A cost-effectiveness analysis of novel stool processing methods for diagnosis of tuberculosis in children under 5 years of age in Uganda

BACKGROUND: Stool-based molecular assays for childhood tuberculosis (TB) diagnosis have shown promise as an alternative to respiratory sample testing. While implementation is underway, evidence on cost-effectiveness is needed. Therefore, we aimed to evaluate the costs of stool testing with Xpert Ultra and model the cost-effectiveness of implementation scenarios at lower levels of care. METHODS: We measured costs for three new stool processing methods: Simple One-Step (SOS), Stool Processing Kit, and Optimized Sucrose Flotation. Each method mixed stool with Xpert Sample Reagent buffer, incubated to allow sedimentation, and then dispensed the supernatant into the Xpert Ultra cartridge. While the other methods required additional buffer and supplies, SOS used only the Sample Reagent. Using the least costly method, we modeled implementation for children under 5 years with presumptive TB at primary health clinics or district hospitals in Uganda. Clinical diagnosis with treatment-decision algorithms was compared to stool testing at primary clinics, stool testing at primary clinics with referral to district hospitals if negative, or evaluation only at district hospitals with Xpert Ultra testing on respiratory samples. Using decision-tree models, we calculated the cost in international dollars (I$) per life-years saved (LYS) and the incremental cost-effectiveness ratio (ICER) assessed against the country-specific willingness to pay threshold. One-way and probabilistic sensitivity analyses were conducted. RESULTS: SOS was the least costly stool processing method. Compared to diagnosis with only treatment-decision algorithms, the ICER of SOS/Ultra at primary clinics was I$1041.71/LYS, SOS/Ultra with referral was I$874.82/LYS, while the district hospital strategy was dominated. Sensitivity analyses showed stool testing was cost-effective compared to only clinical diagnosis if TB prevalence at primary clinics was above 5.7%, with higher diagnostic accuracy of stool-based testing, or lower testing costs. CONCLUSIONS: For young children, stool testing at primary clinics, with or without referral to district hospitals, lowered costs in relation to lives saved compared to implementing at district hospitals alone or only clinical diagnosis using the treatment-decision algorithms.