Rapid, automated molecular test for better diagnosis of tuberculosis in children

China: Rapid, automated molecular test-Xpert Mycobacterium tuberculosis and rifampicin (MTB/RIF) Ultra assay has a better performance than traditional bacteriologic and other molecular tests for the diagnosis of tuberculosis in children, a recent study published in the AAP journal Pediatrics has found.

Ultra assay is a rapid, automated molecular test for tuberculosis developed by Cepheid (Sunnyvale, USA). According to WHO, ultra cartridge include a larger chamber for DNA amplification (ie. a larger amount of sputum is used for amplification and detection of DNA) and two additional molecular targets to detect TB. Owing to this, the assay shows increased sensitivity, has improved the ability of the assay to detect low numbers of bacilli.

According to WHO estimates, an estimated 1 million children became ill with TB and 233 000 children died of TB in 2017. However, the actual burden of TB in children is likely higher given the challenge in diagnosing childhood TB.

Ultra assay has increasingly been used in adult tuberculosis diagnosis, but data relating to its diagnostic accuracy in children are lacking. A qualified sputum specimen is difficult to obtain in children. Lin Sun, Capital Medical University, Beijing, China, and colleagues evaluated the diagnostic value of Ultra in childhood tuberculosis using bronchoalveolar lavage fluid in this study.

For the purpose, the researchers enrolled 93 children with pulmonary tuberculosis and 128 children with respiratory tract infections. The accuracy of Ultra was calculated by using bacteriologic results and clinical evidence as reference standards.

Key findings include:

• The sensitivity of Ultra, in all pulmonary tuberculosis cases and in bacteriologically confirmed tuberculosis cases, was 70% and 91%, respectively.


• Ultra could detect Mycobacterium tuberculosis in 58% of cases with negative culture or acid-fast–staining results.


• The specificity of Ultra was 98%.


• There was no significant difference in sensitivity between samples with a volume ≤1 and >1 mL (66% vs 73%).


• Among 164 children for which Ultra and Xpert were simultaneously performed, the sensitivity was 80% and 67%, respectively, indicating good agreement.


• An additional 6 children were identified as Ultra-positive but Xpert-negative.


• The positive rate decreased from 93% to 63% after 1 month and to 71% after 2 months of antituberculosis treatment.

"Ultra using bronchoalveolar lavage fluid has good sensitivity compared with bacteriologic tests and adds clinical value by assisting the rapid and accurate diagnosis of pulmonary tuberculosis in children," concluded the authors.

However, they also note that the current cost of the Ultra assay is a prohibitive factor in its implementation as a point-of-care test, especially in low-income countries where there is a high burden of tuberculosis. "To be financially viable in low-income countries, a large increase in tuberculosis funding and/or a further reduction in the price of the Ultra test would be needed," they write.

More Information: "A Test for More Accurate Diagnosis of Pulmonary Tuberculosis" published in the Pediatrics journal.

DOI: https://doi.org/10.1542/peds.2019-0262

Journal Information: Pediatrics