Skip to main content
Top
Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Cost analysis of rapid diagnostics for drug-resistant tuberculosis

Authors: Erik J. Groessl, Theodore G. Ganiats, Naomi Hillery, Andre Trollip, Roberta L. Jackson, Donald G. Catanzaro, Timothy C. Rodwell, Richard S. Garfein, Camilla Rodrigues, Valeriu Crudu, Thomas C. Victor, Antonino Catanzaro

Published in: BMC Infectious Diseases | Issue 1/2018

Login to get access

Abstract

Background

Growth-based drug susceptibility testing (DST) is the reference standard for diagnosing drug-resistant tuberculosis (TB), but standard time to result (TTR) is typically ≥ 3 weeks. Rapid tests can reduce that TTR to days or hours, but accuracy may be lowered.
In addition to the TTR and test accuracy, the cost of a diagnostic test may affect whether it is adopted in clinical settings. We examine the cost-effectiveness of rapid diagnostics for extremely drug-resistant TB (XDR-TB) in three different high-prevalence settings.

Methods

1128 patients with confirmed TB were enrolled at clinics in Mumbai, India; Chisinau, Moldova; and Port Elizabeth, South Africa. Patient sputum samples underwent DST for first and second line TB drugs using 2 growth-based (MGIT, MODS) and 2 molecular (Pyrosequencing [PSQ], line-probe assays [LPA]) assays. TTR was the primary measure of effectiveness. Sensitivity and specificity were also evaluated. The cost to perform each test at each site was recorded and included test-specific materials, personnel, and equipment costs. Incremental cost-effectiveness ratios were calculated in terms of $/day saved. Sensitivity analyses examine the impact of batch size, equipment, and personnel costs.

Results

Our prior results indicated that the LPA and PSQ returned results in a little over 1 day. Mean cost per sample without equipment or overhead was $23, $28, $33, and $41 for the MODS, MGIT, PSQ, and LPA, respectively. For diagnosing XDR-TB, MODS was the most accurate, followed by PSQ, and LPA. MODS was quicker and less costly than MGIT. PSQ and LPA were considerably faster but cost more than MODS. Batch size and personnel costs were the main drivers of cost variation.

Conclusions

Multiple factors must be weighed when selecting a test for diagnosis of XDR-TB. Rapid tests can greatly improve the time required to diagnose drug-resistant TB, potentially improving treatment success, and preventing the spread of XDR-TB. Faster time to result must be weighed against the potential for reduced accuracy, and increased costs.

