Genetic insights into the connection between pulmonary TB and non-communicable diseases: An integrated analysis of shared genes and potential treatment targets.

BACKGROUND: Pulmonary Tuberculosis (PTB) is a significant global health issue due to its high incidence, drug resistance, contagious nature, and impact on people with compromised immune systems. As mentioned by the World Health Organization (WHO), TB is responsible for more global fatalities than any other infectious illness. On the other side, WHO also claims that noncommunicable diseases (NCDs) kill 41 million people yearly worldwide. In this regard, several studies suggest that PTB and NCDs are linked in various ways and that people with PTB are more likely to acquire NCDs. At the same time, NCDs can increase susceptibility to active TB infection. Furthermore, because of potential drug interactions and therapeutic challenges, treating individuals with both PTB and NCDs can be difficult. This study focuses on seven NCDs (lung cancer (LC), diabetes mellitus (DM), Parkinson's disease (PD), silicosis (SI), chronic kidney disease (CKD), cardiovascular disease (CVD), and rheumatoid arthritis (RA)) and rigorously presents the genetic relationship with PTB regarding shared genes and outlines possible treatment plans. OBJECTIVES: BlueThis study aims to identify the drug components that can regulate abnormal gene expression in NCDs. The study will reveal hub genes, potential biomarkers, and drug components associated with hub genes through statistical measures. This will contribute to targeted therapeutic interventions. METHODS: Numerous investigations, including protein-protein interaction (PPI), gene regulatory network (GRN), enrichment analysis, physical interaction, and protein-chemical interaction, have been carried out to demonstrate the genetic correlation between PTB and NCDs. During the study, nine shared genes such as TNF, IL10, NLRP3, IL18, IFNG, HMGB1, CXCL8, IL17A, and NFKB1 were discovered between TB and the above-mentioned NCDs, and five hub genes (NFKB1, TNF, CXCL8, NLRP3, and IL10) were selected based on degree values. RESULTS AND CONCLUSION: In this study, we found that all of the hub genes are linked with the 10 drug components, and it was observed that aspirin CTD 00005447 was mostly associated with all the other hub genes. This bio-informatics study may help researchers better understand the cause of PTB and its relationship with NCDs, and eventually, this can lead to exploring effective treatment plans.

Bilateral chronic cavitary pulmonary aspergillomas in an adult patient with recurrent tuberculosis: a case report and literature review.

BACKGROUND: Aspergillomas are globular growths of Aspergillus fumigatus, a benign aspergillosis of the lungs. It usually affects patients who are immunocompromised and have anatomically defective lung structures. The majority of aspergilloma cases are asymptomatic, despite the fact that 10% of cases spontaneously resolve. Most patients do not have any symptoms from their lesions. Direct serological or microbiological evidence of an Aspergillus species along with radiologic evidence is required for the diagnosis of an aspergilloma. CASE: We describe a 35-year-old adult Oromo male patient who had been experiencing night sweats, an intermittent productive cough with sparse whitish sputum, loss of appetite, and easy fatigability for 3 months. At 5 years prior, he received treatment for pulmonary tuberculosis that was smear-positive and was subsequently certified healed. Objectively, he was tachypneic and had intercostal, subcostal, and supraclavicular retractions with symmetric chest movement. A high-resolution computed tomography scan revealed bilateral apical cavitary lesions with core soft tissue attenuating spherical masses and an air crescentic sign suggestive of aspergillomas, which were confirmed by sputum light microscopic examination. The patient was managed with antibiotics and antifungals. CONCLUSION: Aspergilloma is a symptom of chronic pulmonary aspergillosis, a category of lung disorders caused by a persistent Aspergillus infection. Primary aspergillomas are uncommon and frequently occur in people with compromised immune systems. A prolonged cough, fever, chest pain, and hemoptysis are all symptoms of pulmonary aspergillomas. The majority of the time, pulmonary aspergillosis is difficult to identify. Despite high mortality and morbidity rates, surgery is still the most effective treatment for pulmonary aspergilloma.

Machine learning algorithms to predict treatment success for patients with pulmonary tuberculosis.

