Cost-effectiveness of latent tuberculosis infection testing and preventive treatment among TB contacts in China: a Markov model

Abstract

Objective

This study evaluates the costs and cost-effectiveness of latent tuberculosis infection (LTBI) testing and preventive treatment (TPT) strategies among close contacts of active tuberculosis (ATB) patients in China using a Markov model, with the aim of informing the optimization of national TPT strategies.

Methods

A Markov model was developed to evaluate the cost-effectiveness of LTBI testing with purified protein derivative (PPD), Mycobacterium TB antigen-based skin test (TBST), or interferon-gamma release assay (IGRA), each followed by either a 4-week thrice-weekly rifapentine plus isoniazid regimen (1 H₃P₃) or a 3-month twice-weekly rifapentine plus isoniazid regimen (3 H₂P₂), in a hypothetical cohort of 10,000 close contacts of ATB patients with a mean age of 38 years. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALY) gained, and strategies were judged against China’s 2024 per-capita GDP–based willingness-to-pay (WTP) threshold (¥95,754 per QALY).

Results

In the base-case analysis, LTBI testing with TBST or IGRA followed by treatment with 1 H₃P₃ was the dominant strategy. Specifically, LTBI testing with TBST followed by 1 H₃P₃ resulted in a cost of ¥8,367.79 (95% UI: ¥-76549.62, ¥79,656.24) per QALY gained, which is below WTP threshold. Sensitivity analysis indicated that LTBI prevalence and utility values assigned to cure ATB or self-healing in ATB substantially influenced incremental cost-effectiveness ratios.

Conclusion

LTBI testing with TBST followed by treatment with 1 H₃P₃ is a cost-effective strategy and may represent an optimum for tuberculosis control among close contacts of ATB patients in China.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1186/s12913-026-14482-6.

Introduction

Tuberculosis (TB) remains a chronic infectious disease that continues to pose significant threats to public health and constitutes a major global health challenge. According to the 2025 Global TB Report [1], an estimated 10.7 million people developed TB worldwide in 2024, corresponding to an incidence rate of 131 per 100,000 population. This figure reflects only a 12.0% reduction since 2015, which is substantially below the World Health Organization (WHO) End TB Strategy’s milestone target of a 50% reduction in incidence by 2025, as established in 2014 [1]. Latent tuberculosis infection (LTBI) is defined as a persistent immune response to Mycobacterium tuberculosis antigens in the absence of clinical evidence of active tuberculosis disease (ATB) [2]. In the absence of effective intervention, LTBI can progress to ATB, creating new sources of transmission and significantly impeding progress toward the WHO’s End TB strategy. China remains one of the world’s high TB burden countries, reporting approximately 740,000 new TB cases in 2023, the third highest globally, and accounting for 6.8% of worldwide incidence, with a national incidence rate of 52 per 100,000 population. The implementation of effective LTBI testing and tuberculosis preventive treatment (TPT) represents a crucial intervention strategy for reducing TB incidence rates [3]. There is an urgent need to investigate and provide appropriate LTBI testing and TPT in China.

Currently, no gold standard exists for diagnosing LTBI. Existing approaches rely on the operational definition of LTBI and utilize indirect testing to infer infection status. Diagnostic tools are categorized into three main types [3]: (1) the tuberculin skin test (TST), which uses purified protein derivative (PPD); (2) the Mycobacterium tuberculosis antigen-based skin test (TBST), which employs recombinant TB antigens; and (3) interferon-gamma release assays (IGRAs). TPT was incorporated by the WHO in 2014 as a core component of the ‘End TB Strategy,’ with updated guidance released in 2015, 2018, 2020, and 2024 [3–8], due to its ability to reduce mycobacterial load and lower the risk of progression to ATB. Conventional TPT regimens include isoniazid at 300 mg daily for either 6 months (6 H) or 9 months (9 H), which remain the most widely used options. However, their effectiveness is limited by poor treatment adherence [3]. The WHO-recommended 3-month weekly regimen of rifapentine plus isoniazid (3HP, maximum dose 900 mg each) has higher completion rates than 6 H and 9 H [3, 9]. In China, due to genetic differences between Asian and Caucasian populations, a 3-month regimen of twice-weekly rifapentine plus isoniazid (3 H₂P₂, maximum dose 600 mg each) has been routinely used for decades and has demonstrated efficacy [9, 10]. The WHO has conditionally recommended an alternative 1-month daily regimen (1HP), although the 2024 WHO preventive treatment report indicates insufficient new evidence to support 1HP [3]. In a 2019 randomized controlled trial involving patients with silicosis, Chinese researchers evaluated a novel 4-week regimen of thrice-weekly rifapentine plus isoniazid (1 H₃P₃, 400 mg isoniazid and 450 mg rifapentine) for LTBI. The study demonstrated both safety and efficacy of this ultra-short-course regimen [11]. These findings support further exploration of shorter TPT regimens among key populations with LTBI in China to reduce incidence rates.

