Prevalence, Progression, and Treatment of Asymptomatic Tuberculosis: A Prospective Cohort Study in Lanxi County, Zhejiang Province, China

Abstract

Background

Individuals with asymptomatic tuberculosis (TB) are considered a significant risk to the disease burden and transmission. However, the progression and treatment for asymptomatic TB remain incompletely described.

Methods

This prospective cohort study was embedded within a prevalence survey conducted in 2021 and 2022 in Lanxi County, China. All patients with pulmonary TB who consented to participate would be included in the study and were categorized as asymptomatic or symptomatic. For the primary analysis, asymptomatic TB was defined as the absence of current cough, fever, night sweats, weight loss, or hemoptysis. Patients were followed up until 10 November 2024.

Results

Among 109 345 individuals screened, 193 were included, of whom 101 (52.3%) were symptomatic and 92 (47.7%) were asymptomatic. The proportion of asymptomatic TB varied from 32.5% to 62.7% depending on varying symptom negative threshold. Fewer asymptomatic patients were bacteriologically confirmed compared to symptomatic patients (71.7% [66/92] vs 90.1% [91/101], P = .001). The median time for asymptomatic patients at screening to develop symptoms was 102 days. Most patients in both groups received treatment for active TB (97.8% vs 99.0%, P = .606). The treatment success rate among asymptomatic patients was comparable to that of symptomatic patients (93.3% vs 96.0%, P = .521), but their treatment duration was significantly shorter (196 vs 273 days, P < .001).

Conclusions

In the community setting, a significant number of TB cases were asymptomatic and remained so for months. These cases demonstrated satisfactory treatment coverage and outcomes, with shorter durations compared to symptomatic TB, suggesting the potential for developing shorter regimens for asymptomatic TB.

A considerable number of tuberculosis cases were asymptomatic and remained clinically silent for months. They achieved satisfactory outcomes comparable to those of symptomatic patients but with shorter anti-tuberculosis treatment durations.

Graphical Abstract

Graphical Abstract.

Tuberculosis (TB) is one of the leading causes of morbidity and mortality worldwide, with 10.8 million people falling ill with TB and 1.25 million deaths from TB according to World Health Organization (WHO) estimates [1]. There is an urgent need to substantially interrupt Mycobacterium tuberculosis transmission to ramp up the fight against TB.

It is generally accepted that asymptomatic individuals with bacteriologically confirmed TB could contribute significantly to the global TB burden and to M tuberculosis transmission [2]. For the state, the term asymptomatic TB—also referred to as subclinical TB—has been introduced and underlined, defined as a person with TB disease who did not report symptoms suggestive of TB during screening [1, 3]. Previous prevalence surveys suggested that asymptomatic TB accounts for approximately 50% of all TB cases [4–7]. One study estimated that 68% of global transmission is from asymptomatic TB [8]. Therefore, asymptomatic TB should be a priority in TB control.

However, we still have limited understanding of asymptomatic TB. Research on the prevalence of asymptomatic TB in different populations, under varying definitions, remains insufficient [5]. Additionally, studies on the treatment and disease progression of asymptomatic TB are inconclusive. Currently, the diagnosis and treatment of asymptomatic TB still follow symptomatic TB guidelines, and there is a need to refine the diagnostic and treatment process for asymptomatic TB.

Since 2021, a prevalence survey program targeting certain high-risk populations has been conducted in Lanxi County, Zhejiang, China. Lanxi County is located in eastern China, with a resident population of 574 801 in 2020. The notification rate of pulmonary TB in 2021 was 74.46 per 100 000 persons. Chest X-ray (CXR) was performed as the screening method, and those with abnormalities on their CXR were referred for further examination.

This observational study aimed to describe the proportion of individuals with asymptomatic TB and their characteristics and disease progression. The study also compared the treatment regimens and outcomes between asymptomatic and symptomatic patients.

METHODS

Study Design and Procedure

This prospective observational cohort study was embedded within a prevalence survey in Zhejiang, China. All of the pulmonary TB cases identified and willing to provide informed consent were included in the study, whether or not they had been diagnosed before the screening. Patients identified with TB were divided into the asymptomatic group and symptomatic group according to certain definitions (see below).

