The Feasibility and Acceptability of a Diagnostic Algorithm for Timely Post-tuberculosis Lung Disease Diagnosis at Primary Health Care Facilities in Mbarara, Uganda.

Background Tuberculosis (TB) remains a major cause of death globally, with around 1.5 million deaths in 2020. These figures account only for deaths during the active disease phase, not those occurring after microbiologic cure. People who complete pulmonary TB treatment are about four times more likely to die early compared to the general population. Studies show up to 50% of TB survivors report health issues consistent with post-TB lung disease (PTLD). In Malawi, 61% of TB patients still had symptoms at treatment completion, and 28% had irreversible lung damage after five years. Pulmonary TB is now seen as a risk factor for chronic lung disease and poor quality of life. Between 60-90% of TB survivors face limited exercise ability, respiratory symptoms, and reduced quality of life. PTLD is marked by abnormal spirometry (airflow obstruction or low forced vital capacity) and recurrent symptoms often misdiagnosed as TB relapse. This leads to unnecessary TB treatment and drug-related side effects, especially with false-positive Xpert tests in the absence of smear or culture confirmation. PTLD is frequently missed in low-income, TB-endemic settings due to limited resources. Chest imaging shows lung cavities, bronchiectasis, and fibrosis. Spirometry reveals obstructive, restrictive, or mixed patterns, but these tests are not routinely available at primary health centers. Newer tests to distinguish PTLD from TB relapse have not been widely adopted, and culture-the gold standard-is not easily accessible. PTLD receives little attention in global TB guidelines, leading to limited research and diagnostic tools in low- and middle-income countries. Patients at risk of PTLD could be identified using pre-treatment chest X-rays, history, and physical exams, but these approaches are underused. The burden of PTLD varies across sub-Saharan Africa depending on local settings and case definitions. For example, a study in Tanzania found that 90% of people treated for TB in the past five years showed signs of PTLD. Despite a proposed definition from a recent post-TB symposium, no standard PTLD diagnostic criteria exist for low-resource settings. A study in three African countries showed inconsistent PTLD diagnosis, including in Ethiopia, where providers failed to diagnose PTLD in eligible patients. This highlights a critical gap in PTLD diagnosis. More research is needed to create a practical diagnostic tool and understand the barriers to clinical diagnosis. The overall aim of this trial is to build on an existing cohort and design a diagnostic algorithm for PTLD suitable for TB-endemic, low-income settings. PTLD presents a serious but often ignored challenge in TB-endemic areas. People finishing TB treatment should be assessed for overall health, including lung function and nutrition. However, low-income settings lack access to advanced tests like spirometry, relying only on symptom checks. TB programs often overlook PTLD, and health workers at primary facilities may have limited awareness. This trial focuses on improving early PTLD diagnosis at primary health centers, which can impact care for other chronic diseases. While training programs have improved diagnosis of non-communicable diseases, few focus on PTLD. A simple screening algorithm is needed for use at the primary care level. This trial aims to address both personal and system-level barriers to diagnosis. In Uganda, TB treatment is offered at primary health facilities, so early PTLD diagnosis depends on front-line clinicians. PTLD diagnosis is especially difficult at level-three health centers (HC3s) due to limited knowledge, no access to spirometry or imaging, and lack of clear guidelines.

Innovation Innovation A pilot cluster randomized clinical trial in post-TB morbidity is a step closer to improving post-TB care. Importantly, the selected health facilities will focus on post-TB diagnosis and care which has not been part of routine care. Despite the recommendation by the first PTLD symposium, this study aim presents an opportunity to solve this health challenge using locally generated data that can be applied to other low-income settings eliminating a one-size-fits-all approach.

Approach The main idea is that adding a clinical diagnostic algorithm to TB clinicians' workflow will support timely PTLD diagnosis and referrals for advanced care.

Design: This will be a prospective two-arm cluster randomized clinical trial (RCT) using the diagnostic algorithm designed in Aim 1 as the intervention. The primary outcome will be the duration of appropriate referral from level three health centers (HC3s) to a post-TB clinic at Mbarara Regional Referral Hospital (MRRH). The aim is to test the feasibility of implementing a clinical diagnostic algorithm for PTLD aiding clinicians at primary healthcare facilities (HC3s) in making accurate diagnoses of PTLD and facilitating timely referrals for effective treatment.

Study Setting: This study will be conducted at HC3s within Mbarara district Study Participants: The study will involve HC3s selected from the health facilities used for the qualitative interviews in Aim 2. TB clinicians at each health facility will screen individuals who have completed TB treatment for potential PTLD.