Despite advancements in detection and treatment, tuberculosis (TB), an infectious illness caused by the Mycobacterium TB bacteria, continues to pose a serious threat to world health. The TB diagnosis phase includes a patient's medical history, physical examination, chest X-rays, and laboratory procedures, such as molecular testing and sputum culture. In artificial intelligence (AI), machine learning (ML) is an advanced study of statistical algorithms that can learn from historical data and generalize the results to unseen data. There are not many studies done on the ML algorithm that enables the prediction of treatment success for patients with pulmonary TB (PTB). The objective of this study is to identify an effective and predictive ML algorithm to evaluate the detection of treatment success in PTB patients and to compare the predictive performance of the ML models. In this retrospective study, a total of 1236 PTB patients who were given treatment under a randomized controlled clinical trial at the ICMR-National Institute for Research in Tuberculosis, Chennai, India were considered for data analysis. The multiple ML models were developed and tested to identify the best algorithm to predict the sputum culture conversion of TB patients during the treatment period. In this study, decision tree (DT), random forest (RF), support vector machine (SVM) and naïve bayes (NB) models were validated with high performance by achieving an area under the curve (AUC) of receiver operating characteristic (ROC) greater than 80%. The salient finding of the study is that the DT model was produced as a better algorithm with the highest accuracy (92.72%), an AUC (0.909), precision (95.90%), recall (95.60%) and F1-score (95.75%) among the ML models. This methodology may be used to study the precise ML model classification for predicting the treatment success of TB patients during the treatment period.

The effect of corticosteroids in developing active pulmonary tuberculosis among patients with COVID-19.

Corticosteroids can reduce the mortality rate among patients with severe COVID-19 pneumonia. However, opportunistic infections such as Mycobacterium tuberculosis are of concern, especially among those on high doses of corticosteroids. It is unknown whether the risk of developing subsequent TB infection is high or not among COVID-19 patients on high doses of corticosteroids. Hence, this study was conducted to address this gap of knowledge. We conducted a retrospective, cross-sectional study at the King Chulalongkorn Memorial Hospital from October 12, 2022 to June 30, 2023. Two hundred forty-three participants with documented COVID-19 diagnosis on high dose corticosteroids were enrolled into the study. Baseline characteristics and risk factors of developing TB were collected. The prevalence of TB was significantly different among participants with chronic kidney disease (CKD) stages 2-4 and chronic lung diseases. The incidence of TB post 1-year diagnosis of COVID-19 was 4 out of 243 patients (1.6%) or 1,646 cases per 100,000 person-year. The mortality rate among subsequent TB group was significantly much higher than the non-TB group (50% vs 0.4%; p-value = 0.001). COVID-19 participants on high doses of corticosteroids also were co-infected with other infections such as bacteria (37.1%), fungi (5.3%), and Pneumocystis jirovecii (PJP) (1.2%). We found that the incidence of TB in participants with COVID-19 on high doses of corticosteroids was 11 times higher than the general population. Therefore, we recommend screening for latent TB among these patients to prevent/early diagnose TB disease.

Intestinal obstruction following antituberculosis therapy in a patient with pancreatic carcinoma and pulmonary tuberculosis: a case report.

INTRODUCTION: Intestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare. CASE PRESENTATION: We report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient's symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction. CONCLUSIONS: This case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects.

Multidrug-resistant tuberculosis treatment outcomes and associated factors at Yirgalem General Hospital, Sidama Region, South Ethiopia: a retrospective cohort study.