Information on diagnosis and treatment was collected from the case management system in hospitals and the electronic Tuberculosis Information Management System. Information on symptoms was extracted from the medical records. All patients with recurrence were reconfirmed by the investigators. Untreated patients were also followed to obtain their current health status.

The study was approved by the Ethics Review Committee of Huashan Hospital, Fudan University. Informed consent was obtained from all participants included in the study.

Screening and Diagnostic Procedure

In 2021 and 2022, a prevalence survey was conducted for key populations in Lanxi County, Zhejiang Province, China. The targeted key populations included the following 3 groups: residents aged >60 years, individuals with diabetes mellitus aged >35 years under community follow-up management, and individuals with a history of TB treatment in the past 10 years (excluding those currently receiving anti-TB treatment).

The prevalence survey was integrated with existing public health services, mobilizing these key populations to undergo CXR screening at nearby clinics. The interpretation of CXR findings and subsequent assessments followed the same procedures as described in our previous study [9]. In brief, CXR images were reviewed online by 2 radiologists independently. Participants with TB-suggestive CXR findings were referred to a designated local hospital for further examinations.

All of the participants with TB-suggestive CXR findings were examined through bacteriological tests unless they could not produce sputum and refused to receive bronchoscopy. Those who had a negative bacteriological result or were unable to complete any bacteriological test were adjudicated by a TB specialist based on a combination of epidemiological history, clinical manifestations, and chest imaging, following the National Tuberculosis Diagnosis Standard [10]. Specifically, for bacteriologically unconfirmed cases, the diagnostic criteria were as follows: chest imaging revealing lesions consistent with active pulmonary TB without an alternative diagnosis to explain the radiographic abnormality; additionally, at least 1 of the following conditions needed to be met: (1) presenting with suspected symptoms of pulmonary TB (eg, cough, expectoration, hemoptysis); (2) a positive tuberculin skin test (TST) at a moderate level or above or a positive interferon-γ release assay (IGRA); and/or (3) a positive test for M tuberculosis antibodies.

Definitions

In the primary analysis, asymptomatic TB was defined as TB either bacteriologically confirmed or unconfirmed in the absence of symptoms of current cough, fever, night sweats, weight loss, or hemoptysis. Patients presenting at least 1 of these symptoms were categorized as symptomatic TB cases. When discussing the proportion of asymptomatic TB using different definitions, this study adapted 4 different definitions of asymptomatic TB:

• Definition 1: TB either bacteriologically confirmed or unconfirmed in the absence of any symptoms.

• Definition 2 (used in the primary analysis): TB either bacteriologically confirmed or unconfirmed in the absence of current cough, fever, night sweats, weight loss, or hemoptysis.

• Definition 3: TB either bacteriologically confirmed or unconfirmed in the absence of current cough, fever, night sweats, or weight loss.

• Definition 4: TB either bacteriologically confirmed or unconfirmed in the absence of a prolonged cough (>2 weeks).

Alcohol consumption was categorized into 3 groups: never, occasional (less than once a week), and frequent (at least 2 times a week). Diabetes mellitus was defined as a prior diagnosis (collected through health records) or a positive fasting glucose test [11]. Smoking status was classified into 3 categories: never smoker, former smoker, and current smoker.

Treatment success was defined as completion of the prescribed treatment course with stable culture and smear conversion based on the Chinese National Tuberculosis Diagnosis and Treatment Guidelines [12].

Statistical Analysis

Categorical variables were described with counts (percentages), and continuous variables were described as mean ± standard deviation or median with interquartile range (IQR). The t test, Wilcoxon rank-sum test, χ² test, and Fisher exact test were used for variable comparisons as appropriate. Univariate and multivariate logistic regression models were used to identify factors associated with asymptomatic TB. Univariate logistic regression was first performed and variables with a P value <.1 were then included in the multivariate logistic regression model. Odds ratios (ORs), adjusted ORs, and their corresponding 95% confidence intervals (CIs) were reported. Time to symptom development was assessed by use of the Kaplan-Meier method. A 2-sided P value of .05 was considered statistically significant. All analyses were conducted in R software (version 4.3.1).

