An assessment of nucleic acid amplification testing for active mycobacterial infection



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Incidence of TB based on WHO estimates from 2012: high incidence = > 100 cases per 100,000 people; medium incidence = 10–100 cases per 100,000 people; low incidence = ≤ 10 cases per 100,000 people

FL = fluorescent staining; K = the number of studies; NAAT = nucleic acid amplification testing; TB = tuberculosis; ZN = Ziehl-Neelsen staining



Deek’s Funnel plot asymmetry test to assess publication bias for the diagnostic accuracy of AFB microscopy compared with culture

Figure 52 Deek’s Funnel plot asymmetry test to assess publication bias for the diagnostic accuracy of AFB microscopy compared with culture

Publication bias is assessed visually by using the inverse of the square root of the effective sample size versus the diagnostic log odds ratio, which should have a symmetrical funnel shape when publication bias is absent (Light & Pillemer 1984). A regression slope coefficient, weighting by ESS, with p<0.05 indicates significant asymmetry (Deeks, Macaskill & Irwig 2005).

There was little to no difference in sensitivity and specificity between studies conducted in high-TB-incidence countries compared with low-incidence countries. The anomaly seen for medium-incidence countries was likely due to chance, given the variability between studies, as seen in Figure 38 and Figure 39 (Appendix D).



LR scattergrams plot LR+ against LR– where the likelihood of correctly identifying patients with MTB infections (as diagnosed by culture) increases along the x-axis and the likelihood of correctly eliminating the presence of MTB decreases along the y-axis. The summary LR+ and LR– values for studies investigating the ability of AFB microscopy to correctly diagnose patients with or without TB, compared with culture, were within the upper right quadrant of the graph (Figure 53). This quadrant represents LR+ and LR– values that suggest that AFB microscopy is likely to correctly confirm the presence of MTB, but a negative test result does not eliminate the likelihood of a positive culture result in patients suspected of having TB. The observed difference in sensitivity of AFB microscopy compared with culture in sputum and non-sputum specimens did not affect the clinical utility of the AFB test. The LRs for both sputum (LR+ 27.0 [95% CI 15.9, 45.6]; LR– 0.29 [95%CI 0.20, 0.43] and non-sputum (LR+ 23.3 [95%CI 13.7, 39.7]; LR– 0.55 [95%CI 0.47, 0.65] specimens were also in the same upper right quadrant. Thus, AFB microscopy is useful for those patients with a positive AFB test result as it identifies those patients as having TB and requiring immediate treatment. However, the clinician gains no further knowledge if a patient has a negative AFB test result, as this patient may still have TB.

LR scattergram for diagnosis of MTB infection by AFB microscopy compared with culture in studies using in-house NAAT or the Xpert NAAT

Figure 53 LR scattergram for diagnosis of MTB infection by AFB microscopy compared with culture in studies using in-house NAAT or the Xpert NAAT



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