BACKGROUND: The spread of multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to TB control efforts. This study evaluated the treatment outcomes and associated factors among patients receiving treatment for MDR-TB in southern Ethiopia. METHODS: A retrospective follow-up study covering ten years, from 2014 to 2023, analyzed the records of confirmed cases of pulmonary TB admitted to Yirgalem General Hospital, an MDR-TB treatment initiation center in the Sidama Region. To compare the successful treatment outcomes across the years, a chi-square test of independence was conducted. Bivariate and multivariable logistic regression models were used to identify factors associated with treatment outcomes for MDR-TB. RESULTS: Out of 276 confirmed MDR-TB cases, 4(1.4%) were diagnosed with resistance to second-line drugs (SLDs). Overall, 138 patients achieved favourable treatment outcomes, resulting in a treatment success rate of 50.0% [95% CI 44.1-55.9%]. Among these 138 patients, 105(76.1%, 95 CI 68.7-83.5%) were cured, while 33(23.9%, 95 CI 16.5-31.3%) completed their treatment. The successful treatment outcomes varied significantly across the years, ranging from 3.6% in 2020 to 90% in 2021. The analysis indicated a statistically significant difference in treatment outcomes when considering data from 2014 to 2023 (χ2 = 44.539, p = 0.001). The proportion of patients with deaths, lost-to-follow-up (LTFU), treatment failures and not evaluated were 7.9% [95% CI 4.8-11.2%], 10.9% [95% CI 7.2-14.6%), 2.2% [95% CI 1.1-3.3%), and 28.9% [95% CI 23.7-34.2%] respectively. Individuals with a positive HIV status had significantly lower odds of a favorable treatment outcome [AOR = 0.628, 95% CI (0.479-0.824), p = 0.018]. Similarly, patients with a BMI of less than 18 are more likely to have unfavorable treatment outcomes compared to those with a BMI of 18 or higher [AOR = 2.353, 95% CI 1.404-3.942, p < 0.001]. CONCLUSION: The study revealed a concerning 1.4% prevalence of additional resistance to SLDs. The 50% rate of unfavorable treatment among MDR-TB cases exceeds the target set by the WHO. A significant number of patients (10.9%) were LTFU, and the 28.9% categorized as 'not evaluated' is also concerning. Enhanced strategic interventions are needed to reduce such cases, and factors associated with poor treatment outcomes should receive greater attention. Future prospective studies can further explore the factors influencing improved treatment success.

Prevalence of rifampicin and isoniazid mono-resistance among cases of pulmonary tuberculosis from Western Uttar Pradesh, North India.

BACKGROUND: Mono-resistance to rifampicin/isoniazid increases poor treatment outcomes and the risk of multi-drug resistance (MDR) in tuberculosis (TB) patients. Limited information exists about mono-resistance status of TB patients in Uttar Pradesh, North India. This study aimed to estimate the burden of rifampicin and isoniazid mono-resistance in Western Uttar Pradesh. METHODS AND RESULTS: 153 sputum samples of suspected pulmonary tuberculosis patients were processed to isolate Mycobacterium tuberculosis using the Lowenstein-Jensen (L-J) culture medium. The isolates were identified using an immuno-chromatographic test and IS6110 PCR. The confirmed Mycobacterium tuberculosis isolates were tested for drug susceptibility testing against rifampicin and isoniazid anti-tuberculosis drugs. The results of the drug susceptibility testing were compared with demographic information and analyzed statistically. Out of 153 sputum samples, 83 (54.24%) samples were positive for growth on L-J medium, including 82 (98.79%) Mycobacterium tuberculosis isolates. Of the 82 Mycobacterium tuberculosis isolates, 16 (19.51%), 7 (8.54%), and 5 (6.10%) isolates were MDR, mono-resistant to rifampicin and isoniazid, respectively. The occurrence of RIF/INH mono-resistant-TB was higher in patients of male gender, age above 45 years, living in rural conditions, history of weight loss, and previous anti-TB treatment, but the effect was not statistically significant. CONCLUSIONS: The study reported the status of rifampicin and isoniazid mono-resistance among TB patients and highlighted the need for continuous monitoring and improved intervention for the initial detection of mono-drug-resistant cases. This will improve clinical treatment outcomes and decrease the rate of drug-resistant TB in Uttar Pradesh, North India.

Silicosis predicts drug resistance and retreatment among tuberculosis patients in India: a secondary data analysis from Khambhat, Gujarat (2006-2022).

