Strengthening health systems to improve the value of TB diagnostic tools

The national rollout of Xpert as a first-line tuberculosis (TB) diagnostic test in South Africa, following WHO recommendations in 2011, was expected to reduce the time to multi-drug-resistant (MDR) TB treatment. However, studies found no significant impact on TB-related morbidity, mortality, loss-to-follow-up, or time-to-treatment for drug-sensitive TB (DS-TB). While Xpert did reduce time to appropriate treatment for MDR-TB, it did not achieve same-day or same-week treatment initiation as initially expected. An economic evaluation (XTEND trial) found that Xpert implementation was cost- and effect-neutral, with similar findings in other countries. Integration into the healthcare system and patient linkages to treatment were key factors influencing cost and effectiveness. The study also highlighted the limitations of sputum-based diagnostics, particularly in extra-pulmonary TB and advanced HIV cases.[1]

Cost-effectiveness analysis estimated provider costs at $89.66 per symptomatic individual tested, with societal costs at $169.94. Reducing initial loss-to-follow-up (iLTFU) slightly increased treatment costs but had limited impact on health outcomes. Immediate treatment initiation for all positives had minor mortality benefits, especially for HIV-positive patients. Supporting same-day clinical diagnosis after a negative test increased costs by $21.12 per symptomatic person. Further diagnostic testing (negative pathway) raised costs by $35 per patient due to additional visits and delays. Although further testing reduced mortality more effectively than empirical treatment, it had significantly higher provider and societal costs.[1]

The most cost-effective approach depended on the cost-effectiveness threshold. Reducing iLTFU was optimal at lower thresholds, while the negative pathway was favored at higher thresholds. However, as per-transaction costs rose, empirical treatment became the preferable option due to fewer healthcare visits. These findings suggest that in high TB prevalence settings with well-developed laboratory infrastructure, implementing new TB diagnostics should be accompanied by additional investments in the health system. Current international policy aims to expand and intensify TB detection, but without support for decision-making after a negative test result, these efforts alone are unlikely to significantly impact the TB epidemic.[1]

Different diagnostic strategies vary in effectiveness depending on HIV prevalence, drug-resistant TB levels, and healthcare infrastructure. Tests that minimize patient visits can reduce costs and follow-up losses, while early TB detection improves treatment outcomes. Although new diagnostic tools may reduce lab delays, they can create bottlenecks elsewhere in the healthcare system and shift demand to other areas. Accurate diagnostics alone are not enough for TB control—their true impact depends on whether they expedite effective treatment. Evaluating their epidemiological effects is challenging due to TB’s slow progression, but operational and dynamic models can help assess their overall impact.[2]

References:

1. Foster, N., Cunnama, L., McCarthy, K., Ramma, L., Siapka, M., Sinanovic, E., Churchyard, G., Fielding, K., Grant, A.D. and Cleary, S., 2021. Strengthening health systems to improve the value of tuberculosis diagnostics in South Africa: A cost and cost-effectiveness analysis. Plos one, 16(5), p.e0251547.

2. Lin, H.H., Langley, I., Mwenda, R., Doulla, B., Egwaga, S., Millington, K.A., Mann, G.H., Murray, M., Squire, S.B. and Cohen, T., 2011. A modelling framework to support the selection and implementation of new tuberculosis diagnostic tools. The International journal of tuberculosis and lung disease, 15(8), pp.996-1004.