RESULTS

Study Population

The prevalence survey encompassed 109 345 individuals. The median age of all participants in the prevalence survey was 69.0 years (IQR, 65.0–74.0 years). The age distribution of all participants in the prevalence survey and that of the general population in Lanxi County are shown in Supplementary Table 1. Among participants in the prevalence survey, 46% (50 121/109 345) were male, compared to 51% (292 974/574 801) in the general population of Lanxi County. Consequently, a total of 199 individuals were identified with pulmonary TB disease and 193 of them provided informed consent and were included in this study, including 143 (74.1%) who were newly diagnosed during the prevalence survey (Figure 1). At the time of establishing the diagnosis of TB, 101 (52.3%) were symptomatic and 92 (47.7%) were asymptomatic. Of the 193 participants in the study, 157 (81.3%) were bacteriologically confirmed. The median follow-up duration was 1128 days (range, 688–1405 days) after diagnosis.

Figure 1.

Flowchart of tuberculosis (TB) screening, diagnosis, treatment, and outcomes. Asymptomatic is defined as having no symptoms of current cough, fever, night sweats, weight loss, or hemoptysis, and symptomatic is defined as having at least 1 of these symptoms.

Characteristics of Participants

Table 1 presents the baseline characteristics of participants. The median age was 69.0 years (IQR, 65.0–74.0 years), and 77.2% of them were male. Diabetes mellitus was found in 26.1% of participants with asymptomatic TB and 20.8% of participants with symptomatic TB. Though not significant, presence of cavity was more common in participants with symptoms than those without symptoms (25.4% vs 19.0%).

Table 1.

Baseline Characteristics of the Patients

Variable	Overall (n = 193)	Asymptomatic TB (n = 92)	Symptomatic TB (n = 101)
Age, y, median (IQR)	69.0 (65.0–74.0)	69.0 (65.0–73.0)	69.0 (65.0–74.0)
Male sex	149 (77.2)	78 (84.8)	71 (70.3)
Education level
Illiterate	48 (24.9)	19 (20.7)	29 (28.7)
Elementary school	98 (50.8)	49 (53.3)	49 (48.5)
Middle school or high school	47 (24.4)	24 (26.1)	23 (22.8)
Body mass index, kg/m2, median (IQR)	21.2 (19.1–22.9)	21.5 (19.3–23.2)	21.1 (19.1–22.4)
Smoking status
Never smoker	123 (63.7)	51 (55.4)	72 (71.3)
Prior smoker	14 (7.3)	10 (10.9)	4 (4.0)
Current smoker	56 (29.0)	31 (33.7)	25 (24.8)
Alcohol consumption
Never	120 (62.2)	49 (53.3)	71 (70.3)
Occasional	15 (7.8)	9 (9.8)	6 (5.9)
Frequent	58 (30.1)	34 (37.0)	24 (23.8)
Diabetes mellitus	45 (23.3)	24 (26.1)	21 (20.8)
Hypertension	66 (34.2)	38 (41.3)	28 (27.7)
Prior TB history	9 (4.7)	1 (1.1)	8 (7.9)
Presence of cavitya	26 (22.2)	11 (19.0)	15 (25.4)

Data are presented as No. (%) unless otherwise indicated.

Abbreviations: IQR, interquartile range; TB, tuberculosis.

^aChest computed tomography scan was not performed in 44 participants and data were missing in 32 participants.

Among bacteriologically unconfirmed asymptomatic cases, 90.5% (19/21) were positive for IGRA, while 9.5% (2/21) did not undergo IGRA but had a strongly positive TST. Among bacteriologically unconfirmed symptomatic cases, 50.0% (4/8) were positive for IGRA and 37.5% (3/8) were positive for M tuberculosis antibodies.

The proportion of participants bacteriologically confirmed was significantly lower in the asymptomatic group compared to the symptomatic group (71.7% [66/92] vs 90.1% [91/101], P = .001). The proportions of participants with positive sputum smear, culture, or Xpert MTB/RIF results were significantly lower among asymptomatic participants compared to symptomatic participants (smear: 9.3% vs 49.4%, P < .001; culture: 48.1% vs 76.6%, P = .004; Xpert MTB/RIF: 54.7% vs 83.1%, P = .001; Table 2). Twenty-two patients with negative sputum results were finally bacteriologically confirmed via bronchoalveolar lavage fluid. Additionally, 1 case (1.0%) in the symptomatic group was rifampicin resistant.

