Clinical and Public Health Impact of Nucleic Acid Amplification Tests (NAATs) for Tuberculosis

Transcription

1 Clinical and Public Health Impact of Nucleic Acid Amplification Tests (NAATs) for Tuberculosis Amit S. Chitnis, MD, MPH; Pennan M. Barry, MD, MPH; Jennifer M. Flood, MD, MPH. California Tuberculosis Controllers Association Fall Conference October 18, 2013

2 Objectives Review NAATs approved for TB diagnosis Describe performance characteristics of NAATs Evaluate clinical and public health impact of NAATs Discuss how NAATs are currently utilized and strategies to increase utilization

3 Principles of NAATs Amplify TB specific DNA Performed directly on clinical specimens Two types of NAATs In-house assay (e.g., pyrosequence) Commercial kit Image obtained from:

4 U.S. FDA Approved NAATs for Pulmonary TB Amplified MTD test Gen-Probe Amplicor * Roche Diagnostics Xpert MTB/RIF Cepheid All tests approved for AFB smear-positive specimens; MTD and Xpert also approved for AFB smear-negative specimens. NOTE: AFB: acid-fast bacilli. *No longer commercially available.

5 CDC Guidelines for NAATs 1 1) CDC. MMWR Morb Mortal Wkly Rep. 2009;58(1):7-10.

6 Performance of In-House and Commercial NAATs: Pre-Xpert Summary measures of diagnostic accuracy difficult to generate in meta-analyses 1-3 Heterogeneity Threshold effect Nevertheless, important principles regarding NAAT performance AFB smear-positive Sensitivity 95%; Specificity~98% AFB smear-negative Sensitivity 50%-80%; Specificity~98% 1) BMC Microbiol. 2005;5:55. 2) Thorax. 2006;61(9): ) PLoS One. 2008;3(2):e1536.

7 Performance of Xpert in Meta-Analysis 1 Use of Xpert Pooled Sensitivity Median, (95% CrI) Pooled Specificity Median, (95% CrI) TB detection replacing microscopy 88%, (83%, 92%) 98%, (97%, 99%) TB detection in smear-positive group 98%, (97%, 99%) NA Add on following negative smear 67%, (58%, 74%) 98%, (97%, 99%) Rifampin resistance detection 94% (87%, 97%) 98%, (97%, 99%) CrI: credible interval; NA: not applicable 1. Cochrane Database Syst Rev. 2013;1:CD009593

8 Clinical Suspicion Impacts NAAT Performance JAMA. 2000;283(5):

9 Impact of NAATs: Clinical Outcomes* Reduce time to TB diagnosis for culturepositive patients Smear-positive 17 days vs. 24 days; P <.05 1 Decrease duration of TB treatment for culture-negative patients without TB 6 days vs. 31 days; P = Smear-positive 4 days vs. 57 days; P <.05 1 Smear-negative 58 days vs. 100 days; P <.05 1 Detect multidrug-resistant TB 3 NOTE: *Comparisons are NAAT positive vs. NAAT not used. 1) Clin Infect Dis. 2013;57(4): ; 2) Chest. 2007;132(3): ; 3) Thorax. 2008;63(4):

10 Impact of NAATs: Patients and Healthcare Facilities Reduce utilization of respiratory isolation* 16% vs. 31%; P <.05 1 Decrease need for diagnostic tests* CT scan 31% vs. 77%; P <.05 1 Bronchoscopy 13% vs. 28%; P <.05 1 Lower cost to healthcare system for certain TB suspects 1 ** (i.e., HIV infected or homeless) NOTE: *Restricted to AFB smear-positive and culture-positive patients. Comparisons are for NAAT negative vs. NAAT not used. **Comparisons are for NAAT vs. no NAAT. 1) Clin Infect Dis. 2013;57(4):

11 Impact of NAATs: Public Health Decrease contact investigations initiated for smear-positive culture-negative patients 5% vs. 28%; P <.05 1 Prioritize time and resource-intensive contact investigations (e.g., prisons, hospitals) 2 1) Clin Infect Dis. 2013;57(4): ; 2) Thorax. 2008;63(4):

12 What Has Limited Use of NAATs for TB? Cost Labor-intensive Availability Low sensitivity for smear-negative patients Laboratories may exclude NAATs for smearnegative patients

13 Emerging Data on Cost-Effectiveness of NAATs in United States 1 Xpert testing of single sputum for TB suspects Reduced cost per patient Improved outcomes Highly cost-effective compared to other NAATs 1) Int J Tuberc Lung Dis. 2013;17(10):

14 Clinical Prediction Rules Identify TB among Patients Admitted to Hospitals 1 1) J Gen Intern Med. 2005;29(10):

15 Nontuberculous Mycobacteria: Trends in Prevalence and Spatial Clustering Am J Respir Crit Care Med. 2012;185(8): Am J Respir Crit Care Med. 2012;186(6):

16 Possible Algorithm for Maximizing Clinical and Public Health Impact of NAATs for TB Use of NAAT for TB suspect TB Risk Factors, Signs/Symptoms, Radiographic Findings Local Prevalence of TB and Nontuberculous Mycobacteria

17 Hot Topics in NAATs for TB Diagnosis Type (e.g., sputum 1, nasopharyngeal 2, stool 3 ) and number of specimens needed to detect TB among pediatric patients using NAAT Use and performance of NAAT to detect extrapulmonary TB 4 1) Lancet Infect Dis. 2011;11(11): ) Clin Infect Dis. 2012;55(8): ) Clin Infect Dis. 2013;57(3):e18-e21. 4) Eur J Clin Microbiol Infect Dis (3):

18 Discussion Items How are NAATs currently being utilized by local health department labs? Commercial kit vs. in-house assay Algorithm for smear-positive vs. smear-negative pulmonary TB Pediatric patients Extrapulmonary TB Would targeted use of NAATs in certain healthcare facilities in your jurisdiction improve TB detection and outcomes?

19 Thank You!