The economic value of health interventions is increasingly recognized as a critical factor for policymakers in public health programs. The WHO consolidated guidelines on TB from 2021 and 2024 highlight the need to conduct long-term cost-effectiveness analyses of LTBI testing and TPT to assess both potential costs and long-term impacts [3, 12]. Despite this emphasis, there are limited health economic evaluations in China that assess combined strategies of LTBI testing and short-course TPT, including the 1 H₃P₃ regimen, particularly among close contacts of ATB patients. This study evaluates the costs and cost-effectiveness of LTBI testing and preventive treatment strategies from the healthcare system perspective using a Markov model, thereby providing a valuable reference for optimizing TPT strategies in China.

Methods

Model overview

A decision tree followed by a Markov state-transition model was constructed using TreeAge Pro (version 2022; TreeAge Software Inc., Williamstown, MA, USA) to estimate and compare the costs, health outcomes, and cost-effectiveness of seven strategies for contacts of ATB patients from the health system perspective. The strategies (Table 1) were applied to a hypothetical cohort of 10,000 contacts of ATB who met the criteria for tuberculosis infection testing and TPT as outlined in the WHO consolidated guidelines on tuberculosis: Module 1, second section [3]. The baseline scenario for comparison was the absence of LTBI testing or TPT (no intervention). The hypothetical population comprised 10,000 adults with an average initial age of 38 years and a history of contact with ATB patients within the previous three months.

Table 1.

Summary table of intervention strategies

Strategy	LTBI testing regimen	LTBI treatment regimen
Strategy 1	Passive case finding	No treatment
Strategy 2	PPD	1 H3P3
Strategy 3	PPD	3 H2P2
Strategy 4	TBST	1 H3P3
Strategy 5	TBST	3 H2P2
Strategy 6	IGRA	1 H3P3
Strategy 7	IGRA	3 H2P2

^*PPD, tuberculin purified protein derivative tests; TBST, Mycobacterium tuberculosis antigen-based skin test; IGRA, interferon-gamma release assays; 1 H₃P₃, a 4-week regimen with thrice-weekly isoniazid and rifapentine; 3 H₂P₂, a 3-month regimen of twice-weekly isoniazid and rifapentine

Model structure

Figure 1 provides a simplified schematic diagram of the model. The LTBI testing regimens include PPD, TBST, and IGRA. Individuals who test positive for LTBI and meet the eligibility criteria for TPT through pre-intervention tests, regardless of true or false positivity, receive either 1 H₃P₃ or 3 H₂P₂. Both LTBI treatment regimens are assumed to be delivered via Direct Observation treatment (DOT). All ATB cases identified through passive case finding and pre-intervention tests must receive a standardized TB treatment regimen. Individuals who received preventive treatment were assumed not to develop ATB during TPT, and further categorized based on treatment completion [13, 14]. The intervention was assumed not to alter baseline mortality risk because current evidence indicates that TPT primarily reduces progression to ATB, whereas a direct effect on mortality among generally healthy close contacts has not been well quantified [15]. Each intervention is modeled to exert uniform effects across all subjects within the same cohort. Disease progression to ATB was modeled using epidemiological data from drug-susceptible TB cases in China. Participants enter the Markov cycle according to their health states (Fig. 1B). For model simplification, initial healthy participants or those who clear infection are assumed not to experience reinfections. LTBI patients who have received TPT, regardless of completion status, remain at risk for progression to ATB. The model incorporates recurrent ATB cases, defined as subsequent episodes following a TB-free interval. TB-related mortality is restricted to ATB cases only.

Fig. 1.

A simplified schematic diagram of the decision analysis model. The model first implements a decision tree among a hypothetical group of contacts of ATB in China who are screened for latent tuberculosis infection (LTBI) using PPD, TBST, or IGRA. Those who test positive and meet the eligibility criteria for TPT are treated with a 4-week regimen with thrice-weekly isoniazid and rifapentine (1 H₃P₃) in one scenario or with a 3-month regimen of twice-weekly isoniazid and rifapentine (3 H₂P₂) in the alternative scenario. Suspected ATB patients will receive further examination and standardized tuberculosis treatment regimen. Participants will exhibit different health states under the influence of intervention measures (A) and enter Markov model (B) based on their health states. The ovals represent mutually exclusive health states that each individual may reach during each Markov cycle

In this study, 1 H₃P₃ was introduced as an innovative therapy. The TB prevalence rate, treatment success rate, and population mortality rate were calculated annually [16–19]. Additionally, previous research indicated that the protective effect of isoniazid persists for nearly 20 years [20]. Consequently, a Markov cycle duration of 1 year was selected, and patient outcomes were monitored from the initiation of LTBI treatment for over 20 years.

