Persistent respiratory, psychological and quality-of-life impairments 2 years post-tuberculosis: evidence from a cohort study in Cambodia

Extract

Tuberculosis (TB) remains a major global public health challenge. TB programmes have traditionally focused on bacteriological cure and treatment completion as the final milestone of care. However, negative post-TB-related health outcomes have been increasingly documented in several high-TB-burden settings [1, 2].

Shareable abstract

TB survivors may improve substantially in the first year after diagnosis, yet persistent respiratory symptoms, depressive symptoms and stigma can remain for years, highlighting the need for post-TB follow-up and integrated care in high-burden settings https://bit.ly/44jQUVu

To the Editor:

Tuberculosis (TB) remains a major global public health challenge. TB programmes have traditionally focused on bacteriological cure and treatment completion as the final milestone of care. However, negative post-TB-related health outcomes have been increasingly documented in several high-TB-burden settings [1, 2]. Nevertheless, most studies focus on clinical indicators of pulmonary impairment, with comparatively limited attention to broader patient-centred outcomes such as quality of life, mental health, and stigma. Evidence from many high-burden countries, particularly those in Asia, remains scarce. Using cohort data from Cambodia, this study describes the longitudinal trajectory of respiratory and psychosocial health among TB survivors, highlighting the persistent burden of post-TB morbidity beyond treatment completion.

We conducted a prospective cohort study of adults newly diagnosed with all forms of TB in Cambodia, recruited through active case-finding interventions under the Community Mobilization Initiatives to End Tuberculosis (COMMIT) project [3]. Baseline data were collected within 1 month of TB diagnosis, and follow-up assessments were conducted at approximately 1 and 2 years post-baseline (i.e. 7–19 months post-treatment completion). Data were collected using a structured questionnaire administered face-to-face by trained data collectors using REDCap (Research Electronic Data Capture).

Respiratory symptoms (shortness of breath and wheezing) were assessed using the St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease (SGRQ-C) [4]. Overall respiratory health was assessed using the SGRQ-C total score, with higher scores indicating worse respiratory health. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (score ≥10 indicating depressive symptoms) [5]. Quality of life was assessed using the World Health Organization Quality of Life – Brief Version, which covers physical, psychological, social and environmental domains, with higher scores reflecting better quality of life [6, 7]. Stigma was measured using the “self-stigma” subsection of the Van Rie TB patient stigma scale (12 items); higher scores reflect greater self-stigma [8].

Analyses were restricted to participants who completed all three assessments (complete-case). Participant characteristics and outcomes were summarised as frequencies and percentages or mean±sd, as appropriate. Changes between time points were reported as percentage-point differences for binary outcomes and mean differences for continuous outcomes, with 95% confidence intervals based on paired observations.

Out of 837 participants enrolled at baseline, 566 (67.6%) completed all three assessment rounds. Of these, the median age at baseline was 61 years, 49.1% were male, and most had pulmonary TB, with 34.5% bacteriologically confirmed and 61.7% clinically diagnosed. Participants who were lost to follow-up and excluded from this study were significantly younger (aged 50 years versus 61 years, p<0.001), had a higher monthly income (median USD 260 versus USD 200, p<0.001), and were more likely to have bacteriologically confirmed TB (50.9% versus 34.5%, p<0.001).

Respiratory symptoms were common at baseline, with 52.3% reporting shortness of breath and 32.9% reporting wheezing (figure 1). Reported shortness of breath and wheezing declined sharply during the first year after treatment (−32.7% and −16.1%, respectively), with smaller additional reductions thereafter (∼4%). At 2 years, 15.7% of participants continued to report shortness of breath, and 12.4% reported wheezing. Mean SGRQ-C total scores improved from 35.4 at baseline to 15.4 at 1 year and 11.7 at 2 years.

FIGURE 1.

Post-tuberculosis (TB) health outcomes among participants over 2 years of follow-up (n=566). Δ represents a percentage-point difference between time points for binary outcomes and a mean difference for continuous outcomes. Δ values were calculated using paired observations between time points; therefore, sample sizes vary due to missing data. ^#: respiratory symptoms (shortness of breath and attacks of wheezing) were derived from the St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease (SGRQ-C) questionnaire: “I have shortness of breath/have attacks of wheezing: most days of the week/several days a week/a few days a month” (only for attacks of wheezing). ^¶: depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D-10); participants were classified as “having depressive symptoms” if the CES-D-10 score was ≥10 based on the CES-D-10 guideline [5]. ⁺: stigma was assessed using the Van Rie TB Stigma Scale, using the self-stigma questionnaire; the score was calculated and then standardised into a summary score ranging from 0 to 50; higher scores indicate higher self-stigma [8]. WHOQOL-BREF: World Health Organization Quality of Life – Brief Version.