Table 2.

Positivity Rate of Different Bacteriological Tests by Asymptomatic and Symptomatic Tuberculosis Groups

Tests	Overall	Asymptomatic TB	Symptomatic TB	P Value
Sputum
Smear	29.9% (46/154)	9.3% (7/75)	49.4% (39/79)	<.001
Culture	61.6% (61/99)	48.1% (25/52)	76.6% (36/47)	.004
Xpert MTB/RIF	69.6% (78/112)	54.7% (29/53)	83.1% (49/59)	.001
Bronchoalveolar lavage fluid
Smear	28.0% (7/25)	8.3% (1/12)	46.2% (6/13)	.073
Culture	33.3% (8/24)	16.7% (2/12)	50.0% (6/12)	.193
Xpert MTB/RIF	70.4% (19/27)	53.8% (7/13)	85.7% (12/14)	.103
NGS	100.0% (12/12)	100.0% (7/7)	100.0% (5/5)

Data are shown as percentage (number positive/number tested).

Abbreviations: NGS, next-generation sequencing; TB, tuberculosis.

Proportions of Participants With Asymptomatic TB

Figure 2 shows the proportions of asymptomatic TB depending on varying symptom negative threshold. Of all of the 193 participants with pulmonary TB, the proportion of asymptomatic TB at the time of diagnosis was 37.8% by definition 1 (cases without any symptom), 47.7% by definition 2 (cases without current cough, fever, night sweats, weight loss, or hemoptysis), 50.3% by definition 3 (cases without current cough, fever, night sweats, or weight loss), and 62.7% by definition 4 (cases without prolonged cough >2 weeks) (Figure 2A). Among bacteriologically confirmed patients, these proportions were 32.5%, 42.0%, 44.6%, and 57.3%, respectively (Figure 2B).

Figure 2.

The number and proportions of asymptomatic tuberculosis (TB) according to 4 definitions among all patients with TB (A) or patients with bacteriologically confirmed TB (B). The 4 definitions of asymptomatic TB differ in the threshold of symptoms used to define “asymptomatic”: Definition 1 includes cases without any symptoms; Definition 2 includes cases without current cough, fever, night sweats, weight loss, or hemoptysis; Definition 3 includes cases without current cough, fever, night sweats, or weight loss; Definition 4 includes cases without a prolonged cough (>2 weeks). “Other symptoms” included dyspnea, chest pain, chest tightness, anorexia, fatigue, and low back pain.

Risk Factors Associated With Presenting With Asymptomatic TB

In the univariable model, male sex, prior smoking, frequent alcohol consumption, hypertension, and no history of TB were all associated with a higher likelihood of asymptomatic TB. In the multivariable model, history of TB was significantly associated with lower likelihood of asymptomatic TB (adjusted OR, 0.09 [95% CI, .00–.55]; P = .030; Table 3).

Table 3.

Risk Factors Associated With Presenting With Asymptomatic Tuberculosis Compared to Symptomatic Tuberculosis

Variable	Univariable Regression			Multivariable Regression
	OR	(95% CI)	P Value	Adjusted OR	(95% CI)	P Value
Male sex	2.35	(1.17–4.91)	.018	1.82	(.82–4.16)	.143
Smoking status
Never smoker	Reference	…		Reference	…
Prior smoker	3.53	(1.11–13.4)	.042	2.72	(.76–11.8)	.144
Current smoker	1.75	(.93–3.33)	.085	1.28	(.56–2.94)	.555
Alcohol consumption
Never	Reference	…		Reference	…
Occasional	2.17	(.74–6.85)	.165	1.60	(.49–5.58)	.443
Frequent	2.05	(1.09–3.91)	.027	1.54	(.67–3.57)	.310
Hypertension	1.83	(1.01–3.37)	.048	1.66	(.88–3.17)	.120
Prior TB history	0.13	(.02–1.04)	.055	0.09	(.00–.55)	.030

Abbreviations: CI, confidence interval; OR, odds ratio; TB, tuberculosis.

