GeneXpert MTB/RIF Ultra in Pediatric Tuberculosis: How Disease Characteristics Modify Test Performances

Introduction: The diagnosis of pediatric tuberculosis (TB) is challenging, due to the lower sensitivity of microbiological tests, such as culture and microscopy, compared to their performance in adult cases. Guidelines have introduced molecular tests, including GeneXpert MTB/ RIF and GeneXpert MTB/RIF Ultra. These tests use a real-time polymerase chain reaction method and provide information on M. tuberculosis detection and drug-resistance-associated mutations in less than 2 hours. This retrospective single-center study aimed to evaluate the accuracy of GeneXpert and GeneXpert Ultra for the diagnosis of pediatric TB.

Methods: This retrospective study was conducted on a total of 95 children diagnosed with probable or confirmed TB disease (74 diagnosed with pulmonary TB, 21 with extrapulmonary TB), who referred to the infectious disease unit at Meyer Children's Hospital in Florence, Italy, and tested with GeneXpert MTB/RIF or GeneXpert Ultra, from 2013 to 2023.

Results: GeneXpert and GeneXpert Ultra demonstrated a detection rate of 0.357 (95% CI 0.180 to 0.535) and 0.537 (95% CI 0.417-0.657), respectively. No child was tested with both tests. Patients' characteristics, including age and sex, did not significantly influence the test's performances. Notably, GeneXpert Ultra had a significantly higher detection rate in children with extrapulmonary TB (0.813, 95% CI 0.621 to 1.004) compared to that in children with pulmonary TB (p = 0.020). Gastric aspirate was the most tested specimen. Specimens that did not require invasive procedures for collection (including stool) yielded poor results. GeneXpert and GeneXpert Ultra permitted rapid evaluation of genotypic drug-sensitivity testing (DST), even though limited to rifampicin resistance, making necessary confirmation through phenotypic DST (performed on culture).

Conclusion: The introduction of GeneXpert and GeneXpert Ultra improved TB diagnosis in children, by providing microbiological information in a short time, complementing results from culture, which remains the reference test in pediatric TB diagnosis.