Model parameters

Transition probability

Parameter source comprises field survey data, high-quality published studies and meta-analyses conducted in China, international economic evaluation literature, statistical yearbooks, publicly available authoritative databases, and the Chinese Disease Prevention and Control Information System. Transition probability parameters are presented in Table 2. Among close contacts of ATB patients, the estimated prevalence of LTBI and the ATB incidence rate were 42.40% [21, 22] and 2.60% [23], respectively. The proportion of ATB cases detected through passive case finding was estimated by Xu’s [44] and the 2024 China Tuberculosis Surveillance Report [24]. Due to the lack of direct methods to distinguish true infection clearance from persistent LTBI, the global paucity of experimental evidence on spontaneous TB infection clearance [25], Richards’ [26] estimated self-resolution rate of 40.00% for TB-infected asymptomatic individuals was adopted in the modeling framework and converted into an indicator of LTBI natural clearance rate. The proportion of non-ATB patients who tested positive for infection and were eligible for TPT was 82.19%, based on field data obtained from an ongoing, unpublished study. The self-healing probability for ATB was 1.00% [27], and the treatment initiation rate among ATB cases was 82.700% [28]. Published evidence-informed transition outcomes, including treatment success (93.23%) [18], recurrence after self-resolution (3.18%) [29, 30], recurrence after treatment (2.49%) [31], and drug-susceptible TB case mortality (7.68%) [32]. Age-specific probability of death was obtained from the 2024 China Population and Employment Statistical Yearbook [19] (Supplement 1. Table 1). Test performance was assumed to be 75.50%/73.00% (PPD), 78.70%/98.50% (TBST), and 84.00%/95.00% (IGRA) for sensitivity and specificity, respectively [33–35]. Treatment acceptance (88.41%) and completion rates (96.80%) for the 1 H₃P₃ regimen were derived from unpublished field data. The treatment acceptance (76.28%) and completion rates (87.20%) for the 3 H₂P₂ regimen were based on field data from Ren [45] and Belknap [36].

Table 2.

Model parameters

Parameter*	Based value	Uncertainty range	Source
LTBI prevalence in close contacts of ATB patients	42.40%	17.60%, 46.40%	Velen [20] Xu [21]
ATB prevalence in close contacts of ATB patients	2.60%	0.90%, 4.30%	Li [22]
Proportion of ATB detected through passive case finding	72.78%	54.59%, 90.98%	Xu [21], 2024 China Tuberculosis Surveillance Report [23]
Probability of infection natural clearance in LTBI	9.72%	7.23%, 12.26%	Richards [24]
Proportion of infection positive patients suitable for TPT	82.19%	79.68%, 84.46%	Field data
Probability of self-healing in ATB	1.00%	0.75%, 1.25%	Suárez [25]
Probability of treatment initiation among ATB cases	82.70%	80.36%, 85.04%	Xu [26]
Probability of treatment success for ATB	93.23%	90.95%, 95.61%	Wang [17]
Probability of recurrence after self-healing in ATB	3.18%	1.03%, 7.41%	Zu [27], Chiang [28]
Probability of recurrence in cured ATB	2.49%	1.87%, 3.11%	Ruan [29]
Mortality in ATB	1.77%	1.67%, 1.87%	Abuaku [30]
Age-specific probability of death	-	-	2024 China Population and Employment Statistics Yearbook [18]
PPD sensitivity	75.50%	65.00%, 85.00%	Peng [31]
PPD specificity	73.00%	57.00%, 87.00%	Peng [31]
TBST sensitivity	78.70%	68.00%, 88.00%	Peng [31]
TBST specificity	98.50%	96.00%, 99.00%	Peng [31]
IGRA sensitivity	84.00%	70.00%, 91.40%	Diel [32], Oh CE [33]
IGRA specificity	95.00%	94.00%, 98.00%	Diel [32], Oh CE [33]
Treatment acceptance rate by regimen
1 H3P3	88.41%	86.30%, 90.22%	Field data
3 H2P2	76.28%	73.74%, 78.66%	Ren [34]
Treatment completion rate by regimen
1 H3P3	96.80%	95.50%, 97.78%	Field data
3 H2P2	87.20%	83.10%, 90.50%	Belknap [35]
Annual risk of progression from LTBI to ATB in different LTBI treatments
No TPT
First 2 years	2.50%	1.00%, 5.00%	Zu [27]
After 2 years	0.10%	0.00%, 0.016%	Zu [27]
After TPT
First 2 years
1 H3P3 Complete treatment	0.15%	0.09%, 0.26%	Ruan [11]
3 H2P2 Complete treatment	0.05%	0.04%, 0.07%	Ruan [36], Cao [13]
After 2 years
1 H3P3 Complete treatment	0.02%	0.02%, 0.04%	Ruan [11]
3 H2P2 Complete treatment	0.01%	0.01%, 0.01%	Ruan [36], Cao [13]
Age of cohort at start (years)	38	-	China’s 13th Five-Year Plan for National TB Prevention and Control final evaluation report [37]
Cost for LTBI testing in baseline (¥)			China CDC’s TPT funding estimates [38]
Costs of PPD related reagents and consumables	18.80	14.100, 23.50
Costs of TBST related reagents and consumables	32.50	24.39, 40.63
Costs of IGRA related reagents and consumables	500.00	375.00, 625.00
Cost for pre-intervention phase (¥)	438.50	328.88, 548.13	Cao [13]
Cost per complete regimen (¥)			China CDC’s TPT funding estimates [38]
1 H3P3	212.00	159.00, 265.00
3 H2P2	375.00	281.25, 468.75
Cost per incomplete regimen (¥)
1 H3P3	133.00	99.75, 166.25
3 H2P2	143.00	107.25, 178.75
Cost of treatment for ATB (¥)	13707.50	10280.63, 17,134.38	China’s 13th Five-Year Plan for National TB Prevention and Control final evaluation report [37]
Utility weigh
Health	1.00	-	-
LTBI
No TPT or incomplete treatment	0.97	0.95, 1.00	Zu [27]
Complete preventive treatment	0.97	0.95, 1.00	Zu [27]
ATB	0.83	0.75, 0.87	Sadatsafavi [39]
Cured ATB or self-healing in ATB	0.94	0.87, 1.00	Zu [27], Doan [40], Tiemersma [41]
Death	0.00	-	Kittikraisak [42]
Discount rate (annual)	0.03	0.01, 0.07	Smith [43]