Progression From Asymptomatic TB to Symptom Onset

At the time of screening, 106 of 143 (74.1%) participants who had not been diagnosed with TB before were asymptomatic. Among them, 31 (29.2%) developed at least 1 symptom (cough, fever, night sweats, weight loss, or hemoptysis) between screening and diagnosis, while the other 75 (70.8%) remained asymptomatic. Survival analysis of the 106 participants showed that the median duration from detection of CXR abnormalities to the onset of symptoms was 102 days, with diagnosis before symptom onset identified as censor (Figure 3). The lower bound of the 95% CI for the median duration was 95 days. However, since 70.8% of participants were diagnosed before developing symptoms, the upper bound could not be estimated.

Figure 3.

Time to symptom onset from screening. Symptoms includes current cough, fever, night sweats, weight loss, or hemoptysis. Individuals diagnosed with tuberculosis before symptom onset were identified as censor.

Asymptomatic Duration

Individual data on the durations of the asymptomatic and symptomatic period for all participants are presented in Figure 4. To estimate the community transmission risk for asymptomatic individuals, we calculated the number of infectious person-days spent in the community for each participant before diagnosis (from the onset of illness), as well as the number of remaining asymptomatic person-days for all asymptomatic participants and those who eventually developed symptoms. These values were then summed to obtain the total infectious person-days and the total asymptomatic person-days. We found that the number of remaining asymptomatic person-days accounted for 37.6% (5666/15 083) of the total infectious person-days, after excluding 3 participants who had symptoms for >3 years before TB diagnosis (Figure 4A). Among bacteriologically confirmed cases, asymptomatic person-days accounted for 33.7% (4453/13 202) of the total infectious person-days (Figure 4B).

Figure 4.

Duration of asymptomatic and symptomatic periods from onset of illness to diagnosis of tuberculosis for all participants (A) or bacteriologically confirmed participants (B). The x-axis represents each participant, with each bar indicating the duration of asymptomatic periods above the x-axis and symptomatic periods below the x-axis. The y-axis is limited to 0–3 years and 3 participants with a symptomatic period >3 years are not fully shown in the figure. Asymptomatic is defined as having no symptoms of current cough, fever, night sweats, weight loss, or hemoptysis, while symptomatic is defined as having at least 1 of these symptoms.

Treatment Regimens and Outcomes

Most participants in both the asymptomatic TB group and the symptomatic TB group received treatment for active TB (97.8% [90/92] vs 99.0% [100/101], P = .606). Two participants in the asymptomatic group refused treatment due to the absence of symptoms, and 1 participant in the symptomatic group refused treatment due to poor health status. The 2 untreated participants with asymptomatic TB still remained asymptomatic at the recent follow-up (1181 days and 688 days after TB diagnosis, respectively) and did not start any TB treatment.

The most common initial treatment regimen was a 4-drug combination consisting of isoniazid, rifamycins (rifampicin or rifapentine), pyrazinamide, and ethambutol in both groups (67.5% [52/77] vs 53.6% [45/84], P = .071). The initial treatment regimens were detailed in Supplementary Figure 1.

There was no significant difference in the treatment success rate between the 2 groups (93.3% [84/90] vs 96.0% [96/100], P = .521). Three participants with asymptomatic TB and 3 participants with symptomatic TB died due to reasons unrelated to TB or anti-TB treatment. The percentage of participants who had their treatment regimens adjusted due to adverse reactions was similar between the 2 groups (26.0% [19/73] vs 24.1% [19/79], P = .778). Among participants who completed treatment, the median treatment duration for participants with asymptomatic TB was 196 days (IQR, 188–288 days), significantly shorter than that in the symptomatic group (273 days [IQR, 203–365 days]) (P < .001). We further stratified treatment duration by pyrazinamide use. Among participants receiving pyrazinamide, the median treatment duration in the asymptomatic group was 190 days (IQR, 186–206 days), significantly shorter than that in the symptomatic group (248 days [IQR, 194–365 days]; P < .001). In the pyrazinamide-free group, the median treatment duration was also shorter in the asymptomatic group (217 days [IQR, 189–340 days]), compared to the symptomatic group (276 days [IQR, 209–365 days]) (P = .018).

