Unfavorable Tuberculosis Treatment Outcomes Research Articles

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.

Cohort study on association between catastrophic costs and unfavorable tuberculosis treatment outcomes among TB-HIV and TB-diabetes comorbid patients in India

BackgroundIndia grapples with an alarming burden of tuberculosis (TB), reporting 2.6 million incident cases in 2023, necessitating intensified efforts toward TB elimination. The prevalence of catastrophic costs, defined as expenses exceeding 20% of annual household income, varies widely. Our objective was to determine the association between catastrophic costs from TB-HIV and TB-diabetes care and unfavorable TB treatment outcomes.MethodsWe conducted a cohort study in Bhavnagar, India, from July 2019 to January 2021, involving 234 TB-HIV and 304 TB-diabetes patients. Catastrophic costs were assessed using the World Health Organization’s tool. Unfavorable TB treatment outcomes included positive results from sputum smear, nucleic acid amplification, or culture tests at treatment completion, death during treatment, or treatment cessation for a month (for drug-sensitive TB) or two months (for drug-resistant TB). Firth regression was employed to address quasi-separation issues and identify predictors.ResultsAmong TB-HIV patients, 12% faced catastrophic costs, with 20% experiencing unfavorable TB outcomes. In this group, significant predictors included weight (OR: 0.93, 95% CI: 0.89–0.98), family type (OR: 2.5, 95% CI: 1.2–5.5), and initial hospitalization (OR: 2.6, 95% CI: 1.1–6.3). For TB-diabetes patients, 5% faced catastrophic costs, and 14% had unfavorable outcomes, with significant predictors being below the poverty line (BPL) (OR: 2.9, 95% CI: 1.5–5.9) and initial hospitalization (OR: 3.4, 95% CI: 1.1–11.1). Catastrophic cost incidence was higher in TB-HIV (12% vs. 4% in TB only) and TB-diabetes (5% vs. 4% in TB only) patients. However, catastrophic costs did not show a direct association with unfavorable outcomes in either group.ConclusionsOur study found no direct association between catastrophic costs and unfavorable TB outcomes among TB-HIV/TB-diabetes patients. Instead, factors such as weight, family type, BPL status, and initial hospitalization were significant predictors. These findings underscore the importance of socio-economic conditions and initial hospitalization, advocate for enhanced support mechanisms including nutritional and financial aid, especially for BPL families.

Distinct TB-antigen stimulated cytokine profiles as predictive biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis.

The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB. However, their potential as indicators for unfavorable treatment outcomes remains uncertain. This study was conducted within a well-characterized cohort comprising newly diagnosed patients with drug-sensitive pulmonary TB, confirmed through sputum smear and culture positivity. Our objective was to elucidate the TB antigen-stimulated cytokine profile at pre-treatment and at 2 months into anti-TB treatment (ATT) in patients with unfavorable treatment outcomes (cases, n = 27) in comparison to recurrence-free, microbiologically cured controls (n = 31). Whole blood was stimulated with TB antigens using the QuantiFERON In-tube gold method, and plasma supernatants were subjected to a panel of 14 cytokine measurements. In our study, pre-treatment analysis revealed that eight cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-10, IL-17A, IL-18, and GM-CSF) were significantly elevated at baseline in cases compared to cured controls, both in unstimulated conditions and following TB antigen (CFP10, ESAT6, and TB7.7) stimulation. A similar pattern was observed at the 2-month mark of ATT, with eight cytokines (IL-2, IL-10, IL-13, IFN-γ, IL-6, IL-12p70, IL-17A, and TNF-α) showing significant differences between the groups. Importantly, no variations were detected following mitogen stimulation, underscoring that these distinctive immune responses are primarily driven by TB-specific antigens. Our findings indicate that individuals with unfavorable TB treatment outcomes display a characteristic cytokine profile distinct from TB-cured patients, even before commencing ATT. Therefore, the levels of specific cytokine pre-treatment and at the 2-month point in the course of treatment may serve as predictive immune markers for identifying individuals at risk of unfavorable TB treatment outcomes, with these responses being predominantly influenced by TB-specific antigens.

