"CTRI Bulletin"
#2,(3),2018.
CTRI BULLETIN №2 (3) 2018
Journal Information: Read
Chief Editor: Ergeshov A.E.
Year of foundation: 2017
ISSN (Print): Browse
Publisher site: http://critub.ru
http://tb-bulletin.ru
CONTENT
| 1) | Nontuberculous mycobacteria, mycobacteriosis Litvinov V.I. | 5 | READ MORE | |
| 2) | The central tb research institute and the international integration of tb control Ergeshov A.E., Demikhova O.V. | 21 | READ MORE | |
| 3) | The influence of rifampicin and its encapsulated form on functional activity of the multidrug resistance protein pgp in human myeloid cells Erokhina M.V., Lepekha L.N., Rybalkina E.Yu., Pavlova E.Yu., Onishchenko G.E. | 28 | READ MORE | |
| 4) | Effectiveness of tb control in an economically developing region Lapshina I.S., Myakisheva T.V. | 40 | READ MORE | |
| 5) | The lethality among new tb cases in kishinev in different time periods Popa V.F., Ustiyan A.I., Yavorsky K.M., Malik A.M, Nigulyanu A.V., Kulchitskaya S.S. | 47 | READ MORE | |
| 6) | Some aspects of drug resistant tb in the republic of moldova Sain D.O., Aleksandru S.M., Donika A.F., Khaidarly I.N., Kula E.N., Ryvnyak L.P. | 55 | READ MORE | |
| 7) | Gender differences in the distribution of different genotypes of mycobacterium tuberculosis among male and female patients with tb in saratovskaya oblast Salina T.Yu., Morozova T.I. | 61 | READ MORE | |
| 8) | The model of the epidemiological situation of tb with extensive drug resistance in the regions of russia Sterlikov S.A., Rusakova L.I. | 66 | READ MORE | |
| 9) | Alterations in the genes pnca and rpsa and pyrazinamidase activity in m. Tuberculosis strains with phenotypic sensitivity and resistance to pyrazinamide Andreevskaya S.N., Andrievskaya I.Yu., Smirnova T.G., Ustinova V.V., Alvarez Figeroa M.V., Maslov D.A., Larionova E.E., Chernousova L.N. | 74 | READ MORE | |
Nontuberculous mycobacteria, mycobacteriosis
| Article 1. | Page 5. |
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| ARTICLE TITLE: | Nontuberculous mycobacteria, mycobacteriosis |
| AUTORS: | Litvinov V.I. Moscow Research and Clinical Center for Tuberculosis Control of Moscow Government Health Department, Moscow, Russia |
| DESCRIPTION OF ARTICLE: | Submitted as of 25.12.2017 The review is devoted to the main aspects of the investigation of nontuberculous mycobacteria (NTM) and the pathology caused by them – mycobacteriosis: NTM in the environment, routes of infection, pathology in humans and animals, mechanisms of host-pathogen interaction, mycobacteriosis treatment and drug susceptibility of NTM. The conclusion contains the conceptual issues about the state of the topic and its perspectives. |
| KEYWORDS: | non-tuberculous mycobacteria, mycobacteriosis. |
| FOR CORRESPONDENCE: | Moscow Research and Clinical Center for Tuberculosis Control of Moscow Government Health Department 10, Stromynka St., 107014, Moscow, Russia Vitaly I. Litvinov, Principal Researcher, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences Tel.: +7 (499) 268 04 15 E-mail: mnpcbtlv@yandex.ru |
The central tb research institute and the international integration of tb control
| Article 2. | Page 21. |
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| ARTICLE TITLE: | The central tb research institute and the international integration of tb control |
| AUTORS: | Ergeshov A.E., Demikhova O.V. Central TB Research Institute, Moscow, Russia |
| DESCRIPTION OF ARTICLE: | Submitted as of 06.10.2017 In order to familiarize the audience with the input made by the Central TB Research Institute (CTRI) into the international integration of TB control, we provide a historical overview of different aspects of the international collaboration with CTRI, inputs made by its directors and leading researchers into creation and development of international projects on TB control, interrelations with international agencies, foreign research institutes and recognized TB experts, from the foundation of the institute in 1921 to the present. |
| KEYWORDS: | TB, international integration, collaboration. |
| FOR CORRESPONDENCE: | Central TB Research Institute 2, Yauzskaya alley, 107564, Moscow Atadzhan E. Ergeshov, Director, PHD, Professor Phone: +7 (499) 785-90-19 E-mail: cniit@ctri.ru |
