Сравнительная характеристика иммунологических тестов для выявления туберкулезной инфекции. Возможность массового скрининга

Goal: to evaluate efficiency of various immunological tests (tuberculin tests, IGRA tests, skin tests containing proteins specific for M. tuberculosis – ESAT-6, CFP10) in the detection of tuberculous infection, their sensitivity, specificity and opportunities to be used for mass screening in children and adolescents.Materials. 122 Russian and foreign publications have been analyzed including reviews and meta-analyses.Results. The specificity of tuberculin testing is fairly low due mass BCG vaccination among children and adolescents, IGRA tests possess high specificity but can not be used for mass screening due to high costs, intravenous manipulations and need for the well-equipped laboratory. Skin tests with agents containing the same proteins as IGRA tests are highly specific, sensible and effective for mass screening. Detection rate of tuberculosis and post-tuberculous changes in children with positive reaction to these tests is significantly higher compared to those with positive reactions to Mantoux testing with 2 TU PPD-L. Цель: оценка эффективности различных иммунологических тестов (туберкулиновые пробы, тесты IGRA и кожные пробы с препаратами, содержащими специфичные для M. tuberculosis белки - ESAT-6, CFP10) для выявления туберкулезной инфекции, их чувствительности, специфичности и возможности использования для массового скрининга у детей и подростков.Материалы. Проанализированы 122 источника российской и иностранной литературы, включая обзоры и метаанализы.Результаты. Туберкулинодиагностика в условиях массовой вакцинации БЦЖ детей и подростков обладает низкой специфичностью, тесты IGRA обладают высокой специфичностью, но не применимы при массовом скрининге из-за высокой стоимости, внутривенных манипуляций и необходимости оснащенной лаборатории. Кожные пробы с препаратами, содержащими те же белки, что и тесты IGRA, обладают высокой специфичностью, чувствительностью, а также эффективностью при массовом скрининге. Выявляемость туберкулеза и посттуберкулезных изменений у детей с положительными реакциями на эти пробы значительно выше, чем у лиц с положительными реакциями на пробу Манту с 2 ТЕ PPD-L

Surgical treatment of urethral tuberculosis in men – history and present (literature review)

The literature review provides data on tuberculosis of the urethra in men. This disease is rarely recorded, as a rule, at the stage of formation of the urethral stricture, which can develop many years after the onset of the disease. Urethral tuberculosis is usually secondary to other localizations of extrapulmonary tuberculosis, such as tuberculosis of the prostate, penis, kidney, and bladder, but there are also isolated forms of this disease. The most common symptoms of urethral tuberculosis are the presence of strictures, skin-urethral and recto-prostatic fistulas, and purulent urethritis. Almost always, with this disease, conservative specific therapy was carried out, which in some cases made it possible to completely eliminate the symptoms and ensure the patient’s clinical recovery. Tuberculous urethral strictures are operated on according to generally accepted rules, but there is no single algorithm for the surgical treatment of strictures of this etiology, often limiting itself only to urine diversion or urethral dilation. Of the urethroplasty, the most commonly used end-to-end urethral anastomosis. In our opinion, a promising direction is the use of various grafts for the surgical treatment of this disease

Six-month therapy of CGRP monoclonal antibodies in real-world clinical practice: an interim analysis of efficacy and safety data

Introduction. Migraine is one of the most common disabling neurological disorders. Recently developed monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor are the first targeted medication for preventive therapy of both episodic and chronic migraine. They have been thoroughly investigated in clinical trials; however, there is little data from real-world clinical practice available to date. The aim of this study is to assess the efficacy and safety of 6 months of treatment with erenumab in real-world clinical practice and investigate the effect of the drug on the patients’ sensitivity to medicines for migraine headaches relief and patient satisfaction after treatment.Materials and methods. Our observational cohort prospective study included patients in our Headache Clinic prescribed monoclonal antibodies blocking the  CGRP-receptor  – erenumab. During the  investigation, we evaluated the  previous preventive therapy and its efficacy, the number of days with migraine per month, adverse events occurring during the erenumab treatment, depression and anxiety (HADS), migraine disability (MIDAS), the presence of allodynia (ACS-12) and improved response to acute therapy after treatment. A total of 42 patients participated in the study: 6 men, 36 women, the average age was 43.9 ± 12.2. Of them, 38 patients (90%) had chronic migraine. Thirty-two patients (76%) had previously been prescribed preventive therapy, which proved ineffective, and 10 patients (24%) had not once received any type of migraine prevention.Results. Among our patients, we identified 11 patients with resistant migraine and one patient with refractory migraine. During the study, two patients dropped out due to adverse events (constipation). Thirty patients continued the administration of erenumab 70 mg for at least six months. The average number of migraine days per month before treatment was 22.8, and after six months of treatment, it dropped to 7.3. Twenty-nine patients (72.5%) also noted that the response to acute headache treatment improved after the therapy.Conclusion. The results of our study are consistent with the international experience of using erenumab and confirm its effectiveness for migraine preventive therapy, including difficult-to-treat migraine cases. However, further studies with more participants and evaluation of predictors of successful monoclonal antibody therapy are still needed