Among 180 participants treated successfully, 6 individuals with recurrent TB were observed. The median time from the end of treatment to recurrence was 1083 days (IQR, 1019–1101 days). Five of them were bacteriologically confirmed. The recurrence rate was similar in the 2 groups (3.6% [3/84] in asymptomatic group vs 3.1% [3/96] in symptomatic group , P = 1.000).

DISCUSSION

This study described the prevalence, progression, characteristics, and treatment of individuals with asymptomatic TB identified through a prevalence survey in a city in eastern China. To the best of our knowledge, this is the first study to comprehensively discuss the long-term outcome and disease progression of asymptomatic TB.

Our study demonstrated that the proportion of asymptomatic TB varied substantially depending on the definition applied. Notably, even under the strictest definition—absence of any symptoms—nearly 30% of patients were classified as asymptomatic, a proportion that should not be overlooked in TB control efforts. This finding is consistent with other studies and suggests the common prevalence of asymptomatic TB in the community setting [4–7]. This variation has important public health implications. In resource-limited settings where imaging tools such as CXRs are not routinely available, symptom-based screening might still remain the primary method for TB identification. Our findings suggest that relying solely on classic symptoms—such as prolonged cough—would identify only about 40% of TB cases. Expanding the symptom criteria to include any cough, fever, night sweats, or weight loss could lead to an additional 15% being identified, and including hemoptysis, dyspnea, chest pain, chest tightness, anorexia, fatigue, and low back pain may capture another 10%–12%.

Moreover, from the earliest traceable onset date to the diagnosis of TB, this study found that the asymptomatic period accounted for 37.6% of the total infectious period in the community, suggesting the ongoing hidden transmission for asymptomatic TB. When calculating this proportion of the asymptomatic period, we excluded 3 participants who had symptoms for >3 years prior to their TB diagnosis. A previous study suggested that the natural course of TB, from onset to cure or death, is approximately 3 years [13]. Therefore, it is highly likely that their long-standing symptoms were attributable to other chronic pulmonary conditions, such as chronic obstructive pulmonary disease. Implementing active case finding may help shorten this duration and thereby reduce potential TB transmission [14, 15].

In the primary analysis, we defined asymptomatic TB as cases who were either bacteriologically confirmed or unconfirmed in the absence of current cough, fever, night sweats, weight loss, or hemoptysis [16]. This definition extended the WHO's symptom screening recommendations for ruling out TB disease in people with human immunodeficiency virus by including hemoptysis as an additional criterion. Hemoptysis is widely recognized as a typical symptom of TB [12] and may also indicate a certain stage of disease progression. Therefore, classifying patients with hemoptysis as asymptomatic might be inappropriate.

This study found that patients with asymptomatic TB had a lower bacterial burden compared to clinical TB patients, in accordance with previous research [17]. These findings suggest that it is more difficult to establish the diagnosis for asymptomatic TB. More sensitive bacteriological testing tools are urgently needed to prevent misdiagnosis or diagnosis delay for asymptomatic TB.

Multivariate analysis showed that individuals with a history of TB were less likely to be asymptomatic than symptomatic. A possible explanation for this might be that people with a history of TB have a poorer underlying lung condition [18] and are more likely to develop symptoms.

This study found that the median time to symptom development for asymptomatic patients at screening was 102 days. To our knowledge, no large-scale studies have reported the time interval between screening abnormalities and symptom onset. Naidoo et al reported that the time to symptom onset from bacteriological diagnosis of TB in 11 antiretroviral therapy–accessing participants ranged from 1.3 to 8 months [19]. Although the populations differed, our median time was similar to that study. Modeling studies estimated an average asymptomatic period for TB of 6 months [20]. Our findings suggested a shorter interval, which may be because we used the screening date as the starting point, while the true disease onset may have occurred earlier.