The influence of rifampicin and its encapsulated form on functional activity of the multidrug resistance protein pgp in human myeloid cells
| Article 3. | Page 28. |
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| ARTICLE TITLE: | The influence of rifampicin and its encapsulated form on functional activity of the multidrug resistance protein pgp in human myeloid cells |
| AUTORS: | Erokhina M.V.1,2, Lepekha L.N.1, Rybalkina E.Yu.1,3, Pavlova E.Yu.2, Onishchenko G.E.2 1Central TB Research Institute, Moscow, Russia 2M.V. Lomonosov Moscow State University, Moscow, Russia 3N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia |
| DESCRIPTION OF ARTICLE: | Submitted as of 11.01.2018 P-glycoprotein (Pgp) is the most universal of all the “multidrug resistance proteins” of human cells. It is known that many drugs are the substrates for Pgp, including one of the main TB drugs, rifampicin. One of the nanotechnology advances is the development of drug encapsulation methods; encapsulation of Pgp substrates enables to avoid drug resistance development. The encapsulated form of rifampicin is based on the lactic acid polymer nanoparticles. Unlike conventional rifampicin, which penetrates human cells through diffusion and accumulates in cytosol, encapsulated rifampicin enters cells through phagocytosis, and then concentrates in phagosomes and phagolysosomes. The aim of the study was to compare the influence of conventional rifampicin and its encapsulated form on functional activity of Pgp in human myeloid cells with high expression of the MDR1 gene and its protein Pgp. We used reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence detection, flow cytometry and MTT assay to characterize human myeloid cells К562 (without expression of MDR1 and Pgp) and К562/i-S9 (with high expression of MDR1 and Pgp). We used these models to study the influence of rifampicin and its encapsulated form on functional activity of Pgp. The experimental concentrations of rifampicin were 10 and 25 μg/ml: these drug concentrations induced insignificant decrease in rhodamine 123 discharge in the K562/i-S9 cells, which witnessed its competitive binding with Pgp. Encapsulated rifampicin (100 μg/ml, rifampicin share ̴ 8%) blocked rhodamine 123 discharge by K562/i-S9, while nanoparticles without drug produced no effect on the stain discharge, i.e. phagocytosis activation (disturbed stability of plasma membrane) did not result in inactivation of Pgp functionality. The obtained data may indicate that a sufficiently high concentration of rifampicin arises in cell cytoplasm after polymer degradation, and rifampicin not only concentrates in phagolysosomes, but also diffuses into cytosol, where it binds with Pgp. Encapsulated rifampicin does not exclude accumulation of free rifampicin in cytosol and its interaction with the main multidrug resistance protein Pgp. The above raises a question about further improvement of the encapsulated form of rifampicin. |
| KEYWORDS: | drug resistance, Pgp, rifampicin, lactic acid polymer, human cells with hyperexpression of the MDR1 gene. |
| FOR CORRESPONDENCE: | Central TB Research Institute 2, Yauzskaya alley, 107564, Moscow, Russia M.V. Lomonosov Moscow State University 1, building 12, Leninskie Gory, 119991, Moscow, Russia Maria V. Erokhina, Senior Researcher, Department of Pathomorphology, Cell Biology and Biochemistry, Central TB Research Institute, Docent, Cell Biology and Histology Department, Biology Faculty, M.V. Lomonosov Moscow State University, Candidate of Biological Sciences Tel.: +7 (499) 785-91-79 E-mail: masha.erokhina@gmail.com |
Effectiveness of tb control in an economically developing region
| Article 4. | Page 40. |
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| ARTICLE TITLE: | Effectiveness of tb control in an economically developing region |
| AUTORS: | Lapshina I.S., Myakisheva T.V. Smolensk State Medical University, Smolensk, Russia |
