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THE DYNAMICS OF THE PREVALENCE OF M. TUBERCULOSIS RESISTANCE TO ANTIBIOTICS IN THE EAST OF THE RUSSIAN FEDERATION IN KHABAROVSKI KRAI
Dyachenko O.
Tuberculosis hospital, Khabarovsk, phthisiologist, Far Eastern State Medical University, candidate of medical sciences, associate professor Kovaleva E.
Tuberculosis hospital, Khabarovsk, phthisiologist, Far Eastern State Medical University, assistant
Gorokhovsky V.
Far Eastern State Medical University, head of department
Dyachenko S.
Far Eastern State Medical University, professor
Abstract
In the structure of primary drug resistance in Khabarovski Krai in 2017 polyresistance was discovered in 18.1% of bacteriostatic agents, multidrug resistance (MDR) in 68.1% of bacteriostatic agents. In the structure of MDR most common was resistance to a combination of three main-line anti-TB drugs: streptomycin, isoniazid, and rifampicin. Wide drug resistance was discovered in 0.9%. According to the prognostic model, in 2020 in Khabarovski Krai we expect the prevalence of patients with MDR MBT in the structure of primary resistance, which will make a negative impact on the effectiveness of treatment and give prerequisites for the progression of the disease with a mutation of the MBT strain to wide drug resistance. Estimation of drug resistance is necessary to estimate the spreading of m. Tuberculosis with MDR, to develop additional anti-epidemic measures at the regional level, to substantiate the choice of optimal chemoprophylactic treatment regimens for people at risk.
Keywords: tuberculosis, M. Tuberculosis, multidrug resistance, wide drug resistance, Khabarovski Krai.
Introduction
The problem spreading of tuberculosis (TB) with multidrug-resistant (MDR) reached international recognition only in the early 1990s, when small epidemics of MDR-TB were detected in patients infected with human immunodeficiency virus (HIV) in the United States and Europe (in hospitals, nursing homes, shelters for the homeless). Regarding the above, in 1994, due to initiative of WHO, the Global Project on Antituberculosis Drug Resistance Surveillance (The WHO / UNION Global Project on ant-tuberculosis drug resistance surveillance) was launched. This made it possible to reasonably compare the situation with the spread of drug resistance of TB in different countries and regions. MDR tuberculosis, according to the WHO definition, is drug resistance to at least two of the most effective drugs - rifampicin (R) and isoniazid (H) (with possible resistance to other anti-TB drugs).
M. Tuberculosis wide drug resistance is the most complicated form of drug resistance, which is characterized by resistance to at least four classes of antibacterial drugs of the main and back up therapy lines (to
isoniazid, rifampicin, any fluoroquinolone and at least one of the three injectable drugs - kanamycin, amika-cin, capreomycin).
According to WHO estimations, in 2016 490,000 people worldwide had MDR-TB. 47% of all causes were in India, China and the Russian Federation. In total, almost half of all MDR tuberculosis patients live in these three countries (45% with MDR tuberculosis patients of all tuberculosis patients according to WHO estimations). At the same time, an even more threating trend is that the wide drug resistance occurred in 6.2% of these patients.
Both multidrug and wide drug resistance of M. Tuberculosis have a negative impact on the effectiveness of anti-tuberculosis therapy and increase mortality. According to the WHO, the spread of tuberculosis with MDR is accompanied by huge economic losses (the cost of treatment for 1 case of TB with MDR is about 10 thousand US dollars).
Khabarovski Krai has a border with China, and historically has a significant cultural exchange, which is expressed on the one hand by massive tourists flow,
and on the other hand, by the high proportion of migration activity of Chinese people (including the territory of Khabarovski Krai).
At the same time, in Khabarovski Krai, a large number of people have historically "settled" after being in prison, which makes a certain contribution to the proportion of patients with tuberculosis.
