metricas
covid
Buscar en
Enfermedades Infecciosas y Microbiología Clínica
Toda la web
Inicio Enfermedades Infecciosas y Microbiología Clínica Advances in rapid diagnosis of tuberculosis disease and anti-tuberculous drug re...
Journal Information
Vol. 29. Issue S1.
Update on tuberculosis
Pages 34-40 (March 2011)
Share
Share
Download PDF
More article options
Vol. 29. Issue S1.
Update on tuberculosis
Pages 34-40 (March 2011)
Full text access
Advances in rapid diagnosis of tuberculosis disease and anti-tuberculous drug resistance
Avances en el diagnóstico rápido de la enfermedad tuberculosa y de la resistencia a los fármacos antituberculosos
Visits
3820
Fernando Alcaidea,b,c,
Corresponding author
falcaide@bellvitgehospital.cat

Corresponding author.
, Pere Collc,d,e
a Servicio de Microbiología, IDIBELL-Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
b Departamento de Patología y Terapéutica Experimental, Universidad de Barcelona, Barcelona, Spain
c Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain
d Servicio de Microbiología, Hospital de Sant Pau i la Santa Creu, Barcelona, Spain
e Departamento de Microbiología, Universidad Autónoma de Barcelona, Barcelona, Spain
This item has received
Article information
Abstract

Rapid diagnosis of tuberculosis (TB) and multidrug-resistant (resistance to at least rifampin and isoniazid) Mycobacterium tuberculosis (MDR-TB) is one of the cornerstones for global TB control as it allows early epidemiological and therapeutic interventions. The slow growth of the tubercle bacillus is the greatest obstacle to rapid diagnosis of the disease. However, considerable progress has recently been made in developing novel diagnostic tools, especially molecular methods (commercial and ‘in-house’), for direct detection in clinical specimens. These methods, based on nucleic acid amplification (NAA) of different targets, aim to identify the M. tuberculosis complex and detect the specific chromosome mutations that are most frequently associated with phenotypic resistance to multiple drugs. In general, commercial methods are recommended since they have a better level of standardization, reproducibility and automation. Although some aspects such as cost-efficiency and the appropriate setting for the implementation of these techniques are not yet well established, organizations such as the WHO are strongly supporting the implementation and universal use of these new molecular methods. This chapter summarizes current knowledge and the available molecular methods for rapid diagnosis of TB and anti-tuberculous drug resistance in clinical microbiology laboratories.

Keywords:
Tuberculosis
Molecular diagnosis
Rapid detection of drug resistance
Resumen

El diagnóstico rápido de la enfermedad tuberculosa y la resistencia múltiple a los fármacos antituberculosos (al menos isoniazida y rifampicina) en Mycobacterium tuberculosis complex (MDR-TB) es una de las piedras angulares en el control de esta enfermedad, ya que permite una acción epidemiológica y terapéutica precoz. El crecimiento lento del bacilo tuberculoso es uno de los mayores impedimentos para un diagnóstico rápido. En los últimos años ha existido un importante avance en el desarrollo de nuevas herramientas diagnósticas, sobre todo moleculares (comerciales y caseras), para el diagnóstico directo de muestra clínica. Estos métodos se basan en la amplificación de diversas dianas de ácidos nucleicos (AAN), para la identificación de M. tuberculosis complex y la detección de las mutaciones cromosómicas más frecuentemente relacionadas con la resistencia fenotípica a diversos fármacos. En general, entre las múltiples técnicas existentes, se recomiendan los métodos comerciales por su mayor estandarización, reproducibilidad y automatización. A pesar de que aspectos como el coste-efectividad y las indicaciones para la adecuada implementación de estas técnicas no están del todo bien establecidos, organizaciones como la OMS están apoyando de forma firme la aplicación y utilización universal de estos nuevos métodos moleculares. Este capítulo resume el conocimiento actual y los métodos moleculares disponibles para el diagnóstico rápido de la TB y la resistencia a los fármacos en los laboratorios de microbiología clínica.

Palabras clave:
Tuberculosis
Diagnóstico molecular
Detección rápida de la resistencia
Full text is only aviable in PDF
References
[1.]