The magnitude of unfavorable tuberculosis treatment outcomes and their relation with baseline undernutrition and sustained undernutrition among children receiving tuberculosis treatment in central Ethiopia

BackgroundOne of the global key indicators for monitoring the implementation of the World Health Organization's End Tuberculosis (TB) Strategy is the treatment outcome rate. ObjectiveThis study aims to assess the magnitude of unfavorable treatment outcomes and estimate their relationship with baseline undernutrition and sustained undernutrition among children receiving TB treatment in central Ethiopia. MethodsThis retrospective cohort study included children treated for drug-susceptible TB between June 2014 and February 2022. The study comprised children aged 16 and younger who were treated in 32 randomly selected healthcare facilities. A log-binomial model was used to compute adjusted risk ratios (aRR) with 95% confidence intervals (CIs). ResultsOf 640 children, 42 (6.6%; 95% CI = 4.8–8.8%) had an unfavorable TB treatment outcomes, with 31 (73.8%; 95% CI = 58.0–86.1%) occurring during the continuation phase of TB treatment. We confirmed that baseline undernutrition (aRR = 2.68; 95% CI = 1.53–4.71), age less than 10 years (aRR = 2.69; 95% CI = 1.56–4.61), HIV infection (aRR = 2.62; 95% CI = 1.50–4.59), and relapsed TB (aRR = 3.19; 95% CI = 1.79–4.71) were independent predictors of unfavorable TB treatment outcomes. When we looked separately at children who had been on TB treatment for two months or more, we found that sustained undernutrition (aRR = 3.76; 95% CI = 1.90–7.43), age below ten years (aRR = 2.60; 95% CI = 1.31–5.15), and HIV infection (aRR = 2.26; 95% CI = 1.11–4.59) remained predictors of unfavorable outcomes, just as they had in the first two months. However, the effect of relapsed TB became insignificant (aRR = 2.81; 95% CI = 0.96–8.22) after the first two months TB treatment. ConclusionsThe magnitude of unfavorable TB treatment outcomes among children in central Ethiopia met the World Health Organization's 2025 milestone. Nearly three-quarters of unfavorable TB treatment outcomes occurred during the continuation phase of TB treatment. Baseline undernutrition, sustained undernutrition, younger age, HIV infection, and relapsed TB were found to be independent predictors of unfavorable TB treatment outcomes among children receiving TB treatment in central Ethiopia.

Influence of dietary pattern on anti-tuberculosis treatment outcomes in persons with dysglycemia: a Peruvian prospective cohort study.

Dietary patterns (DPs) are associated with overall nutritional status and may alter the clinical prognosis of tuberculosis. This interaction can be further intricated by dysglycemia (i.e., diabetes or prediabetes). Here, we identified DPs that are more common with tuberculosis-dysglycemia and depicted their association with tuberculosis treatment outcomes. A prospective cohort study of persons with tuberculosis and their contacts was conducted in Peru. A food frequency questionnaire and a multidimensional systems biology-based analytical approach were employed to identify DPs associated with these clinical groups. Potential independent associations between clinical features and DPs were analyzed. Three major DPs were identified. TB-dysglycemia cases more often had a high intake of carbohydrates (DP1). Furthermore, DP1 was found to be associated with an increased risk of unfavorable TB outcomes independent of other factors, including dysglycemia. Our findings suggest that the evaluation of nutritional status through DPs in comorbidities such as dysglycemia is a fundamental action to predict TB treatment outcomes. The mechanisms underlying the association between high intake of carbohydrates, dysglycemia, and unfavorable tuberculosis treatment outcomes warrant further investigation.

