8th Regional TB Symposium Tashkent, Uzbekistan Prof. L.N. Chernousova Central Tuberculosis Research Institute (CTRI) Ministry of Health of the Republic of Uzbekistan 28 February 1 March, 2019
1970 1975 1980 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 TB incidence and mortality in Russia, 1970-2017 (per 100K population) 100 90 80 70 60 50 40 30 20 10 0 18.6 72.4 11.7 58.5 14.1 47.4 45.2 9.1 43.8 42.6 8 7.9 40.8 7.6 37.6 7.4 34.234 7.9 8.1 42.9 35.8 9 12.6 14.6 57.9 67.5 48 15.4 17 74 16.7 85.2 15.4 76.1 20.2 90.4 20.6 88.5 19.9 86 83.2 83.1 21.5 21.8 21.3 83.8 22.1 82.4 19.7 85.1 83.2 20 17.9 77.6 82.6 73 68.1 63 16.8 15.3 14.2 12.5 59.5 11.3 10.1 57.7 48.3 53.3 9.2 7.8 6.4 Overall incidence Mortality
Multi-drug resistant TB (MDR-TB) in Russia in 1999-2017, % 60 50 40 30 20 10 0 10.5 11.2 14.4 6.7 7.1 8.9 7.8 16.2 14.5 8.3 8.1 18.7 16.5 9.5 26.5 21.4 23.4 20.3 9.4 9.8 10.7 30.1 13 13 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 34.2 15.5 37.5 16.2 40 20.4 17.4 47.5 43.9 23 51.2 25.7 54 27.4 Доля Proportion МЛУ среди of MDR-TB ВВ случаев in new туберкулеза TB cases Доля Proportion МЛУ среди of MDR-TB контингентов in all TB patient больных populations туберкулезом
Stages of microbiological diagnostics of TB used at CTRI, including rapid methods for detecting MTB and drug susceptibility Stage 1: Perform primary examination of sputum samples using molecular genetic methods; it takes 1-2 days to detect mutations associated with resistance to Rifampicin, Isoniazid and Fluoroquinolones and therefore detect resistance to major TB drugs Admit MDR-TB patients to a specialized hospital unit Stage 2: Detect phenotypic drug susceptibility using the BACTEC MGIT 960 automated system (the fastest standardized method to detect resistance to a wide range of TB drugs; it takes on average 4-14 days to obtain the results after the inoculation) Compose an individual treatment regimen containing the maximum number of TB drugs to which MTB is susceptible
GeneXpert MTB/RIF cartridge technology (Cepheid, Inc.) simultaneously detects MTB and Rifampicin resistance; results are ready within two hours after sputum is obtained from a patient; presents minimal bio-hazard risk and can be used in general laboratories; endorsed by WHO
CTRI performed a study to evaluate the role of rapid microbiological diagnostic methods in improving the efficacy of MDR-TB treatment We evaluated the treatment efficacy in patients with drug-sensitive pulmonary TB and patients with Rifampicin-resistant pulmonary TB; treatment regimens were composed based on the results of the GeneXpert MTB/RIF cartridge-based assay and subsequently adjusted based on the results of drug susceptibility testing (DST) in liquid media using BACTEC MGIT 960. We compared the findings with the treatment outcomes in the control group MDR-TB patients not tested with rapid molecular tests. The study included 185 patients with pulmonary TB, 130 of which were tested using GeneXpert MTB/RIF. Prof. L.N. Chernousova, Head of Microbiology Department at CTRI
Patient groups: Group 1: 76 patients with Rifampicin susceptibility detected by GeneXpert MTB/RIF; the patients started a standard first-line regimen, subsequently adjusted based on the results of liquid media DST (BACTEC MGIT 960). Group 2: 54 patients with Rifampicin resistance detected by GeneXpert MTB/RIF; the patients started an MDR-TB regimen, subsequently adjusted based on the results of liquid media DST (BACTEC MGIT 960). Group 3: 55 patients not tested on GeneXpert MTB/RIF or other molecular tests to detect Rifampicin resistance; the patients started an empiric first-line regimen, subsequently adjusted based on the results of phenotypic DST. Prof. L.N. Chernousova, Head of Microbiology Department at CTRI
% of smear conversion confirmed by microscopy 110 100 90 80 70 60 50 40 30 20 10 0 49 39 Frequency of and time to sputum smear conversion in patient groups confirmed by fluorescence microscopy 0 80 64 17 96 86.4 27.7 Month 1 Month 2 Month 4 Month 6 Treatment duration Group 1 (n=49) Group 2 (n=44) Group 3 (n=47) 100 100 49 Group 1: GX+, R-susc. Group 2: GX+, R-res. Group 3: GX n/e Prof. L.N. Chernousova, Head of Microbiology Department at CTRI
% of smear conversion confirmed by culture 110 100 90 80 70 60 50 40 30 20 10 0 32 28 Frequency of and time to sputum smear conversion in patient groups confirmed by culture 0 72 52 5.5 82 79.6 29 100 100 36.4 Month 1 Month 2 Month 4 Month 6 Treatment duration Group 1 (n=71) Group 2 (n=54) Group 3 (n=55) Group 1: GX+, R-susc. Group 2: GX+, R-res. Group 3: GX n/e
Study findings: Group 1 showed the lowest time to sputum smear conversion confirmed by fluorescence microscopy. The smear conversion rates were comparable in Group 1 and Group 2 (р1-2 > 0.05). Group 3 had the statistically lowest frequency of smear conversion. Group 1 also showed the highest results in sputum smear conversion confirmed by culture: all patients in the group were smear-negative after six months of treatment. Group 2 showed relatively lower sputum conversion rates; however, all patients in the group also achieved sputum smear conversion after six months of treatment (р1-2 > 0.05). The highest time to sputum smear conversion was in Group 3. Prof. L.N. Chernousova, Head of Microbiology Department at CTRI
Study findings: Therefore, Group 2 (MDR-TB patients who were tested by GeneXpert MTB/RIF and started an MDR-TB regimen without delay) showed the higher frequency of and lower time to sputum smear conversion than Group 3 (MDR-TB patients who started an adequate regimen with delay after obtaining the results of phenotypic DST). In Group 2 and Group 3, the proportions of patients who achieved sputum smear conversion after six months of treatment were 100% and 49% (р < 0.05) as confirmed by microscopy and 100% and 36.4% (р < 0.05) as confirmed by culture, respectively.
Study findings: Regeneration of destructive lung lesions was more frequent in Group 2 (MDR-TB patients who started an effective treatment regimen after rapid Rifampicin resistance detection using GeneXpert MTB/RIF) than in Group 3 (MDR-TB who started an empiric first-line regimen). Lung lesions regenerated in 92% and 63% patients of Group 2 and Group 3 (р < 0.05) after six months of treatment, respectively.
Conclusion MDR-TB treatment is more effective with the use of rapid molecular genetic tests to detect Rifampicin resistance directly from sputum samples, as well as the immediate initiation of a personalized treatment regimen and its subsequent adjustment based on the results of phenotypic DST in liquid media.
THANK YOU FOR YOUR ATTENTION! Co-authors: E.V. Sevastyanova E.E. Larionova T.G. Smirnova S.N. Andreevskaya M.V. Burakova Prof. L.N. Chernousova, Hеаd of Microbiology department at CTRI