Trial registration

ClinicalTrials.gov Identifier: NCT02170441.
Appendix
Available only for authorised users
Literature
1.
go back to reference World Health Organization (WHO): Global tuberculosis report 2013. 2013. World Health Organization (WHO): Global tuberculosis report 2013. 2013.
2.
go back to reference Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, Fujiwara P, Grzemska M, Hopewell PC, Iseman MD, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167(4):603–62.CrossRefPubMed Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, Fujiwara P, Grzemska M, Hopewell PC, Iseman MD, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167(4):603–62.CrossRefPubMed
3.
go back to reference Andrews JR, Shah NS, Weissman D, Moll AP, Friedland G, Gandhi NR. Predictors of multidrug- and extensively drug-resistant tuberculosis in a high HIV prevalence community. PLoS One. 2010;5(12):e15735.CrossRefPubMedPubMedCentral Andrews JR, Shah NS, Weissman D, Moll AP, Friedland G, Gandhi NR. Predictors of multidrug- and extensively drug-resistant tuberculosis in a high HIV prevalence community. PLoS One. 2010;5(12):e15735.CrossRefPubMedPubMedCentral
4.
go back to reference Dharmadhikari AS, Mphahlele M, Venter K, Stoltz A, Mathebula R, Masotla T, van der Walt M, Pagano M, Jensen P, Nardell E. Rapid impact of effective treatment on transmission of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2014;18(9):1019–25.CrossRefPubMedPubMedCentral Dharmadhikari AS, Mphahlele M, Venter K, Stoltz A, Mathebula R, Masotla T, van der Walt M, Pagano M, Jensen P, Nardell E. Rapid impact of effective treatment on transmission of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2014;18(9):1019–25.CrossRefPubMedPubMedCentral
5.
go back to reference Engstrom A, Morcillo N, Imperiale B, Hoffner SE, Jureen P. Detection of first- and second-line drug resistance in mycobacterium tuberculosis clinical isolates by pyrosequencing. J Clin Microbiol. 2012;50(6):2026–33.CrossRefPubMedPubMedCentral Engstrom A, Morcillo N, Imperiale B, Hoffner SE, Jureen P. Detection of first- and second-line drug resistance in mycobacterium tuberculosis clinical isolates by pyrosequencing. J Clin Microbiol. 2012;50(6):2026–33.CrossRefPubMedPubMedCentral
6.
go back to reference McNerney R, Maeurer M, Abubakar I, Marais B, McHugh TD, Ford N, Weyer K, Lawn S, Grobusch MP, Memish Z, et al. Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities. J Infect Dis. 2012;205(Suppl 2):S147–58.CrossRefPubMed McNerney R, Maeurer M, Abubakar I, Marais B, McHugh TD, Ford N, Weyer K, Lawn S, Grobusch MP, Memish Z, et al. Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities. J Infect Dis. 2012;205(Suppl 2):S147–58.CrossRefPubMed
7.
go back to reference Toosky M, Javid B. Novel diagnostics and therapeutics for drug-resistant tuberculosis. Br Med Bull. 2014;110(1):129–40.CrossRefPubMed Toosky M, Javid B. Novel diagnostics and therapeutics for drug-resistant tuberculosis. Br Med Bull. 2014;110(1):129–40.CrossRefPubMed
8.
go back to reference Catanzaro A, Rodwell TC, Catanzaro DG, Garfein RS, Jackson RL, Seifert M, Georghiou SB, Trollip A, Groessl E, Hillery N, et al. Performance comparison of three rapid tests for the diagnosis of drug-resistant tuberculosis. PLoS One. 2015;10(8):e0136861.CrossRefPubMedPubMedCentral Catanzaro A, Rodwell TC, Catanzaro DG, Garfein RS, Jackson RL, Seifert M, Georghiou SB, Trollip A, Groessl E, Hillery N, et al. Performance comparison of three rapid tests for the diagnosis of drug-resistant tuberculosis. PLoS One. 2015;10(8):e0136861.CrossRefPubMedPubMedCentral
9.