Single-stage combined urethroplasty for extended strictures of the anterior urethra of tuberculous origin

Background. Urethral strictures are currently one of the most complex pathologies in reconstructive urology. The most promising direction in this area is the development of single-stage surgical interventions that meets modern requirements for the quality of life of patients.The aim of the study. To evaluate the possibility and the effectiveness of surgical treatment of extended recurrent tuberculous urethral strictures in men using a combination of a skin flap and a buccal graft. In the literature, there is no description of the use of this technique in patients with urethral tuberculosis.Materials and methods. We observed 44 patients with urethral tuberculosis. Three men from this group of patients were diagnosed with tuberculous (post-tuberculous) extended recurrent stricture of the anterior urethra and they underwent combined single-stage urethroplasty with a ventral fasciocutaneous flap and a buccal graft using the inlay method in the penile region and with a buccal graft using the ventral onlay method in the bulbous urethra. Ultrasound of the urethra served as a method that determines the possibility of performing this surgery in case of maintaining a sufficient width of the urethral plate with a moderate degree of spongiofibrosis.Results. Patients were under observation for 34, 50 and 54 months and have good long-term functional results – all patients have unassisted urination and no residual urine. Post-micturition dribbling persists in 1 patient. The overall effectiveness of the treatment of these strictures, taking into account the treatment of repeated cases of the disease recurrence, is high.Conclusion. This technique demonstrates the possibility of performing a single-stage reconstruction of the anterior urethra in patients with extended recurrent tuberculous (post-tuberculous) urethral strictures and is also applicable for the surgical treatment of urethral strictures of other origins

Difficulties in the differential diagnosis of intestinal tuberculosis and Crohn‘s disease

The differential diagnosis of intestinal tuberculosis and Crohn’s disease is a difficult task for most specialists due to their high similarity in clinical manifestations, instrumental diagnosis and histological pattern.The aim: to consider the clinical and diagnostic features of intestinal tuberculosis and Crohn’s disease, to show the role of various methods of their diagnosis (CT of the abdominal cavity, CT-enterography, colonoscopy with biopsy).A clinical example shows a case illustrating the difficulties of diagnosing intestinal tuberculosis, initially diagnosed as Crohn’s disease. The features of the course, complex diagnosis and treatment of intestinal tuberculosis and its complications during immunosuppression are demonstrated. At the first stage of treatment, the patient’s data related to CT of the chest organs, colonoscopy and histological examination of biopsy samples were incorrectly interpreted. As a result, a wrong diagnosis of Crohn’s disease was made, and immunosuppressive therapy was prescribed that provoked a generalization of the existing tuberculosis process. Subsequently, repeated surgical interventions were performed for complications of intestinal tuberculosis – perforation of tuberculous ulcers, peritonitis. Based on the analysis of the literature data and our own observation, it is shown that granulomatous inflammation in the study of intestinal biopsies doesn’t always allow us to make a clear diagnosis, first of all, there are intestinal tuberculosis and Crohn’s disease in the differential diagnostic series. The use of histobacterioscopy according to Ziehl – Neelsen, the study of fecal matter by luminescent microscopy, as well as molecular genetic methods for detecting DNA MTB allow us to verify the diagnosis. If Crohn’s disease is misdiagnosed as intestinal tuberculosis, then the prescribed anti-tuberculosis therapy can cause harm and lead to a delay in the underlying disease treatment. The reverse misdiagnosis is potentially more dangerous: if tuberculosis is misdiagnosed as Crohn’s disease, then the appointment of immunosuppressive therapy can lead to the generalization of tuberculosis and the development of fatal complications

