Treatment decision algorithms for tuberculosis screening and diagnosis in children below 5 years hospitalised with severe acute malnutrition: a cost-effectiveness analysis

Abstract

Background: Children with severe acute malnutrition (SAM) are an important risk group for underdiagnosis and death from tuberculosis. In 2022, the World Health Organization (WHO) recommended use of treatment decision algorithms (TDAs) for tuberculosis diagnosis in children. There is currently no cost-effectiveness evidence for TDA-based approaches compared to routine practice.

Methods: The TB-Speed SAM study developed i) a one-step TDA including Xpert, clinical, radiological and echography features, and ii) a two-step TDA, which also included a screening phase, for children under 5 years hospitalised with SAM at three tertiary hospitals in Uganda and Zambia from 4th November 2019 to 20th June 2022. This study is registered with ClinicalTrials.gov, NCT04240990. We assessed the diagnostic accuracy and cost-effectiveness of deploying TB-Speed and WHO TDA-based approaches compared to the standard of care (SOC). Estimated outcomes included children started on tuberculosis treatment, false positive rates, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs).

Findings: Per 100 children hospitalised with SAM, averaging 19 children with tuberculosis, the one-step TDA initiated 17 true positive children (95% uncertainty intervals [UI]: 12-23) on tuberculosis treatment, the two-step TDA 15 (95%UI: 10-22), the WHO TDA 14 (95%UI: 9-19), and SOC 4 (95%UI: 2-9). The WHO TDA generated the most false positives (35, 95%UI: 24-46), followed by the one-step TDA (18, 95%UI: 6-29), the two-step TDA (14, 95%UI: 1-25), and SOC (11, 95%UI: 3-17). All TDA-based approaches had ICERs below plausible country cost-effectiveness thresholds compared to SOC (one-step: $44-51/DALY averted, two-step: $34-39/DALY averted, WHO: $40-46/DALY averted).

Interpretation: Our findings show that these TDA-based approaches are highly cost-effective for the vulnerable group of children hospitalised with SAM, compared to current practice.

Funding: Unitaid Grant number: 2017-15-UBx-TB-SPEED.

Keywords: Cost-effectiveness analysis; Diagnosis; Low- and middle-income countries; Paediatric tuberculosis; Severe acute malnutrition; Treatment decision algorithms.

Fig. 1

Model patient care pathways for the diagnosis and treatment of tuberculosis in children hospitalised with severe acute malnutrition (SAM). ∗Tuberculosis (TB) diagnosis includes the possibility of rifampicin-resistant TB. CXR = chest X-ray; GA = gastric aspirate; LAM = lipoarabinomannan lateral flow assay; TB = tuberculosis; TDA = treatment decision algorithm.

Fig. 2

Cost-effectiveness planes for the TB-Speed SAM and WHO treatment decision algorithms, compared to the standard of care, by country. DALYs: disability-adjusted life years. Numerical annotations represent pairwise incremental cost-effectiveness ratios corresponding to the dashed line of the convex hull. Error bars represent one standard deviation.

Fig. 3

Cost-effectiveness acceptability frontiers and probability of highest net benefit for the TB-Speed SAM and WHO treatment decision algorithms and the standard of care, by country (in US$ per DALY averted). DALYs: disability-adjusted life years. Lines represent the proportion of simulations in which each option had the highest net benefit. Colours along the top denote the optimal choice (the option with the highest mean net benefit across all simulations) at each threshold. Dashed lines show the values of the cost-effectiveness threshold at which the optimal choice changes.