Tuberculosis Treatment Outcomes Research Articles

Undernutrition increases the risk of unsuccessful treatment outcomes of patients with tuberculosis in Ethiopia: A multicenter retrospective cohort study

While undernutrition has been identified as a common risk factor for tuberculosis (TB), its impact on treatment outcomes has yet to be investigated in high TB burden and low-income countries such as Ethiopia. Therefore, this study aimed to investigate the effect of undernutrition on treatment outcomes among patients with TB in northwest Ethiopia. A retrospective cohort study was conducted using data from different hospitals in northwest Ethiopia, for the period from July 2017 to August 2023. A Cox proportional hazard model was performed to determine the effect of undernutrition on TB treatment outcomes, which were defined as a composite of death, treatment failure, or loss to follow-up. A total of 602 patients with TB were included in the analysis. Of these, 367 (60.9%) were male, and 344 (57.1%) were undernourished. Upon completion of the follow-up period, 65 (10.8%) adults with TB had unsuccessful treatment outcomes. After adjusting for potential confounders, patients with undernutrition had a two times higher risk of experiencing unsuccessful treatment outcomes compared to well-nourished patients (AHR: 2.0, 95% CI: 1.2, 3.6). In addition, patients residing in rural areas (AHR: 3.1, 95% CI: 1.7, 5.4), having a history of prior TB treatment (AHR: 2.2, 95%CI: 1.1, 4.1), and the presence of diabetes comorbidity (AHR: 2.4, 95% CI: 1.1, 5.2) were at higher risk of unsuccessful treatment outcomes. Undernutrition increases the risk of unsuccessful treatment outcomes in Ethiopia. This finding suggests that nutritional support during TB treatment can improve successful treatment outcomes in high TB burden and low-income countries such as Ethiopia.

Treatment outcomes of tuberculosis cases by HIV status in Haramaya General Hospital, Ethiopia: A retrospective cross-sectional study.

Tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection pose significant challenges to global health, particularly in achieving the target of ending TB. However, the impact of HIV status on TB treatment outcomes remains unclear, especially in eastern Ethiopia. This study aimed to assess the treatment outcomes of TB cases by HIV status and associated factors in Haramaya General Hospital from November 15 to December 30, 2022. A retrospective cross-sectional study was conducted, reviewing the TB registry and treatment cards of patients who received anti-TB treatment between September 2017 and August 2022. Of the 420 samples addressed, 91.0% (95% CI: 88.3%-96.7%) of all TB patients had successful treatment outcomes. The treatment success rates of HIV-positive and HIV-negative TB patients were 80.0% and 91.9%, respectively. Being HIV-negative (AOR: 2.561, 95% CI: 1.002-6.542), being in the age group of 20 to 35 years (AOR: 2.950, 95% CI: 1.171-7.431), and urban residence (AOR: 2.961, 95% CI: 1.466-5.981) were associated with the TB treatment success rate. There was a high treatment success rate among all patients with TB. HIV status was associated with TB treatment outcomes. Strengthening TB-HIV collaborative activities, providing patient-centered care and support, and frequent monitoring and evaluation are recommended to improve the TB success rate.

Glycemic control during TB treatment among Filipinos: The Starting Anti-Tuberculosis Treatment Cohort Study.