^* TB, tuberculosis; LTBI, latent tuberculosis infectious; ATB, active tuberculosis disease; TPT, tuberculosis preventive treatment; PPD, tuberculin purified protein derivative tests; TBST, Mycobacterium tuberculosis antigen-based skin test; IGRA, interferon-gamma release assays; 1 H₃P₃, a 4-week regimen with thrice-weekly isoniazid and rifapentine; 3 H₂P₂, a 3-month regimen of twice-weekly isoniazid and rifapentine

^* For probabilistic analyses, cost parameters followed a gamma distribution, and the other variables followed a triangular distribution. The likeliest, minimum, and maximum parameters of the triangular distributions were set to equal the base-case, lower and upper values, respectively

The annual risk of progression from LTBI to ATB without treatment was set at 2.50% for the first two years post-infection and 1.00% thereafter [29]. Owing to insufficient research data on the 1 H₃P₃ regimen among close contacts of ATB patients, progression risks for 1 H₃P₃ completers (first 2 years: 0.15%; after 2 years: 0.02%) were calculated by calculating results from Cao’s [13] study and Ruan’s [11] 3-year follow-up in silicosis patients. Given the limited number of doses administered and findings from previous studies, this study conservatively assumed no treatment efficacy for the 1 H₃P₃ and 3 H₂P₂ non-completer groups; their progression risks were considered equivalent to those of the untreated cohort: 0.57% in the first 2 years and 0.09% thereafter [13, 29, 37]. Among treatment completers, progression risks declined substantially: 1 H₃P₃ (0.15% to 0.02%) [11, 13], and 3 H₂P₂ (0.05% to 0.01%) [11, 13, 38]. The cohort entry age was set at 38 years, reflecting the mean age of 1,956 LTBI cases eligible for tuberculosis preventive treatment (TPT) in the ‘13th Five-Year Plan’ research cohort of close contacts of pulmonary TB patients, observed from January 1, 2018, to October 30, 2019 [42]. Parameter uncertainty ranges were established using two methods: for parameters with published estimates, the maximum and minimum values from the literature were adopted; for parameters without reported bounds, 95% confidence intervals were calculated using Wilson’s score estimation.

