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Published in: BMC Infectious Diseases 1/2010

Open Access 01-12-2010 | Research article

Rapid screening of MDR-TB using molecular Line Probe Assay is feasible in Uganda

Authors: Heidi Albert, Freddie Bwanga, Sheena Mukkada, Barnabas Nyesiga, Julius Patrick Ademun, George Lukyamuzi, Melles Haile, Sven Hoffner, Moses Joloba, Richard O'Brien

Published in: BMC Infectious Diseases | Issue 1/2010

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Abstract

Background

About 500 new smear-positive Multidrug-resistant tuberculosis (MDR-TB) cases are estimated to occur per year in Uganda. In 2008 in Kampala, MDR-TB prevalence was reported as 1.0% and 12.3% in new and previously treated TB cases respectively. Line probe assays (LPAs) have been recently approved for use in low income settings and can be used to screen smear-positive sputum specimens for resistance to rifampicin and isoniazid in 1-2 days.

Methods

We assessed the performance of a commercial line probe assay (Genotype MTBDRplus) for rapid detection of rifampicin and isoniazid resistance directly on smear-positive sputum specimens from 118 previously treated TB patients in a reference laboratory in Kampala, Uganda. Results were compared with MGIT 960 liquid culture and drug susceptibility testing (DST). LPA testing was also performed in parallel in a University laboratory to assess the reproducibility of results.

Results

Overall, 95.8% of smear-positive specimens gave interpretable results within 1-2 days using LPA. Sensitivity, specificity, positive and negative predictive values were 100.0%, 96.1%, 83.3% and 100.0% for detection of rifampicin resistance; 80.8%, 100.0%, 100.0% and 93.0% for detection of isoniazid resistance; and 92.3%, 96.2%, 80.0% and 98.7% for detection of multidrug-resistance compared with conventional results. Reproducibility of LPA results was very high with 98.1% concordance of results between the two laboratories.