World Health Organization. Global tuberculosis control: epidemiology, strategy and financing. WHO report 2009. WHO/HTM/TB/2009.411. WHO Press, 2009 [consulted 3 December 2010]. Available at: http://www.who.int/tb/publications/global_report/2009/en/index.html.
[2.]
D.B. Young, M.D. Perkins, K. Duncan, C.E. Barry 3rd..
Confronting the scientific obstacles to global control of tuberculosis.
J Clin Invest, 118 (2008), pp. 1255-1265
[3.]
M.A. Behr, S.A. Warren, H. Salamon, P.C. Hopewell, A. Ponce de León, C.L. Daley, et al.
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli.
Lancet, 353 (1999), pp. 444-449
[4.]
American Thoracic Society; Centers for Disease Control and Prevention; Council of the Infectious Disease Society of America.
Diagnostic standards and classification of tuberculosis in adults and children.
Am J Respir Crit Care Med, 161 (2000), pp. 1376-1395
[5.]
Alcaide F, Esteban J, González J, Palacios JJ. Micobacterias. In: Cercenado E, Cantón R, editores. Procedimientos en Microbiología Clínica. Recomendaciones de la Sociedad de Enfermedades Infecciosas y Microbiología Clínica [9a]. SEIMC; 2005. Available at: http://www.seimc.org/documentos/protocolos/microbiologia/cap9a.pdf
[6.]
G.E. Pfyffer.
Mycobacterium: general characteristics, laboratory detection, and staining procedures.
Manual of Clinical Microbiology, 9th ed, pp. 543-572
[7.]
V. Vincent, M.C. Gutiérrez, Mycobacterium:.
Laboratory characteristics of slowly growing mycobacteria.
Manual of Clinical Microbiology, 9th ed., pp. 573-588
[8.]
M. Salfinger, G.E. Pfyffer.
The new diagnostic mycobacteriology laboratory.
Eur J Clin Microbiol Infect Dis, 13 (1994), pp. 961-979
[9.]
K.C. Jost Jr, D.F. Dunbar, S.S. Barth, V.L. Headley, L.B. Elliott.
Identification of Mycobacterium tuberculosis and M. avium complex directly from smear-positive sputum specimens and BACTEC 12B cultures by high-performance liquid chromatography with fluorescence detection and computer-driven pattern recognition models.
J Clin Microbiol, 33 (1995), pp. 1270-1277
[10.]
D. Cha, D. Cheng, M. Liu, Z. Zeng, X. Hu, W. Guan.
Analysis of fatty acids in sputum from patients with pulmonary tuberculosis using gas chromatography-mass spectrometry preceded by solid-phase microextraction and post-derivatization on the fiber.
J Chromatogr A, 1216 (2009), pp. 1450-1457
[11.]
E. Kaal, A.H. Kolk, S. Kuijper, H.G. Janssen.
A fast method for the identification of Mycobacterium tuberculosis in sputum and cultures based on thermally assisted hydrolysis and methylation followed by gas chromatography-mass spectrometry..
J Chromatogr A, 1216 (2009), pp. 6319-6325
[12.]
M.Y. Park, Y.J. Kim, S.H. Hwang, H.H. Kim, E.Y. Lee, S.H. Jeong, et al.
Evaluation of an immunochromatographic assay kit for rapid identification of Mycobacterium tuberculosis complex in clinical isolates.
J Clin Microbiol, 47 (2009), pp. 481-484
[13.]
W.R.J. Jacobs, R.G. Barletta, R. Udani, J. Chan, G. Kalkut, G. Sosne, et al.
Rapid assessment of drug susceptibilities of Mycobacterium tuberculosis by means of luciferase reporter phages.
Science, 260 (1993), pp. 819-822
[14.]
F. Alcaide, N. Galí, J. Domínguez, P. Berlanga, S. Blanco, P. Orus, et al.
Usefulness of a new mycobacteriophage-based technique for rapid diagnosis of pulmonary tuberculosis.
J Clin Microbiol, 41 (2003), pp. 2867-2871
[15.]