Cost input

Table 2 presents the cost parameters. Testing costs (PPD: ¥18.80; TBST: ¥32.50; IGRA: ¥500.00) and preventive treatment costs (complete 1 H₃P₃: ¥212.00; complete 3 H₂P₂: ¥375.00; incomplete 1 H₃P₃: ¥133.00; incomplete 3 H₂P₂: ¥143.00) were calculated using China CDC’s TPT funding estimates [39]. In the base scenario, the cost of incomplete treatment for 1 H₃P₃ was assumed to include half of the medication and DOT costs, while incomplete 3 H₂P₂ was assumed to include one-third of the medication and DOT costs [29, 37]. Details of cost input calculations are provided in Supplement 1. Pre-intervention examination costs (¥438,50) were primarily derived from Cao’s study [13]. The treatment cost for ATB (¥13,707.50) was obtained from the final evaluation report of China’s 13th Five-Year Plan for National TB Prevention and Control [42]. All future costs and health outcomes were discounted at an annual rate of 3.00%.

Health utility and discount

The parameters of health utility and discount are likewise presented in Table 2. Effectiveness was quantified in quality-adjusted life years (QALY), with utilities assigned as follows: 1.00 for the healthy state and 0.00 for death [40]. For LTBI, regardless of acceptance or completion of the preventive treatment, a utility of 0.97 was applied based on published literature [29]. ATB was associated with a utility of 0.83, while cured or self-healing yielded a utility of 0.94, based on published estimates [29, 41, 43, 46].

Base-case analyses

For each strategy, the expected costs, QALY, and cases of ATB prevented were calculated. Furthermore, incremental cost-effectiveness ratios (ICERs) were estimated, as the additional cost per QALY gained relative to the next least expensive non-dominated strategy. We reported 95% un-certainty ranges (95% URs) around projected point estimates. A strategy was deemed cost-effective—representing good value for money—if its ICER did not exceed China’s willingness-to-pay (WTP) threshold (¥95,754.00/QALY), defined as Chinese 2024 per capita gross domestic product (GDP) [47].

Sensitivity analyses

A one-way sensitivity analysis was carried out to identify key determinants of ICERs and assess the sensitivity of the results to individual variables. Cost, probability, and utility parameters were systematically varied within their respective uncertainty ranges, while all other parameters were held constant. For parameters with unknown uncertainty ranges, a conservative approach was used by applying a 25% variation around base values [13]. The results of the one-way sensitivity analysis were presented as tornado diagrams that illustrated the impact of each parameter on the ICER.

A probabilistic sensitivity analysis (PSA) was conducted to evaluate the impact of simultaneously varying multiple parameters. Gamma distributions were assigned to cost parameters, while triangular distributions were used for other variables. The results were displayed as a scatter plot of 500 ICERs on the cost-effectiveness plane and subsequently converted into a cost-effectiveness acceptability curve according to the decision-makers’ WTP for an additional QALY.

Results

Base‑case results

Table 3 presents the results of the base-case analysis. Over a 20-year time horizon, LTBI testing with TBST (Strategies 4 and 5) incurred lower costs than testing with PPD (Strategies 2 and 3) or IGRA (Strategies 6 and 7), with average lifetime costs per capita of ¥563.00 and ¥590.11, respectively. Relative to no intervention, the six intervention strategies, ranked by cost per capita, could prevent an additional 42.47, 35.73, 38.99, 32.52, 46.51, or 39.47 cases of ATB per 10,000 patients, respectively.

Table 3.

Results of cost-effectiveness analysis (20 years)

Strategya	Cost per capita (¥) (95% UI)	Incremental cost (¥)b (95% UI)	QALY per capita (year) (95% UI)	Incremental QALY (year)b (95% UI)	ICER (¥/QALY) (95% UI)	Incident cases of ATB per 10,000 patients	Cases prevented d (n)
Strategy 1	441.09 (247.21, 686.90)	-	14.18 (11.69, 16.94)	-	-	187.51	-
Strategy 4	563.00 (376.48, 769.35)	121.91 (20.53, 226.58)	14.19 (11.70, 16.97)	0.01 (−0.03, 0.06)	8,367.79 (−76,549.62, 79,656.24)	145.04	42.47
Strategy 5	590.11 (393.28, 809.48)	27.11 (2.02, 57.95)	14.19 (11.70, 16.97)	0.00 (−0.01, 0.01)	−9,187.05 c (−775,165, 65,531.11)	151.78	35.73
Strategy 2	637.78 (457.88, 840.85)	74.78 (4.78, 148.19)	14.19 (11.70, 16.97)	0.00 (−0.01, 0.01)	−37,455.28 c (−472,273.20, 466,186.30)	148.52	38.99
Strategy 3	667.32 (477.46, 882.38)	104.32 (25.50, 183.79)	14.19 (11.70, 16.96)	0.00 (−0.02, 0.01)	−21,593.13 c (−261,486.50, 271,067.50)	154.99	32.52
Strategy 6	1,052.47 (827.03, 1,296.98)	489.47 (363.01, 627.99)	14.19 (11.71, 16.97)	0.00 (−0.01, 0.01)	210,804.17 (−2,572,882.00, 2,860,409.00)	141.00	46.51
Strategy 7	1,081.09 (846.77, 1,334.27)	28.63 (1.51, 61.36)	14.19 (11.70, 16.97)	0.00 (−0.01, 0.01)	−9,278.79 c (−75953.25, 66,339.33)	148.04	39.47