go back to reference Hillery N, Groessl EJ, Trollip A, Catanzaro D, Jackson L, Rodwell TC, Garfein RS, Lin SY, Eisenach K, Ganiats TG, et al. The global consortium for drug-resistant tuberculosis diagnostics (GCDD): design of a multi-site, head-to-head study of three rapid tests to detect extensively drug-resistant tuberculosis. Trials. 2014;15(1):434.CrossRefPubMedPubMedCentral Hillery N, Groessl EJ, Trollip A, Catanzaro D, Jackson L, Rodwell TC, Garfein RS, Lin SY, Eisenach K, Ganiats TG, et al. The global consortium for drug-resistant tuberculosis diagnostics (GCDD): design of a multi-site, head-to-head study of three rapid tests to detect extensively drug-resistant tuberculosis. Trials. 2014;15(1):434.CrossRefPubMedPubMedCentral
10.
go back to reference Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, Gler MT, Blakemore R, Worodria W, Gray C, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011;377(9776):1495–505.CrossRefPubMedPubMedCentral Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, Gler MT, Blakemore R, Worodria W, Gray C, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011;377(9776):1495–505.CrossRefPubMedPubMedCentral
11.
go back to reference Pang Y, Li Q, Ou X, Sohn H, Zhang Z, Li J, Xia H, Kam KM, O'Brien RJ, Chi J, et al. Cost-effectiveness comparison of Genechip and conventional drug susceptibility test for detecting multidrug-resistant tuberculosis in China. PLoS One. 2013;8(7):e69267.CrossRefPubMedPubMedCentral Pang Y, Li Q, Ou X, Sohn H, Zhang Z, Li J, Xia H, Kam KM, O'Brien RJ, Chi J, et al. Cost-effectiveness comparison of Genechip and conventional drug susceptibility test for detecting multidrug-resistant tuberculosis in China. PLoS One. 2013;8(7):e69267.CrossRefPubMedPubMedCentral
12.
go back to reference Pantoja A, Fitzpatrick C, Vassall A, Weyer K, Floyd K. Xpert MTB/RIF for diagnosis of tuberculosis and drug-resistant tuberculosis: a cost and affordability analysis. Eur Respir J. 2013;42(3):708–20.CrossRefPubMed Pantoja A, Fitzpatrick C, Vassall A, Weyer K, Floyd K. Xpert MTB/RIF for diagnosis of tuberculosis and drug-resistant tuberculosis: a cost and affordability analysis. Eur Respir J. 2013;42(3):708–20.CrossRefPubMed
13.
go back to reference Dowdy DW, van't Hoog A, Shah M, Cobelens F. Cost-effectiveness of rapid susceptibility testing against second-line drugs for tuberculosis. Int J Tuberc Lung Dis. 2014;18(6):647–54.CrossRefPubMed Dowdy DW, van't Hoog A, Shah M, Cobelens F. Cost-effectiveness of rapid susceptibility testing against second-line drugs for tuberculosis. Int J Tuberc Lung Dis. 2014;18(6):647–54.CrossRefPubMed
14.
go back to reference Balabanova Y, Drobniewski F, Nikolayevskyy V, Kruuner A, Malomanova N, Simak T, Ilyina N, Zakharova S, Lebedeva N, Alexander HL, et al. An integrated approach to rapid diagnosis of tuberculosis and multidrug resistance using liquid culture and molecular methods in Russia. PLoS One. 2009;4(9):e7129.CrossRefPubMedPubMedCentral Balabanova Y, Drobniewski F, Nikolayevskyy V, Kruuner A, Malomanova N, Simak T, Ilyina N, Zakharova S, Lebedeva N, Alexander HL, et al. An integrated approach to rapid diagnosis of tuberculosis and multidrug resistance using liquid culture and molecular methods in Russia. PLoS One. 2009;4(9):e7129.CrossRefPubMedPubMedCentral
15.
go back to reference Rodrigues C, Jani J, Shenai S, Thakkar P, Siddiqi S, Mehta A. Drug susceptibility testing of mycobacterium tuberculosis against second-line drugs using the Bactec MGIT 960 system. Int J Tuberc Lung Dis. 2008;12(12):1449–55.PubMed Rodrigues C, Jani J, Shenai S, Thakkar P, Siddiqi S, Mehta A. Drug susceptibility testing of mycobacterium tuberculosis against second-line drugs using the Bactec MGIT 960 system. Int J Tuberc Lung Dis. 2008;12(12):1449–55.PubMed
16.