Poor TB treatment outcomes are observed in patients with type 2 diabetes mellitus (DM) comorbidity and glycemic control throughout treatment may play a role. The objective of this study was to investigate glycemic control longitudinally among Filipino adults undergoing TB treatment using mixed-effects linear and logistic regression. Analyses were conducted in 188 DM-TB patients out of 901 enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, with a median baseline glycosylated hemoglobin (HbA1c) of 8.2% (range 4.5-13.3%). Previous versus new DM diagnosis was associated with higher mean HbA1c (worse glycemic control) during treatment, with a smaller effect amongst those with central obesity (coefficient 0.80, 95% confidence interval [CI] 0.26, 1.57, P = 0.043) than amongst those without central obesity (coefficient 3.48, 95% CI 2.16, 4.80, P<0.001). In those with a new DM diagnosis, central obesity was associated with higher blood glucose (coefficient 1.62, 95% CI 0.72, 2.53, P = 0.009). Of 177 participants with ≥2 HbA1c results, 40% had uncontrolled glycemia (≥2 HbA1c results ≥8%). Of 165 participants with ≥3 HbA1c results, 29.9% had consistently-controlled glycemia, 15.3% had initially-uncontrolled glycemia, and 18.6% had consistently-uncontrolled glycemia. Previous versus new DM diagnosis and glucose-lowering medication use versus no use were associated with having uncontrolled versus controlled glycemia (adjusted odds ratio [aOR] 2.50 95%CI 1.61, 6.05, P = 0.042; aOR 4.78 95% CI 1.61,14.23, P<0.001) and more likely to have consistently-uncontrolled versus consistently-controlled glycemia (adjusted relative risk ratio [aRRR] 5.14 95% CI 1.37, 19.20, P = 0.015; aRRR 10.24 95% CI 0.07, 0.95, P = 0.003). Relapse cases of TB were less likely than new cases to have uncontrolled (aOR 0.20 95%CI 0.06, 0.63, P = 0.031) or consistently-uncontrolled (aRRR 0.25 95%CI 0.07, 0.95, P = 0.042) versus controlled glycemia. Those with long-term DM, suggested by previous diagnosis, glucose-lowering medication use and possibly central obesity, may require additional support to manage blood glucose during TB treatment.

Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains.

Bacterial diversity could contribute to the diversity of tuberculosis infection and treatment outcomes observed clinically, but the biological basis of this association is poorly understood. The aim of this study was to identify associations between phenogenomic variation in Mycobacterium tuberculosis and tuberculosis clinical features. We developed a high-throughput platform to define phenotype-genotype relationships in M tuberculosis clinical isolates, which we tested on a set of 158 drug-sensitive M tuberculosis strains sampled from a large tuberculosis clinical study in Ho Chi Minh City, Viet Nam. We tagged the strains with unique genetic barcodes in multiplicate, allowing us to pool the strains for in-vitro competitive fitness assays across 16 host-relevant antibiotic and metabolic conditions. Relative fitness was quantified by deep sequencing, enumerating output barcode read counts relative to input normalised values. We performed a genome-wide association study to identify phylogenetically linked and monogenic mutations associated with the in-vitro fitness phenotypes. These genetic determinants were further associated with relevant clinical outcomes (cavitary disease and treatment failure) by calculating odds ratios (ORs) with binomial logistic regressions. We also assessed the population-level transmission of strains associated with cavitary disease and treatment failure using terminal branch length analysis of the phylogenetic data. M tuberculosis clinical strains had diverse growth characteristics in host-like metabolic and drug conditions. These fitness phenotypes were highly heritable, and we identified monogenic and phylogenetically linked variants associated with the fitness phenotypes. These data enabled us to define two genetic features that were associated with clinical outcomes. First, mutations in Rv1339, a phosphodiesterase, which were associated with slow growth in glycerol, were further associated with treatment failure (OR 5·34, 95% CI 1·21-23·58, p=0·027). Second, we identified a phenotypically distinct slow-growing subclade of lineage 1 strains (L1.1.1.1) that was associated with cavitary disease (OR 2·49, 1·11-5·59, p=0·027) and treatment failure (OR 4·76, 1·53-14·78, p=0·0069), and which had shorter terminal branch lengths on the phylogenetic tree, suggesting increased transmission. Slow growth under various antibiotic and metabolic conditions served as in-vitro intermediate phenotypes underlying the association between M tuberculosis monogenic and phylogenetically linked mutations and outcomes such as cavitary disease, treatment failure, and transmission potential. These data suggest that Mtuberculosis growth regulation is an adaptive advantage for bacterial success in human populations, at least in some circumstances. These data further suggest markers for the underlying bacterial processes that contribute to these clinical outcomes. National Health and Medical Research Council/A∗STAR, National Institutes of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the Wellcome Trust Fellowship in Public Health and Tropical Medicine.

