Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study

Abstract

Background: Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis (TB), but there are limited data on their accuracy, acceptability and usability.

Methods: We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with three methods: Stool Processing Kit (SPK), Simple One-Step (SOS), and Optimized Sucrose Flotation (OSF). Children <15 years old with presumptive TB had sputum testing with Xpert Ultra and culture. We compared the accuracy of each method to a microbiological reference standard (MRS, TB if Xpert Ultra or culture positive) and a composite reference standard (CRS, TB if Confirmed or Unconfirmed TB). We surveyed laboratory staff to assess acceptability and usability of the methods.

Results: We included 607 children, with a median age of 3.5 years (IQR 1.3-7) and 15.5% HIV positive. Against the MRS, the sensitivities of SPK, SOS and OSF were 36.9% (95% CI 28.6-45.8), 38.6% (95% CI 17.2-51.0), and 31.3% (95% CI 20.2-44.1), respectively. The specificities of SPK, SOS and OSF were 98.2% (95% CI 96.4-99.3), 97.3% (95% CI 93.7-99.1), and 97.1% (95% CI 93.3-99), respectively. The methods were acceptable and usable, but SOS was reported as most feasible to implement in a peripheral facility. Across methods, sensitivity increased among children who were culture-positive (55.0-77.3%) and was low (13-16.7%) against the CRS. Adding stool Xpert Ultra increased sensitivity 0% (OSF) to 11.8% (SPK/SOS) over sputum alone.

Conclusions: Stool processing methods for Xpert Ultra were acceptable, usable, and performed similarly, with highest sensitivity among children with culture-positive TB.

Keywords: Xpert Ultra; centrifuge-free; child; diagnostics; stool; tuberculosis.