| DESCRIPTION OF ARTICLE: | Submitted as of 01.02.2018 The authors analyzed effectiveness of TB control in an economically developing region, namely Kaluzhskaya oblast. They studied the main indicators of treatment effectiveness: clinical cure and sputum conversion. They also carried out a statistical comparison of the above indicators in the areas divided in two groups by their socioeconomic level. Based on the analysis, the authors concluded that clinical cure of TB and sputum conversion did not depend on the economic development of the region. Then, the authors analyzed the outcomes of the intensive treatment phase in two cohorts of patients (effective treatment, treatment failure, died from TB, died from reasons other than TB, transferred out, treatment interruption, reregistration as MDR TB) and the results of a two-year follow-up (clinical cure, died during the follow-up, died from reasons other than TB, treatment continuation, treatment interruption, relapse). The authors revealed significant changes in the intensive treatment outcomes and the effectiveness of dispensary follow-up after the reformation of TB services. In the cohort registered in 2014 more patients were transferred out during the treatment (χ2=4.25, р=0.039) or reregistered as MDR TB (χ2=4.18, р=0.041) versus the cohort registered in 2010. The analysis of the two-year follow-up revealed that the patients registered in 2014 were oftener transferred to group III (χ2=8.78, р=0.003) versus those registered in 2010; and there were more deaths from reasons other than TB in the cohort of 2010 (χ2=9.14, р=0.003). |
| KEYWORDS: | clinical cure, sputum conversion, TB control, treatment outcomes. |
| FOR CORRESPONDENCE: | State Regional Clinical Hospital of the Kaluga Region “Regional TB Hospital” 70, Lugovaya street, 248008, Kaluga, Russia Irina S. Lapshina, phthisiatrician, Сorrespondence Postgraduate, Smolensk State Medical University Tel .: +8 (965) 703-87-63 Е-mail: geparin.86@yandex.ru |
The lethality among new tb cases in kishinev in different time periods
| Article 5. | Page 47. |
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| ARTICLE TITLE: | The lethality among new tb cases in kishinev in different time periods |
| AUTORS: | Popa V.F.1, Ustiyan A.I.2, Yavorsky K.M.3, Malik A.M.2, Nigulyanu A.V.2, Kulchitskaya S.S.2 1Municipal Clinical Phthisiopulmonology Hospital, Kishinev, Moldova 2Nicolae Testemițanu State University of Medicine and Pharmacy, Kishinev, Moldova 3Kirill Draganyuk Phthisiopulmonology Institute, Kishinev, Moldova |
| DESCRIPTION OF ARTICLE: | Submitted as of 01.11.2017 The aim: to study lethality from progressive TB among new TB cases, who died in hospital in different time periods. Materials and methods. We carried out a retrospective analysis of deaths from TB in Kishinev in three time periods conditioned by the epidemiological situation: period 1 – from 2001 through 2003, period 2 – from 2007 through 2009, and period 3 – from 2013 through 2015. In hospital progressive TB caused deaths in 64 (31.7%) cases in period 1, 77 (72%) cases in period 2, and 36 (60%) cases in period 3. Results. Exposure to TB was established in half of the cases. In all the periods TB was mainly detected at patients’ referrals. The most cases diagnosed with infiltrative TB had caseous pneumonia. In period 3 we observed the growing number of cases with generalized TB and emergence of extensively drug resistant TB. Among concomitant diseases most common were chronic alcoholism, HIV-infection, chronic hepatitis, anaemia. Two thirds of the cases died during the first month after hospitalization. |
| KEYWORDS: | lethality, progressive TB, new TB case. |
| FOR CORRESPONDENCE: | Municipal Clinical Phthisiopulmonology Hospital 147, Grenoblya, 2025, Kishinev, Moldova Vasily F. Popa, Deputy Director for Treatment Tel.: +373 69-572-062 E-mail: popa.vasile@mail.ru |
Some aspects of drug resistant tb in the republic of moldova
| Article 6. | Page 55. |
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| ARTICLE TITLE: | Some aspects of drug resistant tb in the republic of moldova |
| AUTORS: | Sain D.O., Aleksandru S.M., Donika A.F., Khaidarly I.N., Kula E.N., Ryvnyak L.P. Kirill Draganyuk Phthisiopulmonology Institute, Kishinev, Moldova |
