Pulmonary Multidrug-resistant Tuberculosis Research Articles

The course of multidrug-resistant pulmonary tuberculosis in HIV-infected people with COVID-19

Aim. To analyze the course of multidrug-resistant tuberculosis (MDR-TB) in HIV-infected people, depending on the time to COVID-19 diagnosis, using the example of clinical cases from our own observation. Materials and methods. The article presents 3 clinical cases of our own observation of MDR-TB in HIV-infected persons depending on the time to COVID-19 diagnosis in patients, who were treated in the Pulmonary Tuberculosis Department No. 2, clinical base of the Department of Tuberculosis and Pulmonology ZSMU – Municipal non-profit enterprise “Zaporizhzhia Regional Phthisiopulmonology Clinical Medical and Diagnostic Center” of Zaporizhzhia Regional Council. Results. In clinical case 1, in an HIV-infected patient, MDR TB was detected after COVID-19. This clinical case has shown that after mild and treated COVID-19, even on the background of severe immunosuppression, but with AMBT and ART timely prescribed, MDR-TB in the patient had a favorable course with positive dynamics. In clinical case 2, in an HIV-infected patient, MDR-TB was detected concomitantly with COVID-19. The clinical case indicated that the patient received all 3 therapies for MDR-TB, HIV and COVID-19 in full and on time. In contrast to clinical case 1, the patient was diagnosed with a more severe process that required a longer period of treatment, although it was effective. In clinical case 3, an HIV-infected patient with COVID-19 was diagnosed after 5 months of MDR-TB treatment. Against this background, there was culture positivity. But after prescription of appropriate COVID-19 treatment against the background of AMBT and ART, positive dynamics and culture negativity were determined. All 3 patients completed antimycobacterial therapy of MDR-TB with results – recovery. Conclusions. Regardless of the HIV infection duration with underlying severe immunosuppression (<200 CD4 lymphocyte cells) and the time to COVID-19 diagnosis (before, during or after the diagnosis of MDR-TB) on the background of timely therapy of MDR-TB, HIV and COVID-19, positive results can be achieved while saving the lives of patients.

Bedaquiline: A Novel Diarylquinoline for Multidrug-Resistant Pulmonary Tuberculosis.

A new drug Bedaquiline, a diarylquinoline agent has been approved by the Food and Drug Administration for the treatment of pulmonary multidrug-resistant tuberculosis. It has been given approval for use along with the basic regimen with only conditional access through the National Program for tuberculosis in India. The major problem with existing antitubercular drugs used for the treatment of multi-drug resistant tuberculosis is antimicrobial resistance, less efficacy, and poor side effect profile. Bedaquiline might be a solution to these issues. Bedaquiline is a first of its class drug with a unique and specific mechanism of action. It inhibits mycobacterial adenosine triphosphate (ATP) synthase's proton pump. There are many randomized clinical trials and cohort studies that reported a higher culture conversion rate with bedaquiline treatment as compared to the control group. Many meta-analyses and systematic reviews have reported higher culture conversion rate, higher cure rate, and lower mortality rate in patients with drug-resistant tuberculosis treated with a bedaquiline-containing regimen. Here is a detailed drug profile of bedaquiline to help health care workers treat tuberculosis patients.Keywords:

Features of the simultaneous course of pulmonary aspergillosis and tuberculosis on the background of type 1 diabetes mellitus (clinical case)

