Algorithms for diagnosing tuberculosis with and without a nucleic acid amplification test and associated resources consumed.

<p>Definition of abbreviations: AFB = Acid-fast bacillus; AII = airborne infection isolation; NAAT = nucleic acid amplification test; TB = tuberculosis. Legend: The squares represent decision nodes, circles a chance node, and triangles a terminal node. Each condition represents the sequence of events that may occur to patients with an AFB smear-positive respiratory specimen. Using cost inputs described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100649#pone-0100649-t001" target="_blank">Table 1</a>, we compared average cost per patient under each condition: “NAAT conditions” versus “no NAAT conditions”.</p

Model parameters, base case and reasonable ranges.

<p>AFB = Acid fast bacillus; AII = airborne infection isolation; GMH = Grady Memorial Hospital, Atlanta, GA, USA; NAAT = nucleic acid amplification test; PPV = positive predictive value; TB = tuberculosis</p><p>*Base case was determined by multiplying charge by cost/charge ratio.</p><p>∧This upper bound was determined in the cited publication by considering all aspects of outpatient care in calculating treatment cost and was included for sensitivity analyses.</p>†<p>We could not find estimates of exposure investigation cost in the literature, so for sensitivity analyses we took the extreme position of varying the cost from one tenth to 100 times the base case cost (for low and high bounds, respectively).</p>‡<p>TB prevalence among patients in our study population, i.e. those with an AFB smear-positive sputum sample. This is equivalent to the PPV of AFB smear microscopy.</p><p>#The TB prevalence among AFB smear positives in our study (i.e. PPV of AFB smear) was lower than any found in the literature. For lower bound of TB prevalence we used PPV among HIV patients in our study, i.e. as if all AFB smear-positive patients had HIV.</p

Performance of a nucleic acid amplification test (NAAT) on AFB smear-positive respiratory specimens stratified by HIV status.

<p>AFB = Acid-fast bacillus; HIV+ = HIV seropositive; HIV- = HIV seronegative; NAAT = nucleic acid amplification test; NPV = negative predictive value; PPV = positive predictive value; TB = tuberculosis; + = positive; − = negative.</p

Positive predictive value of an AFB smear-positive respiratory specimen for culture-confirmed tuberculosis stratified by HIV status.

<p>AFB = Acid-fast bacillus; HIV+ = HIV-seropositive; HIV - =  HIV-seronegative; NTM = non-tuberculous mycobacteria; PPV = positive predictive value; TB = tuberculosis</p

Sputum culture results for all AFB smear positive tuberculosis suspects and corresponding complete MTBDRplus assay results.

<p>Sputum culture results for all AFB smear positive tuberculosis suspects and corresponding complete MTBDRplus assay results.</p

Performance parameters of MTBDR<i>plus</i> in detecting INH R^∧, RIF R^∧, and MDR^∧ compared to conventional DST (reference standard)^#.

#<p>Values are percentages with 95% confidence interval in parentheses.</p><p>*PPV = positive predictive value, NPV = negative predictive value.</p>∧<p>INH R = isoniazid resistance, RIF R = rifampin resistance, MDR = multidrug resistance.</p

Distribution of MTBDR<i>plus</i> assay results according to phenotypic drug resistance patterns using conventional drug susceptibility testing for specimens with both valid culture and MTBDRplus assay results.

<p>Distribution of MTBDR<i>plus</i> assay results according to phenotypic drug resistance patterns using conventional drug susceptibility testing for specimens with both valid culture and MTBDRplus assay results.</p

Pattern of genetic mutations in phenotypic drug-resistant <i>Mycobacterium tuberculosis</i> isolates using the Genotype MTBDRplus assay.

<p>*Definitions of abbreviations: INH = isoniazid; RIF = rifampicin; MDR = multidrug-resistant.</p>∧<p>Values are numbers, with percentages in parentheses.</p

Average time to results in days for detection of TB and associated drug resistance (N = 458)^*.

<p>*Values are average number of days with one standard deviation in parentheses.</p>∧<p>DST = drug susceptibility testing.</p