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In parts of Eastern Europe and the developing world, where a lack of diagnostic tuberculosis (TB) laboratory facilities exist, the prevalence of multidrug and extensive drug resistance is rising. Conventional sputum microscopy, using Ziehl–Neelsen or auramine stains, have low sensitivities, and the accuracy of these results rely on the skill of technical staff. Because the doubling time of Mycobacterium tuberculosis is slower than conventional bacteria, considerable delays occur in obtaining mycobacterial speciation and susceptibility results. In patients with drug-resistant TB, suboptimal treatment results in worse clinical outcomes and inadequate treatment leads to failure to control disease and increases the risk of transmission to close contacts.1
In a recently published paper, Boehme and colleagues investigated the utility of automated mycobacterial speciation and rifampicin susceptibility testing by real-time PCR of sputum obtained from patients with suspected pulmonary TB. Rifampicin resistance is a reliable surrogate marker for multidrug-resistant (MDR) TB. The automated platform, Xpert MTB/RIF, uses real-time PCR and, unlike work in existing laboratories, requires minimal skill and training, despite the availability of speciation and rifampicin susceptibility results within 90 min.
Three sputum samples were collected from adults aged 18 years or older with suspected pulmonary TB, including patients at risk of MDR TB. Patients originated from different geographical areas; Peru, Azerbaijan, South Africa and India. Three sputum samples were obtained from each patient and two samples were processed by microscopy and culture (the gold standard) and Xpert MTB/RIF testing. The other sample underwent direct microscopy and Xpert MTB/RIF testing.
One thousand eight hundred and forty-three patients were screened for TB and 1462 (79.3%) were included in the final analysis. The coinfection rate with HIV varied, being highest in the South African cohort, 159/209 (76.1%). In patients with smear-positive and culture-positive TB, MTB/RIF testing demonstrated high sensitivity, detecting 551 (98.2%) of 561 cases. In patients with smear-negative and culture-positive pulmonary TB, Xpert MTB/RIF testing was more sensitive than smear, detecting 124 (72.5%) of 171 cases. Xpert MTB/RIF testing was also highly specific and was negative in 604 (99.2%) of 609 patients with smear-negative and culture-negative TB.
Xpert MTB/RIF testing also demonstrated high sensitivity for rifampicin resistance detection, correctly identifying rifampicin resistance in 200 (96.6%) of 205 rifampicin-resistant cases. Of the 514 rifampicin sensitive TB cases, 504 (98.1%) cases were also correctly identified, demonstrating high specificity.
In this well-designed diagnostic study, Xpert MTB/RIF testing compared favourably to conventional microscopy, culture and susceptibility testing in patients with sputum culture–positive TB. These results are generalisable because the study included patients from different parts of the world, patients with HIV coinfection and patients with a high likelihood of MDR TB. Importantly, this study has shown that detection of TB by PCR is more sensitive than sputum smear microscopy, but further work is required to demonstrate reproducibility. Inclusion of a control group who were unlikely to have pulmonary TB might have been included in the study design to demonstrate that detection by PCR was not over sensitive.
rpoB resistance genotyping accurately predicts rifampicin resistance, but the PCR platforms used in the 1990s were cumbersome and skill dependent. A contained real-time PCR platform, like Xpert MTB/RIF, does not require a biosafety level 3 laboratory, requires minimal technical skills, negates the need for sputum decontamination, does not result in cross contamination and reduces the time taken to obtain results from weeks to 90 min. It remains to be seen if this platform can be used in settings outside reference laboratories, and whether diagnostic companies reduce the price of the PCR assay, particularly for those in resource-poor countries where the burden of drug-resistant TB is greatest.
Competing interests None.
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