Aim. To analyze the features of the simultaneous course of pulmonary aspergillosis and multidrug-resistant pulmonary tuberculosis (MDR-TB) on the background of type 1 diabetes mellitus, on the example of a clinical case of our practice. Materials and methods. Clinical case of our practice of simultaneous pulmonary aspergillosis and MDR-TB on the background of type 1 diabetes mellitus in a patient, who was treated in Pulmonary tuberculosis department No. 2 of clinical base of Phthisiatry and Pulmonology Department of Zaporizhzhia State Medical University at Communal Non-Commercial Enterprise of the “Zaporizhzhia Regional Clinical and Diagnostic Center of Phthisiatry and Pulmonology” of Zaporizhzhia Regional Council. Results. In the presented clinical case, the patient had been suffering from diabetes mellitus for 8 years and had been receiving insulin therapy for all these years. One year before the TB disease, he had contact with an index patient, but he categorically refused a course of preventive chemotherapy. Also, the patient did not make a comparison X-ray TCO after 6 months, as a contact person. MDR-TB and aspergilloma of the left lung of the patient were diagnosed simultaneously on the background of severe condition with decompensated form of type 1 diabetes mellitus, severe intoxication syndrome and inflammatory process, massive hemoptysis. Aspergilloma of the left lung was diagnosed using X-ray TCO and cultural examination of bronchial aspirate for Aspergillus, which was not difficult to diagnose. Diagnosis of MDR-TB was also not difficult, because the patient had MBT, which contributed to the timely and correct appointment of antimycobacterial therapy. Surgery for aspergilloma of the left lung was contraindicated, as the type 1 diabetes was in decompensation. Persistent hyperglycemia remained, despite the fact of antifungal therapy and constant correction of insulin therapy prescribed for the patient. Endocarditis quickly developed in the patient, which was the reason of patient’s death. Conclusions. The decompensated form of type 1 diabetes mellitus caused persistent hyperglycemia, which was the reason of immune disorders and this made the patient’s body susceptible to bacterial (MDR-TB) and fungal (aspergillosis) infections, which led to the development of the complication of endocarditis and death. A big mistake in his case, was a categorical refusal by the patient to receive a course of preventive chemotherapy, as a contact person with an index patient. In view of this, in the presence of type 1 diabetes, the patient should have not neglected it. And as a result, the patient had a MDR-TB, one year after. At the same time, the patient did not make a comparison X-ray TCO, after 6 months, as a contact person, which was a possible reason for the missing of early diagnosis of pulmonary aspergilloma. That’s why, a correct treatment of type 1 diabetes mellitus and timely preventive radiological examination of the thoracic cavity organs are especially important, as the diabetes mellitus is the most common premorbid background for TB and aspergillosis.

Endobronchial Valve Treatment of Tuberculous Cavities in Patients with Multidrug-Resistant Pulmonary Tuberculosis: A Randomized Clinical Study.

Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity.

Immune Regulatory Effect of Osteopontin Gene Therapy in a Murine Model of Multidrug Resistant Pulmonary Tuberculosis.

Tuberculosis (TB) has been for many years a major public health problem since treatment is long and sometimes ineffective favoring the increase of multidrug-resistant mycobacteria (MDR-TB). Gene therapy is a novel and effective tool to regulate immune responses. In this study we evaluated the therapeutic effect of an adenoviral vector codifying osteopontin (AdOPN), a molecule known for their roles to favor Th1 and Th17 type-cytokine expression which are crucial in TB containment. A single dose of AdOPN administration in BALB/c mice suffering late progressive pulmonary MDR-TB produced significant lower bacterial load and pneumonia, due to higher expression of IFN-γ, IL-12, and IL-17 in coexistence with increase of granulomas in number and size, resulting in higher survival, in contrast with mice treated with the control adenovirus that codify the green fluorescent protein (AdGFP). Combined therapy of AdOPN with a regimen of second line antibiotics produced a better control of bacterial load in lung during the first days of treatment, suggesting that AdOPN can shorten chemotherapy. Taken together, gene therapy with AdOPN leads to higher immune responses against TB infection, resulting in a new potential treatment against pulmonary TB that can co-adjuvant chemotherapy.

Randomised trial to evaluate the effectiveness and safety of varying doses of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant or treatment intolerant/non-responsive multidrug-resistant pulmonary tuberculosis: study protocol

IntroductionDrug-resistant tuberculosis (DR-TB) is a global public health problem. Patients suffer for months if undiagnosed or treated inadequately, transmitting DR-TB in the community before succumbing to the disease. Early diagnosis,...

Bedaquiline, Delamanid, Linezolid and Clofazimine for Treatment of Pre-extensively Drug-Resistant Tuberculosis.

Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with Bedaquiline and Delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). We prospectively determined the effectiveness and safety of combining two new drugs with two repurposed drugs - Bedaquiline, Delamanid, Linezolid, and Clofazimine for 24-36 weeks in adults with pulmonary MDR-TBFQ+ or/and MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as two consecutive negative cultures taken four weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during treatment period. Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: four deaths, seven treatment changes, two bacteriological failures, and one withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500msec. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. After 24-36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully.