| DESCRIPTION OF ARTICLE: | Submitted as of 01.11.2017 The phenomenon of drug resistance poses a serious problem to TB control. The high frequency of M. tuberculosis resistant strains is bserved in both high- and low-burden areas. It is necessary to coordinate measures aimed to provide effective infection control, especially control of TB with multi/extensive/total drug resistance, which has placed a tremendous burden on the country. The preliminary analysis of 76 patients with extensive drug resistance (XDR) demonstrated the necessity of a tailored scientific research. The research would help to understand, analyze and estimate the scale of the problem. It would evaluate the main causes of XDR development and analyze the populations with primary and secondary extensive/total drug resistance. The research would also include genetic studies of Mycobacterium tuberculosis. |
| KEYWORDS: | epidemiology, TB, treatment, drug resistance. |
| FOR CORRESPONDENCE: | Kirill Draganyuk Phthisiopulmonology Institute 13, K. Vyrnav St., 2025, Kishineu, Moldova Dmitry O. Sain, Head of Department Tel.: +373 22 57-23-52 E-mail: dmitriisain@rambler.ru |
Gender differences in the distribution of different genotypes of mycobacterium tuberculosis among male and female patients with tb in saratovskaya oblast
| Article 7. | Page 61. |
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| ARTICLE TITLE: | Gender differences in the distribution of different genotypes of mycobacterium tuberculosis among male and female patients with tb in saratovskaya oblast |
| AUTORS: | Salina T.Yu., Morozova T.I. Saratov State Medical University named after V.I. Rasumovsky, Saratov, Russia |
| DESCRIPTION OF ARTICLE: | Submitted as of 20.02.2018 The aim: a comparative study of genetic polymorphism of Mycobacterium tuberculosis (MTB) circulating among men and women ill with TB in Saratov oblast. We studied 307 patients with newly-detected pulmonary TB aged 22-62. The patients were divided in two groups by gender. Group 1 consisted of 49 women, group 2 – 258 men. The both groups were comparable by clinical forms, severity of the disease, destruction in the lung tissue and bacterioexcretion. We performed MTB spoligotyping in sputum samples by hybridization on a biological microchip using the Spoligo-biochip reagent kit (JSC “BIOCHIP-IMB”, Moscow). The results were processed using the Chipdetector-01 hardware/software complex and a special programme ImaGeWare®, which allowed comparing a spoligotype and a spoligotyping profile from the SpolDB4 database (http//www.pasteur-guadeloupe.fr/tb/bd_myco.html). We established that 11 MTB families (Beijing, Beijing-like, Haarlem+Ural, LAM, T, Microti, Rus 1, EAI, Canetti, Cas, Manu) circulated among men (group 2). In our study we combined Haarlem and Ural groups as two relative groups. In sputum samples obtained from women (group 1) we detected 6 MTB families (Beijing, Beijing-like, Haarlem+Ural, LAM, T, Microti). The prevailing genotypes in group 1 were Beijing – 15 (30.6%), Beijing-like –13 (26.5%) Haarlem+Ural – 14 (28.6%); in group 2 prevailed Haarlem+Ural – 53 (20.5%), T – 68 (26.4%), Beijing – 46 (17.8%), and Beijing-like – 44 (17.1%). The Beijing strain was reliably more common in group 1 vs. group 2: 15 (30.6%) vs. 46 (17.8%) respectively, p=0.0381. In group 2 the T strain was significantly more common than in group 1: 68 (26.4%) vs. 3 (6.1%), p=0.0024. There was no reliable difference in the spoligotypes distribution within genetic families among men and women. |
| KEYWORDS: | spoligotyping, Mycobacterium tuberculosis genotypes, men, women. |
| FOR CORRESPONDENCE: | Saratov State Medical University named after V.I. Rasumovsky 22, Volskaya St., 410056, Saratov, Russia Tatiana Yu. Salina, Professor of the Department of Phthisiology of IDPO, Docent, Doctor of Medical Sciences Теl.: +8 (917) 209-68-51 E-mail: SalinaTU@rambler.ru |
The model of the epidemiological situation of tb with extensive drug resistance in the regions of russia
| Article 8. | Page 66. |
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| ARTICLE TITLE: | The model of the epidemiological situation of tb with extensive drug resistance in the regions of russia |
| AUTORS: | Sterlikov S.A.1, Rusakova L.I.2 1Central Research Institute of Organization and Informatization of Health, Moscow, Russia 2Central TB Research Institute, Moscow, Russia |