^a Strategies are ranked by their cost per capita

^b Relative to the next least expensive, non-dominated strategy

^c Dominated because the strategy was more expensive and had fewer QALYs than the next least expensive, non-dominated strategy

^d Compared with no intervention

QALY quality-adjusted life year, ICER incremental cost-effectiveness ratio, ATB active tuberculosis

Strategy 1 No intervention; Strategy 2 LTBI testing with PPD followed by treatment with 1 H₃P₃; Strategy 3 LTBI testing with PPD followed by treatment with 3 H₂P₂; Strategy 4 LTBI testing with TBST followed by treatment with 1 H₃P₃; Strategy 5 LTBI testing with TBST followed by treatment with 3 H₂P₂; Strategy 6 LTBI testing with IGRA followed by treatment with 1 H₃P₃; Strategy 7 LTBI testing with IGRA followed by treatment with 3 H₂P₂

The cost-effectiveness analysis indicated that LTBI testing with TBST followed by treatment with 1 H₃P₃ (Strategy 4) and LTBI testing with IGRA followed by treatment with 1 H₃P₃ (Strategy 6) were both undominated, meaning each offered lower cost with greater QALY compared to other strategies (Table 3; and Supplemental Fig. 1). Strategy 4 demonstrated greater effectiveness than strategy 1 with an incremental cost of ¥8,367.79 (95% UI: ¥-76,549.62, ¥79,656.24) per QALY gained. Similarly, strategy 6 was more effective than strategy 4, but required substantially higher incremental cost of ¥210,804.17 (95% UI: ¥-2,572,882.00, ¥2,860,409.00) per QALY gained (Table 3). Therefore, strategy 4 was considered cost-effective according to China’s WTP threshold (¥95,754.00/QALY), whereas strategy 6 was not.

Sensitivity analyses

Figure 2 presents the results of one-way sensitivity analysis of key parameters and their impact on the ICERs for strategy 4 compared to strategy 1 over a 20-year time horizon. In this comparison, variations in the prevalence of LTBI among close contacts, the mortality of patients with ATB, and the utility values assigned to cured ATB or self-healing in ATB substantially influenced the ICER.

Fig. 2.

The results of the one-way sensitivity analysis of the ICERs for LTBI testing with TBST followed by treatment with 1 H₃P₃ (Strategy 4) versus no intervention (Strategy 1). Bars show the ICER (¥/QALY gained) of Strategy 4 relative to Strategy 1, within the uncertainty range of the parameter in question, while holding all other parameters constant over the 20-year time horizon. The vertical line indicates the reference scenario (¥95,749.00/QALY gained)

In the PSA, the incremental cost-effectiveness (ICE) scatterplot comparing Strategy 4 with Strategy 1 (Fig. 3A) showed that most simulations fell in the northeast quadrant, indicating that Strategy 4 was typically more effective but also more costly. As the WTP threshold increases, the probability that Strategy 4 is cost-effective also rises. At a WTP threshold of ¥8,425.91 per QALY, the cost-effectiveness acceptability curve indicates that Strategy 4 has a 49.89% probability of being cost-effective, compared to 49.93% for Strategy 1. When the WTP increases to ¥8,808.91 per QALY, the probability for Strategy 4 increases slightly to 51.05%, while that for Strategy 1 decreases to 48.75%. At a higher WTP of ¥95,749 per QALY, the CE acceptability curve shows that Strategy 4 has a 43.01% probability of being the cost-effective option, compared to 25.92% for Strategy 1 (Fig. 3B).

Fig. 3.