Depressive symptoms remained prevalent over time. Although the proportion of participants having depressive symptoms decreased from 57.4% at baseline to 42.9% at 1 year and 38.5% at 2 years, more than one-third of TB survivors still experienced depressive symptoms 2 years after diagnosis.

Quality of life improved across most domains over time. Physical and psychological scores increased by 9.5 points (95% CI 8.3–10.8 points) and 6.8 points (95% CI 5.5–8.1 points), respectively, between baseline and the first follow-up, with minimal change thereafter. Social relationship scores improved modestly. In contrast, environmental quality-of-life scores showed little overall change. Self-stigma scores decreased from baseline to the first follow-up (−2.3, 95% CI −2.8 to −1.8), with minimal further change between the first and second follow-up (−0.4, 95% CI −0.7 to 0.0). The proportion of self-stigma item responses endorsed as “agree” or “strongly agree” decreased from 23.0% at baseline to 20.1% at 1 year and 18.7% at 2 years.

This study demonstrated that a substantial proportion of TB survivors continue to experience persistent respiratory, psychological, and quality-of-life impairments long after diagnosis, and beyond treatment completion.

Approximately one in six participants continued to report shortness of breath and wheezing 2 years after the diagnosis. This is broadly consistent with studies from Malawi and Uganda showing persistent respiratory symptoms, abnormal lung function, or both, after TB treatment completion [9, 10]. Our findings extend this emerging literature by providing longitudinal evidence from Cambodia and showing substantial improvement after treatment, but residual symptoms persisted for up to 2 years after diagnosis. In the absence of a control group and premorbid condition data, these symptoms cannot be attributed solely to prior TB, but they remain consistent with an ongoing burden of post-TB respiratory morbidity.

More than one-third of participants reported depressive symptoms 2 years after TB diagnosis, suggesting a substantial and persistent psychological burden among TB survivors. Evidence from lower-middle-income countries, including Asia, indicates that mental health disorders among TB-affected populations, including those who have completed treatment, are underdiagnosed and undertreated [11], highlighting the need for mental health support.

Quality-of-life findings further underscore the multidimensional nature of post-TB health. Although physical and psychological domains improved, gains were modest and limited to the first year of follow-up, similar to findings from Nigeria [12, 13]. Social and environmental quality-of-life scores showed little overall change, suggesting that social and environmental well-being remains constrained in this cohort.

TB-related stigma remains a barrier to care-seeking and social reintegration [14]. Our study found that although self-stigma scores decreased over time, TB-related stigma persisted, with 18.7% responding “agree” or “strongly agree” to self-stigma items in the questionnaire at 2 years. Persistent stigma among TB survivors may contribute to ongoing psychological distress and reduced quality of life, highlighting the need for stigma-reduction interventions beyond the treatment phase [2].

There are some limitations to this study. First, these findings were limited to participants who completed all follow-up assessments. Participants lost to follow-up differed in several baseline characteristics from those who completed follow-ups. However, sensitivity comparisons between intention-to-treat and complete-case estimates showed similar prevalence and change estimates across outcomes, suggesting that attrition was unlikely to substantially bias the observed trends. Second, without a non-TB comparison group or pre-morbid data, outcomes cannot be solely attributed to prior TB. Third, outcomes were assessed without clinical measures such as spirometry or imaging, which may introduce self-report biases. Nonetheless, the longitudinal design and the use of standardised instruments provide important foundational evidence from a setting where post-TB health has not previously been described systematically.

In conclusion, TB survivors in Cambodia experienced persistent respiratory and psychological impairments up to 2 years after TB diagnosis. These findings highlight the need to extend TB care beyond treatment completion and integrate post-TB assessment and support into national TB programmes, following the clinical standards on post-TB lung diseases [15]. The care package should holistically address the multidimensional impact of TB on health and well-being and be evaluated in programmatic settings [16]. The findings also accentuate the need for more comprehensive studies, incorporating clinical assessments such as spirometry and chest imaging, to better characterise the magnitude and mechanisms of post-TB health impairment [17].

Data availability

Data may be available upon request. Requests for anonymised data or collaboration enquiries may be made to the corresponding author.