Discovery and preclinical evaluations of JBD0131, a novel nitrodihydro-imidazooxazole anti-tuberculosis agent

Multidrug-resistant pulmonary tuberculosis (MDR-TB) is a major health problem worldwide. The treatment for MDR-TB requires medications for a long duration (up to 20–24 months) with second-line drugs resulting in unfavorable outcomes. Nitroimidazoles are promising antimycobacterial agents known to inhibit both aerobic and anaerobic mycobacterial activity. Delamanid and pretomanid are two nitroimidazoles approved by the regulatory agencies for MDR-TB treatment. However, both agents possess unsatisfactory absorption and QTc prolongation. In our search for a safer nitroimidazole, we discovered JBD0131 (2). It exhibited excellent anti-mycobacterial activity against M. tuberculosis H37Rv in vitro and in vivo, improved PK and absorption, reduced QT prolongation potential of delamanid. JBD0131 is currently in clinical development in China for pulmonary tuberculosis (CTR20202308).

Pattern of Drug-resistance and Treatment Outcome in Multidrug-resistant Pulmonary Tuberculosis

To study the pattern of drug-resistance and treatment outcomes among patients with confirmed multidrug-resistant pulmonary tuberculosis (MDR-PTB). A prospective study was conducted at Rajiv Gandhi Institute of Chest Diseases, Bengaluru, Karnataka, India. Between January 2005 and December 2008, 224 confirmed MDR-PTB cases were studied for various drug-resistance patterns, and their treatment outcomes were analysed until November 2010. Sputum culture and drug sensitivity tests (DST) were carried out at National Tuberculosis Institute, Bengaluru; DST was done for all first-line drugs except pyrazinamide. Of the 224 MDR-PTB patients, 146 (65.2%) were resistant to all first-line drugs, 39 (17.4%) to isoniazid, rifampicin and streptomycin; 19 (8.5%) to isoniazid, rifampicin and ethambutol; and 20 (8.9%) to isoniazid and rifampicin. Among them, 145 (64.7%) patients were cured, 5 (2.2%) had treatment-failure, 10 (4.4%) died, and 64 (28.5%) defaulted. Among 145 cured cases, 100 (69%) were resistant to all first-line drugs, 23 (16%) to isoniazid, rifampicin and streptomycin, 11(8%) to isoniazid, rifampicin and ethambutol, and 11(8%) to isoniazid and rifampicin. The most common pattern observed in this study was resistance to all four first-line drugs followed by resistance to isoniazid, rifampicin and streptomycin. Patients resistant to all first-line drugs had early sputum culture conversion and better cure rate as compared to other resistance patterns.

Pulmonary Disease due to Mycobacterium massiliense

We report a case of a patient suffering from multidrug-resistant pulmonary tuberculosis (MDR-PTB) who later developed an invasive infection of the respiratory tract with a rapidly growing non-tuberculous mycobacteria (NTM), recently identified as Mycobacterium massiliense, closely related to M. abscessus. To the best of our knowledge, this is the first case of M. massiliense infection being reported from India.

TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II–III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis

BackgroundGlobally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9–24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis.MethodsTB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site.DiscussionTB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment.Trial registrationClinicaltrials.gov NCT02589782. Registered on 28 October 2015.

Radiological evidence in clinical prevalence of hematological changes in multidrug resistant pulmonary tuberculosis

Background: Globally, tuberculosis is the leading cause of death. India accounts for the highest proportion of drug resistant tuberculosis among all other countries. Objectives: This study investigated the changes in hematological parameters with respect to radiological evidences in multidrug resistant tuberculosis patients. Materials and Methods: The study enrolled a total of 273 patients with the confirmative diagnosis of multidrug resistant tuberculosis. The radiological evidences were classified into mild, moderate and severe lung involvement. Results: The chest radiographs illustrated tracheal deviation (74), loss of lung volume (35), pleural effusion (25), lobar collapse and fibrotic manifestations. The defensive leucocytes, phagocytic neutrophils, anucleated platelet cells and platelet volume observed an increase with severe lung grading (p&lt;0.0001). Reduced lymphocyte count, mean platelet size observed with the intense lung involvement. Prevalence of normocytic, normochromic anemia, anisocytosis was prominent in these patients. The erythrocyte sedimentation rate observed no significant changes in the categorized radiological grades of lung. Radiological grading reported a weak positive correlation with the hematological parameters. Conclusion: The study noticed the changes in the complete blood count parameters with radiological signs and recommend monitoring of these investigations in determining the progression of the lung involvement in the multidrug resistant pulmonary tuberculosis patients.

