Geographical analysis and evaluation of M. tuberculosis genome sequencing at the national level.


  • Elena TUDOR IMSP Institutul de Ftiziopneumologie “Chiril Draganiuc”
  • Nadejda TRCAN IMSP Institute of Phthisiopneumology "Chiril Draganiuc"
  • Nelly CIOBANU IMSP Institutul de Ftiziopneumologie “Chiril Draganiuc”



Mycobacterium tuberculosis, tuberculosis with extensive drug resistance, multidrug-resistant tuberculosis, drug sensitivity testing, molecular genetic methods


Tuberculosis, one of the ancient infections that especially affects humans, the main target organ of this disease being the lung, is caused by M. tuberculosis and remains one of the most important public health problems, especially in developing countries. The emergence of multidrug-resistant and extensively drug-resistant tuberculosis is considered a serious threat to tuberculosis control worldwide. The burden of drug-resistant tuberculosis remains increasing in countries endemic for this infection. The risk factors that influence this situation and that are elucidated more frequently in the specialized literature are the abusive use of drugs, the failure of the therapeutic regimen, the relapse of tuberculosis, the difficulty of obtaining drug sensitivity testing in a fast time. In Moldova, but also in other regions of Eastern Europe, drug resistance represents a serious obstacle in the effective control of this disease. There is evidence that the transmission of resistant strains, as opposed to the acquisition of resistance mutations through inadequate treatment of drug-susceptible tuberculosis, is the main driver of the high level of multidrug-resistant and extensively drug-resistant tuberculosis in these countries.

Author Biographies

Elena TUDOR, IMSP Institutul de Ftiziopneumologie “Chiril Draganiuc”

dr. în șt. med., conf. cercet., membru cor. al AȘMM

Nadejda TRCAN, IMSP Institute of Phthisiopneumology "Chiril Draganiuc"

cercet. șt.

Nelly CIOBANU, IMSP Institutul de Ftiziopneumologie “Chiril Draganiuc”

cercet. șt


Global tuberculosis report. Geneva: World Health Organization, 2022.

Vesga JF, Alexandru S, Vilc V, Crudu V, Bivol S, Celan C, Arinaminpathy N. Lancet Glob Health. 2019 May; 7(5):e585-e595. doi: 10.1016/S2214-109X(19)30037-3. PubMed PMID: 30904521

Jenkins HE, Crudu V, Soltan V, Ciobanu A, Domente L, Cohen T. High risk and rapid appearance of multidrug resistance during tuberculosis treatment in Moldova. Eur Respir J. 2014 April; 43(4):1132–1141. doi:10.1183/09031936.00203613.

Günther G, Alexandru S, , Crudu V, Lange C. Am J Respir Crit Care Med. 2018 Aug 1;198(3):379-386. doi: 10.1164/rccm.201710-2141OC. PubMed PMID: 29509468.

Matthias Merker, Valeriu Crudu, Ulrich Nübel, Philip Supp, Stefan Niemann, Thierry Wirth. Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade towards extensively drug resistant tuberculosis. Nature Genetics, 2021,11

The New Profile of Drug-Resistant Tuberculosis in Russia: A Global and Local Perspective: Summary of a Joint Workshop. Washington (DC)2011.

Kendall EA, Fofana MO, Dowdy DW. Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med 2015;3:963-72.

Crudu V, Merker M, Lange C, et al. Nosocomial transmission of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2015;19:1520-3.

Grenfell BT, Pybus OG, Gog JR, et al. Unifying the epidemiological and evolutionary dynamics of pathogens. Science 2004;303:327-32.

Lemey P, Rambaut A, Welch JJ, Suchard MA. Phylogeography takes a relaxed random walk in continuous space and time. Mol Biol Evol 2010;27:1877-85.

Pybus OG, Suchard MA, Lemey P, et al. Unifying the spatial epidemiology and molecular evolution of emerging epidemics. Proc Natl Acad Sci U S A 2012;109:15066-71.

Casali N, Nikolayevskyy V, Balabanova Y, et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet 2014;46:279-86.

Wollenberg K, Harris M, Gabrielian A,Crudu V. et al. A retrospective genomic analysis of drug-resistant strains of M. tuberculosis in a high-burden setting, with an emphasis on comparative diagnostics and reactivation and reinfection status. BMC Infect Dis 2020;20:17.

Merker M, Barbier M, Cox H, et al. Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia. Elife 2018;7.

Tyler S. Brown VE, Sofia Alexandru, Ecaterina Noroc, Nelly Ciobanu, Valeriu Crudu, Ted Cohen,, Mathema B. Evolution and emergence of multidrug-resistant Mycobacterium tuberculosis in Chisinau, Moldova. medRxiv 2021;

Jenkins HE, Crudu V., Cohen T., et al. Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country. Eur Respir J 2013;42:1291-301.

Nelly Ciobanu, Alexandru Codreanu, Nadejda Țurcan și Valeriu Crudu. Nivelul de rezistență fenotipică și paternul de mutații genice a M.tuberculosis. Buletinul AȘM, 1(69)/2021, p.38





Research Article