go back to reference Almeida D, Rodrigues C, Udwadia ZF, Lalvani A, Gothi GD, Mehta P, Mehta A. Incidence of multidrug-resistant tuberculosis in urban and rural India and implications for prevention. Clin Infect Dis. 2003;36(12):e152–4.CrossRefPubMed Almeida D, Rodrigues C, Udwadia ZF, Lalvani A, Gothi GD, Mehta P, Mehta A. Incidence of multidrug-resistant tuberculosis in urban and rural India and implications for prevention. Clin Infect Dis. 2003;36(12):e152–4.CrossRefPubMed
17.
go back to reference Jenkins HE, Plesca V, Ciobanu A, Crudu V, Galusca I, Soltan V, Serbulenco A, Zignol M, Dadu A, Dara M, et al. Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country. Eur Respir J. 2013;42(5):1291–301.CrossRefPubMed Jenkins HE, Plesca V, Ciobanu A, Crudu V, Galusca I, Soltan V, Serbulenco A, Zignol M, Dadu A, Dara M, et al. Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country. Eur Respir J. 2013;42(5):1291–301.CrossRefPubMed
19.
go back to reference Latimer EA, Becker ER. Incorporating practice costs into the resource-based relative value scale. Med Care. 1992;30(11 Suppl):NS50–60.PubMed Latimer EA, Becker ER. Incorporating practice costs into the resource-based relative value scale. Med Care. 1992;30(11 Suppl):NS50–60.PubMed
20.
go back to reference Physician Payment Review Commission. Practice expenses under the Medicare fee schedule: a resource-based approach. Washington, DC: Physician Payment Review Commission; 1992. Physician Payment Review Commission. Practice expenses under the Medicare fee schedule: a resource-based approach. Washington, DC: Physician Payment Review Commission; 1992.
21.
go back to reference Groessl EJ, Kaplan RM, Blair SN, Rejeski WJ, Katula JA, King AC, Fielding RA, Glynn NW, Pahor M. A cost analysis of a physical activity intervention for older adults. J Phys Act Health. 2009;6(6):767–74.CrossRefPubMedPubMedCentral Groessl EJ, Kaplan RM, Blair SN, Rejeski WJ, Katula JA, King AC, Fielding RA, Glynn NW, Pahor M. A cost analysis of a physical activity intervention for older adults. J Phys Act Health. 2009;6(6):767–74.CrossRefPubMedPubMedCentral
22.
go back to reference Herman WH, Brandle M, Zhang P, Williamson DF, Matulik MJ, Ratner RE, Lachin JM, Engelgau MM. Costs associated with the primary prevention of type 2 diabetes mellitus in the diabetes prevention program. Diabetes Care. 2003;26(1):36–47.CrossRef Herman WH, Brandle M, Zhang P, Williamson DF, Matulik MJ, Ratner RE, Lachin JM, Engelgau MM. Costs associated with the primary prevention of type 2 diabetes mellitus in the diabetes prevention program. Diabetes Care. 2003;26(1):36–47.CrossRef
23.
go back to reference Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York, NY: Oxford University Press; 1996. Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York, NY: Oxford University Press; 1996.
24.
go back to reference Catanzaro A, Rodwell TC, Catanzaro DG, Garfein RS, Jackson RL, Seifert M, Georghiou SB, Trollip A, Groessl EG, Hillery N, et al. Performance comparison of three rapid tests for the diagnosis of drug-resistant tuberculosis. PLoS One. in press; Catanzaro A, Rodwell TC, Catanzaro DG, Garfein RS, Jackson RL, Seifert M, Georghiou SB, Trollip A, Groessl EG, Hillery N, et al. Performance comparison of three rapid tests for the diagnosis of drug-resistant tuberculosis. PLoS One. in press;
25.
go back to reference Ogwang S, Asiimwe BB, Traore H, Mumbowa F, Okwera A, Eisenach KD, Kayes S, Jones-Lopez EC, McNerney R, Worodria W, et al. Comparison of rapid tests for detection of rifampicin-resistant mycobacterium tuberculosis in Kampala, Uganda. BMC Infect Dis. 2009;9:139.CrossRefPubMedPubMedCentral Ogwang S, Asiimwe BB, Traore H, Mumbowa F, Okwera A, Eisenach KD, Kayes S, Jones-Lopez EC, McNerney R, Worodria W, et al. Comparison of rapid tests for detection of rifampicin-resistant mycobacterium tuberculosis in Kampala, Uganda. BMC Infect Dis. 2009;9:139.CrossRefPubMedPubMedCentral
