IMPACT OF MOLECULAR GENETIC METHODS ON THE INITIATION OF CHEMOTHERAPY IN MULTIPLE DRUG RESISTANTTUBERCULOSIS PATIENTS IN ARKHANGELSK REGION
https://doi.org/10.21292/2075-1230-2017-95-12-10-17
Abstract
In the Arkhangelsk Region, the prevalence of multiple drug-resistant tuberculosis is one of the highest in the world. In 2016, the portion of multiple drug resistant tuberculosis made 33.1% among new cases and 59.5% among relapses. Using new molecular genetic diagnostic techniques allows reducing the time for diagnostics of tuberculosis and drug resistance and should result in the earlier start of adequate treatment.
The goal of the study is to assess the impact of new diagnostic molecular genetic methods on the time period from the first referral for medical care till the start of MDR-TB treatment. It was assumed that the introduction of molecular genetic tests would lead to early initiation of treatment in MDR TB patients (the research project of the International Union Against Tuberculosis and Lung Diseases and Tuberculosis Control Program of Arkhangelsk Region on The PROVE-IT LPA; Policy Relevant Outcomes from Validating Evidence on Impact of Line Probe Assays).
Subjects and Methods. The results of the diagnostic procedure using cultures were compared with the results of the procedure based on molecular genetic tests aimed to detect MDR-TB. 295 MDR TB patients were enrolled into the study, of them, 163 had culture and 132 had molecular genetic tests.
Results. The use of molecular genetic tests in smear-positive patients (AFB+) resulted in the reduction of the time period before initiation of MDRTB treatment by 50 and 66 days (median) versus culture by BacTAlert and absolute concentration on Lowenstein-Jensen medium respectively (p <0.001).
Patients with a negative smear (AFB-), in whom MDR TB was detected by molecular genetic methods started treatment by 78 days earlier (median) versus patients who had culture (Lowenstein-Jensen, p < 0.001). Despite the significant reduction in the time period, even using molecular genetic methods, it took 24 days for cases with AFB+ and 62 days for cases with AFB- to be notified and start treatment of MDR TB.
About the Authors
P. I. EliseevRussian Federation
Platon I. Eliseev – Researcher.
51, Troitsky Ave., Arkhangelsk, 163000
A. Detjen
France
Anne Detjen –, Healthcare Specialist.
Paris
R. Dacombe
United Kingdom
Russel Dacombe – Senior Researcher.
Liverpool
P. Pillips
United Kingdom
Dr. Patrick Pillips – Senior Statistician,
London,
S. B. Squire
United Kingdom
Stephen Bertel Squire – Professor.
Liverpool
A. O. Maryandyshev
Russian Federation
Andrey O. Maryandyshev – Professor.
51, Troitsky Ave., Arkhangelsk, 163000
References
1. Pravitelstvo Arkhangelskoy oblasti. [The government of Arkhangelsk Region]. 2016. http://www.dvinaland.ru/region/
2. Russian Phthisiologists' Society. Federal'nye klinicheskie rekomendatsii po organizatsii i provedeniyu mikrobiologicheskoy i molekulyarno-geneticheskoy diagnostiki tuberkuleza, 2014 [Federal clinical recommendations in organisation and implementation of microbiological and molecular-genetic diagnostics of tuberculosis, 2014].
3. Arentz M., Sorensen B., Horne D.J., Walson J.L. Systematic Review of the Performance of Rapid Rifampicin Resistance Testing for Drug-Resistant Tuberculosis. Dheda K., ed.. PLoS ONE, 2013, vol. 8, no. 10. pp. e76533. doi:10.1371/journal.pone.0076533.
4. BacT/Alert User manual. Biomerieux. 2010. http://www.biomerieux-diagnostics.com/bact-alert-3d- microbial-detection-systems-overview
5. Canetti G., Froman S., Grosset J., Haudoruy P., Langerova M., Mahler H.T. et al. Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull World Health Organ., 1963, vol. 29. pp. 565-578.
