Linked evidence of effectiveness of NAAT in the diagnosis of MTB
Is it accurate?
Summary—What is the diagnostic accuracy of NAAT (with or without AFB microscopy) versus culture compared with AFB versus culture in the detection of MTB?
Diagnostic accuracy meta-analyses were conducted for multiple comparisons and the results are summarised below.
Culture as the reference standard
Even though culture is considered to be the ‘gold standard’ diagnostic test for TB, it is an imperfect reference standard because not all patients who receive a clinical diagnosis of TB based on other findings such as histopathology, clinical symptoms and responsiveness to anti-TB drugs will be culture-positive.
The pooled sensitivity and specificity of culture and NAAT using clinical diagnosis as a reference standard showed that:
24% of patients clinically diagnosed with TB had a false-negative culture result compared with 14% having a false-negative NAAT.
Thus, a large proportion of NAAT ‘false-positive’ patients (i.e. NAAT-positive, culture-negative) would be clinically diagnosed as having TB.
Therefore, NAAT is likely to be more effective at confirming the presence of an MTB infection than the meta-analysis using culture as the reference standard would suggest.
AFB microscopy plus NAAT compared with culture
The pooled sensitivity and specificity for AFB microscopy plus NAAT compared with culture was 94% (95%CI 91, 98) and 88% (95%CI 82, 92), respectively, and did not differ significantly to those for sputum and non-sputum specimens when analysed separately:
6% of patients will have a false-negative result and 12% of patients will have false-positive results.
The summary LR+ and LR– values for the ability of AFB plus NAAT to correctly diagnose the presence or absence of TB in patients when compared with culture suggest that:
In sputum specimens AFB plus NAAT correctly identified most patients as either culture-positive or culture-negative.
In non-sputum specimens AFB plus NAAT correctly identified most patients who were culture-negative and showed strong diagnostic evidence for confirmation of culture-positive TB.
NAAT versus culture
Compared with culture the pooled sensitivity and specificity of NAAT for all specimens were 89% (95%CI 85, 92) and 94% (95%CI 91, 96), respectively, and did not differ significantly when sputum and non-sputum specimens were analysed separately:
Overall, 11% of patients had false-negative results and 6% false-positive results.
The SROC curve showed some threshold effect, suggesting that in-house NAAT was less specific than commercial NAAT when compared with culture, especially in countries with a high incidence of TB and when testing non-sputum specimens.
The summary LR+ and LR– values for the ability of NAAT to correctly diagnose the presence or absence of TB in patients when compared with culture suggest that:
Both in-house NAATs and the commercial Xpert NAAT had diagnostic value in confirming or excluding culture-positive disease.
Overall, patients with a positive NAAT result were likely to have culture-positive TB, whereas patients with a negative NAAT result were unlikely to be falsely negative.
In the context of interpreting NAAT results in conjunction with AFB findings:
When specimens are AFB-positive, NAAT could confidently exclude the likelihood of culture-positive TB, but a positive NAAT result did not eliminate the possibility of being culture-negative. The explanation for this result is that culture is an imperfect reference standard. Culture in AFB-positive specimens likely resulted in misclassification of many of the 22% false-positive results seen for NAAT.
In AFB-negative specimens a positive NAAT result was likely to correctly confirm the presence of MTB. However, interpretation of a negative NAAT result is dependent on the type of specimen tested:
In patients with AFB-negative sputum a negative NAAT indicated that the patient may not be culture-positive but it could not be ruled out.
In patients with AFB-negative non-sputum specimens a negative NAAT result provided no additional useful information. This is likely due to the paucibacillary nature of AFB-negative specimens.
There was no difference in the diagnostic accuracy of NAAT compared with culture between HIV-positive and HIV-negative patients.
NAAT was both highly sensitive (93%; 95%CI 85, 97) and highly specific (98%; 95%CI 96, 99) compared with culture-based DST in identifying rifampicin-resistant MTB.
Comparison of NAAT, AFB microscopy and AFB plus NAAT using culture as the reference standard
AFB plus NAAT had the highest false-positive rate, at 12%, with NAAT at 6% and AFB at 2%:
A false-positive result means a patient will receive treatment for a short time (until clinical unresponsiveness is noted or culture results are available) for a disease they do not have.
AFB microscopy had the highest false-negative rate, at 38%; NAAT and AFB plus NAAT were much lower at 11% and 6%m, respectively:
The consequences of a false-negative result are much more severe, as the patient may remain untreated for a longer time period and could potentially spread the disease to more individuals.
Studies were included to assess the accuracy of NAAT according to criteria outlined in Box .
Box PICO criteria for identification of studies relevant to an assessment of the accuracy of NAAT