Rapid decrease in IL-1Ra and IP-10 plasma levels following tuberculosis treatment initiation

ObjectivesMonitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. MethodsANRS12394-LILAC-TB was a proof-of concept prospective study: HIV-negative and HIV-infected adults with a rifampicin-susceptible TB, documented by a positive Xpert MTB/RIF test, were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of IL-1Ra, IP-10 and sCD163 were measured by commercial ELISA kits. A Wilcoxon test for paired data was used for longitudinal comparisons. Results55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10/13 HIV-infected participants: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared to baseline, IL-1Ra plasma levels significantly decreased as soon as Week (W)1, independently of HIV status (-71% in HIV-positive vs. -33% in HIV-negative; p<0.001). IP-10 plasma levels significantly decreased at W1 and W2 compared to baseline (p<0.0001), but that decrease was less marked in HIV-infected participants. ConclusionOur findings suggest that measuring IL-1Ra plasma levels with a standard ELISA technique at baseline then one week after TB treatment onset could help clinicians to quickly assess TB treatment response.

Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Mental health issues associated with the management of tuberculosis in Homabay, Busia and Kakamega Counties, Kenya.

Despite the implementation of patient-centred care, mental health issues remain a significant risk factor and comorbidity for Tuberculosis (TB) disease. Mental health issues being co-morbidities to TB are likely to increase the disease burden of the affected population. This study therefore investigated the prevalence and impact of mental health issues in Tuberculosis (TB) patients. This cross-sectional study design used mixed methods in data collection. The study used structured questionnaires, key informant interviews and focus group discussions. 127 TB patients were purposively selected from a group of patients who previously recovered successfully, with a history of relapse or are currently on TB treatment in high-volume facilities in Homa Bay, Busia and Kakamega Counties. 30 Key informant interviews were conducted with Healthcare workers. Quantitative data analysis was done using STATA version 14. Thematic analysis was employed to analyze qualitative data using NVivo version 10. The findings showed that the most common mental health issues affecting TB patients were anxiety (66%) and depression (55%), which were commonly experienced during the presumptive stage of TB. Qualitative data revealed that stigma was the main barrier that hindered TB patients from accessing care. TB patients articulated the benefits of support structures ranging from positive encouragement, reminders on taking drugs, accompaniment to the clinic, and financial support in TB management. Furthermore, the study established that the majority of Health Care Workers (HCWs) were not prepared to handle TB patients' mental issues, a gap that is likely to impact the quality of care TB patients receive. The study established that mental health issues impact TB treatment outcomes. Healthcare systems should prioritize the integration of mental health care into TB programs to address the high prevalence of mental health issues among TB patients.

Impact of immune checkpoint inhibitors (ICIs) therapy on interferon-γ release assay (IGRA) and diagnostic value in non-small cell lung cancer (NSCLC) patients

BackgroundTuberculosis (TB), a highly contagious respiratory disease, presents a significant global health threat, with a notable increase in incidence reported by the WHO in 2022. Particularly, the interplay between TB and non-small cell lung cancer (NSCLC) gains attention, especially considering the rising use of immune checkpoint inhibitors (ICIs) in cancer treatment. This interplay may influence TB diagnostics and reactivation, warranting a closer examination.MethodsA retrospective analysis was conducted on clinical data of NSCLC patients with positive T-SPOT results before undergoing anti-tumor treatment at Zhongshan Hospital (Xiamen), Fudan University, from January 1, 2021 to December 31, 2022. We assessed the incidence of tuberculosis reactivation and treatment outcomes among these patients. Moreover, we compared the differences in tuberculosis activity between the ICIs and non-ICIs treatment groups. Additionally, we observed the changes in T-SPOT spot count before and after immunotherapy, analyzing their association with tuberculosis activity and prognosis.ResultsA total of 40 NSCLC patients with positive T-SPOT results before treatment were included in the study, with 26 patients in the ICIs treatment group and 14 patients in the non-ICIs treatment group. The study found no significant differences between the two groups in terms of gender, age, stage, histological type, performance status, driver gene expression, and distant metastasis. With a median follow-up time of 10.0 (6.0-14.5) months, three cases (11.5%) in the ICIs treatment group developed tuberculosis activity, diagnosed at 2, 3, and 12 months after ICIs treatment initiation. Conversely, no tuberculosis activity was observed in the non-ICIs treatment group, and the difference between the two groups was not significant (P = 0.186). Among the 32 patients who received ICIs treatment, spot count dynamics were diverse: four cases (12.5%) showed an increase, 12 cases (37.5%) had no change, and 16 cases (50.0%) had a decrease. During the follow-up, the progression rate (PD) was 50.0%, 75.0%, and 62.5% in the three groups, respectively (P = 0.527). Similarly, the mortality rate was 0%, 25.0%, and 25.0%, respectively (P = 0.106). Interestingly, among the patients with decreased spot counts, three cases (18.75%) were diagnosed with active pulmonary tuberculosis.ConclusionsFor NSCLC patients with a positive T-SPOT response undergoing ICIs treatment, our study observed indications of active tuberculosis. The varied T-SPOT spot count changes post-ICIs treatment suggest a complex interaction, potentially linking T-SPOT spot count reduction to tuberculosis reactivation risk. These preliminary findings underscore the importance of further research to more accurately assess T-SPOT’s diagnostic utility in this context.

Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial.

Children living with HIV(CLWH) are at high risk of tuberculosis(TB) and face poor outcomes, despite antiretroviral treatment(ART). We evaluated outcomes in CLWH and HIV-uninfected children treated for non-severe TB in the SHINE trial. SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, non-severe TB who were randomized to receive 4 vs 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CLWH. Of 1204 enrolled, 127(11%) were CLWH, of similar age (median(IQR) 3.6(1.2, 10.3) vs. 3.5(1.5, 6.9)years, p= 0.07), but more underweight (WAZ; -2.3(-3.3, -0.8) vs -1.0(-1.8, -0.2), p<0.01) and anemic (hemoglobin 9.5(8.7, 10.9) vs 11.5(10.4, 12.3)g/dl, p<0.01) compared to HIV-uninfected children. 68(54%) CLWH were ART-naïve; baseline median CD4 count 719(241-1134) cells/mm3, CD4% 16(10-26)%). CLWH were more likely to be hospitalized (aOR=2.4(1.3-4.6)) and die (aHR(95%CI) 2.6(1.2,5.8)). HIV status, age <3 years (aHR 6.3(1.5,27.3)), malnutrition (aHR 6.2(2.4,15.9)) and hemoglobin <7g/dl(aHR 3.8(1.3,11.5) independently predicted mortality. Among children with available VL, 45% and 61% CLWH had VL<1000copies/ml at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 vs 6 months) on TB treatment outcomes by HIV status (p for interaction=0.42). We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CLWH treated for non-severe TB. Irrespective of TB treatment duration, CLWH had higher rates of mortality and hospitalization than HIV-uninfected counterparts.

Determinants of Type II Diabetes Mellitus among Tuberculosis Patients in Yangon Region, Myanmar

Background: Although having Diabetes Mellitus might adversely affect tuberculosis treatment outcomes and reduce the likelihood of a favorable outcome, studies are still limited to identify many problems related to diabetes mellitus. Objectives: To identify factors influencing Type 2 diabetes mellitus among tuberculosis patients in Yangon region, Myanmar. Methods: A case control study conducted in the Yangon Region of Myanmar. Structured interview questionnaires were used for data collection after obtaining the informed consent. This study included 73 cases (TB patients with DM) and 146 controls (TB patients without DM) who were under tuberculosis treatment in 2023. Unconditional multivariable logistic regressions, crude odds ratios, and Adjusted Odds Ratios (AOR) with 95% confidence intervals and P-values &lt; 0.05 were applied for significant association.       Results: Of the 219 TB patients, 112 (51.14%) were male and 107 (48.86%) were female. The study observed that the risk factors of type 2 diabetes mellitus comorbidity among tuberculosis patients were: female TB patients (AOR= 2.84, 95% CI:1.36-5.94), aged 45 years and older (AOR=3.04, 95% CI: 1.45-6.37), who were married (AOR=2.28,95% CI:1.03-5.04), diagnosed by GeneXpert (AOR=2.66, 95% CI:1.22-5.79), those who had a family history of DM (AOR=4.08, 95% CI: 1.94-8.58), and those who had BMI ≥25 (AOR=9.00, 95% CI: 2.71-29.95). Conclusion: Based on findings, women TB patients, TB patients aged 45 years and older, married TB patients, TB patients detected by GeneXpert results, and TB patients with a family history of DM and a higher BMI were strong determinants of having TBDM. Therefore, encouraging health promotion on physical exercise, TB awareness campaign, pre-diabetes and diabetes screening and management among TB patients is crucial for the management of lifestyle and effective measures for the TB and comorbid disease control program.

