Optimizing Diagnosis of Pediatric Tuberculosis: The Value of Stool Samples for GeneXpert Testing

Abstract

Tuberculosis (TB) remains a leading infectious cause of morbidity and mortality worldwide, afflicting an estimated 10.7 million people in 2024 and causing approximately 1.23 million deaths, despite decades of public health efforts. Of these cases, children under 15 accounted for around 1.2 million, underscoring a persistent global challenge in pediatric TB diagnosis and care. TB disproportionately affects low- and middle-income countries, with eight countries including India, Indonesia, the Philippines, China, and Pakistan—bearing two-thirds of the global burden. Pakistan alone contributed an estimated 6.3 % of total global cases in 2024, ranking among the top five high-burden countries. Pediatric TB is largely underdiagnosed due to nonspecific symptoms and challenges inherent in specimen collection from young children, who often cannot produce sputum. Conventional tools such as sputum smear microscopy fail to detect many pediatric cases due to paucibacillary disease. The GeneXpert MTB/RIF and Xpert Ultra assays have transformed TB diagnostics by enabling rapid nucleic acid amplification with high specificity, significantly improving case detection, especially in smear-negative disease. Because children commonly swallow respiratory secretions containing Mycobacterium tuberculosis, stool samples have emerged as a feasible, non-invasive specimen for GeneXpert testing. Evidence from multiple studies demonstrates that stool GeneXpert yields moderate sensitivity and high specificity, expanding diagnostic opportunities where respiratory specimens are difficult to obtain. This review synthesizes global and national epidemiology, diagnostic performance, operational considerations, and research advances, culminating in recommendations for enhanced implementation and future research to close the pediatric TB detection gap.