1875. Factors associated with unfavorable tuberculosis treatment outcomes, Almaty, Kazakhstan, 2018-2021

Abstract Background The COVID-19 pandemic negatively influenced the availability of TB related services around the world, including detection, diagnosis and treatment. The purpose of this research is to assess the impact of the COVID-19 pandemic on TB treatment outcomes in Almaty, and to determine risk factors associated with said outcomes by examining data from before (2018-2019) and during the pandemic (2020-2021). Methods We conducted a retrospective cohort study among all people newly diagnosed with drug-sensitive tuberculosis over 18 years old who initiated treatment from 2018-2021 in Almaty. We abstracted data from the national tuberculosis electronic database. Unfavorable treatment outcomes were sorted as follows: ineffective treatment, death, loss for follow-up, results not evaluated, and transferred for treatment with second-line anti-TB drugs. We used multivariate Poisson regression to calculate adjusted relative risk [aRR] and 95% confidence intervals [95%CI]. Risk factors associated with TB treatment outcomes among people newly diagnosed with drug-susceptible TB, Almaty, Kazakhstan, 2018-2022 Results Among 1548 people newly diagnosed with TB during the study period, average age of was 43 years (range 18-93) and 52% were male. A higher proportion of people had unfavorable outcomes during the pandemic (2020-21) than before the pandemic (2018-19) (20% vs 11%, respectively, and aRR=1.8; CI: 1.4-2.2). Among those with unsuccessful outcomes, 1% were lost to follow-up, 3% had treatment failures, and 9% died. Risk factors for unfavorable TB treatment outcomes were: being male (aRR=1.4, 95%CI=1.1-1.8), having HIV (aRR=2.4, 95%CI=1.8-3.3), having drinking disorder (aRR=2.3, 95%CI=1.6-3.3) and experiencing homelessness (aRR=2.6, 95%CI=1.5-4.3) (Table 1). Protective factors for unfavorable TB treatment outcomes were: being 18-39 years old (aRR=0.4, 95%CI=0.3-0.6), 40-59 years old (aRR=0.6, 95%CI=0.4-0.8), and being student (aRR=0.1, 95%CI=0.02-0.9). Conclusion COVID-19 pandemic was associated with unfavorable treatment outcomes for people newly diagnosed with drug-sensitive tuberculosis in Almaty, Kazakhstan. People with lower social stability were at increased risk. Results point to the need for improved continuity of care for TB treatment for people at increased risk of unfavorable outcomes, especially during disease outbreaks and pandemics. Disclosures All Authors: No reported disclosures

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

COVID-19 pandemic and other factors associated with unfavorable tuberculosis treatment outcomes-Almaty, Kazakhstan, 2018-2021.

The COVID-19 pandemic negatively influenced the availability of tuberculosis (TB) services, such as detection, diagnosis and treatment, around the world, including Kazakhstan. We set out to estimate the COVID-19 pandemic influence on TB treatment outcomes by comparing outcomes among people starting treatment before the pandemic (2018-2019) and during the pandemic (2020-2021) and to determine risk factors associated with unfavorable outcomes. We conducted a retrospective cohort study among all people newly diagnosed with drug-sensitive pulmonary or extrapulmonary TB at least 18 years old who initiated treatment from 2018 to 2021 in Almaty. We abstracted data from the national electronic TB register. Unfavorable treatment outcomes were ineffective treatment, death, loss to follow-up, results not evaluated, and transferred. We used multivariable Poisson regression to calculate adjusted relative risk (aRR) and 95% confidence intervals (95%CI). Among 1548 people newly diagnosed with TB during the study period, average age was 43 years (range 18-93) and 52% were male. The number of people initiating treatment was higher before than the pandemic (935 vs. 613, respectively). There was significantly different proportions before compared to during the pandemic for people diagnosed through routine screening (39% vs. 31%, p < 0.001), 60 years and older (16% vs. 22%, p = 0.005), and with diabetes (5% vs. 8%, p = 0.017). There was no difference in the proportion of HIV (8% in both periods). Unfavorable outcomes increased from 11 to 20% during the pandemic (aRR = 1.83; 95% CI: 1.44-2.31). Case fatality rose from 6 to 9% (p = 0.038). Risk factors for unfavorable TB treatment outcomes among all participants were being male (aRR = 1.44, 95%CI = 1.12-1.85), having HIV (aRR = 2.72, 95%CI = 1.99-3.72), having alcohol use disorder (aRR = 2.58, 95%CI = 1.83-3.62) and experiencing homelessness (aRR = 2.94, 95%CI = 1.80-4.80). Protective factors were being 18-39 years old (aRR = 0.33, 95%CI = 0.24-0.44) and 40-59 years old (aRR = 0.56, 95%CI = 0.41-0.75) compared to 60 years old and up. COVID-19 pandemic was associated with unfavorable treatment outcomes for people newly diagnosed with drug-sensitive TB in Almaty, Kazakhstan. People with fewer comorbidities were at increased risk. Results point to the need to maintain continuity of care for persons on TB treatment, especially those at higher risk for poor outcomes during periods of healthcare service disruption.