Conclusions

LPA is an appropriate tool for rapid screening for MDR-TB in Uganda and has the potential to substantially reduce the turnaround time of DST results. Careful attention must be paid to training, supervision and adherence to stringent laboratory protocols to ensure high quality results during routine implementation.
Literature
2.
go back to reference Lukoye D, Cobelens F, Ezati N, Kirimunda S, Adatu F, Konde J, Joloba M: Anti-tuberculosis drug resistance in Kampala, Uganda, has not changed and shows no association with HIV infection. The 27th Uganda Medical Laboratory Technology Association Scientific Conference, Kabale, Uganda. 2009 Lukoye D, Cobelens F, Ezati N, Kirimunda S, Adatu F, Konde J, Joloba M: Anti-tuberculosis drug resistance in Kampala, Uganda, has not changed and shows no association with HIV infection. The 27th Uganda Medical Laboratory Technology Association Scientific Conference, Kabale, Uganda. 2009
4.
go back to reference Ling D, Zwerling A, Pai M: GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur Respir J. 2008, 32: 1165-1174. 10.1183/09031936.00061808.CrossRefPubMed Ling D, Zwerling A, Pai M: GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur Respir J. 2008, 32: 1165-1174. 10.1183/09031936.00061808.CrossRefPubMed
6.
go back to reference Master RN: Mycobacteriology. Clinical Microbiology Procedures Handbook. Section 3. Edited by: Isenburg HD. 1992, American Society for Microbiology, Washington DC, 1: Master RN: Mycobacteriology. Clinical Microbiology Procedures Handbook. Section 3. Edited by: Isenburg HD. 1992, American Society for Microbiology, Washington DC, 1:
7.
go back to reference World Health Organisation: WHO Laboratory Services in Tuberculosis Control. Part II: Microscopy. WHO/TB/98.258. 1998, Geneva, Switzerland: WHO World Health Organisation: WHO Laboratory Services in Tuberculosis Control. Part II: Microscopy. WHO/TB/98.258. 1998, Geneva, Switzerland: WHO
9.
go back to reference Barnard M, Albert H, Coetzee G, O'Brien R, Bosman ME: Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa. Am J Respir Crit Care Med. 2008, 177 (7): 787-792. 10.1164/rccm.200709-1436OC.CrossRefPubMed Barnard M, Albert H, Coetzee G, O'Brien R, Bosman ME: Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa. Am J Respir Crit Care Med. 2008, 177 (7): 787-792. 10.1164/rccm.200709-1436OC.CrossRefPubMed
10.
go back to reference Telenti A, Imboden P, Marchesi F, Cole S, Colston MJ, Matter L, Schopfer K, Bodmer T: Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet. 1993, 341: 647-650. 10.1016/0140-6736(93)90417-F.CrossRefPubMed Telenti A, Imboden P, Marchesi F, Cole S, Colston MJ, Matter L, Schopfer K, Bodmer T: Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet. 1993, 341: 647-650. 10.1016/0140-6736(93)90417-F.CrossRefPubMed
11.
go back to reference Van Rie A, Warren R, Mshanga I, Jordaan A, Spuy van der GD, Richardson M, Simpson J, Gie RP, Enarson DA, Beyers N, van Helden PD, Victor TC: Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community. J Clin Microbiol. 2001, 39: 636-641. 10.1128/JCM.39.2.636-641.2001.CrossRefPubMedPubMedCentral Van Rie A, Warren R, Mshanga I, Jordaan A, Spuy van der GD, Richardson M, Simpson J, Gie RP, Enarson DA, Beyers N, van Helden PD, Victor TC: Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community. J Clin Microbiol. 2001, 39: 636-641. 10.1128/JCM.39.2.636-641.2001.CrossRefPubMedPubMedCentral
12.
go back to reference Mokrousov I, Narvskaya O, Otten T, Limenschenko E, Steklova L, Vyshnevskiy B: High prevalence of katG Ser315Thr substitution among isoniazid-resistant Mycobacterium tuberculosis isolates from Northwestern Russia, 1996-2001. Antimicr Agents Chem. 2002, 46: 1417-1424. 10.1128/AAC.46.5.1417-1424.2002.CrossRef Mokrousov I, Narvskaya O, Otten T, Limenschenko E, Steklova L, Vyshnevskiy B: High prevalence of katG Ser315Thr substitution among isoniazid-resistant Mycobacterium tuberculosis isolates from Northwestern Russia, 1996-2001. Antimicr Agents Chem. 2002, 46: 1417-1424. 10.1128/AAC.46.5.1417-1424.2002.CrossRef
13.
go back to reference Baker LV, Brown TJ, Maxwell O, Gibson AL, Fang Z, Yates MD, Drobniewski FA: Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC-46A polymorphism. Antimicr Agents Chem. 2005, 49: 1455-1464. 10.1128/AAC.49.4.1455-1464.2005.CrossRef Baker LV, Brown TJ, Maxwell O, Gibson AL, Fang Z, Yates MD, Drobniewski FA: Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC-46A polymorphism. Antimicr Agents Chem. 2005, 49: 1455-1464. 10.1128/AAC.49.4.1455-1464.2005.CrossRef
14.
go back to reference Behr MA, Warren SA, Salamon H, Hopewell PC, Ponce de Leon A, Daley CL, Small PM: Transmission of Mycobacterium tuberculosis from patients smear negative for acid fast bacilli. Lancet. 1999, 353: 444-449. 10.1016/S0140-6736(98)03406-0.CrossRefPubMed Behr MA, Warren SA, Salamon H, Hopewell PC, Ponce de Leon A, Daley CL, Small PM: Transmission of Mycobacterium tuberculosis from patients smear negative for acid fast bacilli. Lancet. 1999, 353: 444-449. 10.1016/S0140-6736(98)03406-0.CrossRefPubMed
15.
go back to reference Getahun H, Harrington M, O'Brien R, Nunn P: Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet. 2007, 369 (9578): 2042-2049. 10.1016/S0140-6736(07)60284-0.CrossRefPubMed Getahun H, Harrington M, O'Brien R, Nunn P: Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet. 2007, 369 (9578): 2042-2049. 10.1016/S0140-6736(07)60284-0.CrossRefPubMed
Metadata
Title
Rapid screening of MDR-TB using molecular Line Probe Assay is feasible in Uganda
Authors
Heidi Albert
Freddie Bwanga
Sheena Mukkada
Barnabas Nyesiga
Julius Patrick Ademun
George Lukyamuzi
Melles Haile
Sven Hoffner
Moses Joloba
Richard O'Brien
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2010
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-10-41

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