6. Eliseev P.I., Maryandyshev A.O., Nikishova E.I., Tarasova I.V., Gorina G.P., Chryssanthou E. et al. Epidemiological analyses of tuberculosis in Archangelsk, Russia and implementation of a rapid assay for detection of resistance in this high burden setting. Int. J. Mycobacteriol., 2013, vol. 2, pp. 103-108.
7. FIND. Annual Report. 2008. http://www.finddiagnostics.org/export/
8. sites/default/about/annual_reports/annual_report_2008.pdf
9. Genotype MTBDRplus, Genotype MTBDRsl . Instructions for use. Hain Lifescience. 2008. http://www.hain-lifescience.de/en/technologies/dnastrip.html
10. Jacobson K.R., Theron D., Kendall E.A., Franke M.F., Barnard M., van Helden P.D. et al. Implementation of genotype MTBDRplus reduces time to multidrug-resistant tuberculosis therapy initiation in South Africa. Clin. Infect Dis., 2013, vol. 56, no. 4, pp. 503-508.
11. Ling D.I., Zwerling A.A., Pai M. GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur. Respir. J., 2008, 32, no. 5, pp. 1165-1174.
12. Mann G., Squire S.B., Bissell K., Eliseev P., Toit E.D., Hesseling A. et al. Beyond accuracy: creating a comprehensive evidence base for tuberculosis diagnostic tools. Int. J. Tuberc. Lung Dis., 2010, vol. 14, pp. 1518-1524.
13. Naidoo P., du Toit E., Dunbar R., Lombard C., Caldwell J., Detjen A. et al. (2014) A Comparison of Multidrug-Resistant Tuberculosis Treatment Commencement Times in MDRTBPlus Line Probe Assay and Xpert® MTB/RIF-Based Algorithms in a Routine Operational Setting in Cape Town. PLoS ONE, vol. 9, no. 7: e103328. doi:10.1371/journal.pone.0103328. pmid:25079599
14. Narasimooloo A. Ross, Delay in commencing treatment for MDR TB at a specialised TB treatment centre in KwaZulu-Natal. S. Afr. Med. J., 2012, vol. 102, no. 6 Pt. 2. ‒ P. 360-362.
15. Perelman M.I. Tuberculosis in Russia. Int. J. Tuberc. Lung Dis., 2000, vol. 4, no. 12, pp. 1097-1103.
16. Salman H., Rusch-Gerdes S. MGIT Procedure Manual For BACTEC™ MGIT 960™ TB System. 2006.
17. Singla N., Satyanarayana S., Sachdeva K.S., Van den Bergh R., Reid T., Tayler-Smith K. et al. (2014) Impact of Introducing the Line Probe Assay on Time to Treatment Initiation of MDR-TB in Delhi, India. PLoS ONE, vol. 9, no. 7: e102989. doi:10.1371/journal.pone.0102989. pmid:25058124
18. World Health Organisation. Molecular Line Probe Assays For Rapid Screening Of Patients At Risk Of Multidrug-Resistant Tuberculosis. Policy Statement, 2008. http://www.who.int/tb/features_archive/policy_statement.pdf
19. World Health Organization, European Respiratory Society. Digital health for the End TB Strategy: an agenda for action (WHO/HTM/TB/2015.21). www.who.int/tb/publications/digitalhealth-TB-agenda/en/
20. Yagui M., Perales M.T., Asencios L., Vergara L., Suarez C., Yale G. et al. Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility testing sufficient? Int. J. Tuberc. Lung Dis., 2006, vol. 10, no. 8, pp. 838-843.
Review
For citations:
Eliseev P.I., Detjen A., Dacombe R., Pillips P., Squire S.B., Maryandyshev A.O. IMPACT OF MOLECULAR GENETIC METHODS ON THE INITIATION OF CHEMOTHERAPY IN MULTIPLE DRUG RESISTANTTUBERCULOSIS PATIENTS IN ARKHANGELSK REGION. Tuberculosis and Lung Diseases. 2017;95(12):10-17. (In Russ.) https://doi.org/10.21292/2075-1230-2017-95-12-10-17