BACKGROUND: India, with the highest global burden of tuberculosis (TB) and drug-resistant TB, aims to eliminate TB by 2025. Yet, limited evidence exists on drug resistance patterns and retreatment among patients with silico-tuberculosis. This study explores these patterns and assesses the impact of silicosis on TB retreatment in India. METHODS: This secondary data analysis stems from a larger retrospective cohort study conducted in Khambhat, Gujarat, between January 2006 and February 2022. It included 138 patients with silico-tuberculosis and 2,610 TB patients without silicosis. Data from the Nikshay TB information portal were linked with silicosis diagnosis reports from the Pneumoconiosis Board using the unique Nikshay ID as the linking variable. Drug-resistant TB was defined as resistance to any anti-TB drug recorded in Nikshay. Retreatment refers to TB patients who have previously undergone anti-TB treatment for one month or more and need further treatment. Recurrent TB denotes patients who were previously declared cured or had completed treatment but later tested positive for microbiologically confirmed TB. Multivariable logistic regression was used to determine the impact of co-prevalent silicosis on drug resistance and retreatment. RESULTS: Patients with silico-tuberculosis showed a higher proportion of retreatment compared to those without silicosis (55% vs. 23%, p < 0.001). Notably, 28% of patients with silico-tuberculosis were recurrent TB cases, compared to 11% among those without silicosis. Regarding drug resistance, the silico-tuberculosis group exhibited a higher rate (6% vs. 3%), largely due to rifampicin resistance (5% vs. 2%, p = 0.022). Co-prevalent silicosis was associated with a 2.5 times greater risk of drug-resistant TB (adjusted OR 2.5, 95% CI, 1.1-5.3; p = 0.021). Additionally, patients with silico-tuberculosis had a fourfold increased risk of retreatment for TB (adjusted OR 4, 95% CI, 3-6; p < 0.001). CONCLUSIONS: Co-prevalent silicosis significantly elevates the risk of drug resistance, recurrence, and retreatment among TB patients in India. This study indicates a need for improved treatment protocols and suggests that future research should focus on randomized controlled trials to evaluate appropriate anti-TB regimen and duration of therapy for this high-risk group. Given India's goal to eliminate TB by 2025, addressing the challenges posed by silico-tuberculosis is critical.

Screening and management of depression among patients on TB treatment in Papumpare district, Arunachal Pradesh, India.

The TB-depression syndemic is a complex health condition. This study demonstrates a collaborative model to screen and manage depression among TB patients and understand the enablers and challenges from the healthcare workers perspective regarding its implementation. The PHQ-9 questionnaire was used to screen for depression and in-depth interviews among five healthcare workers were taken to explore its feasibility. Eight healthcare workers were trained for the screening that was carried out in two tuberculosis units of Papumpare district over a period of three months. Of 46 eligible patients screened, 43 (93.4%) screened positive for depression. Fifteen patients with moderate, moderately severe and severe depression were referred, of which five (33.3%) visited the psychiatric OPD. Two patients were diagnosed with clinical depression by a psychiatrist and started on treatment. The reasons for smaller number of patients being screened were time constraints, lack of manpower, lackadaisical attitude towards TB disease and patients' parents or guardians coming to take medicines. Enablers and challenges were explored under the heads of training, screening tool and PHQ-9 questionnaire, psychiatrist referral and counselling. This study demonstrates implementation of a feasible model for screening of depression among TB patients using the PHQ-9 questionnaire within programmatic settings using available resources.

Involving religious organizations in improving TB medication adherence.

BACKGROUND: Health is a state of health, both physically, mentally, spiritually, and socially that allows everyone to live a productive life socially and economically. Pulmonary tuberculosis is a global health problem that could impact on productivity and quality of life. The number of TB cases in Indonesia According to WHO, there are an estimated 1,020,000 new TB cases per year (399 per 100,000 population) with 100,000 deaths per year (41 per 100,000 population). Pulmonary tuberculosis is a global health problem that can impact productivity and quality of life. The persistence of family support in improving the compliance of pulmonary tuberculosis patients in taking medication is the key to the success of tuberculosis treatment. AIMS: This study aims to determine the involvement of religious organizations in supporting tuberculosis patients to improve treatment adherence. METHODS: This research is a qualitative study with a phenomenological approach. Data were collected using in-depth interviews and then analyzed by content analysis. The informants in this study consisted of 8 participants. RESULT: The results of this study found three themes, namely Understanding TB treatment, Socialinteraction management, and Socialsupport. CONCLUSIONS: It was concluded that the support of religious organizations during the patient's treatment can increase the patient's compliance to take medicine regularly and make regular controls/visits. It is also recommended that families encourage patients to continue to participate in religious activities while still complying with health procedures.

Nutritional status and adherence to anti-tubercular treatment among tuberculosis patients in a community development block of Eastern India.