The scatter plot of ICER (A) and the cost-effectiveness acceptability curve (B) from probabilistic sensitivity analysis. The scatter plot of ICER illustrates the variation in the incremental cost-effectiveness ratio (ICER) for Strategy 4 compared to Strategy 1 across different willingness-to-pay (WTP) thresholds. The cost-effectiveness(CE) acceptability curve shows the percentage of simulations in which strategy 4 would be considered cost-effective compared to no intervention at varying WTP thresholds at the 20-year time horizon. Strategy 1 No intervention; Strategy 2 LTBI testing with PPD followed by treatment with 1 H₃P₃; Strategy 3 LTBI testing with PPD followed by treatment with 3 H₂P₂; Strategy 4 LTBI testing with TBST followed by treatment with 1 H₃P₃; Strategy 5 LTBI testing with TBST followed by treatment with 3 H₂P₂; Strategy 6 LTBI testing with IGRA followed by treatment with 1 H₃P₃; Strategy 7 LTBI testing with IGRA followed by treatment with 3 H₂P₂

Discussion

This study is the first to evaluate the cost-effectiveness of LTBI testing and treatment (1 H₃P₃ and 3 H₂P₂) among contacts of ATB patients in China from the healthcare system perspective. The findings indicate that, following LTBI testing with TBST, treating contacts with 1 H₃P₃ is less expensive and more effective than the alternative strategies examined. Compared with no intervention, the incremental cost per QALY gained for LTBI testing with TBST followed by 1 H₃P₃ treatment is below the WTP threshold of ¥95,749.00, thereby meeting the criteria for cost-effectiveness in the Chinese context, although substantial uncertainty remained.

In China, the development of preventive treatment strategies to reduce the incidence of TB should prioritize key populations that make a substantial contribution to disease burden, such as close contacts of ATB patients. According to the national TB surveillance report [17, 48], in 2022 and 2023, 90,350 close contacts of active pulmonary TB patients initiated preventive treatment. Of these, 71,346 received short-course regimens, and 65,896 successfully completed treatment. While these figures are derived from reporting forms and may underestimate the true number of individuals receiving preventive therapy due to underreporting in certain regions, the data underscore the increasing emphasis on TB preventive treatment in China. Additionally, the statistics suggest that short-course regimens are more acceptable to patients (72.93%, 65,896/90,350). Expanding the implementation of ultra-short regimens, such as 1 H₃P₃, among close contacts of ATB patients would therefore have significant public health benefits.

The model demonstrated that treatment with 3 H₂P₂ was less cost-effective than 1 H₃P₃. Although 3 H₂P₂ was more effective than 1 H₃P₃, the additional costs did not justify the incremental benefit. These findings are aligned with previous studies, which reported that 1 H₃P₃ was more cost-effective than 3 H₂P₂ in silicosis patients [11], and that LTBI testing with TBST was more cost-effective than PPD or IGRA in high-TB-burden settings [49]. Besides, compared with no intervention, testing with TBST followed by treatment with 1 H₃P₃ was more effective at a cost of ¥8,367.79/QALY, which is below the WTP threshold of ¥95,749.00/QALY, and it could prevent approximately 50 additional cases of ATB per 10,000 patients over a 20-year time horizon. This finding indicates that, if policy decision-makers are unwilling to pay more than ¥95,749.00 per additional QALY gained, LTBI testing with TBST followed by treatment with 1 H₃P₃ should be considered a cost-effective strategy among close contacts of ATB patients in China. Additionally, this result supports the perspective that nationwide implementation of prevention among close contacts of ATB patients could greatly reduce the number of TB cases [3].

The one-way sensitivity analysis demonstrated that cost-effectiveness was most influenced by LTBI prevalence among close contacts. This observation aligns with previous studies: Cao et al. [13] reported that LTBI testing with the IGRA, followed by the 6-week H₂P₂ regimen (twice-weekly rifapentine and isoniazid), is more appropriate in settings with high LTBI prevalence. Similarly, Wingate et al. [50] found that LTBI testing followed by 3HP treatment is particularly advantageous for refugees from countries with moderate to high LTBI prevalence. These results indicate that LTBI prevalence directly determines the number of individuals who may benefit from preventive treatment. In settings with higher LTBI prevalence, the intervention is expected to prevent more ATB cases, thereby improving health outcomes and reducing the ICER. In contrast, in settings with lower prevalence, the cost per QALY gained may increase, potentially diminishing cost-effectiveness. Therefore, the value of the intervention is highly context-dependent, and prioritizing high-risk populations, such as household contacts, ATB contacts, or individuals in high-burden regions, would optimize efficiency.

In addition, the mortality of patients with ATB emerged as another important driver of cost-effectiveness. Higher ATB-related mortality increases the potential life-years and QALYs that can be preserved through effective preventive treatment, thereby lowering the ICER and strengthening the economic attractiveness of the intervention. Conversely, when ATB mortality is assumed to be lower, the absolute health gains achievable through prevention are reduced, potentially attenuating cost-effectiveness. This finding is consistent with the study by Lim et al. [51], who reported that higher active tuberculosis–related mortality was associated with lower ICERs. Together, these results highlight that local epidemiological conditions—particularly case-fatality rates shaped by access to timely diagnosis and treatment—play a critical role in determining the economic value of LTBI screening and preventive therapy strategies.

