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Xpert Ultra assay identifies pediatric TB with high sensitivity

An updated version of the Xpert Mycobacterium tuberculosis and rifampin assay, known as Ultra, demonstrated high sensitivity in diagnosing pulmonary tuberculosis in children compared with traditional bacteriologic testing, according to research published in Pediatrics.

“In general, the diagnosis of pediatric tuberculosis in the clinic mainly depends on contact history, clinical symptoms and chest radiography results,” Lin Sun, PhD, from the Beijing Pediatric Research Institute, and colleagues wrote. “On the basis of their higher sensitivity, molecular tests have increasingly been used to confirm the presence of Mycobacterium tuberculosis in patients with active tuberculosis as a promising alternative to traditional diagnostic methods.”

According to the researchers, WHO has endorsed the Xpert M. tuberculosis and rifampin (MTB/RIF) assay for children with suspected multidrug-resistant TB or HIV-related TB. WHO also recommends its use as a conditional test for children with suspected TB.

A newer version of the test, the Xpert MTB/RF Ultra was developed to overcome difficulties related to sample collection and low bacterial loads.

“Although Ultra has gradually been introduced for diagnosing tuberculosis in adults, data are still lacking regarding its diagnostic accuracy in children,” Sun and colleagues wrote.

The researchers retrospectively calculated Ultra’s accuracy using bacteriologic results and clinical evidence collected at the Beijing Children’s Hospital. They enrolled 93 children with pulmonary TB and 128 children with other respiratory tract infections.

The Xpert MTB/RIF Ultra test demonstrated 70% sensitivity in all pulmonary TB cases and 91% in bacteriologically confirmed cases, the researchers found. The assay detected M. tuberculosis in 58% of cases that had a negative culture or negative acid fast-staining results. The researchers also reported a specificity of 98%.

Sun and colleagues identified no significant differences in Ultra’s sensitivity when different sample sizes of bronchoalveolar lavage fluid were used (1 mL or less = 66%; more than 1 mL = 73%; P = .5; OR = 0.71).

When both Ultra and Xpert were used for cases (n = 164), Ultra had higher sensitivity (80% vs. 64%). According to the researchers, this difference in sensitivity represented good agreement ( = 0.84). The Ultra test identified six children who had TB but were negative when tested with Xpert.

The rate of children who tested positive with Ultra decreased from 93% to 63% after 1 month of treatment for TB (P = .01; OR = 0.12). The rate decreased to 71% after 2 months of treatment, the researchers wrote (P = .03; OR = 0.18).

“It was highlighted by the WHO that existing tests included in the diagnostic algorithms of active tuberculosis can be tailored to be highly specific to each country’s settings and resources,” Sun and colleagues wrote. “Our data provide insight into the added value of Ultra in the diagnosis of pulmonary tuberculosis in children in China, a country with a high burden of tuberculosis.”

In a related editorial, Heather J. Zar, MD, PhD, professor and head of the department of pediatrics and child health and director of the School of Child and Adolescent Health at the University of Cape Town, South Africa, and Mark P. Nicol, MD, PhD, a professor of microbiology at the University of Western Australia, wrote that the number of children who tested TB-positive after 2 months of treatment raises concerns.

“False-positive Ultra results have been reported in adults, particularly those previously treated for tuberculosis, and it is evident from the current study that Ultra results remained persistently positive through 2 months of treatment in most children,” they wrote.

They also noted that no comparisons were made between yield for repeated induced sputum samples and bronchoalveolar lavage. They wrote that the high yield with bronchoalveolar lavage suggests that this comparison should be a first-line investigation, along with culture testing, for children with suspected pulmonary TB who received bronchoscopy.

“There remains a large group of children who are clinically diagnosed with negative culture results, highlighting the pressing need for a better diagnostic test to distinguish those children who truly have tuberculosis among unconfirmed tuberculosis cases,” Zar and Nicol wrote. “Because most cases of childhood tuberculosis occur in low- and middle-income countries, a better, rapid, accurate, point-of-care diagnostic for use in these settings is a priority.”

References:

Sun L, et al. Pediatrics. 2019;doi:10.1542/peds.2019-0262.

Zar HJ, Nicol MP. Pediatrics. 2019;doi:10.1542/peds.2019-2944.

Disclosures: The authors report no relevant financial disclosures.