BACKGROUND: Undernutrition is a risk factor for developing tuberculosis (TB) and adherence to treatment leads to successful treatment outcomes. OBJECTIVES: To assess the nutritional status and adherence to treatment among tuberculosis patients in Bhatar Community Development Block of Purba Bardhaman district, West Bengal, India. MATERIAL & METHODS: A cross sectional descriptive study was conducted among all the 82 tuberculosis patients registered between April to June, 2021, under NTEP in Bhatar tuberculosis unit (TU), who completed at least 1 month of therapy. Nutritional status was assessed based on BMI and adherence to treatment was evaluated by interviewing with a validated version of Morisky Medication Adherence Scale (MMAS-8-Item). Data was analysed using SPSS v23. RESULTS: Among the 82 subjects, 51 (62.2%) were found to be underweight and overall high level of adherence to treatment was found among 51 (62.2%) of study subjects. Subjects aged >45 years (AOR 3.686, 95% CI: 1.147-11.842) and having extra-pulmonary Tuberculosis (AOR 8.539, 95% CI: 1.305-55.871) were significantly associated as being adherent to treatment. CONCLUSION: Health education, awareness and more vigilant monitoring is still needed so that TB patients can be cured successfully. Special attention needs to be given on the nutritional status of the TB patients.

Change in psychological parameters and quality of life among individuals with pulmonary and extrapulmonary tuberculosis following the intensive phase of therapy: A longitudinal observational study from central India.

BACKGROUND: Tuberculosis (TB) is a global health concern, impacting millions annually, with limited attention to the psychological distress it inflicts. Psychological comorbidities, such as depression, anxiety, and stress, significantly affect the quality of life (QoL) of TB patients. Available literature on this topic is restricted to the pulmonary TB (PTB) patients; while psychological issues of the extrapulmonary TB (EPTB) patients who comprise a significant proportion of this disease entity remains unexplored. Additionally, the impact of anti-TB treatment on psychological parameters has received limited attention and vice-versa. This study aimed to assess depression, anxiety, stress, and QoL of TB patients at diagnosis and to understand how these parameters change after the intensive phase of treatment. METHODS: A longitudinal observational study involving 40 TB patients (31 EPTB and 9 TB) was conducted to assess depression, anxiety, stress and QoL among them. Participants were followed up after the intensive treatment phase. RESULTS: At baseline, 32.5% (n = 13) and 65% (n = 26) participants experienced moderate-severe depression, and moderate-severe anxiety, and stress, respectively. QoL was notably compromised, especially in the psychological domain. Post-intensive treatment, anxiety and depression showed significant improvement (Z = -2.271, p = 0.023 and Z = -2.093, p = 0.036), but QoL and stress levels remained largely unchanged (p > 0.05). CONCLUSION: This study highlights the high prevalence of psychological distress and poor QoL among TB patients. Following intensive phase of therapy, severity of depression and anxiety reduced significantly; however, change in stress-level and QoL was non-significant. Although study is limited by in terms for small sample size, the need of holistic, multidisciplinary treatment approach (including mental health professionals) for such patients can't be overemphasized. Implementing baseline psychological screenings and providing mental health support if required, are critical to improve the overall health and QoL of these individuals.

Comparison of treatment adherence among TB patients with and without COVID-19 in South India.

AIM: The present study aimed to compare the adherence to anti-TB treatment among post-COVID-19 pulmonary TB cases and TB patients without a history of COVID-19 in South India. METHODS: A prospective, cross sectional study was conducted in all drug-sensitive pulmonary tuberculosis patients in National TB Elimination Program. The research investigates the impact of the COVID-19 pandemic on TB management, considering both subjective and objective measures of adherence. Data were collected using a validated instrument for subjective assessment and urine metabolite testing for objective evaluation. RESULTS: The results reveal significant differences (p < 0.05) between subjective and objective adherence measures, emphasizing the need for accurate and comprehensive assessment methods. However, there is no statistically significant difference (p > 0.05) in adherence to anti-TB treatment among post-COVID-19 pulmonary TB cases and TB patients without a history of COVID-19 in South India. The reason for non-adherence in both groups were ATT side effects, loss of daily wages, forgetting to take medication and lazy to take medications. CONCLUSION: The study concluded that there is no statistically significant difference (p > 0.05) in adherence to anti-TB treatment among post-COVID-19 pulmonary TB cases and TB patients without a history of COVID-19.