26.
go back to reference Pooran A, Pieterson E, Davids M, Theron G, Dheda K. What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa? PLoS One. 2013;8(1):e54587.CrossRefPubMedPubMedCentral Pooran A, Pieterson E, Davids M, Theron G, Dheda K. What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa? PLoS One. 2013;8(1):e54587.CrossRefPubMedPubMedCentral
27.
go back to reference Shah M, Chihota V, Coetzee G, Churchyard G, Dorman SE. Comparison of laboratory costs of rapid molecular tests and conventional diagnostics for detection of tuberculosis and drug-resistant tuberculosis in South Africa. BMC Infect Dis. 2013;13:352.CrossRefPubMedPubMedCentral Shah M, Chihota V, Coetzee G, Churchyard G, Dorman SE. Comparison of laboratory costs of rapid molecular tests and conventional diagnostics for detection of tuberculosis and drug-resistant tuberculosis in South Africa. BMC Infect Dis. 2013;13:352.CrossRefPubMedPubMedCentral
28.
go back to reference Leung E, Minion J, Benedetti A, Pai M, Menzies D. Microcolony culture techniques for tuberculosis diagnosis: a systematic review. Int J Tuberc Lung Dis. 2012;16(1):16–23. i-iiiCrossRefPubMed Leung E, Minion J, Benedetti A, Pai M, Menzies D. Microcolony culture techniques for tuberculosis diagnosis: a systematic review. Int J Tuberc Lung Dis. 2012;16(1):16–23. i-iiiCrossRefPubMed
29.
go back to reference Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, Sanchez E, Pinedo Y, Saravia JC, Salazar C, et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med. 2006;355(15):1539–50.CrossRefPubMedPubMedCentral Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, Sanchez E, Pinedo Y, Saravia JC, Salazar C, et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med. 2006;355(15):1539–50.CrossRefPubMedPubMedCentral
30.
go back to reference Solari L, Gutierrez A, Suarez C, Jave O, Castillo E, Yale G, Ascencios L, Quispe N, Valencia E, Suarez V. Cost analysis of rapid methods for diagnosis of multidrug resistant tuberculosis in different epidemiologic groups in Peru. Revista peruana de medicina experimental y salud publica. 2011;28(3):426–31.CrossRefPubMed Solari L, Gutierrez A, Suarez C, Jave O, Castillo E, Yale G, Ascencios L, Quispe N, Valencia E, Suarez V. Cost analysis of rapid methods for diagnosis of multidrug resistant tuberculosis in different epidemiologic groups in Peru. Revista peruana de medicina experimental y salud publica. 2011;28(3):426–31.CrossRefPubMed
31.
go back to reference Georghiou SB, Seifert M, Lin SY, Catanzaro D, Garfein RS, Jackson RL, Crudu V, Rodrigues C, Victor TC, Catanzaro A, et al. Shedding light on the performance of a pyrosequencing assay for drug-resistant tuberculosis diagnosis. BMC Infect Dis. 2016;16:458.CrossRefPubMedPubMedCentral Georghiou SB, Seifert M, Lin SY, Catanzaro D, Garfein RS, Jackson RL, Crudu V, Rodrigues C, Victor TC, Catanzaro A, et al. Shedding light on the performance of a pyrosequencing assay for drug-resistant tuberculosis diagnosis. BMC Infect Dis. 2016;16:458.CrossRefPubMedPubMedCentral
Metadata
Title
Cost analysis of rapid diagnostics for drug-resistant tuberculosis
Authors
Erik J. Groessl
Theodore G. Ganiats
Naomi Hillery
Andre Trollip
Roberta L. Jackson
Donald G. Catanzaro
Timothy C. Rodwell
Richard S. Garfein
Camilla Rodrigues
Valeriu Crudu
Thomas C. Victor
Antonino Catanzaro
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3013-0

Other articles of this Issue 1/2018

BMC Infectious Diseases 1/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.