Tuberculosis treatment outcomes and associated factors among tuberculosis patients treated at healthcare facilities of Motta Town, Northwest Ethiopia: a five-year retrospective study

Tuberculosis (TB) remains a significant public health concern, particularly in low-resource settings. The treatment outcome is a crucial indicator of the effectiveness of TB treatment programs. Assessing the current treatment outcome and its associated factors is essential for improving patient care and reducing the spread of TB. Therefore, this study aimed to assess TB treatment outcomes and their associated factors among TB patients who received treatment at public healthcare facilities in Motta Town, Northwest Ethiopia. A facility-based retrospective cross-sectional study design was employed in two TB treatment centers in Motta town from January 2017 to December 2021. The study participants were all patients diagnosed with TB who received treatment. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 362 TB patients were included in the study. The overall treatment success rate was 88.4% (95% CI 85.1, 91.7). Male gender (AOR = 2.40, 95% CI 1.16, 4.98), normal nutritional status (AOR = 3.11, 95% CI 1.33, 7.25), HIV negative status (AOR = 3.35, 95% CI 1.31, 8.60), and non-presumptive drug resistance to TB (AOR = 3.72, 95% CI 1.74, 7.98) were significantly associated with successful TB treatment outcomes (p < 0.05). In the current study, nine out of ten study participants had successful TB treatment outcome rates. Male gender, normal nutritional status, non-presumed drug resistance to TB, and HIV-negative status were significantly associated with successful TB treatment outcomes. By taking risk factors associated with poor treatment outcomes like those found in this study into account, patient management and treatment can be optimized. Sufficient TB control measures for populations are imperative and could significantly reduce the nation's total TB burden.

The Impact of Optimal Glycemic Control on Tuberculosis Treatment Outcomes in Patients With Diabetes Mellitus: Systematic Review and Meta-Analysis.

Diabetes mellitus (DM) increases the risk of developing tuberculosis (TB), and optimal glycemic control has been shown to reduce the risk of complications and improve the TB treatment outcomes in patients with DM. This study aims to investigate the role of glycemic control in improving TB treatment outcomes among patients with DM. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) assessing the impact of oral glycemic control in patients with TB who have DM. Outcomes of interest were radiological findings, treatment success, sputum positivity, and mortality. Evaluations were reported as risk ratios (RRs) with 95% CIs using weighted random-effects models. The analysis included 6919 patients from 7 observational studies. Our meta-analysis showed significant differences between patients with optimal glycemic control and those with poor glycemic control with regard to improved treatment outcomes (RR 1.13, 95% CI 1.02-1.25; P=.02; I²=65%), reduced sputum positivity (RR 0.23, 95% CI 0.09-0.61; P=.003; I²=66%), and fewer cavitary lesions (RR 0.59, 95% CI 0.51-0.68; P<.001; I²=0%) in radiological findings. There was no significant difference between the 2 groups in terms of mortality (RR 0.57, 95% CI 0.22-1.49; P=.25; I²=0%), multilobar involvement (RR 0.57, 95% CI 0.22-1.49; P=.25; I²=0%) on radiologic examination, and upper lobe (RR 0.94, 95% CI 0.76-1.17; P=.58; I²=0%) and lower lobe (RR 1.05, 95% CI 0.48-2.30; P=.91; I²=75%) involvement on radiologic examination. We concluded that optimal glycemic control is crucial for reducing susceptibility, minimizing complications, and improving treatment outcomes in patients with TB with DM. Emphasizing effective health management and health care strategies are essential in achieving this control. Integrating comprehensive care among patients with TB with DM will enhance patient outcomes and alleviate the burden of disease in this population. PROSPERO CRD42023427362; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=427362.

