diagnosis were proved by histological and bacteriological methods. After complex of examination patients were divided in two groups: I group (n=32) – pulmonary TB; II group (n=17) – sarcoidosis II study. All of patients were examined with immunologic tests (tuberculin skin test (TST), Diaskintest® (DST) QuantiFERON ®-TB Gold (QFT) and T.-SPOT.TB test (T-SPOT). In the I group this tests was significant different positive results with QFT (78,1%), T-SPOT (71,9%), DST (81,3%) in comparison with negative results of this tests (p˂0,001). Diagnostic value was: TST (DSe – 84,4%, DSp – 40,0%, Dv – 70,2%, PVPR – 75,0%, PVNR – 54,5%); QFT (DSe – 74,2%, DSp – 88,2%, Dv – 79,2%, PVPR – 92,0%, PVNR – 65,2%); TB.SPOT (DSe – 80,6%, DSp – 87,5%, Dv – 83,0%, PVPR – 92,6%, PVNR – 70,0%); DST (DSe – 81,3%, DSp – 94,1%, Dv – 85,7%, PVPR – 96,3%, PVNR – 72,7%); Сonclusion: diagnostic value of immunologic tests QFT, TB.SPOT and DST was more significantly higher in comparison with TST. The use of immunological tests can help in differential diagnosis of tuberculosis and sarcoidosis

Особенности диагностики полиорганных нарушений, ассоциированных с COVID-19, у ребёнка младшего школьного возраста

   The advent of the COVID-19, specialists are increasingly encountering previously unknown pathological conditions in their practice. For some time, we have believed that COVID-19 in children is most often mild and asymptomatic. However, with the passage of time and the accumulation of the experience, it became obvious that the new infectious disease it will be quite severe in children. Differential diagnosis of multiple organ disorders in children during the COVID-19 pandemic should be primary carried out with the Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C), as well as Long-COVID-19. According to published data, the manifestations of these conditions are due to frequent lesions of the gastrointestinal tract (60–100 %), cardiovascular (80 %), nervous (29–58 %) and respiratory (21–65 %) systems. At present, there is no exact idea of these pathological conditions, the criteria for their diagnosis and the tactics of managing children, not only at the stage of diagnosis, but also at the stage of observation. The authors present a diagnostically complex clinical case describing the development of multiple organ damage in a 7-year-old child after contact with a mother who was sick with COVID-19. The data on the course features, the results of the examination and the difficulties of differential diagnosis of this case with other diseases with a similar clinic are summarized.   С появлением COVID-19 специалисты все чаще встречаются в своей практике с ранее неизвестными патологическими состояниями. Некоторое время считалось, что COVID-19 у детей протекает чаще всего в легкой и бессимптомной форме. Однако с течением времени и накоплением опыта стало очевидным, что новое инфекционное заболевание достаточно коварно и в отношении детского населения. Дифференциальная диагностика полиорганных нарушений у детей во время пандемии COVID-19 прежде всего должна проводиться с мультисистемным воспалительным синдромом у детей, ассоциированным с COVID-19 (Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C), а также Long-COVID-19. Согласно опубликованным данным, проявления этих состояний обусловлены частым поражением желудочно-кишечного тракта (60–100 %), сердечно-сосудистой (80 %), нервной (29–58 %) и респираторной (21–65 %) систем. Однако с появлением новых характеристик вируса SARS-CoV-2 полиорганные изменения, ассоциированные с COVID-19, а также сроки развития данных нарушений могут существенно изменяться. В настоящее время нет точного представления о данных патологических состояниях, критериях их диагностики и тактике ведения детей не только на этапе диагностики, но и на этапе наблюдения. Авторами представляется диагностически сложный клинический случай с описанием развития полиорганного поражения у ребенка 7 лет после контакта с больной COVID-19 матерью. Обобщены данные об особенностях течения, результатах обследования и сложностях дифференциальной диагностики данного случая с другими заболеваниями с похожей клиникой

Эффективность терапии туберкулеза легких с сохраненной лекарственной чувствительностью микобактерий

The article describes the study of comparative efficiency of fenazid (isonicotinoilhydrazine-О,N’) ferrous dihydrate sulphate (II) and isoniazid in drug susceptible pulmonary tuberculosis patients.The high treatment efficiency namely significant improvement and improvement was observed in the patients of Group 1 – 84.1% which could be compared to the standard treatment regimen (85-7%) in Group 2. The total number of adverse reactions in the main group was confidently lower – 18.6% against 33.9%, p < 0.05. Hepatotoxic reactions with 2-3 fold increase of alaninetransferase level was registered significantly less (9.3%) in Group 1 compared to the Group treated with isoniazid.Статья посвящена изучению сравнительной эффективности феназида (изоникотиноилгидразин-О,N’) железа (II) сульфат дигидрат и изониазида у больных туберкулезом легких с сохраненной лекарственной чувствительностью возбудителя. Получена высокая эффективность лечения «значительное улучшение» и «улучшение» у пациентов 1-й группы - 81,4%, что сопоставимо со стандартной схемой терапии (85,7%) во 2-й группе. Общее число нежелательных побочных реакций в основной группе отмечалось достоверно реже - 18,6% против 33,9%, p < 0,05. Гепатотоксические реакции с повышением в 2-3 раза уровня аланинтрансаминазы зарегистрированы значительно реже (9,3%) в I группе по сравнению с группой получавших изониазид - 23,2%