Observation of Therapeutic Effect of Beta-quinoline in Patients with Multidrug-resistant Pulmonary Tuberculosis

Observation of Therapeutic Effect of Beta-quinoline in Patients with Multidrug-resistant Pulmonary Tuberculosis

The level of neutrophil elastase as an indication for surgical treatment of pulmonary tuberculosis

The pathogenesis of tuberculosis is complex. The participation of the proteolytic system in it is not in doubt, at least in the decay phase. Clarification of this link in the pathogenesis, in our opinion, will be able to expand the diagnostic capabilities and treatment of pulmonary tuberculosis, including surgery. However, in practice, the state of the proteolytic system and its components in tuberculosis have not been studied, which emphasizes the urgency of the problem.&#x0D; Objective — to study the level of neutrophil elastase (NE) as a leading enzyme of the proteolytic system in patients with pulmonary tuberculosis to expand the diagnostic possibilities in suspected tuberculosis and clarify its features and possible volume and indications for surgery.&#x0D; Materials and methods. Under our clinical observation were, 66 patients with pulmonary tuberculosis were divided into two groups depending on the resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs. The first group consisted of 39 (59.1 %) individuals whose mycobacteria were susceptible to anti-TB medicines. The second group included 27 (40.9 %) patients with multidrug-resistant pulmonary tuberculosis.Results and discussion. In patients with susceptible forms of a specific process, the level of elastase was in the range of 35.2—215.1 nmol/min ⋅ ml and averaged 110.1 nmol/min ⋅ ml. In patients with multidrug-resistant tuberculosis (group II), the elastase level was in the range of 34.6—163.1 nmol/min ⋅ ml, which averaged 78.4 nmol/min ⋅ ml (p &lt; 0.05). The highest level of NE (93.0 nmol/min ⋅ ml) occurred in patients with infiltrative pulmonary tuberculosis. In disseminated pulmonary tuberculosis, the level of NE was 74.5 nmol/min ⋅ ml, which is significantly less (18.5 nmol/min ⋅ ml, or 1.25 times) than in infiltrative tuberculosis. In tuberculoma, the level of elastase was 68.1 nmol/min ⋅ ml. In fibrocavernous pulmonary tuberculosis, the level was not the lowest (30.9 nmol/min ⋅ ml).&#x0D; Conclusions. The level of neutrophil elastase in patients with susceptible pulmonary tuberculosis compared to patients with multidrug-resistant pulmonary tuberculosis was significantly higher (1.4 times). Decreased levels of neutrophil elastase characterize the reduced activity of the proteolytic blood system and may be a sign of chronicization of tuberculosis, which justifies the use of surgical treatment.

Multidrug-resistant Tuberculosis and COVID-19 Coinfection with Diabetes Mellitus in Medan, Indonesia: A Case Report

BACKGROUND: Coronavirus disease 2019 (COVID-19) has distracted the global health system due to significant morbidity and mortality. There are increasing mortality rates related to the existence of comorbidities. Due to immunologic conditions, other infectious diseases, such as multidrug-resistant tuberculosis (MDR-TB), might coinfect with COVID-19. We describe a case of MDR-TB with diabetes mellitus and critical COVID-19 patient with fatal outcome. CASE REPORT: A 60-year-old man was admitted to our hospital with shortness of breath for 2 days. A history of recurrent shortness of breath has had developed for about 7 months. Room air oxygen saturation was at 66%. RT-PCR SARS-CoV-2 nasopharynx swab result was positive. The chest X-ray series result showed destroyed left lung with increasing infiltrate in the lower right lung. The patient was diagnosed with pulmonary MDR-TB based on GeneXpert and LPA (Line Probe Assay) test 6 months prior and also has had history of diabetes mellitus for 7 years. Then, the patient was diagnosed with COVID-19, pulmonary MDR-TB, and diabetes mellitus. MDR-TB regimen, anti-diabetic medication, and management of COVID-19 were carried out. On the 6th day, the patient’s condition worsened to the point, where he needed intubation. The patient eventually passed away. CONCLUSION: The treatment outcome was highly related to the severity of COVID-19 symptoms and complications of comorbidities when patients are admitted to the hospital. The early screening and treatment of COVID-19 are important to prevent deteriorating clinical conditions caused by comorbidities.

Tongue Ulcer as a Manifestation of Secondary HIV-Associated Multidrug-Resistant Tuberculosis

Tuberculosis of the tongue is one of the rare localizations of extrapulmonary tuberculosis. The article presents a clinical case of secondary tuberculous glossitis with concurrent multidrug-resistant pulmonary tuberculosis in a 35-year-old HIV-infected patient. Despite relatively rapid verification of the diagnosis, the clinical situation was difficult due to differential diagnosis with nonspecific lesions, unknown HIV status, and detection of drug resistance of Mycobacterium tuberculosis. This case illustrates the step-by-step diagnosis and treatment of tuberculous ulcers of the tongue and lungs. The comprehensive examination with the use of molecular genetic, bacteriological, histological, and X-ray diagnostic tools contributed to the timely prescription of the adequate anti-tuberculosis therapy regimen.