S. Kalantri, M. Pai, L. Pascopella, L. Riley, A. Reingold.
Bacteriophage- based tests for the detection of Mycobacterium tuberculosis in clinical specimens: a systematic review and meta- analysis.
BMC Infect Dis, 5 (2005), pp. 59
[16.]
N. Galí, J. Domínguez, S. Blanco, C. Prat, F. Alcaide, P. Coll, et al.
Use of a mycobacteriophage-based assay for rapid assessment of susceptibilities of Mycobacterium tuberculosis isolates to isoniazid and influence of resistance level on assay performance.
J Clin Microbiol, 44 (2006), pp. 201-205
[17.]
R. McNerney, B.S. Kambashi, J. Kinkese, R. Tembwe, P. Godfrey-Faussett.
Development of a bacteriophage phage replication assay for diagnosis of pulmonary tuberculosis.
J Clin Microbiol, 42 (2004), pp. 2115-2120
[18.]
F. Alcaide.
New methods for mycobacteria identification.
Enferm Infecc Microbiol Clin, 24 (2006), pp. 53-57
[19.]
J. Domínguez, S. Blanco, A. Lacota, N. García-Sierra, C. Prat, V. Ausina.
Utility of molecular biology in the microbiological diagnosis of mycobacterial infections.
Enferm Infecc Microbiol Clin, 26 (2008), pp. 33-41
[20.]
J.C. Palomino.
Nonconventional and new methods in the diagnosis of tuberculosis: feasibility and applicability in the field.
Eur Respir, 26 (2005), pp. 339-350
[21.]
J. Dinnes, J. Deeks, H. Kunst, A. Gibson, E. Cummins, N. Waugh, et al.
A systematic review of rapid diagnostic tests for the detection of tuberculosis infection.
Health Technol Assess, 11 (2007), pp. 1-96
[22.]
A. Catanzaro, S. Perry, J.E. Clarridge, S. Dunbar, S. Goodnight-White, P.A. LoBue, et al.
The role of clinical suspicion in evaluating a new diagnostic test for active tuberculosis. Results of a multicenter prospective trial.
J.A.M.A., 283 (2000), pp. 639-645
[23.]
CDC. Update Guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. Morb Mortal Wkly Rep. 2009;58:7-10.
[24.]
J.C. Palomino.
Molecular detection, identification and drug resistance detection in Mycobacterium tuberculosis.
FEMS Immunol Med Microbiol, 56 (2009), pp. 103-111
[25.]
F. Alcaide.
What does molecular biology contribute to the diagnosis of tuberculosis?.
Enferm Infecc Microbiol Clin, 27 (2009), pp. 493-495
[26.]
C. Piersimoni, C. Scarparo.
Relevance of commercial amplification methods for direct detection of Mycobacterium tuberculosis complex in clinical samples.
J Clin Microbiol, 41 (2003), pp. 5355-5365
[27.]
I.K. Neonakis, Z. Gitti, E. Krambovitis, D.A. Spandidos.
Molecular diagnostic tools in mycobacteriology.
J Microbiol Methods, 75 (2008), pp. 1-11
[28.]
V. Ausina, F. Gamboa, E. Gazapo, J.M. Manterola, J. Lonca, L. Matas, et al.
Evaluation of the semiautomated Abbott LCx Mycobacterium tuberculosis assay for direct detection of Mycobacterium tuberculosis in respiratory specimens.
J Clin Microbiol, 35 (1997), pp. 1996-2002
[29.]
I.K. Neonakis, Z. Gitti, S. Baritaki, E. Petinaki, M. Baritaki, D.A. Spandidos.
Evaluation of GenoType mycobacteria direct assay in comparison with Gen-Probe Mycobacterium tuberculosis amplified direct test and GenoType MTBDRplus for direct detection of Mycobacterium tuberculosis complex in clinical samples.
J Clin Microbiol, 47 (2009), pp. 2601-2603
[30.]
H. Syre, V.P. Myneedu, V.K. Arora, H.M. Grewal.
Direct detection of mycobacterial species in pulmonary specimens by two rapid amplification tests, the gen-probe amplified Mycobacterium tuberculosis direct test and the genotype mycobacteria direct test.