The dynamics of morbidity and mortality from tuberculosis in Khabarovski Krai annually is almost 1.5 times higher than in the Russian Federation avg. At the same time, the territorial morbidity in Khabarovski Krai from 2002 to 2018 was characterized by a moderate decline; however, morbidity of bacillary forms of tuberculosis has remained stable for several years (Fig. 1). Positive changes in the dynamics are also characterized by the decreased mortality rate from tuberculosis
in Khabarovski Krai for the period from 2002 to 2018 by 2 times (from 30.2 to 12.4 per 100 thousand of the population; p <0.05) (Fig. 1). On the one hand, a high mortality rate from tuberculosis exists due to the presence of severe concomitant diseases in a significant number of patients. On average, one patient has 2-3 concomitant diseases: HIV, diabetes mellitus, gastrointestinal tract diseases, taking immunosuppressive therapy and others. On the other hand, the behavioral features of the most socially unadapted patients with tuberculosis, which leads to more frequent deaths. The lack of high-quality, full-fledged treatment of non-tuberculous concomitant diseases due to the lack of essential drugs in TB hospitals also leads to negative treatment outcomes.
i i CiwepTHOCTb PO tVn-M CMepTHOCTb flOO ■■■ CMepTHOCTb XK
-is- 3a60^eBaeM0CTb PO —x— 3a60^eBaeM0CTb flOO —♦— 3a60^eBaeM0CTb XK
Figure 1. The dynamics of morbidity and mortality from tuberculosis in the Russian Federation, the Far Eastern Federal District, Khabarovski Krai (per 100 thousand people, taking into account the departments off. No. 8)
Purpose of the research:
Study the spread of drug resistance of M. tuberculosis strains gotten from newly diagnosed patients with respiratory tuberculosis in Khabarovski Krai from 2009 to 2017.
Research Tasks:
1. Study the dynamics of spreading M. Tuberculosis with multiple and wide drug resistance in Khabarov-ski Krai
2. Calculate the proportion of patients with MDR and wide drug resistance.
3. Upbuild a short-term mathematical forecast for the dynamics of M. Tuberculosis isolation with MDR and wide drug resistance to increase the effectiveness of organizational measures to provide medical care to this category of patients
Materials and methods
The materials for the epidemiological study of tuberculosis morbidity in Khabarovski Krai were data from the federal statistical surveillance forms No. 8 "Information on Active Tuberculosis Diseases", No. 33 "Information on Patients with Tuberculosis", data from bacteriostatic registers, as well as statistical collections during the period from 2009 to 2018 "Socially significant diseases of the Russian population (statistical materials)" https://www.rosminzdrav.ru/minis-try/61/22/stranitsa-979/statisticheskie-i-infor-matsionnye-materialy/statisticheskiy-sbornik-2014-god). Epidemiological, bacteriological and statistical research methods were used.
The objects of the study were 2438 newly diagnosed patients with respiratory tuberculosis, taken to the record of TB facilities in Khabarovski Krai.
A retrospective continuous copying of the effective studies from the records of bacteria excreta was done during the period from 2009 to 2017. (2009, n = 257, 2010, n = 314, 2011, n = 316, 2012, n = 287, 2013, n = 260, 2014, n = 250, 2015, n = 274, 2016, n = 264, 2017, n = 216). The spectrum and structure of the primary drug resistance of M. Tuberculosis were carried both on solid media and in the Bactec MGIT 320/960 automated system.
Statistical processing of the results was carried out using methods of descriptive statistics (the MS Office EXCEL 2003 software and the x2 method), the significance level of the differences was taken as p <0.05.
Research results
The number of patients with multidrug resistance (a form of DR-TB, which is manifested by MBT resistance to any two first line anti-tuberculosis drugs or more without simultaneous resistance to isoniazid and rifampicin) in the region is declining. Thus, in 2009 it was 27.3% (n = 70), and in 2017, 18.1% (n = 39) (p <0.05). The largest number of patients with multidrug
resistance in 2017 were identified in the Nanai municipal region - 71.4% (n = 5), in the Komsomolski and Solnechny municipal regions were 50% of all bacteriostatic agents.
At the same time, the increase in the proportion of patients with multidrug resistance of the MBT is an unfavorable indicator (a form of DR-TB in which myco-bacterium tuberculosis always has a resistance to isoni-azid and rifampicin, with or without resistance to other anti-tuberculosis drugs). In 2009 there were 45.9% of such patients (n = 118), and in 2017 68.1% (n = 147) (p <0.05). The most unfavorable situation in 2017 developed in Vanino, Verkhnebureinsky, Tuguro-Chumi-kansky municipal districts, where the level of patients with MDR was 100%, in Vyazemsky municipal district and in Komsomolsk-on-Amur it was 90% and 74.4% respectively.
In the structure of wide drug resistance most common was the resistance to the combination of three main series of anti-TB drugs: streptomycin, isoniazid, and rifampicin.
1 1% МЛУ ♦ Заболеваемость ХК
.......Линейный (% МЛУ) -Линейный (Заболеваемость ХК)
Figure 2. A prognostic model of the dynamics of tuberculosis morbidity and the specific gravity of bacteria with MDR pathogen in Khabarovsk Krai (incidence per 100 thousand people, taking into account departments f. No.