Optimizing cardio, hepato and phospholipidosis toxicity of the Bedaquiline by chemoinformatics and molecular modelling approach

ABSTRACT The FDA granted expedited approval for Johnson and Johnson’s Bedaquiline to treat pulmonary multidrug resistant tuberculosis on 28 December 2012 which is more common in China, Russian Federation and India. Bedaquiline is the first anti-tubercular drug approved by the FDA in the last 40 years, and it has become a cynosure in the circles of synthetic chemists researching new anti-tubercular drugs. Bedaquiline’s highly lipophilic nature raises major concerns like suppression of the hERG gene, hepatotoxicity, and phospholipidosis despite its potential antitubercular profile. To address these toxicity concerns, in the present work, we have employed the structural optimization of Bedaquiline using the ADMETopt web server, which optimizes lead with scaffold hopping and ADMET screening. The ADMETopt web server yielded the 476 structures through optimization of three sites in Bedaquiline. Further, we have validated the optimized structures for their activity by performing molecular docking and molecular dynamics (MD) simulations against the mycobacterial ATP synthase enzyme and density functional theory (DFT) study further provides insight into the reactivity of the compounds. After screening and analysis, compound #449 was observed to be the most promising mycobacterial ATP synthase inhibitor with minimal cardiotoxicity, hepatotoxicity and phospholipidosis.

Трудности диагностики центральной эндофитной опухоли легкого, возникшей на фоне туберкулеза

Актуальность. Проблема раннего выявления рака легких, возникшего на фоне специфического процесса, является чрезвычайно актуальной и сложной. Целью работы стало изучение роли рентгенологических и бронхоскопических методов исследования в диагностике центральной эндофитной опухоли легкого у больных туберкулезом легких. Материалы и методы. Анализ литературы, клинический случай. Результаты. Такие рентгенологические методы исследования, как обзорная рентгенограмма, информативны на поздних стадиях развития эндофитной опухоли легкого. Самым информативным методом на ранних стадиях является многосрезовое спиральное сканирование, особенностью которого является изотропность изображений (равное качество во всех плоскостях). Приведен клинический случай развития центральной эндофитной опухоли легкого у больного мультирезистентным туберкулезом легких. Выводы. Необходимо сочетание таких инструментальных методов исследования, как рентгенологические и фибробронхоскопия (с исследованием аспирата из бронхов), что дает в совокупности значительный объем информации о развитии у больного туберкулезом центральной эндофитной опухоли легкого.

Особливості цитокінової регуляції при мультирезистентному туберкульозі залежно від ступеня ендогенної інтоксикації