J Clin Microbiol, 47 (2009), pp. 3635-3639
[31.]
N. Kiraz, I. Saglik, A. Kiremitci, N. Kasifoglu, Y. Akgun.
Evaluation of the GenoType Mycobacteria Direct assay for direct detection of the Mycobacterium tuberculosis complex obtained from sputum samples.
J Med Microbiol, 59 (2010), pp. 930-934
[32.]
J.H. Kim, Y.J. Kim, C.S. Ki, J.Y. Kim, N.Y. Lee.
Evaluation of COBAS TaqMan® MTB PCR for the detection of Mycobacterium tuberculosis.
J Clin Microbiol, 49 (2010), pp. 173-176
[33.]
R. Blakemore, E. Story, D. Helb, J. Kop, P. Banada, M.R. Owens, et al.
Evaluation of the analytical performance of the Xpert MTB/RIF assay.
J Clin Microbiol, 48 (2010), pp. 2495-2501
[34.]
C.C. Boehme, P. Nabeta, D. Hillemann, M.P. Nicol, S. Shenai, F. Krapp, et al.
Rapid molecular detection of tuberculosis and rifampin resistance.
N Engl J Med, 363 (2010), pp. 1005-1015
[35.]
D. Helb, M. Jones, E. Story, C. Boehme, E. Wallace, K. Ho, et al.
Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, nearpatient technology.
J Clin Microbiol, 48 (2010), pp. 229-237
[36.]
R. Moure, L. Muñoz, M. Torres, M. Santín, R. Martín, F. Alcaide.
Rapid detection of Mycobacterium tuberculosis complex and rifampin resistance in smear-negative clinical samples using an integrated real time PCR method.
J Clin Microbiol, 49 (2011),
[37.]
World Health Organization. Roadmap for rolling out Xpert MTB/RIF for rapid diagnosis of TB and MDR-TB. 2010 [consulted 7 December 2010]. Available at: http://www.who.int/entity/tb/laboratory/roadmap_xpert_mtb-rif.pdf
[38.]
Y. Mori, K. Nagamine, N. Tomita, T. Notomi.
Detection of loop-mediated isothermal amplification reaction by turbidity derived from magnesium pyrophosphate formation.
Biochem Biophys Res Commun, 289 (2001), pp. 150-154
[39.]
M.F. Lee, Y.H. Chen, C.F. Peng.
Evaluation of reverse transcription loop-mediated isothermal amplification in conjunction with ELISA-hybridization assay for molecular detection of Mycobacterium tuberculosis.
J Microbiol Methods, 76 (2009), pp. 174-180
[40.]
D.L. Williams, L. Spring, L. Collins, L.P. Miller, L.B. Heifets, P.R. Gangadharam, et al.
Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 42 (1998),
[41.]
A. Zaczek, A. Brzostek, E. Augustynowicz-Kopec, Z. Zwolska, J. Dziadek.
Genetic evaluation of relationship between mutations in rpoB and resistance of Mycobacterium tuberculosis to rifampin.
BMC Microbiol, 9 (2009), pp. 10
[42.]
M.H. Hazbon, M. Brimacombe, M. Bobadilla del Valle, M. Cavatore, M.I. Guerrero, M. Varma-Basil, et al.
Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 50 (2006), pp. 2640-2649
[43.]
P.L. Coll, M. Aragón, F. Alcaide, M. Espasa, M. Garrigó, J. González, et al.
Molecular analysis of isoniazid and rifampin resistance in Mycobacterium tuberculosis isolates recovered from Barcelona.
Microb Drug Resist, 11 (2005), pp. 107-114
[44.]
A. Sandgren, M. Strong, P. Muthukrishnan, B.K. Weiner, G.M. Church, M.B. Murray.
Tuberculosis drug resistance mutation database.
[45.]
A. Meier, P. Kirschner, F.C. Bange, U. Vogel, E.C. Bottger.
Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance.
Antimicrob Agents Chemother, 38 (1994), pp. 228-233
[46.]
