title: Accuracy of line probe assays for the diagnosis of pulmonary and multidrug-resistant tuberculosis: a systematic review and meta-analysis.
abstract: Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin (RIF) and isoniazid (INH) resistance and Mycobacterium tuberculosis detection. Genotype MTBDRplusV1 was WHO-endorsed in 2008 but newer LPAs have since been developed.This systematic review evaluated three LPAs: Hain Genotype MTBDRplusV1, MTBDRplusV2 and Nipro NTM+MDRTB. Study quality was assessed with QUADAS-2. Bivariate random-effects meta-analyses were performed for direct and indirect testing. Results for RIF and INH resistance were compared to phenotypic and composite (incorporating sequencing) reference standards. M. tuberculosis detection results were compared to culture.74 unique studies were included. For RIF resistance (21 225 samples), pooled sensitivity and specificity (with 95% confidence intervals) were 96.7% (95.6-97.5%) and 98.8% (98.2-99.2%). For INH resistance (20 954 samples), pooled sensitivity and specificity were 90.2% (88.2-91.9%) and 99.2% (98.7-99.5%). Results were similar for direct and indirect testing and across LPAs. Using a composite reference standard, specificity increased marginally. For M. tuberculosis detection (3451 samples), pooled sensitivity was 94% (89.4-99.4%) for smear-positive specimens and 44% (20.2-71.7%) for smear-negative specimens.In patients with pulmonary TB, LPAs have high sensitivity and specificity for RIF resistance and high specificity and good sensitivity for INH resistance. This meta-analysis provides evidence for policy and practice.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA rnathavi@bidmc.harvard.edu.
authors.forename: Ruvandhi R
authors.identifier: 0000-0002-3544-5021
authors.initials: RR
authors.lastname: Nathavitharana
authors.affiliation: Division of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Patrick G T
authors.initials: PG
authors.lastname: Cudahy
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Schumacher
authors.affiliation: Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Steingart
authors.affiliation: McGill International TB Centre, McGill University, Montreal, QC, Canada.
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.|FIND, Geneva, Switzerland.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Denkinger
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D015342:DNA Probes; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D015342:DNA Probes; D007538:Isoniazid; D012293:Rifampin