Возможности иммунологических методов в дифференциальной диагностике саркоидоза и туберкулеза органов дыхания

Differential diagnosis disseminated diseases provides sarcoidosis and tuberculosis. Frequency of mistakes consists over 40% [Visel AA, 2013]. That’s why including of new diagnosis methods is weary important. Оbjective: to indicat diagnosis value of immunologic methods in differential diagnosis with sarcoidosis and tuberculosis. In the department of phthisiopulmonology were examined 66 patients with lung over 2013 to 2014. Complex of examination included: examination of the respiratory excretion material (sputum) for detection of MBT using laboratory methods, X-ray examination (computed tomography), histological examination after transbronchial biopsy of lung tissue. All of diagnosis were proved by histological and bacteriological methods. After complex of examination patients were divided in two groups: I group (n=32) – pulmonary TB; II group (n=17) – sarcoidosis II study. All of patients were examined with immunologic tests (tuberculin skin test (TST), Diaskintest® (DST) QuantiFERON ®-TB Gold (QFT) and T.-SPOT.TB test (T-SPOT). In the I group this tests was significant different positive results with QFT (78,1%), T-SPOT (71,9%), DST (81,3%) in comparison with negative results of this tests (p˂0,001). Diagnostic value was: TST (DSe – 84,4%, DSp – 40,0%, Dv – 70,2%, PVPR – 75,0%, PVNR – 54,5%); QFT (DSe – 74,2%, DSp – 88,2%, Dv – 79,2%, PVPR – 92,0%, PVNR – 65,2%); TB.SPOT (DSe – 80,6%, DSp – 87,5%, Dv – 83,0%, PVPR – 92,6%, PVNR – 70,0%); DST (DSe – 81,3%, DSp – 94,1%, Dv – 85,7%, PVPR – 96,3%, PVNR – 72,7%); Сonclusion: diagnostic value of immunologic tests QFT, TB.SPOT and DST was more significantly higher in comparison with TST. The use of immunological tests can help in differential diagnosis of tuberculosis and sarcoidosis. Дифференциальная диагностика саркоидоза и туберкулеза органов дыхания до настоящего времени представляет значительные трудности. Частота ошибок при постановке диагноза составляет более чем 40% (Визель А.А., 2013). Значение иммунологических методов в дифференциальной диагностике с саркоидоза и туберкулеза не определено, что послужило основанием для настоящего исследования. В ФГБУ «СПб НИИФ» Минздрава России было обследовано 66 пациентов с изменениями в легких и внутригрудных лимфатических узлах за период с 2013 по 2014 г. Все диагнозы были доказаны с применением гистологического и бактериологического методов. Пациенты были разделены на две группы: I группа (n = 32) – туберкулезом легких; группа II (n = 17) – саркоидозом органов дыхания II ст. и обследованы с постановкой иммунологических тестов (проба Манту с 2ТЕ, проба с Диаскинтестом® (ДСТ), QuantiFERON ®-TB Gold (QFT) и Т.-SPOT.TB тест (T-SPOT). Достоверные различия были получены при сравнении положительных и отрицательных результатов тестов (p˂0,001) в I и II группе. Диагностическое значение тестов: проба Манту с 2ТЕ (ДЧ – 84,4% , ДС – 40,0%, ДЭ –70,2%, ПЗПР – 75,0%, ПЗОР – 54,5%); QFT (ДЧ – 74,2%, ДС – 88,2%, ДЭ – 79,2%, ПЗПР – 92,0%, ПЗОР – 65,2%); T.SPOT (ДЧ – 80,6%, ДС – 87,5%, ДЭ – 83,0%, ПЗПР – 92,6%, ПЗОР – 70,0%); ДСТ (ДЧ – 81,3%, ДС – 94,1%, ДЭ – 85,7%, ПЗПР – 96,3 %, ПЗОР – 72,7%). Выводы: диагностическое значение иммунологических тестов QFT, TB.SPOT и ДСТ значительно выше был в сравнении с пробой Манту с 2ТЕ. Применение данных методов может существенно помочь в дифференциальной диагностике туберкулеза и саркоидоза.

