Background Population-wide screening may accelerate the decline of tuberculosis (TB) incidence, but the optimal screening algorithm and duration must weigh resource considerations.

Methods We calibrated a deterministic transmission model to TB epidemiology in Viet Nam. We designed three population-wide screening algorithms from 2025: sputum nucleic acid amplification tests (NAAT, Xpert MTB/RIF Ultra) only; chest radiography (CXR) followed by NAAT; and CXR-only without microbiological confirmation. We determined the annual screening rounds required to reduce pulmonary TB prevalence below 50 per 100,000 people. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs), representing the additional costs (in US$) per disability-adjusted life year (DALY) averted compared to business-as-usual by 2050. Additionally, we evaluated the impact of NAAT cartridges costing US$1 each.

Findings NAAT-based algorithms required at least six rounds to reach the prevalence threshold, while CXR-only required three. NAAT-only achieved a prevalence reduction consistent with the ACT3 trial after three rounds. The CXR+NAAT algorithm averted 4.29m DALYs (95%UI:2.86-6.14) at US$225 (95%UI:85-520) per DALY averted compared with business-as-usual. The front-loaded investment of US$161m (95%UI:111-224) annually during the intervention resulted in average annual cost savings of US$12.7m (95%UI:6.7-21.4) up to 2050 compared to the business-as-usual counterfactual. Reducing the cost of NAAT to US$1 led to a 50% and 15% reduction in budget impact and a 63% and 26% reduction in the estimated ICER for the NAAT-only and CXR+NAAT algorithms, respectively.

Interpretation In Viet Nam, population-wide screening could achieve ambitious policy goals. Substantial front-loaded investment is immediately followed by persistent cost savings and could be further offset by more affordable NAATs.

Funding European Research Council, National Health and Medical Research Council Australia.

Evidence before this study Community-wide screening interventions for tuberculosis (TB) have historically been implemented in countries that are now considered low-burden. It has been hypothesised that such interventions could significantly alter TB epidemiology in current high-burden settings if applied with multiple screening rounds and broad coverage. A recent systematic review identified two contemporary cluster-randomised trials evaluating the effect of screening interventions on TB prevalence. The ACT3 trial in Viet Nam demonstrated a significant reduction in microbiologically confirmed TB prevalence after three annual rounds of screening with Xpert MTB/RIF for all, regardless of symptoms. In contrast, the ZAMSTAR trial in Zambia and South Africa, which used symptom-based screening with sputum smear microscopy, did not show a reduction in TB prevalence, highlighting that the screening algorithm employed plays a role in the impact of the intervention.

Added value of this study This study assessed the impact and cost-effectiveness of annual rounds of different population-wide screening algorithms using a mathematical model calibrated to TB epidemiology in Viet Nam. The model incorporated recent insights into the spectrum of TB disease, including self-clearance of Mycobacterium tuberculosis infection, the presence of unconfirmed, asymptomatic infectious, and symptomatic infectious TB, and the relative contribution of asymptomatic TB to transmission. We evaluated the epidemiological impact— assessed by cumulative TB incidence, TB deaths, and DALYs—along with the associated costs, including budget impact, the cost of front-loading for the duration of the intervention, and average annual cost savings over the time horizon, to inform policy decisions in a high TB burden setting. Additionally, sensitivity analyses allowed us to assess the impact of using alternative tests and reducing their associated costs.

Implications of all the available evidence A substantial reduction in TB prevalence may be achieved by repeated annual rounds of symptom-agnostic, population-wide screening. A two-step algorithm, which uses chest radiography as an initial screen followed by sputum nucleic acid amplification test, is expected to avert 1.31 million individuals developing incident TB and 171,000 dying from TB by 2050.

Despite an estimated budget impact of US$1,478 million and annual intervention-specific costs of US$161 million, annual savings of US$12.7 million begin immediately after the intervention ends and are expected to be sustained well beyond 2050. These findings underscore the need to integrate proactive strategies into existing TB prevention and care practices and consider long term financial and health benefits. Furthermore, they illustrate how rapid achievement of ambitious policy goals can be accomplished through front-loaded investments.

The authors have declared no competing interest.

This work was supported by the European Research Council [grant number 757699 to AS, JCE, KCH, and RMGJH]. KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK Aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. GJF was supported by a Leadership Fellowship from the Australian National Health and Medical Research Council.

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