To the best of our knowledge, this study was one of the few that focused on the treatment of individuals with asymptomatic TB. In this study, the treatment coverage for participants with asymptomatic TB was similar to that of participants with symptomatic TB. A possible explanation for this may be that asymptomatic patients were promptly referred to clinical facilities after being identified through screening. From the clinicians’ perspective, these patients presented with either positive bacteriological results or radiological abnormalities, and regardless of symptom presence, they required regular antituberculosis treatment. Notably, the 2 asymptomatic participants who refused treatment remained asymptomatic and did not start any TB treatment by the end of the study. This finding suggests that the lack of clinical symptoms indeed impacts the treatment willingness for some individuals, highlighting the need for the development of targeted strategies to manage such individuals effectively.

In our study, pyrazinamide was not included in the treatment regimens of 44.0% of asymptomatic and 31.2% of symptomatic participants. This was primarily due to concerns about hepatotoxicity, especially in older adults [21, 22]. The 2016 guidelines recommend caution of pyrazinamide use in elderly patients with mild disease and low risk of drug resistance [23]. Given that most patients in our cohort were >60 years old, the overall utilization of pyrazinamide was relatively low.

The treatment outcome was satisfactory among both groups in this study. These findings are generally consistent with data from a previous study [17]. An active case finding–based cohort study showed a successful outcome in 64.5% of patients with asymptomatic TB [24]. The high rates of loss to follow-up during treatment and nonevaluation probably explain this difference. These findings underline the importance of support for the asymptomatic TB care cascade.

In this study, we observed that none of the recurrent cases occurred among bacteriologically unconfirmed TB cases. Bacteriologically confirmed TB cases may have a higher risk of relapse, suggesting that these patients require more rigorous follow-up and management, even in the absence of symptoms.

It is encouraging to observe in this study that the treatment duration for asymptomatic TB was significantly shorter than that of symptomatic TB without introducing new drugs or increasing the dosage of existing medications. This finding has important implications for developing shorter treatment regimens for asymptomatic TB, considering that a similar concept has already been validated in children with mild TB [25, 26]. Hopefully, shorter treatment could also be guided by predictive biomarkers to determine the optimal treatment duration for each patient.

This study has some limitations. First, the population included in the study was the key population in 1 county, which may limit the generalizability of these findings to the general population. Second, clinical response to anti-TB treatment was not incorporated as part of the formal diagnostic criteria of bacteriologically unconfirmed TB since it is not listed in the National Tuberculosis Diagnosis Standard, which may lead to a potential risk of misclassifying TB cases. However, the clinical response to anti-TB treatment of most bacteriologically unconfirmed TB cases was evaluated in our study for assisting in differential diagnosis. In addition, there are the inherent limitations in confirming active TB in every case, and we were unable to definitively quantify the proportion of true TB cases in the bacteriologically unconfirmed group. Third, genotyping of strains was not performed for patients with recurrent TB, making it impossible to distinguish between relapse and reinfection. Fourth, we did not collect screening data on the close contacts of patients and were unable to provide evidence regarding the infectiousness of asymptomatic TB.

In summary, a significant proportion of individuals with TB presented asymptomatic and could remain so for several months. The treatment coverage and outcomes for asymptomatic TB were satisfactory, with a shorter duration compared to symptomatic TB. This suggests the potential of developing shorter treatment regimens for asymptomatic TB.

Supplementary Data

Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Acknowledgments. We thank all physicians and patients for participating in this study.

Author contributions. Conception and design of the work: Y. L., B. C., S. G., K. L., X. J., and Z. F. Data collection: S. G., K. L., X. J., Z. F., S. C., Y. F., G. J., and Z. Y. Data analysis and interpretation: S. G. and Y. L. Drafting the article: S. G. and Y. L. Critical revision of the article: L. So., L. Sh., Y. Z., F. S., and T. L., Y. L., B. C., and W. Z. Final approval of the version to be published: All authors.

Financial support. This work was supported by the National Key Research and Development Program of China (2024YFC2311202); Shanghai's 3-year plan for Public Health Talent Training (GWVI-11.2-YQ03); the National Natural Science Foundation of China (82102406); the Independent Project of Shanghai Sci-Tech Inno Center for Infection and Immunity (SSIII-202404); and the Shanghai Municipal Science and Technology Major Project (HS2021SHZX001).

Potential conflicts of interest . The authors: No reported conflicts of interest.