Многоцентровое наблюдательное неинтервенционное исследование применения комбинированных противотуберкулезных препаратов при лечении больных туберкулезом легких

The objective of the study: to run a multicenter non-interventional observational study to assess treatment outcomes in tuberculosis patients receiving combination drugs with fixed doses, and to evaluate tolerability and safety of these drugs.Subjects and methods. 13 TB units participated in this study which lasted from 2016 to 2018. The primary population (PP) included of 489 patients, after applying the exclusion criteria – the subpopulation (subPP) included 267 patients with newly detected pulmonary tuberculosis and relapses who received treatment as per chemotherapy regimen I or III. Descriptive statistics methods were used for statistical data processing.Results. Of all PP, 267 (54.6%) completed the main course of chemotherapy. (subPP). Out of 489 patients, treatment was discontinued in 118 (24.1%) of them. Primary drug resistance was detected in 30 (6.1%) patients out of 489 patients, secondary drug resistance – in 74 (15.1%) of 489. In subPP, by the end of the intensive phase the sputum conversion was achieved in 78 (96.3%) of 81 patients. Clinical and X-ray changes had been observed in this subgroup for 106.2 to 63.3 days (median 90). The duration of the intensive phase in the subPP made 107.9 ± 50.5 days. In safety assessment, 191 adverse events (AE) were registered in 149 (30.5%) of 489 patients. By severity, most AEs were minor (164 out of 191), moderate AEs were less frequent (20 out of 191), and there were 7 cases of serious AEs. 61 AEs in 57 (38.2%) out of 149 patients were confidently associated with in-take of the studied drugs. The structure of those AEs, transient transaminase level elevation prevailed (45 (73.8%) of 61 AEs, but there was a single case (1.6%) drug-induced hepatitis). Among the serious AEs, two cases were safely resolved by the end of the protocol, two of them were fatal in TB/HIV co-infection, and three cases were diagnosed with cancer.Цель исследования: оценка в многоцентровом неинтервенционном наблюдательном исследовании результатов лечения больных туберкулезом с использованием комбинированных препаратов с фиксированными дозами, переносимости и безопасности этих препаратов.Материалы и методы. В исследовании, проходившем с 2016 по 2018 г., участвовали 13 противотуберкулезных учреждений. Сформированы первичная популяция (РР) из 489 пациентов, после применения критериев исключения – субпопуляция (subPP) из 267 пациентов с впервые выявленным туберкулезом легких и рецидивом, которые получали лечение по I или III режиму химиотерапии. Для статистической обработки данных использовали методы описательной статистики.Результаты. Из РР основной курс химиотерапии завершили 267 (54,6%) (subPP). Досрочно прекратили лечение 118 (24,1%) пациентов из 489. Первичная лекарственная устойчивость выявлена у 30 (6,1%) из 489, вторичная – у 74 (15,1%) из 489. В subPP прекращение бактериовыделения обнаруживалось к концу интенсивной фазы в 78 (96,3%) случаях из 81. Клинико-рентгенологическая динамика отмечалась в этой подгруппе в течение 106,2 ± 63,3 дня (медиана 90). Длительность интенсивной фазы в subPP составила 107,9 ± 50,5 дня. При оценке безопасности зарегистрировано 191 нежелательное явление (НЯ) у 149 (30,5%) из 489 пациентов. По степени тяжести большинство НЯ были легкой степени (164 из 191), реже (20 из 191) – средней степени и 7 – серьезные НЯ. С приемом исследуемых препаратов установлена связь при 61 НЯ у 57 (38,2%) из 149 пациентов. В структуре этих НЯ преобладало транзиторное повышение уровня трансаминаз (45 (73,8%) из 61 НЯ, но в единичном случае (1,6%) зарегистрирован лекарственный гепатит). Среди серьезных НЯ два случая благополучно разрешились к завершению протокола, два ‒ закончились летальным исходом при сочетании ВИЧ-инфекции и туберкулеза, а в трех случаях диагностированы онкологические заболевания

Diagnostics and management of tuberculosis and COVID-19 in a patient with pneumothorax (clinical case)

The spread of COVID-19 in countries with high and medium incidence of tuberculosis has led to an increased risk of COVID-19 and tuberculosis co-infection, introducing new diagnostic and therapeutic challenges for the clinician. Hereby we describe a first case where tuberculosis and COVID-19 were diagnosed concomitantly in a Russian patient with pneumothorax. We discuss the challenges associated with the diagnosis and treatment of tuberculosis during the COVID-19 pandemic

EFFICIENCY OF INTEGRAL THERAPY AND POTENTIAL SIDE EFFECTS WHEN TREATING RESPIRATORY TUBERCULOSIS WITH MULTIPLE DRUG RESISTANCE

Treatment of multiple drug resistant tuberculosis presents a serious challenge. Use of perchlozon (thioureidoiminomethylpyridini um) in the combination with the other five anti-tuberculosis drugs during 6 months of treatment allowed achieving cessation of bacillary excretion and X-ray improvement in all patients from the main group. Monitoring and evaluation of adverse events have not detected any confident difference in the number of adverse events apart from endocrine and allergic ones while taking perchlozon in the combination with other drugs. All adverse events were minor and moderate as regards severity degree and were managed by symptomatic treatment and did not cause cancellation of the drug. The obtained results will promote achieving the high tuberculosis treatment effciency by the end of the main chemotherapy course and this will require further investigation