Актуальність. Туберкульоз (ТБ) відноситься до інтерлейкінзалежних імунодефіцитів із вираженими змінами в цитокіновій системі. Незважаючи на значні успіхи в досягненні контролю над ТБ, залишається невизначеною роль окремих цитокінів у формуванні резистентних його форм, не вирішені питання ідентифікації інтегральних маркерів прогресування патологічного процесу при мультирезистентному туберкульозі легень (МРТБ), а також відсутнє прогностичне визначення їх ролі в забезпеченні ефективності стандартних програм протитуберкульозної хіміотерапії. У зв’язку із вищезазначеним закономірно виникає необхідність аналізу показників окремих цитокінів у сироватці крові пацієнтів із МРТБ залежно від профілю резистентності, що може відображати ступінь вираженості місцевого та системного характеру специфічного запалення, особливості імуноцитокінової регуляції з метою удосконалення програми лікування. ТБ відноситься до захворювань, які супроводжуються ендогенною інтоксикацією, тобто накопиченням в організмі кінцевих та проміжних продуктів метаболізму при порушеному обміні внаслідок запальної реакції. Шляхами формування ендогенної інтоксикації при ТБ є цитотоксична гіпоксія, порушення внутрішньоклітинного гомеостазу, масивне утворення та подальша резорбція продуктів тканинного розпаду, імуноцитокіновий та гормональний дисбаланс тощо. Мета дослідження — оцінити показники ендогенної інтоксикації, встановити особливості цитокінової регуляції у хворих на мультирезистетний туберкульоз легень залежно від профілю резистентності мікобактерій та визначити їх роль у формуванні системної запальної реакції. Матеріали та методи. Об’єктом дослідження стали 116 пацієнтів із діагнозом вперше діагностованого туберкульозу легень із збереженою чутливістю до антимікобактеріальних препаратів; із МРТБ із діагностованою стійкістю як мінімум до двох препаратів I ряду; хворі на туберкульоз із розширеною резистентністю. Використано клінічні, рентгенологічні, біохімічні, мікроскопічні, мікробіологічні, імуноферментні та статистичні методи дослідження. Результати. Проведений кореляційний аналіз за Пірсоном між про- і протизапальними цитокінами показав, що у хворих на МРТБ коефіцієнт кореляції негативний, слабкої сили між показниками інтерлейкіну (ІЛ)-6 та ІЛ-10, між ІЛ-18 та ІЛ-10 (–0,22, р &lt; 0,001; –0,16, р &lt; 0,001). Продукція ІЛ-6 та ІЛ-10 у групах хворих на ТБ незалежно від резистентності зростає у відповідь на підвищення синтезу ендотоксинів мікобактерій туберкульозу, наростання ендогенної інтоксикації та цитотоксичної гіпоксії створює передумови для розвитку їх резистентності. Дисбаланс співвідношення ІЛ-18 та ІЛ-10 у цих хворих характеризує збільшення ступеня тяжкості стану пацієнта, поширеність запального процесу в легенях і формування резистентності; відзначається істотна перевага лімфоцитів Тх 2-го типу (гуморального), що вказує на розвиток дефекту клітинно-опосередкованого імунного захисту та перевагу неефективної протизапальної імунної активації. Висновки. Комплексна оцінка показників інтегральних індексів ендогенної інтоксикації та рівня окремих про- та протизапальних цитокінів у плазмі крові хворих на МРТБ свідчить про помірно виражену ендогенну інтоксикацію, виснажені клітинні ланки імунної реактивності за рахунок формування умов розвитку резистентності мікобактерій туберкульозу із подальшим наростанням цитотоксичної гіпоксії та активації синдрому системної запальної відповіді. Аналіз вмісту ІЛ-6, ІЛ-10 і ІЛ-18 у плазмі крові хворих із мультирезистентністю довів, що їх рівень залежить від характеру резистентності мікобактерій туберкульозу.

Determinants, risk factors and spatial analysis of multi-drug resistant pulmonary tuberculosis in Jodhpur, India

This study was planned to estimate the proportion of confirmed multi-drug resistance pulmonary tuberculosis (TB) cases out of the presumptive cases referred to DTC (District Tuberculosis Center) Jodhpur for diagnosis; to identify clinical and socio-demographic risk factors associated with the multidrug-resistant pulmonary TB and to assess the spatial distribution to find out clustering and pattern in the distribution of pulmonary TB with the help of Geographic Information System (GIS). In the Jodhpur district, 150 confirmed pulmonary multi-drug resistant tuberculosis (MDR-TB) cases, diagnosed by probe-based molecular drug susceptibility testing method and categorized as MDR in DTC's register (District Tuberculosis Center), were taken. Simultaneously, 300 control of confirmed non-MDR or drug-sensitive pulmonary TB patients were taken. Statistical analysis was done with logistic regression. In addition, for spatial analysis, secondary data from 2013-17 was analyzed using Global Moran's I and Getis and Ordi (Gi*) statistics. In 2012-18, a total of 12563 CBNAAT (Cartridge-based nucleic acid amplification test) were performed. 2898 (23%) showed M. TB positive but rifampicin sensitive, and 590 (4.7%) showed rifampicin resistant. Independent risk factors for MDR TB were ≤60 years age (AOR 3.0, CI 1.3-7.1); male gender (AOR 3.4, CI 1.8-6.7); overcrowding (AOR 1.6, CI 1.0-2.7); using chulha (smoke appliance) for cooking (AOR 2.5, CI 1.2-4.9), past TB treatment (AOR 5.7, CI 2.9-11.3) and past contact with MDR patient (AOR 10.7, CI 3.7-31.2). All four urban TUs (Tuberculosis Units) had the highest proportion of drug-resistant pulmonary TB. There was no statistically significant clustering, and the pattern of cases was primarily random. Most of the hotspots generated were present near the administrative boundaries of TUs, and the new ones mostly appeared in the area near the previous hotspots. A random pattern seen in cluster analysis supports the universal drug testing policy of India. Hotspot analysis helps cross administrative border initiatives with targeted active case finding and proper follow-up.