An assessment of nucleic acid amplification testing for active mycobacterial infection

Comparison of AFB microscopy and NAAT, using culture as a reference standard in HIV-positive and HIV-negative patients

Eight studies provided data to assess the diagnostic accuracy of NAAT and AFB microscopy compared with culture in HIV-positive patients suspected of having an MTB infection. Of these, 2 studies used in-house NAAT and 6 used commercial NAAT. Five of these studies were conducted in countries with a high incidence of TB and only 2 looked at the accuracy of NAAT in AFB-negative specimens (Figure in Appendix ). Six studies provided data to assess the diagnostic accuracy of NAAT and AFB microscopy compared with culture in HIV-negative patients suspected of having an MTB infection, and all were conducted in countries with a high incidence of TB. Of these, 3 studies used in-house NAAT and 3 used commercial NAAT (Figure in Appendix ). It should be noted that the Tuberculosis notifications in Australia, 2010 Annual Report¹¹ stated that HIV and TB co-infection remains rare in Australia and is a relatively minor contributor to annual TB incidence, unlike in many other parts of the world.

The pooled sensitivity and specificity values for AFB microscopy or NAAT compared with culture in HIV-positive and -negative populations were compared with those for all included studies, which largely consisted of patients in whom their HIV status was unknown (Figure ). There were no differences between the pooled values for the three population groups, indicating that HIV status does not affect the performance of either AFB microscopy or NAAT.

Figure Forest plot showing the pooled sensitivity and specificity values for AFB and NAAT compared with culture according to HIV status

AFB = acid-fast bacilli; High TB incidence = > 100 cases per 100,000 people based on WHO estimates from 2012; HIV = human immunodeficiency virus; K = the number of studies; NAAT = nucleic acid amplification testing; TB = tuberculosis

HIV-positive patients with pulmonary TB commonly produce AFB-negative sputum specimens (de Albuquerque et al. 2014; Scherer et al. 2011). Thus, the difficulty associated with diagnosis of TB in HIV-positive patients is related to the reduced sensitivity of NAAT compared with culture in AFB-negative specimens. Figure shows that 33% (1 – sensitivity) of AFB-negative sputum specimens will have a false-negative NAAT result when compared with culture; in contrast, only 3% of AFB-positive specimens will have a false-negative result. The difference in the pooled sensitivity for non-sputum specimens is more modest (14% and 0%, respectively) but still sufficient to be of some concern to clinicians.

Figure Forest plot comparing the pooled sensitivity and specificity values for NAAT versus culture according to AFB result and specimen type in HIV-positive specimens

AFB = acid-fast bacilli; K = the number of studies