| DESCRIPTION OF ARTICLE: | Submitted as of 30.01.2018 Background. The importance of modelling the epidemiological situation of extensively drug resistant tuberculosis (XDR-TB) is preconditioned by high mortality, lack of effective measures for its prevention and treatment, and lack of statistical data describing the prevalence of the disease. Methods. The investigation is based on both the official statistics of the Russian Federation and the frequency of XDR TB detection in cases with multidrug-resistant tuberculosis (MDR TB), new TB cases, relapses and previously treated cases. The model is based on the number of patients with pulmonary MDR TB, coverage of sputum positive patients with pulmonary TB by drug susceptibility testing, including extrapulmonary sputum positive TB, testing of MDR-TB patients for XDR, the proportion of XDR TB patients among those with MDR TB. Results. The estimated number of MDR TB cases by the end of 2016 was 43,025, which exceeded by 5,099 the notification number of cases with pulmonary MDR TB by the end of 2016. The coverage of MDR TB cases by tests for XDR was approaching 100% in the most regions of Russia, but remained low in the following republics: Kalmykia, Karelia, Kabardino-Balkaria. The median proportion of XDR TB cases among MDR TB cases was 12.3%. Discussion. The drawbacks of the model include recording of data on TB provided by only TB facilities of the Russian Ministry of Health, which do not cover cases observed by other departments. The confounding factors may include: uneven quality of culture diagnostics and drug susceptibility testing for the first- and second-line TB drugs, incomplete coverage of TB patients with culture diagnostics. Conclusion. The proposed model let us give an approximate description of the XDR TB prevalence. The estimated number of sputum positive XDR TB cases by the end of 2016 ranged from 5 to 8,5 thousand (the best prognosis is 6,500), and the estimated prevalence ranged from 3.3 to 9 per 100 000 population. Despite the low spread of XDR TB, in 10 regions of the Russian Federation there were more than 100 XDR TB patients, which allowed speaking about the high financial burden of this disease. |
| KEYWORDS: | MDR TB, XDR TB, multidrug-resistant and extensively drug-resistant tuberculosis, epidemiology of tuberculosis, prevalence of extensively drug-resistant tuberculosis, modelling of tuberculosis epidemiology. |
| FOR CORRESPONDENCE: | Central Research Institute of Organization and Informatization of Health 11, Dobrolyubova St., 127254, Moscow, Russia Sergey A. Sterlikov, Deputy Head, TB Monitoring Center for Program Monitoring, Doctor of Medical Sciences Tel.: +7 (925) 507-82-21 E-mail: sterlikov@list.ru |
Alterations in the genes pnca and rpsa and pyrazinamidase activity in m. Tuberculosis strains with phenotypic sensitivity and resistance to pyrazinamide
| Article 9. | Page 74. |
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| ARTICLE TITLE: | Alterations in the genes pnca and rpsa and pyrazinamidase activity in m. Tuberculosis strains with phenotypic sensitivity and resistance to pyrazinamide |
| AUTORS: | Andreevskaya S.N.1, Andrievskaya I.Yu.1, Smirnova T.G.1, Ustinova V.V.1, Alvarez Figeroa M.V.2, Maslov D.A.3, Larionova E.E.1, Chernousova L.N.1 1Central TB Research Institute, Moscow, Russia 2Central Research Institute of Epidemiology, Moscow, Russia 3N.I. Vavilov Institute of General Genetics, Russian Academy of Science, Moscow, Russia |
| DESCRIPTION OF ARTICLE: | Submitted as of 25.01.2018 In order to detect the mechanisms of development of pyrazinamide resistance in M. tuberculosis, we carried out a complex analysis involving simultaneous determination of phenotypic sensitivity to pyrazinamide, pyrazinamidase activity, structures of genes encoding pyrazinamidase, pyrazinamide target and MIC. We demonstrated the key role of impaired pyrazinamidase activity due to mutations in the pncA gene. We described a wide spectrum of mutations in this gene and detected those, which preconditioned the borderline resistance to pyrazinamide. Mutations in the rpsA gene encoding the drug target did not affect the development of pyrazinamide resistance. |
| FOR CORRESPONDENCE: | Central TB Research Institute 2, Yauzskaya alley, 107564, Moscow, Russia Sophya N. Andreevskaya, Candidate of Medical Sciences, Senior Researcher, Microbiology Department Tel.: +7 (499) 785- 90-91 E-mail: andsofia@mail.ru |