title: Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting?
abstract: Information regarding the utility of adjunct diagnostic tests in combination with Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is limited. We hypothesised adjunct tests could enhance accuracy and/or reduce the cost of tuberculosis (TB) diagnosis prior to MTB/RIF testing, and rule-in or rule-out TB in MTB/RIF-negative individuals. We assessed the accuracy and/or laboratory-associated cost of diagnosis of smear microscopy, chest radiography (CXR) and interferon-γ release assays (IGRAs; T-SPOT-TB (Oxford Immunotec, Oxford, UK) and QuantiFERON-TB Gold In-Tube (Cellestis, Chadstone, Australia)) combined with MTB/RIF for TB in 480 patients in South Africa. When conducted prior to MTB/RIF: 1) smear microscopy followed by MTB/RIF (if smear negative) had the lowest cost of diagnosis of any strategy investigated; 2) a combination of smear microscopy, CXR (if smear negative) and MTB/RIF (if imaging compatible with active TB) did not further reduce the cost per TB case diagnosed; and 3) a normal CXR ruled out TB in 18% of patients (57 out of 324; negative predictive value (NPV) 100%). When downstream adjunct tests were applied to MTB/RIF-negative individuals, radiology ruled out TB in 24% (56 out of 234; NPV 100%), smear microscopy ruled in TB in 21% (seven out of 24) of culture-positive individuals and IGRAs were not useful in either context. In resource-poor settings, smear microscopy combined with MTB/RIF had the highest accuracy and lowest cost of diagnosis compared to either technique alone. In MTB/RIF-negative individuals, CXR has poor rule-in value but can reliably rule out TB in approximately one in four cases. These data inform upon the programmatic utility of MTB/RIF in high-burden settings.
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology & UCT Lung Institute, Dept of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Grant
authors.initials: G
authors.lastname: Theron
authors.forename: Anil
authors.initials: A
authors.lastname: Pooran
authors.forename: Jonny
authors.initials: J
authors.lastname: Peter
authors.forename: Richard
authors.initials: R
authors.lastname: van Zyl-Smit
authors.forename: Hridesh
authors.initials: H
authors.lastname: Kumar Mishra
authors.forename: Richard
authors.initials: R
authors.lastname: Meldau
authors.forename: Greg
authors.initials: G
authors.lastname: Calligaro
authors.forename: Brian
authors.initials: B
authors.lastname: Allwood
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Rod
authors.initials: R
authors.lastname: Dawson
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
mesh_terms: D003365:Costs and Cost Analysis; D015658:HIV Infections; D006295:Health Resources; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000191:economics; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D011859:Radiography; D012293:Rifampin; D012680:Sensitivity and Specificity; D013019:South Africa; D013183:Sputum / Q000382:microbiology*; D014374:Tuberculin Test / Q000191:economics; D014376:Tuberculosis / Q000175:diagnosis* / Q000000981:diagnostic imaging
chemical_list: D012293:Rifampin
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