Trends in the Notification Rates and Treatment Outcome of Tuberculosis in Shandong Province, China, 2005-2021.

To analyze the time trends in the notification rates of registered tuberculosis (TB) and bacteriologically confirmed TB in Shandong Province. And analyze the changes in TB treatment outcomes during 2005-2021. The information of TB patients registered in the Shandong Information Center for Disease Control and Prevention (CDC) was collected during 2005-2021. We calculated the notification rates of registered TB and bacteriologically confirmed TB. Moreover, we calculated the year-to-year change rate of TB in treatment outcomes before and after COVID-19. The time trends were analyzed using the joinpoint regression method and illustrated as the annual percentage change (APC) of notification rates. A total of 236,898 cases of TB were diagnosed during 2005-2021, of which 51.11% were bacteriologically confirmed cases. Since 2008, the notification rates of registered TB have declined. The notification rates of bacteriologically confirmed TB had been declining during 2005-2016, then remained stable after 2016. In subgroup, the notification rates of both registered TB and bacteriologically confirmed TB were higher among men, rural residents, and people aged ≥ 60 years. Compared with clinically confirmed TB, bacteriologically confirmed TB has shown higher rates of poor outcomes since 2008 and higher case fatality rate since 2005. The rate of poor outcomes remained stable during 2008-2019. However, after the COVID-19 outbreak, the rate of poor outcomes and case fatality rate of TB has risen significantly. After unremitting efforts to fight against TB, the notification rates of registered TB and bacteriologically confirmed TB declined in Shandong Province. The rate of poor outcomes remained stable during 2008-2019, then rise significantly after the COVID-19 outbreak. In the context of the long-term existence of COVID-19, further efforts should be made in TB diagnosis and treatment among high-risk population, especially with regard to males, rural residents and older adults.

45 Evaluation of Drug-Resistant Tuberculosis Guidelines and Outcomes by Treatment Site in South Africa

OBJECTIVES/GOALS: DR-TB care in South Africa includes decentralized treatment with shorter, all-oral regimens. Treatment guidelines direct regular clinical and laboratory evaluation to assess patient improvement. We therefore measured sputum collection frequency and follow-up time to assess fidelity to these guidelines in Gauteng Province, South Africa. METHODS/STUDY POPULATION: We included Rifampicin-resistant (RR) sputum specimens from the South African National Health Laboratory Service, which provides pathology services to 80% of the population, submitted between August 2022-September 2023. Patient data were obtained from a DR-TB registry and additional sputum specimen data were collected from follow-up laboratory worksheets. Follow-up spanned from first sputum collection date (baseline) to patient outcome date (e.g., completion, lost) or study closure date (if still on treatment). Monthly sputum submission rate was measured for those with ≥1 additional sputum submitted. We compared patient data by treatment site: at the specialized hospital vs. any other site, using Wilcoxon ranksum and χ2 tests. RESULTS/ANTICIPATED RESULTS: Baseline RR-TB specimens were available for 142 patients, of whom 28 (20%) had specimens submitted from the specialized hospital. Patients at the specialized hospital were older (median age 41 vs. 35.5 years, p=0.03), had higher baseline fluoroquinolone resistance (10% vs. 1%, p=0.01), and longer follow-up (median 5.2 vs. 3.5 months, p=0.01) compared to patients elsewhere. Further, 43 (30%) patients had ≥1 additional sputum submitted during follow-up. Among these, monthly sputum collection rates did not differ by site (0.3 vs. 0.3 sputum per month, p=0.89). We anticipate that increased sputum frequency will be associated with successful TB treatment outcomes based on preliminary findings. DISCUSSION/SIGNIFICANCE: These findings highlight ongoing challenges with routine laboratory follow-up according to DR-TB guidelines across treatment sites in South Africa. Future research is needed to determine reasons for low sputum collection rates, such as low patient adherence, variation in practice of healthcare workers, loss to follow-up, and clinical challenges.