Оценка эффективности массового скрининга для выявления туберкулезной инфекции у детей в возрасте от 1 до 7 лет в Москве

The objective: to evaluate effectiveness of mass screening for tuberculosis infection in children aged 1 to 7 years in different periods – before and after the use of tuberculosis recombinant allergen skin test (TRA) in primary health care as an additional diagnostic method.Subjects and Methods. The study was designed as continuous observational prospective-retrospective study. Two different periods were assessed: the first one was 2014-2016 when screening for tuberculosis infection was performed in all children from 1 to 17 years (inclusive) using Mantoux test with 2 TU PPD-L in pediatric primary health care, and then children suspected to have a positive reaction were referred to TB dispensary where they were examined with a skin test with TRA if necessary. The second period was from 2018 to 2020 when children of 1-7 years old were given Mantoux test and if tuberculosis infection was suspected, a skin test with TRA was done both in primary health care network and TB units. In the first 3 years, 1,864,137 children were examined and in the second 3 years, 2,078,800 children from 1 to 7 years old were examined.Results. Among children of 1-7 years old who were screened by two stages (initial Mantoux test, and then in those who had a positive reaction, the TRA test was used), only 10-12% of those referred to a phthisiologist were subject to dispensary follow-up. Thus, with the implementation of the new edict on screening for tuberculosis infection in children with two tests, this proportion has not changed compared to previous years, when screening was carried out only with one Mantoux test. The reason why almost 90% of the children who were referred to TB Dispensary were not subject to dispensary follow-up is the following: children who have had previous conversion of tuberculin tests, along with everyone else are again screened with Mantoux test despite being previously followed up by TB dispensary due to the primary infection.Recommendations:Currently, there is no division of Group VI into Subgroups A, B, C in the dispensary follow up grouping. Why should conversion of Mantoux test reaction from negative into positive not be considered an infection, and the increase in the reaction must be at least 6 mm.Since Order No. 124n of the Russian Ministry of Health allows testing with TRA in the primary health care in case of suspected infection, it is advisable to refer those who have already had this test to a phthisiologist.A child with conversion of Mantoux test should not be re-screened with Mantoux test but the TRA test should be used. If a positive reaction to the TRA test occurs for the first time, it should be considered as conversion of this test, and in this case the child should be examined by computed tomography (CT), and preventive therapy should be prescribed. If in subsequent years the TRA reaction increases by at least 6 mm after previous preventive therapy, the child should be re-referred for CT to rule out the development of active tuberculosis.Цель: оценка эффективности массового скрининга для выявления туберкулезной инфекции у детей в возрасте от 1 до 7 лет в разные периоды ‒ до и после начала использования кожной пробы с аллергеном туберкулезным рекомбинантным (АТР) в учреждениях первичной медико-санитарной помощи в качестве дополнительного метода диагностики.Материалы и методы. Дизайн работы – сплошное наблюдательное проспективно-ретроспективное исследование. Взяты 2 разных периода: первый – 2014-2016 гг., когда скрининг туберкулезной инфекции проводили у всех детей от 1 до 17 лет (включительно) при помощи пробы Манту с 2 ТЕ ППД-Л в учреждениях первичной медико-санитарной помощи детскому населению, а затем детей с увеличением реакции направляли в противотуберкулезный диспансер, где при необходимости их обследовали при помощи кожной пробы с АТР; второй период ‒ 2018-2020 гг., когда детям 1-7 лет проводили пробу Манту и при подозрении на развитие туберкулезной инфекции ‒ кожную пробу с АТР как в учреждениях общей лечебной сети, так и в условиях противотуберкулезного учреждения. В первые 3 года обследовано 1 864 137, а во вторые 3 года – 2 078 800 детей в возрасте 1-7 лет.Результаты. Среди детей 1-7 лет, которым проводится двухэтапный скрининг (сначала пробой Манту, затем у лиц с положительной реакцией ‒ пробой с АТР), из направленных к фтизиатру только 10-12% подлежали диспансерному наблюдению. Таким образом, с внедрением нового приказа по скринингу туберкулезной инфекции у детей двумя пробами эта доля не изменилась по сравнению с предыдущими годами, когда скрининг проводился только одной пробой Манту. Причина, по которой почти 90% детей из тех, кто был направлен в ПТД, не подлежали диспансерному наблюдению, состоит в следующем: дети, у которых ранее уже был зафиксирован «вираж» туберкулиновых проб, наряду со всеми, опять проходят скрининг пробой Манту, несмотря на то что наблюдаются или наблюдались ранее в противотуберкулезном диспансере по поводу первичного инфицирования.Рекомендации:В настоящее время в диспансерной группировке отсутствует деление VI группы на подгруппы А, Б, В. Почему не считать инфицированием переход отрицательной реакции на пробу Манту в положительную, и при этом увеличение реакции должно составить не менее 6 мм.Поскольку приказ МЗ РФ № 124н позволяет проводить постановку пробы с АТР при подозрении на инфицирование уже в первичном звене здравоохранения, целесообразно направлять к фтизиатру уже прошедших предварительно эту пробу.Ребенок с «виражом» реакций на пробу Манту не должен проходить повторно скрининг с помощью этой пробы, ограничившись пробой с АТР. При появлении впервые положительной реакции на пробу с АТР это следует считать «виражом» данной пробы, ребенку в этом случае следует проводить компьютерную томографию (КТ) и превентивную терапию. Если в последующие годы реакция на АТР увеличится не менее чем на 6 мм после проведенной ранее превентивной терапии, ребенка повторно следует направить на КТ для исключения развития туберкулеза