Socio-demographic factors & adherence of newly diagnosed pulmonary tuberculosis patients to the newly introduced daily regimen: A hospital survey based follow up study.

INTRODUCTION: Poor adherence to anti-tuberculosis medication is a major barrier to its global control. Patient adherence to the standard anti-TB therapy (ATT) in developing countries has been estimated to be as low as 40%. Multiple factors influencing adherence to treatment are: Economic and structural factors such as homelessness, unemployment and poverty; patient related factors like ethnicity, gender, age, knowledge about TB, cultural belief systems, mental state etc. AIMS & OBJECTIVES: This study was planned with the aim to study the association between various socio-demographic factors with level of adherence to the daily regimen amongst newly diagnosed pulmonary TB patients at a tertiary care hospital in metropolitan city of Maharashtra. Additionally, we tried to determine the type of non-adherence along with reasons for it. METHOD: ology: An interview based pre-tested and validated questionnaire was developed & used as data collection tool. Total 181 newly diagnosed, FDC naïve, drug sensitive pulmonary TB patients from DOT center of a tertiary care hospital were enrolled & interviewed for sociodemographic, treatment & adherence details. They were followed up at 2nd & 6th month of their treatment, i.e., IP & CP follow up. Their Nikshay portal data & TB treatment cards were accessed for information on treatment adherence. RESULTS: Out of 181 patients, 110 (60.8%) were found to be adherent whereas 71 (39.2%) were found to be non-adherent. Among those non-adherent, 64 (90.9%) had treatment gaps (intermittent missed doses) & 7 (9.9%) showed discontinuation of treatment. Majority of these patients reported personal obligations & starting to feel better as the main reason for non-adherence (p < 0.0001). The sociodemographic factors that had significant impact on level of adherence were patients' age (p = 0.013); level of education (p = 0.035); family size (p = 0.018); family history of TB (p = 0.0001) & current smoking habit (p = 0.025). CONCLUSION: It is evident from the study that socio-demographic factors do have a major impact on patients' levels of adherence to treatment. Family history of TB as well as sputum conversion at end of treatment/CP have been identified as independent risk factors among pulmonary TB patients who are non-adherent to treatment. Thus, ensuring robust availability of DBT & intensive tobacco cessation sessions for all diagnosed patients as well as strengthening system for making prophylaxis available for household & close contacts of patients can help in reducing impact of socio-demographic factors & improving adherence levels. RECOMMENDATIONS: In-patient care option specifically during IP; regular dietary counseling to improve nutrition & help reduce drug side effects & use of alternate adherence technologies like facility-based DOT or Video Observed Therapy (VOT) wherever feasible can help to improve adherence levels for TB patients from all walks of life.

Patient delay, diagnosis delay, and treatment outcomes among migrant patients with tuberculosis in Shanghai, China, 2018-2020: a mixed-methods study.

OBJECTIVES: This study aimed to examine patient delay, diagnosis delay and treatment performance among patients with tuberculosis (TB) in Shanghai, China in 2018-2020 focusing on disparities between migrant and local patients with TB. DESIGN: Mixed-method study. SETTING AND PARTICIPANTS: Quantitative data were collected from the TB information management system in Shanghai; 17 533 bacteriologically confirmed and clinically diagnosed patients with pulmonary TB registered in 2018-2020 were included. Qualitative interviews were conducted with TB administrators (n=3) and community healthcare providers (two groups, n=10 in total) from Shanghai. MAIN OUTCOME MEASURES: Patient delay, diagnosis delay and treatment completion were examined by resident type using descriptive analysis and logistic regressions. Qualitative interviews were conducted to understand factors associated with the disparities. RESULTS: From 2018 to 2020, migrant patients with TB accounted for 44.40% of total cases. There was no significant difference in patient delay between migrant and local patients (18.47 days on average). 22.12% of migrants and 16.52% of locals experienced diagnosis delays exceeding 14 days, respectively. After adjusting for all variables, migrant patients (OR 1.30, 95% CI 1.18 to 1.44) and initial care seeking at general hospitals (OR 3.76, 95% CI 3.45 to 4.09) were associated with a higher probability of diagnosis delay. 93.9% of migrant patients and 89.4% of the local patients had a successful TB treatment without statistically significant difference after adjusting for all variables. Qualitative interviews revealed a standard approach to managing patients with TB in Shanghai no matter their resident type. Young migrant patients who were able to maintain their jobs in Shanghai often had better treatment adherence. Despite patients' COVID-19 fear and limited care access in 2020, TB treatment minimally affected for both due to community-based case management. CONCLUSIONS: Migrant patients were more likely to experience diagnosis delay. It should improve awareness and knowledge of TB among healthcare professionals at general hospitals to mitigate the risk of diagnosis delay.