8; MDR pathogen, %)
A significant increase in cases of primary MDR pathogen since 2009 to 2017 indicates a sharp increase in the reservoir of TB infection, accompanied by the isolation of MDR strains (Fig. 2). This may be as a result of an increase in the number of the main risk group: the socially disadvantaged segment of the population (people without a fixed place of residence, homeless people), people with alcoholism and drug addiction, HIV patients, as well as a large cohort who interrupted the course of treatment and chronic forms of TB. The widespread use of backup antibiotic line in treatment will also contribute to a further increase in the number of MDR-tuberculosis.
Currently, the number of patients with primary wide drug-resistant tuberculosis (resistance to at least
rifampicin and isoniazid, plus any of the fluoroquin-olones, plus one of the second-line injectable drugs (kanamycin, amikacin or capreomycin)) in Khabarov-ski Krai is rare. Only 15 patients were registered during 9 years of observation, and in 2017 2 patients (0.9%) were identified in Khabarovski Krai (in Khabarovsk city and Komsomolsky municipal district).
But we should not underestimate the problem of M. Tuberculosis with wide drug resistance spreading in Khabarovski Krai, since there is a summary effect of M. Tuberculosis with MDR accumulation, which will eventually become wide drug resistance-tuberculosis.
Conclusions
1. A decrease in morbidity and mortality of the population from tuberculosis in Khabarovski Krai
shows not only effectiveness of the treatment from tuberculosis, but also the effectiveness of setting the preventive measures aimed at early discovery of patients and prevention further spreading of tuberculosis infection.
2. Observing the drug resistance allows us to assess spreading of the caust of tuberculosis with MDR pathogen, to develop accurate decisions on the management of additional anti-epidemic measures at the regional level, to substantiate the choice of optimal chem-oprophylactic treatment regimens for people at risk. The replenishment of MDR sources number occurs mainly due to newly discovered TB cases.
3. In 2020/2022, in Khabarovski Krai the prevalence of MDR-TB patients is expected in the structure of primary drug resistance of MDR, which may have a negative impact on the effectiveness of treatment.
References
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ХРОНОСТРУКУРА ПОКАЗАТЕЛЕЙ ГЕМОКОАГУЛЯЦИИ У БОЛЬНЫХ РЕВМАТИЗМОМ
Заславская Р.М.
д.м.н., профессор,
Главный специалист Института космических исследований Российской Академии наук, Москва
Вилковыский Ф.А.
д.м.н., Профессор кафедры терапии и клинической фармакологии Московского Государственного Медико-стоматологического Университета
Тейблюм М.М.
к.б.н., Главный специалист, МСК Согаз-Мед, Москва
CHRONOSTRUCTURE OF HEMOCOAGULATION PARAMEYERS IN PATIENTS WITH
RHEUMATISM
Zaslavskaya R.
MD, professor, Main specialist, Space Research Institute Russian Academy of science, Moscow
Vilkovisky F.
MD, Professor in chair of therapy and clinic pharmacology Moscow State Medico-stomatology University
Tejblum M.
Phd, Main specialist, Sogas-Med, Moscow
Аннотация
Одной из ранних и частых причин, приводящих к инвалидности и смерти при ревматизме, являются тромбозы и эмболии, в развитии которых большую роль играют нарушения в системе гемостаза (М.В.Со-бочинская с соавт., 1973; Л.И. Сидоренко с соавт., 1974). В настоящее время установлено, что свёртывающая система крови находится в тесном структурно-морфологическом единстве с сосудистой стенкой и соединительной тканью и что системное поражение целостности соединительной ткани, возникающее при ревматической деструкции, не может не отразиться на тонких ферментативных процессах в свёртывающей системе крови (Грицюк А.И., 1973; 1974; Зборовский Б.А., Скворцов В.А., 1978). Однако литературные данные по изучению состояния гемостаза довольно противоречивы. Одни авторы отмечают повышение активности свёртывающей системы крови, другие - указывают на её понижение, третьи - отсутствие изменений в системе гемостаза у больных в активной фазе ревматизма. Остаётся не изученным вопрос о состоянии процесса гемокоагуляции с позиции хрономедицины. В частности, не исследована циркадианная организация гемокоагуляции в различные стадии активности ревматического процесса, что может быть весьма важным при разработке программ терапии. Не разрабатывались также вопросы, касающиеся влия-