G. Tudó, E. Rey, S. Borrell, F. Alcaide, G. Codina, P. Coll, et al.
Characterization of mutations in streptomycin-resistant Mycobacterium tuberculosis clinical isolates in the area of Barcelona.
J Antimicrob Chemother, 65 (2010), pp. 2341-2346
[47.]
A. Meier, P. Sander, K.J. Schaper, M. Scholz, E.C. Bottger.
Correlation of molecular resistance mechanisms and phenotypic resistance levels in streptomycinresistant Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 40 (1996), pp. 2452-2454
[48.]
G.J. Alangaden, B.N. Kreiswirth, A. Aouad, M. Khetarpal, F.R. Igno, S.L. Moghazeh, et al.
Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 42 (1998), pp. 1295-1297
[49.]
C.E. Maus, B.B. Plikaytis, T.M. Shinnick.
Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 49 (2005), pp. 3192-3197
[50.]
C.E. Maus, B.B. Plikaytis, T.M. Shinnick.
Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 49 (2005), pp. 571-577
[51.]
S. Feuerriegel, H.S. Cox, N. Zarkua, H.A. Karimovich, K. Braker, S. Rüsch-Gerdes, et al.
Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment.
Antimicrob Agents Chemother, 53 (2009), pp. 3353-3356
[52.]
H.E. Takiff, L. Salazar, C. Guerrero, W. Philipp, W.M. Huang, B. Kreiswirth, et al.
Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations.
Antimicrob Agents Chemother, 38 (1994), pp. 773-780
[53.]
D. Hillemann, S. Rüsch-Gerdes, E. Richter.
Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin-capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens.
J Clin Microbiol, 47 (2009), pp. 1767-1772
[54.]
P. Nahid, M. Pai, P.C. Hopewell.
Advances in the diagnosis and treatment of tuberculosis.
Proc Am Thorac Soc, 3 (2006), pp. 103-110
[55.]
H. De Beenhouwer, Z. Lhiang, G. Jannes, W. Mijs, L. Machtelinckx, R. Rossau, et al.
Rapid detection of rifampicin resistance in sputum and biopsy specimens from tuberculosis patients by PCR and line probe assay.
Tuber Lung Dis, 76 (1995), pp. 425-430
[56.]
M. Morgan, S. Kalantri, L. Flores, M. Pai.
A commercial line probe assay for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis.
BMC Infect Dis, 5 (2005), pp. 62
[57.]
F. Bwanga, S. Hoffner, M. Haile, M.L. Joloba.
Direct susceptibility testing for multi drug resistant tuberculosis: a meta-analysis.
BMC Infect Dis, 9 (2009), pp. 67
[58.]
A. Lacoma, N. García-Sierra, C. Prat, J. Ruiz-Manzano, L. Haba, S. Rosés, et al.
GenoType MTBDRplus assay for molecular detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis strains and clinical samples.
J Clin Microbiol, 46 (2008), pp. 3660-3667
[59.]
L.M. Aragón, F. Navarro, V. Heiser, M. Garrigó, M. Español, P. Coll.
Rapid detection of specific gene mutations associated with isoniazid or rifampicin resistance in Mycobacterium tuberculosis clinical isolates using non-fluorescent low-density DNA microarrays.
J Antimicrob Chemother, 57 (2006), pp. 825-831
[60.]
S. Borrell, S. Gagneux.
Infectiousness, reproductive fitness and evolution of drugresistant Mycobacterium tuberculosis.
Int J Tuberc Lung Dis, 13 (2009), pp. 1456-1466
[61.]
H.R. Van Doorn, P.E. De Haas, K. Kremer, C.M. Vandenbroucke-Grauls, M.W. Borgdorff, D. Van Soolingen.
Public health impact of isoniazid-resistant Mycobacterium tuberculosis strains with a mutation at amino-acid position 315 of katG: a decade of experience in The Netherlands.
Clin Microbiol Infect, 12 (2006), pp. 769-775
[62.]
S. Gagneux, C.D. Long, P.M. Small, T. Van, G.K. Schoolnik, B.J. Bohannan.
The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.
Science, 312 (2006), pp. 1944-1946
Copyright © 2011. Elsevier España S.L.. All rights reserved
Download PDF
Article options
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos