Tuberculosis Treatment Outcomes Research Articles

Tuberculosis treatment outcome of TB/HIV co-infected patients at Adare Hospital, Hawassa City Administration, Sidama Region.

There is lack of evidence on the TB treatment outcomes of TB/HIV co-infected patients who received anti-TB treatment in Sidama region. In this study, we aimed to assess the treatment outcome of TB/HIV co-infected patients receiving care at Adare Hospital in Hawasa City, Sidama Region. A cross sectional study based on retrospective data among TB/HIV co-infected cases was conducted at Adare Hospital. The unit TB registry and antiretroviral therapy (ART) registry were reviewed for the period between September 1, 2016 and August 31, 2022 to measure TB treatment outcomes. Target population for this study was all TB/HIV co-infected cases aged 15 years or more treated at Adare Hospital in the Hawassa City Administration. The data sources for this study were the unit TB register at the TB clinics, patient charts, and the ART register of the facility. Data were entered and analysed using the statistical package SPSS version 26. A summary descriptive analysis was calculated. Bivariable and multivariable analyses were performed to identify associations between variables. During the study period, 298TB/HIV co-infected cases were treated for TB in the Hospital. Thirty three (11.1%), of the cases had an unfavourable TB treatment outcome. The risk of an unfavourable treatment outcome was over three times higher among re-treated TB cases than among the new TB cases (AOR = 3.3, 95% CI (1.4, 7.9)). The risk of death was higher among stage-IV HIV cases (AOR = 8.1, 95% CI (2.3, 28.9)), and among participants who used non-communicable diseases medications during the cohort period (AOR = 7.3, 95% CI (1.6, 33.6). TB treatment success rate among TB/HIV co-infected cases in the current study was comparable to many other reports. There are factors that contributed for unsuccessful TB treatment outcome. Cautious follow-up of cases and managing these factors could help in improving the TB treatment outcome.

Clinical profile, risk factors, disease severity, and outcome for COVID-19 disease in patients with tuberculosis on treatment under the National Tuberculosis Elimination Program: a cohort of 1400 patients.

COVID-19 affected millions of people worldwide, and tuberculosis (TB) continues to affect millions of people each year. The combined pandemic of COVID-19 and TB had a catastrophic effect on healthcare policies and healthcare setups around the globe. The clinical profile and factors affecting the outcome of COVID-19 disease in TB patients on treatment in field conditions have not been studied in detail. The present study attempted to study the occurrence of COVID-19 among patients on TB treatment in terms of severity of COVID-19 disease and outcome of both COVID-19 and TB in patients at National Tuberculosis Elimination Program treatment centers over a period of one year during peak COVID-19 times. Out of 1400 TB patients enrolled, 65 (5%) suffered from COVID-19 disease. Of the 65 TB patients with COVID-19 disease, 37 (57%) were male and under 45 years old, 33 (51%) had a TB diagnosis after first receiving a COVID-19 diagnosis, 29 (45%) had a TB diagnosis first, and received anti-TB treatment before receiving a COVID-19 diagnosis, and only 3 patients (5%) had a COVID-19 and TB diagnosis concurrently. The majority of 59 (91%) patients had mild COVID-19 disease. The outcome of TB treatment was available in 25 patients out of these 65 COVID-19-positive patients, with 21 (84%) patients having a favorable outcome. Out of the 65 COVID-19-positive patients, 4/25 (16%) had unfavorable outcomes, with one patient (4%) failing TB treatment and two patients (8%) dying. This is the first study from India that studied the occurrence and course of COVID-19 among a large number of TB patients taking anti-TB treatment under programmatic conditions. Due to the similarity in symptoms of TB and certain viral respiratory illnesses, a protocol should be established for health care to check patients for both illnesses.

Analysis of the epidemic characteristics and treatment outcomes of rifampicin-resistant pulmonary tuberculosis in Yangzhou City from 2012 to 2020

Information on patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) in Yangzhou City from 2012 to 2020 was obtained from the Information System of the Chinese Center for Disease Control and Prevention. The epidemic characteristics of RR-PTB patients were analyzed by using χ2 test. The average annual registered incidence rate of RR-PTB patients in Yangzhou City from 2012 to 2020 was 0.57/100 000, and the difference between the registered incidence rates in each year was statistically significant (χ2=29.326, P<0.001). The proportion of re-treated patients (64.8%) was higher than that of newly treated patients (35.2%, χ2=50.593, P<0.001). The registered incidence rate in males (0.91/100 000) was higher than that in females (0.24/100 000, χ2=80.566, P<0.001). The age distribution showed that the highest incidence rate was in the age group≥60 years (0.96/100 000) and the lowest was in the age group 0-<45 years (0.31/100 000, χ2=55.853, P<0.001). From 2012 to 2020, Baoying County had the largest number of registered RR-PTB patients (44 cases), and its registered incidence rate (0.64/100 000) was only lower than that of Guangling District (0.98/100 000). The registered incidence rate of RR-PTB patients in Baoying County during 2016-2020 also increased significantly compared to 2012-2015 (P=0.001). Logistic regression was used to analyze the factors related to the treatment outcome of RR-PTB patients. The results showed that patients aged≥60 years and those classified as the re-treatment were risk factors for successful treatment of RR-PTB patients (P<0.05). In summary, males, people aged≥60 years, patients classified as the re-treatment, and residents of Baoying County should be the key populations for RR-PTB epidemic prevention and control in Yangzhou City.

Microbiological Aspects and Clinical Impact of Lower Lung Field Tuberculosis: an Observational Cohort Study in Peru.

Approximately 40% of tuberculosis (TB) cases remain undiagnosed globally. Lower lung field tuberculosis (LLF TB) presents atypically and is often misidentified as other lung diseases, leading to diagnostic delays in resource-limited settings. It may contribute to increased TB transmission and mortality. We aimed to identify microbiological determinants of LLF TB and evaluate treatment responses to optimize care. We conducted an observational cohort study in Lima, Peru, enrolling adults with microbiologically confirmed pulmonary TB (PTB) diagnosed by GeneXpert MTB/RIF assay or sputum culture. Mycobacterium tuberculosis (MTB) lineage was determined using whole-genome sequencing (WGS). Due to the delayed chest radiograph (CXR) changes in LLF TB compared to non-LLF TB, we measured changes in the St. George's Respiratory Questionnaire (SGRQ) score at two-month treatment mark and evaluated World Health Organization (WHO)-specified final treatment outcomes. We used logistic regression to evaluate the associations between LLF TB and microbiological determinants and treatment outcomes. We used linear regression to assess whether the change in SGRQ scores over the first 2 months of treatment varied by LLF TB status. Among 1,316 PTB patients, 84 (6%) had LLF TB. Compared to non-LLF TB patients, LLF TB patients were more likely to be smear-negative (adjusted odds ratio [aOR] [95% CI]=2.04 [1.28-3.23], p=0.002) and to be infected with Lineage 2 (aOR [95% CI]= 1.95 (95% CI: 1.07 to 3.41; p=0.024). People with LLF TB had less improvement in SGRQ scores after two months of treatment (adjusted score difference [95% CI] = -6.29 [-10.99 to -1.59], p = 0.009), while they experienced better final outcomes compared to non-LLF TB patients, though this difference did not reach statistical significance (adjusted odds ratio [aOR] = 0.43 [95% CI: 0.13 to 1.05], p = 0.103). Patients with LLF TB are more likely than those with upper lung lesions to be sputum-negative on conventional tests, to be infected with Lineage 2, and to show less clinical improvement after treatment.

Exploring the Impact of Social Support on Tuberculosis Treatment: A Thematic Review

Aims: Tuberculosis (TB) remains a critical global health issue, characterized by significant morbidity and mortality rates. Recent research highlights the potential of social support interventions to enhance TB treatment outcomes and improve patient quality of life. This study examines the positive effects of social support interventions on TB patients throughout their treatment process. Method: Utilizing a traditional review approach, this study applies thematic analysis to synthesize findings from the literature. The review encompasses 17 articles selected from reputable databases, including PubMed, Wiley Online Library, ProQuest, and Google Scholar, based on predefined inclusion criteria. These articles underwent quality assessment using the Critical Appraisal Skills Programme (CASP) tool. The PRISMA flowchart provided transparency in the selection process. Results: Key themes identified through the analysis include treatment adherence, psychological well-being, motivation to recover, health-related quality of life, prevention of TB transmission, successful TB treatment, and self-efficacy to recover. Conclusion: The findings suggest that social support interventions can play a crucial role in addressing the persistent challenges of TB management globally.

Clinical, Radiological Features and Treatment Outcomes of Tuberculosis in Patients Aged 75 Years and Older.

Tuberculosis (TB) is a significant contributor to morbidity and mortality. With a progressively aging population, TB is increasingly encountered in older adults. Understanding the clinical presentation and optimal treatment strategies for TB in this population is essential. Clinical, radiological features, treatment, and outcome of patients aged 75 and above who were diagnosed with tuberculosis at King Abdulaziz Medical City in Riyadh in the period between January 2015 to December 2021wereevaluated retrospectively. Among 92 elderly tuberculosis patients, most were male (76.1%) with a mean age of 82.5 years. Pulmonary TB was diagnosed in 52.2% of patients, Extra Pulmonary TB in 32.6%, and Disseminated TB in 15.2%. Comorbidities included Diabetes Mellitus (59.8%) and Congestive Heart Failure (41.3%). The most common presentation symptoms included cough (51.1%), fever (43.5%), dyspnea (39.1%), and weight loss (31.5%). Delay of TB diagnosis for up to 3 months was observed in 31.5% of patients. Weight loss and male gender were significant predictors of delayed diagnosis. Laboratory findings varied among TB types, with disseminated TB showing higher eosinophilia and thrombocytopenia. Completion of an initial RIPE treatment protocol was achieved in 67.6% of patients. Mortality during treatment occurred in 23.9% of patients. Pulmonary TB was associated with higher mortality compared to extrapulmonary TB (p = 0.007). Tuberculosis is associated with high mortality in patients above the age of 75. There is still a substantial delay in TB diagnosis in the elderly. RIPE regimen is frequently changed due to side effects. Alternative regimen choices were quite variable. More studies on tuberculosis in this patient's population are needed to define the most effective therapeutic approach.

Determinants of unsuccessful tuberculosis treatment outcome in Southwest Ethiopia regional state public hospitals, 2022: a multi-center case control study.

Tuberculosis is the major cause of morbidity, and it is one of the top ten causes of death globally. In Africa, the overall pooled estimate of unsuccessful tuberculosis treatment outcome was reported to be 21.1%, which is above the World Health Organization defined threshold of 15%. Unsuccessful treatment outcomes result in drug resistance, prolonged periods of infection, and increased morbidity and mortality. Therefore, this study aimed to assess determinants of unsuccessful treatment outcomes among tuberculosis patients in Southwest Ethiopia regional state public hospitals, in 2022. A retrospective unmatched case-control study was employed by recruiting 570 study units (190 cases and 380 controls) in three randomly selected public hospitals from 1 August 2022 to 21 August 2022. Data were collected by using a data extraction checklist adapted from tuberculosis registration logbook. Bivariate and multivariate logistic regression models were employed. A predictor variable with a p-value of less than 0.05 in the multivariate logistic regression model was taken as statistically significant. The odds ratio and 95% confidence level were used to measure the strength of the association. A total of 561 records (187 cases and 374 controls) were included from tuberculosis registers. In this study, the factors independently associated with unsuccessful tuberculosis treatment outcome were older age (AOR = 1.68, 95% CI: 1.142, 2.472), rural residence (AOR = 1.548, 95% CI: 1.055, 2.272), retreatment category (AOR = 2.12, 95% CI: 1.339, 3.357), underweight (BMI < 18.5 kg/m2) (AOR = 1.952, 95% CI: 1.240, 3.071), being HIV positive (AOR = 2.144, 95% CI: 1.372, 3.349) and having no treatment adherence support (AOR = 2.016, 95% CI: 1.270, 3.201). In this study, socio-demographic, clinical, and treatment-related factors contributed to the risk of unsuccessful treatment outcomes. Targeted interventions should be taken into consideration to diminish poor tuberculosis treatment outcomes among high-risk groups throughout the whole tuberculosis treatment course.

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

BackgroundThe 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.MethodsA 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.ResultsOut 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].ConclusionThe 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.

Is Completeness and Timeliness of Public Health Action (PHA) a Robust Tool to Improve the TB Treatment Outcome in the Private Sector?

Background: Public health action (PHA) in tuberculosis (TB) includes six components: doing screening for HIV/diabetes, carrying out drug susceptibility testing, counseling on tobacco, counseling on nutrition, benefits of Nikshay Poshan Yojana, and contact tracing. All the patients notified by the private practitioners (PPs) and missing any of the above components are intervened by the government staff to cover all the above components. Objectives: The aim of the article is (1) to assess the timeliness and completeness of PHA and (2) to assess the impact of PHA on the quality of care for TB patients in the private sector. Methods: A sequential mixed-method (cross-sectional study followed by qualitative study) study was carried out in the Patan district, North Gujarat for a period of one year. Quantitative data were collected through home visits to patients residing in three randomly selected talukas out of nine talukas in the Patan district. Qualitative data were collected purposively from selected clinics of PPs (including a mix of PP notifying and not notifying TB till saturation is achieved) from the above talukas. Results: Out of a total of 176 patients from the private sector, 48 patients took all six components of PHA. Out of them, 98% were cured compared to 82% who did not receive PHA. None of the PP had heard about PHA or its components. Conclusion: The Public–private model for TB management needs strengthening. Regular and mandatory training of PPs on the latest TB management guidelines including importance of timely and complete PHA should be carried out.

Childhood tuberculosis outcomes and factors associated with unsuccessful treatment outcomes in selected public hospitals of Lusaka Zambia from 2015 to 2019.

Treatment outcomes of tuberculosis in children are rarely evaluated. Childhood tuberculosis has been a low priority for tuberculosis programs due to difficulties in diagnosis and treatment. This study evaluated childhood tuberculosis outcomes and factors associated with unsuccessful treatment outcomes in selected public hospitals in Lusaka, Zambia from 2015 to 2019. This was a cross-sectional study conducted in eight public hospitals in Lusaka. All children aged 0-14 years, treated with tuberculosis and had treatment outcomes evaluated were included. The WHO tuberculosis treatment outcomes were grouped into successful treatment outcome (cured, treatment completed) and unsuccessful treatment outcome (death, loss to follow-up, failure). Taking unsuccessful treatment outcome as the outcome variable, logistic regression models were performed. All analyses were done at a 95% confidence interval. Out of 2,531 children managed for TB from 2015 to 2019, only 1,495 (59.1%) had treatment outcomes evaluated. Out of 1,495 participants, majority were 5 to 14 years old (50.9%), males (51.1%), HIV-negative (58.7%), and had pulmonary tuberculosis (74.2%). Bacteriological tests were performed on 59.8% of children, where 21.6% had positive bacteriological results. Bacteriologically confirmed TB was higher in children over 5 years (29.5%), pulmonary TB (25.6%), and retreatment (28.6%). The majority of children (84.2%) completed treatment, while 10.7% were cured, 1.5% were lost to follow-up, 3.1% died, and 0.5% failed treatment. Overall, unsuccessful treatment outcome was 5.1% while successful treatment outcome was 94.1%. Extrapulmonary tuberculosis was associated with unsuccessful treatment outcomes (AOR 1.64; 95% CI: 1.02-2.62). The tuberculosis successful treatment outcome met the World Health Organization's threshold goal of 90%. Children with extrapulmonary tuberculosis should be targeted as a high-risk group to improve treatment outcomes. Tracking children whose treatment outcomes were not evaluated would provide more precise estimates of TB treatment outcomes.

Tuberculosis Treatment Outcomes and Associated Factors at Zewditu Memorial Hospital, Ethiopia

&amp;lt;i&amp;gt;Background:&amp;lt;/i&amp;gt; Tuberculosis (TB) remains a leading cause of morbidity and mortality in Ethiopia, with treatment success rates consistently below the WHO target. Various factors contribute to poor treatment outcomes. &amp;lt;i&amp;gt;Objective:&amp;lt;/i&amp;gt; To assess treatment outcomes for TB and associated factors at Zewditu Memorial Hospital (ZMH) from 2017 to 2021. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; An institutional-based analytical cross-sectional study was conducted using TB logbook data. After bivariable analysis, clinically relevant variables and variables with a p-value &amp;lt; 0.2 were included in multivariable logistic regression analysis. Statistical significance was set at p-value &amp;lt; 0.05. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; The overall successful treatment outcome (cured or completed) was 197 (83.1%). Factors significantly associated with poor treatment outcomes included age group 35 to 44 years (AOR=4.663; 95% CI: 1.215-17.901), extrapulmonary TB (AOR=3.451; 95% CI: 1.172-10.16), and registration in 2019 (AOR=4.367; 95% CI: 1.2-15.87). &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; The treatment success rate falls short of the national target of 85%, highlighting the need for targeted improvements in TB management. The associations with age and extrapulmonary TB emphasize the necessity for focused control measures. Strengthening targeted TB programs at ZMH is recommended.

Bedaquiline versus injectable containing regimens for rifampicin-resistant and multidrug-resistant tuberculosis in a reference center in Brazil – a real-world evidence study using a retrospective design

BackgroundDrug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence.MethodsRetrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute – Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis.ResultsOf the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36–5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14–0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62–3.57, p < 0.001), along with no illicit drug use and primary drug resistance.ConclusionsThe implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion.

Knowledge, attitude and perceived barriers related to directly observed treatment, short-course among patients and caregivers attending tuberculosis clinics: a cross-sectional survey.

Tuberculosis (TB) is a major worldwide health problem, particularly in India, where it accounts for a quarter of infections. Adherence to the directly observed treatment, short-course (DOTS), which is necessary for TB treatment, is difficult in resource-limited circumstances. This study addressed the knowledge, attitude, and perceived barriers related to TB and DOTS adherence among patients and caregivers. A cross-sectional survey was undertaken at the selected TB clinics between November 2023 and March 2024. Purposive sample yielded 180 patients and 217 caregivers. Data were obtained using validated, self-structured questionnaires that assessed knowledge, attitude, and perceived barriers to TB and DOTS adherence. Statistical analysis was carried out with IBM SPSS version 23.0. The study found that caregivers had considerably greater TB knowledge than patients (p<0.05). Many patients misunderstood the cause of TB (50.6%) and embraced various misconceptions about the disease, such as TB spreading by shaking hands or sharing food, swimming in a holy river to cure diseases, and TB being the result of sin or karmic retribution. Distance to treatment facilities (95.6%), the necessity to take time off from work (91.7%), and social stigma (65.0%) were identified as the top three barriers to DOTS adherence. The study highlighted considerable gaps in knowledge, distant healthcare facilities, busy work schedules, and social stigma as barriers to TB treatment adherence in Deoghar, Jharkhand. Addressing these challenges via focused education and support activities is essential for enhancing DOTS adherence and TB treatment outcomes.

Treatment Outcomes of Tuberculosis Among Artisanal and Small-Scale Miners in Zimbabwe: A Follow-Up Observational Study Using Secondary Data.

In Zimbabwe, artisanal and small-scale miners (ASMs) are a key vulnerable group with high risk for tuberculosis (TB), HIV, and silicosis. The main purpose of this study was to investigate treatment outcomes of TB among ASMs. We conducted a follow-up observational study using secondary data. We analyzed data from 208 ASMs treated for TB at two occupational health clinics. We found a high treatment success rate of 87%, comparable to the national average for drug-sensitive TB. Unsuccessful outcomes were due to death (5%) and loss to follow-up (7%). Over a quarter of ASMs had unknown HIV status. Our study is the first to document treatment outcomes of TB among ASMs in Zimbabwe. Encouragingly, this study demonstrates the possibility of achieving good TB treatment outcomes even among highly mobile populations like ASMs. Further research is needed to analyze leakages across the whole TB patient pathway among ASMs. Additionally, addressing the high rate of unknown HIV statuses among ASMs is crucial to further improve overall TB treatment outcomes in this population.

Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility.

A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining feature of human TB: the development of necrotic lung granulomas and determined that the sst1-susceptible phenotype was driven by the aberrant macrophage activation. This study demonstrates that the aberrant response of the sst1-susceptible macrophages to prolonged stimulation with TNF is primarily driven by conflicting Myc and antioxidant response pathways leading to a coordinated failure 1) to properly sequester intracellular iron and 2) to activate ferroptosis inhibitor enzymes. Consequently, iron-mediated lipid peroxidation fueled IFNβ superinduction and sustained the Type I Interferon (IFN-I) pathway hyperactivity that locked the sst1-susceptible macrophages in a state of unresolving stress and compromised their resistance to Mtb. The accumulation of the aberrantly activated, stressed, macrophages within granuloma microenvironment led to the local failure of anti-tuberculosis immunity and tissue necrosis. The upregulation of Myc pathway in peripheral blood cells of human TB patients was significantly associated with poor outcomes of TB treatment. Thus, Myc dysregulation in activated macrophages results in an aberrant macrophage activation and represents a novel target for host-directed TB therapies.

Targeting CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model.

Tuberculosis (TB) remains among the leading infectious causes of death. Due to the limited number of antimicrobials in the TB drug discovery pipeline, interest has developed in host-directed approaches to improve TB treatment outcomes. C-C motif chemokine-like receptor 2 (CCRL2) is a unique seven-transmembrane domain receptor that is upregulated by inflammatory signals and mediates leucocyte migration. However, little is known about its role in the setting of TB infection. Here, we show that Mycobacterium tuberculosis (Mtb) infection increases CCRL2 protein expression in macrophages and in mouse lungs. To target selectively CCRL2-expressing cells in vivo, we developed a novel mouse anti-CCRL2 antibody-drug conjugate (ADC) linked with the cytotoxic drug SG3249. We tested its adjunctive therapeutic efficacy against TB when combined with the first-line regimen for drug-susceptible TB (isoniazid, rifampin, pyrazinamide, ethambutol; RHZE). The anti-CCRL2 ADC treatment potentiated RHZE efficacy in Mtb-infected mice and decreased gross lung inflammation. CCRL2 expression in lung dendritic cells and alveolar macrophages was lower in mice receiving anti-CCRL2 ADC treatment + RHZE compared to those receiving RHZE alone or the control group, although the total innate cell populations did not differ across treatment groups. Interestingly, neutrophils were completely absent in the anti-CCRL2 ADC treatment + RHZE group, unlike in the other treatment groups. IFN-γ+ and IL17-Α+ T-cell responses, which are associated with optimal TB control, were also elevated in the anti-CCRL2 ADC treatment + RHZE group. Collectively, our findings suggest that CCRL2-targeting approaches may improve TB treatment outcomes, possibly through selective killing of Mtb-infected innate immune cells.

Effect of missed clinic visits on treatment outcomes among people with tuberculosis: a quasi-experimental study utilizing instrumental variable analysis

ObjectivesMissed clinic visits disrupt the continuity of care and potentially impact tuberculosis (TB) treatment outcomes negatively. We evaluated the effect of missed clinic visits on mortality and treatment success among people with bacteriologically confirmed pulmonary TB in rural eastern Uganda. MethodsUsing routine TB clinic data, we designed a quasi-experimental study and used instrumental variable analysis to estimate a cause-effect. The exposure was one or more missed clinic visit(s), the instrumental variable was patient residence in the same sub-county as the TB clinic, and the outcomes were mortality and treatment success. We performed a two-stage least squares logistic regression for causal analysis and reported the odds ratio (OR) and 95% confidence interval (CI). ResultsOf 762 participants with similar baseline characteristics, 186 (24.4%) missed ≥1 clinic visit(s), 342 (44.9%) resided in the same sub-county as the TB clinic, 61 (8.0%) had died, and 687 (90.2%) were successfully treated for TB. Missed clinic visits increased mortality (OR 2.88, 95% CI 1.36-6.13) and reduced TB treatment success (OR 0.41, 95% CI 0.20-0.82). ConclusionsMissed clinic visits increase mortality and negatively impact treatment success among people with TB. The reasons for missed clinic visits should be identified and tackled through context-specific measures.

The Predictors of Medication Adherence among TB Patients on the E-Refill Prescription System in Health Care Facilities in Lagos State

Background: Tuberculosis (TB) has continued to be a major health concern to man and has affected majority of the population around the world. In the World Health Organisation (WHO)’s estimate, Nigeria is second in Africa and seventh in the world with regard to cases. Since Lagos is the most populous state in Nigeria, it has made a high number of tuberculosis cases. Since there is no cure for TB without taking the prescription drugs, noncompliance has been as frequent as the disease, leading to treatment failure, drug resistant TB and increased cost of healthcare. The e-refill prescription system which is an electronic prescription refill system is targeted to increase medical compliance amongst TB patients consequently improving overall health.  Aim: The purpose of this study is therefore to evaluate the factors which determine medication compliance among TB patients on the e-refill prescription in health facilities in Lagos state.  Setting: Various healthcare facilities across Lagos.  Methodology: This study employed the cross-sectional method. For sampling, we opted for a purposive sampling approach to select the patients. The sample size, determined using the Kish formula, comprised approximately 338 TB patients. In order to collect data on critical factors such as patient’s satisfaction, factors influencing e-refill medication adherence, and the willingness to adopt the e-refill system, this study made use of in-depth interview and semi- structured question. Furthermore, the collected data was analysed with SPSS software, with two team members independently coding the interview transcripts to identify emerging themes and resolve discrepancies through consensus discussions.  Results: A large proportion of the participants fell between the ages of 28 to 38 years (45.9%), (53.0%) were married, and the Yoruba ethnic group dominated the population at (49.4%). Most patients received care from government- owned facilities (75.1%). 68.6% considered medical adherence important. Of factors influencing medical adherence, (47%) said that forgetfulness often affected their adherence, and (23.7%) cited the side effect. Of those surveyed, 54.4% expressed interest in using the e- Refill system, and 60.7% were knowledgeable about it. Ease of use (32.8%) and system trust (29.9%) are the main variables influencing readiness to utilise the e-Refill system.  Conclusion: The e-Refill system has shown potential for success in improving medication adherence among TB patients in Lagos state. However, it is important to address challenges such as limited access to healthcare and reluctance among certain patient groups need to be addressed. To get maximum result possible from the system, it is important to take steps to enhance patient engagement, address stigma associated with the illness, and ensure sustained support over the duration of the treatment.  Contribution: The study highlights the significance of niche interventions geared towards promoting medication adherence and improving TB treatment outcomes in resource-constrained environments.

Prevalence, treatment, and outcomes of hepatitis C in an MDR/RR-TB trial cohort.

Tuberculosis (TB) and chronic hepatitis C virus infection (HCV) remain significant global health challenges, especially in low- and middle-income countries. In Eastern Europe, a considerable percentage of multi-drug resistant (MDR) and rifampicin resistant (RR) TB populations show high HCV prevalence. Current WHO guidelines do not routinely advise HCV testing during MDR-TB treatment, despite HCV being a risk factor for drug-induced liver complications in TB patients. This study investigates the co-treatment of MDR/RR-TB and HCV, using data from the TB-PRACTECAL trial. Data were collected as part of the TB-PRACTECAL clinical trial. All participants were screened for HCV at baseline. Participants who were HCV antibody positive and those who were treated for hepatitis C with Direct Acting Antivirals (DAAs) were extracted and compared to overall cohort characteristics. The characteristics of participants concomitantly treated with direct-acting antivirals are described including hepatitis treatment outcomes and adverse events. Among 552 participants from Belarus, Uzbekistan, and South Africa, 24 (4.3%) were HCV antibody positive. Unfavourable TB treatment outcomes were noted in 106/523 (22%) of the HCV-negative, 8/18 (44%) of the HCV-seropositive, and 2/7 (29%) of HCV-confirmed participants treated with DAAs. Of the six participants who received concurrent HCV and MDR/RR TB treatment, three were cured of HCV and three had no post-treatment HCV RNA test, five completed TB treatment and one discontinued treatment due to a severe adverse reaction. Concurrent treatment of MDR-TB and HCV, including in HIV patients, showed promising outcomes with no significant adverse events. The findings support the potential benefits of integrating HCV care into MDR-TB management.

The influence of comorbidities on treatment outcomes in patients with tuberculosis

To study the association of comorbidities and treatment outcomes in tuberculosis (TB) patients. A retrospective study includes all TB patients aged 18 years and older registered for treatment in Moscow in period 2021 the end of the 3rd quarter of 2022 using data of regional epidemiological TB monitoring system, a total of 3039 patients. The frequency and spectrum of comorbidities, its impact on the risk of adverse treatment outcome (ATO) and mortality using univariate and regression analysis were assessed. Comorbidities were identified in 1528 (50.3%) patients (95% confidence interval - CI 48.5-52.1); HIV infection (18.0%), chronic nonspecific lung disease (9.6%) and cardiovascular disease (8.2%) were predominant. The presence of comorbid pathology increased the odds of uneffective treatment (odds ratio - OR 2.56, 95% CI 2.22-3.03) and death (OR 2.45, 95% СI 1.67-3.59). Independent risk factors for ATO were HIV infection (OR 4.10, 95% CI 3.36-5.10), substance use (OR 2.57, 95% CI 1.70-3.66), chronic nonspecific lung disease (OR 1.39, 95% CI 1.04-1.88), diabetes mellitus (OR 1.69, 95% CI 1.15-2.48), liver pathology (OR 2.10, 95% CI 1.46-3.03), mental illness (OR 2.01, 95% CI 1.32-3.06). The death rate was 13.4%; the most significant predictors of mortality were HIV infection (OR 3.89, 95% CI 2.42-6.22) and liver disease (OR 1.90, 95% CI 1.27-2.82). A comorbidome model was constructed to assess the importance of different comorbidities for patient prognosis. The presence of comorbidity (predominantly HIV infection and liver disease) is a significant risk factor for ATO and mortality in TB patients, which should be taken into account when organizing and providing TB care to comorbid patients.