Furthermore, the utility associated with cured ATB or self-healing ATB also played a critical role in affecting cost-effectiveness, underscoring the importance of valuing long-term health states within the model. When cured ATB or self-healing is assumed to result in a lower quality of life compared to general health, the relative advantage of preventing ATB is amplified, thereby enhancing the perceived favourability of the intervention. This finding underscores the need for robust, locally derived utility estimates to ensure evaluations accurately reflect patient experiences and societal preferences.

The PSA results further support the robustness of these findings. The majority of ICER estimates for strategy 4 were located in the northeast quadrant, with a smaller proportion in the northwest quadrant. This distribution indicates that strategy 4 is most frequently associated with a “more costly but more effective” profile and can be dominant under specific parameter combinations, highlighting its substantial potential for health benefits. The cost-effectiveness acceptability curve shows that strategy 4 does not dominate at any WTP threshold. At lower thresholds (¥8,425.91~¥8,808.91per QALY), the probability of cost-effectiveness for strategy 4 is nearly equivalent to that of no intervention, indicating a competitive balance. At the higher threshold of ¥95,749 per QALY, strategy 4 attains the highest probability of being cost-effective (43.01% compared to 25.92%), supporting its potential as a favourable option under China’s reference standard. Nevertheless, considerable uncertainty persists, and the conclusions remain sensitive to key parameter values. Further empirical data are needed to enhance the robustness of these cost-effectiveness results.

The strengths of our study include a comprehensive comparison of various LTBI testing tests combined with preventive treatment strategies. We evaluated a novel ultra-short preventive regimen (1 H₃P₃) against the 3 H₂P₂ regimen, and compared it with a no-intervention scenario. Additionally, our model incorporated real-world factors, including treatment acceptance, adherence, spontaneous cure, successful treatment, and relapse among ATB patients, which have rarely been addressed in previous studies. Consequently, our findings offer guidance for selecting optimal treatment regimens and offer data to evaluate whether the current economic context supports the implementation of LTBI testing and preventive therapy.

This analysis has several limitations. First, secondary transmission, drug-resistant tuberculosis, and the treatment of recurrent tuberculosis were not explicitly considered, which may have resulted in an underestimation of the benefits associated with the intervention strategies. Second, the protective effect of 1 H₃P₃ among close contacts of ATB patients was estimated using data from studies of silicosis patients, due to insufficient follow-up, which may have underestimated its effectiveness in this population. Additional studies evaluating the 1 H₃P₃ regimen among close contacts of ATB patients are necessary to substantiate these conclusions. Third, the 1 H₃P₃ regimen is primarily used in China and is not widely practiced in most other countries. Therefore, the generalizability of our findings to international settings may be limited. Finally, the parameters were derived from national averages, so the strategies may not be directly applicable to all regions. Local resources, tuberculosis epidemiology, and risk factors should be considered.

Conclusion

The cost-effectiveness analysis indicates that LTBI testing with TBST, followed by treatment with 1 H₃P₃, can improve health outcomes and reduce costs in China. This strategy may therefore be considered a cost-effective option for TB control in the country. These findings may provide important evidence to support decision-makers in implementing more cost-effective approaches to TB control.

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Abbreviation

1 H₃P₃

A 4-week regimen of thrice-weekly rifapentine plus isoniazid

3 H₂P₂

A 3-month regimen of twice-weekly rifapentine plus isoniazid

ATB

Active Tuberculosis

DOT

Directly Observed Treatment

GDP

Gross Domestic Product

IC

Incremental Cost

ICER

Incremental Cost-Effectiveness Ratio

IGRA

Interferon-Gamma Release Assays.

LTBI

Latent Tuberculosis Infection

PPD

Purified Protein Derivative

PSA

Probabilistic Sensitivity Analysis

QALY

Quality-Adjusted Life Year

TB

Tuberculosis

TBST

Mycobacterium TB antigen-based Skin Test

TPT

Tuberculosis Preventive Treatment

WHO

World Health Organization

WTP

Willingness-To-Pay

Author contributions

JL designed and analyzed the study and drafted the manuscript. YW and FG contributed to the data acquisition. YQ revised the study model and statistical methods. CX were responsible for study conception. All authors reviewed the manuscript for scientific content and approved the final manuscript.

Funding

National Key R&D Program (National Key R&D Program 2025ZD01901000 2024YFC2311204, 2024YFC2310905).

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Consent to participate

Not applicable.

Declaration of Generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the authors used ChatGPT-5 (OpenAI, August 2025) to improve language clarity and grammar. All content was reviewed and edited by the authors, who take full responsibility for the final version.

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Competing interests

The authors declare no competing interests.