Туберкулезный перитонит: эпидемиологические и гендерно-возрастные особенности в городе Москве

The objective: to assess the incidence of tuberculous peritonitis, to identify its gender and age characteristics, to describe typical comorbidities preceding the development of peritoneal tuberculosis.Subjects and Methods. The following documents were statistically analyzed: Forms no. 003/u Medical Record of an In-patient Patient for new tuberculous peritonitis patients for 2013–2020, who were treated at Clinic 2 of Moscow Municipal Scientific Practical Center of Tuberculosis Control, Moscow Health Department, and Rosstat Forms No. 8 on Active Tuberculosis Cases for the same period, as well as information from registers of the city tuberculosis monitoring system that has been operating in Moscow since 1996.Results. According to different definitions, the expected incidence of tuberculous peritonitis in the coming years will make from 0.03 to 0.1 per 100,000 population per year in Moscow and 0.1–0.2 per 100,000 in Russia. In Moscow, the main cohort of tuberculous peritonitis patients includes young women after pregnancy and childbirth, who came from other regions of the Russian Federation or neighboring countries. Men develop tuberculous peritonitis 1.6 times less frequently versus women. The most common factors influencing the development of peritoneal tuberculosis in men are drug-induced immunosuppression, dialysis, and diabetes mellitus. HIV infection, unlike other forms of extrapulmonary tuberculosis, is not a major risk factor faced by individuals with tuberculous peritonitis.Цель исследования: оценить заболеваемость туберкулезным перитонитом, выявить его гендерные и возрастные особенности, описать характерный коморбидный фон, предшествующий развитию туберкулеза брюшины.Материалы и методы. Проводился статистический анализ форм No 003/у «Медицинская карта стационарного больного» у впервые выявленных больных туберкулезным перитонитом за период с 2013 по 2020 г., проходивших лечение в клинике 2 «МНПЦ борьбы с туберкулезом ДЗМ», и форм No 8 Росстата «Сведения о заболеваниях активным туберкулезом» за тот же период, а также сведений регистров городской системы мониторинга туберкулеза, действующей в Москве с 1996 года.Результаты. По разным вариантам определения ожидаемая заболеваемость туберкулезным перитонитом в ближайшие годы составит от 0,03 до 0,1 на 100 000 населения в год в городе Москве и 0,1–0,2 на 100 000 в целом по России. Основным контингентом заболевших в Москве туберкулезным перитонитом являются молодые женщины после беременности и родов, приехавшие из других регионов РФ или ближнего зарубежья. Мужчины заболевают туберкулезным перитонитом в 1,6 раза реже женщин. Наиболее частыми факторами, влияющими на возникновение туберкулеза брюшины у мужчин, являются лекарственные иммуносупрессии, диализ и сахарный диабет. ВИЧ-инфекция, в отличие от других форм внелегочного туберкулеза, не является основным фактором риска у лиц с туберкулезным перитонитом