Epidemiology and Treatment Outcomes of Tuberculosis with Chronic Hepatitis B Infection-California, 2016-2020.

Improved epidemiologic and treatment data for active tuberculosis (TB) with chronic hepatitis B virus (cHBV) infection might inform and encourage screening and vaccination programs focused on persons at risk of having both conditions. We matched the California Department of Public Health TB registry during 2016-2020 to the cHBV registry using probabilistic matching algorithms. We used chi-square analysis to compare the characteristics of persons with TB and cHBV with those with TB only. We compared TB treatment outcomes between these groups using modified Poisson regression models. We calculated the time between reporting of TB and cHBV diagnoses for those with both conditions. We identified 8,435 persons with TB, including 316 (3.7%) with cHBV.- Among persons with TB and cHBV, 256 (81.0%) were non-U.S.-born Asian vs 4,186 (51.6%) with TB only (P <0.0001). End-stage renal disease (26 [8.2%] vs 322 [4.0%]; P <0.001) and HIV (21 [6.7%] vs 247 [3.0%]; P value = 0.02) were more frequent among those with TB and cHBV compared with those with TB only. Among those with both conditions, 35 (11.1%) had TB diagnosed >60 days before cHBV (median 363 days) and 220 (69.6%) had TB diagnosed >60 days after cHBV (median 3,411 days). Persons with TB and cHBV were found more frequently in certain groups compared with TB only, and infrequently had their conditions diagnosed together. This highlights an opportunity to improve screening and treatment of TB and cHBV in those at high risk for coinfection.

Effect of NAT2, GSTM1 and CYP2E1 genetic polymorphisms on plasma concentration of isoniazid and its metabolites in patients with tuberculosis, and the assessment of exposure-response relationships.

Objectives: Isoniazid is a key drug in the chemotherapy of tuberculosis (TB), however, interindividual variability in pharmacokinetic parameters and drug plasma levels may affect drug responses including drug induced hepatotoxicity. The current study investigated the relationships between isoniazid exposure and isoniazid metabolism-related genetic factors in the context of occurrence of drug induced hepatotoxicity and TB treatment outcomes. Methods: Demographic characteristics and clinical information were collected in a prospective TB cohort study in Latvia (N = 34). Time to sputum culture conversion (tSCC) was used as a treatment response marker. Blood plasma concentrations of isoniazid (INH) and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) were determined at three time points (pre-dose (0h), 2h and 6h after drug intake) using liquid chromatography-tandem mass spectrometry. Genetic variations of three key INH-metabolizing enzymes (NAT2, CYP2E1, and GSTM1) were investigated by application PCR- and Next-generation sequencing-based methods. Depending on variables, group comparisons were performed by Student's t-test, one-way ANOVA, Mann-Whitney-Wilcoxon, and Kruskal-Wallis tests. Pearson correlation coefficient was calculated for the pairs of normally distributed variables; model with rank transformations were used for non-normally distributed variables. Time-to-event analysis was performed to analyze the tSCC data. The cumulative probability of tSCC was obtained using Kaplan-Meier estimators. Cox proportional hazards models were fitted to estimate hazard rate ratios of successful tSCC. Results: High TB treatment success rate (94.1%) was achieved despite the variability in INH exposure. Clinical and demographic factors were not associated with either tSCC, hepatotoxicity, or INH pharmacokinetics parameters. Correlations between plasma concentrations of INH and its metabolites were NAT2 phenotype-dependent, while GSTM1 genetic variants did not showed any effects. CYP2E1*6 (T > A) allelic variant was associated with INH pharmacokinetic parameters. Decreased level of AcINH was associated with hepatotoxicity, while decreased values of INA/INH and AcINH/INH were associated with month two sputum culture positivity. Conclusion: Our findings suggest that CYP2E1, but not GSTM1, significantly affects the INH pharmacokinetics along with NAT2. AcINH plasma level could serve as a biomarker for INH-related hepatotoxicity, and the inclusion of INH metabolite screening in TB therapeutic drug monitoring could be beneficial in clinical studies for determination of optimal dosing strategies.