Mitigating adverse outcomes in tuberculosis treatment: analyzing a non-compliance risk assessment strategy in a case report.

Tuberculosis (TB) is a global public health concern and a leading cause of death. Its persistence occurs mainly because barriers in the care cascade are not being fully addressed. Healthcare professionals and scientists have been addressing treatment challenges such as abandonment and irregular drug intake via strategies such as directly observing treatment and singular therapeutic projects to improve adherence. However, while protocols and guidelines advocate these strategies, their implementation requires a broader approach from healthcare teams. This article examines the importance of such strategies in clinical TB management and analyzes an unfavorable outcome in an immunocompetent patient treated for pulmonary tuberculosis (PTB) from 2017 to 2022. After recurrence and treatment, the patient continued to have persistent acid-fast bacilli in the sputum, positive cultures for Mycobacterium tuberculosis, and progressive lung lesions, despite receiving the recommended treatment. Although categorized as having an intermediate risk of treatment abandonment, the patient faced challenges, such as the COVID-19 pandemic, pregnancy, and being diagnosed with COVID-19. After therapeutic failure and the loss of beneficial prospects, palliative care was initiated. This case illustrates the complexities of managing TB in patients with recurrent disease despite apparent adherence to treatment. After reassessing the risk of abandonment score, the patient was categorized as high-risk. This underscores the importance of singular therapeutic projects, such as psychological support for high-risk or intermediate patients, to prevent negative outcomes. This case reinforces the critical need for comprehensive patient-centered approaches to successfully treat and manage TB.

Approaches and processes for paediatric chest X-ray classification used in the SHINE TB treatment-shortening trial.

SHINE (Shorter Treatment for Minimal Tuberculosis in Children) was the first Phase 3 paediatric TB treatment-shortening trial. Robust chest X-ray (CXR) classification methods were integral to excluding severe disease for trial eligibility and to retrospectively adjudicating TB status at baseline. We describe and critically evaluate the CXR classification approaches and processes used in the SHINE trial.Children with non-severe TB were randomised to 4- vs 6-months anti-TB treatment. Radiologically non-severe TB was defined on CXR. CXRs were systematically interpreted by on-site clinicians prospectively for eligibility determination and retrospectively by experts to inform adjudication of baseline TB status and disease severity.A screening CXR was successfully obtained from all 1,204 enrolled children; 1,134 CXRs from children with intra-thoracic TB were reviewed by expert readers. Compared with the expert panel, enrolling clinicians classified more CXRs as abnormal and 'typical TB' and all as radiologically non-severe. The expert panel retrospectively classified 71/1,134 (6%) CXRs as severe. Of these, 4 (5.6%) had unfavourable outcomes compared with 34 (3.0%) in the trial overall.Using CXRs to classify radiological disease severity and inform eligibility decisions in real-time by local enrolling clinicians was feasible and safe in this large paediatric TB trial. Retrospective central expert CXR review was successful. Refinement of the CXR methods for the classification of both disease severity and TB status could support standardised implementation in routine care and research..

Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

TB or Not TB, That is the Question?

A 26-year-old female presented with a 3-month history of dry cough, unintentional weight loss, night sweats and fatigue. Her background history was significant for ulcerative colitis, managed with Adalimumab for almost 2 years. Clinical examination was unremarkable, apart from some mild pallor. Abnormal chest x-ray findings prompted a computerised tomography (CT) thorax which demonstrated multifocal peri-bronchial consolidation. The differential diagnosis was multifocal organising pneumonia and tuberculosis (TB). Extensive investigations, including invasive bronchial imaging and biopsy, ultimately ruled out TB. This paper reports a case of Adalimumab-induced organising pneumonia and discusses its clinical implications.