Stacked ensemble modeling for improved tuberculosis treatment outcome prediction in pediatric cases

SummaryThe promising results of ML (machine learning) methods in various disciplines have led to the frequent use of these methods in health fields such as disease diagnosis, personalized medicine, medical image‐based diagnosis, and predicting the number of deaths and cases in a pandemic. However, a neglected area in the field of healthcare is the lack of study with ML to predict treatment outcomes for tuberculosis (TB) patients, particularly children experiencing failed treatment. This need has become more apparent as the coronavirus pandemic has reversed the gains of health institutions with TB disease, especially in children. Therefore, this article conducted a study using the stacked ensemble ML method to early predict the risk for children experiencing a failed treatment outcome of TB. To fulfill this need and determine the most appropriate technique, a two‐stage methodology was followed in this work. First, predictions were obtained by combining the information gain feature selection (IGFS) approach with a variety of single‐based ML algorithms, including logistic regression (LR), deep belief neural networks (DBN), random forest (RF), and decision tree (DT). Second, the proposed method, which includes a stacked ensemble ML technique, was used. The latter model uses LR as a meta‐learner and the aforementioned single‐based ML algorithms (DBN, LR, RF, and DT). The performance results of ML models used in the two stages were compared, and the proposed model which is the combination of the stack‐based ensemble learning model and the IGFS technique provided better ROC curves, accuracy, precision, and recall results.

Assessment of treatment outcome among HIV positive tuberculosis patients in Visakhapatnam

In March 2016, RNTCP revised its technical and operational guidelines. One of the major additions was introduction of Daily Regimen in the treatment of Drug sensitive TB, started initially among TB-HIV co-infected patients in 2017. The present study was taken up to assess the treatment outcomes of Tuberculosis among TB-HIV co-infected patients and certain factors related to the poorer outcome of the treatment.An Observational Longitudinal study conducted at an ART centre, attached to King George Hospital in Visakhapatnam District, Andhra Pradesh, among all TB-HIV co-infected patients newly diagnosed with Drug Susceptible Tuberculosis, aged above 18years, at the selected ART centre, from the month of June 2018 to December 2018. The sample size calculated was 88 with an absolute precision of 10. Ethical clearance from Institutional Ethics Committee, Andhra Medical College; Written informed consent from all the study participants were taken prior to start of study. Confidentiality of the study participants was maintained Qualitative variables were presented as proportions. Analytical statistics include chi-square test and regression analysis. 74% of the patients had a favourable treatment outcome, 15% of the patients died and 11% of the patients were lost to follow up. Occupational status of the study participant, Socio- economic class, tobacco using habit and their CD4 counts had a statistically significant impact on their TB treatment outcome.CD4 count below 200cells/mm, Tobacco use, Diabetes Mellitus- factors responsible for unfavourable treatment outcome of Tuberculosis treatment Case-specific approaches among LFUs may be carried out to bring improvements in the strategies which are already existing or framing new strategies.

Evaluating tuberculosis treatment outcomes in Haiti from 2018 to 2019: A competing risk analysis

ObjectivesThis study assesses tuberculosis (TB) treatment outcomes in Haiti. MethodsData from drug-susceptible patients with TB (2018-2019) were analyzed using the Fine & Gray model with multiple imputation. ResultsOf the 16,545 patients, 14.7% had concurrent HIV coinfection, with a 66.2% success rate. The median treatment duration was 5 months, with patients averaging 30 years (with an interquartile range of 22-42 years). The estimated hazard of achieving a successful treatment outcome decreased by 2.5% and 8.1% for patients aged 45 and 60 years, respectively, compared with patients aged 30 years. Male patients had a 6.5% lower estimated hazard of success than their female counterparts. In addition, patients coinfected with HIV experienced a 35.3% reduction in the estimated hazard of achieving a successful treatment outcome compared with those with a negative HIV serologic status. ConclusionsIntegrated health care approaches should be implemented, incorporating innovative solutions, such as machine learning algorithms combined with geographic information systems and non-conventional data sources (including social media), to identify TB hotspots and high-burden households.

Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption. We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant. Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%). Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.