Clinic presentation delay and tuberculosis treatment outcomes in the Lake Victoria region of East Africa: A multi-site prospective cohort study.

In the Lake Victoria region of East Africa, little is known about delays between tuberculosis (TB) symptom onset and presentation at a clinic. Associations between clinic presentation delay and TB treatment outcomes are also poorly understood. In 2019, we abstracted data from routine TB treatment records for all adults (n = 776) initiating TB treatment in a 6-month period across 12 health facilities near Lake Victoria. We interviewed 301 cohort members and assessed whether they experienced a clinic presentation delay longer than 6 weeks. We investigated potential clinical and demographic correlates of clinic presentation delay and examined the association between clinic presentation delay and an unfavorable TB treatment outcome (death, loss to follow-up, or treatment failure). Clinic presentation delay was common, occurring among an estimated 54.7% (95% CI: 48.9%, 61.2%) of cohort members, though no specific correlates were identified. Clinic presentation delay was slightly associated with unfavorable TB treatment outcomes. The 180-day risk of an unfavorable outcome was 14.2% (95% CI: 8.0%, 20.4%) among those with clinic presentation delay, compared to 12.7% (95% CI: 5.1%, 20.3%) among those presenting earlier. Multi-level community-based interventions may be necessary to reduce clinic presentation delays in communities near Lake Victoria.

The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. Registration: PROSPERO (CRD42022309818).

Effect of prediabetes on tuberculosis treatment outcomes: A study from South India

Background and aimsThe aim was to assess the effect of prediabetes on tuberculosis(TB) treatment outcomes. MethodsThis is a prospective observational cohort study of 569 eligible new smear positive cases screened for DM between 2014 and 2018 in TB units in North Chennai, South India. Based on study criteria, a total of 187 subjects were included and categorised into two groups: TB with normoglycaemia (groupI) (HbA1c<5.7%) and TB with prediabetes (group II) (HbA1c = 5.7–6.4%) and followed them at 3rd and 6th month and treatment outcomes were assessed at the end of the TB treatment. ResultsTotal cure rate was 72.7% with no significant difference between the groups. Higher proportion of deaths occurred in group II (6.3%) compared to group I (1.3%) (p = 0.09). At the end of intensive phase of directly observed therapy (DOTS) treatment, about 23.8% were observed to have positive sputum smear in group II compared to 8.6% in group I(p = 0.019). The estimated relative risk to remain as sputum smear positive among people with prediabetes at the end of intensive phase was 3.0(95% CI: 1.2–7.6). There was a significant association found with HbA1c at enrollment and unfavourable TB treatment outcomes (β = 1.38, [odds ratio (95% CI) 3.98(1.65–9.64); p = 0.007]. ConclusionDeath rate was high and there was a delay in sputum conversion among TB patients with prediabetes at the end of the intensive phase of TB treatment. HbA1c at the time of diagnosis of prediabetes was significantly associated with unfavourable TB treatment outcomes.

Geographic mobility and treatment outcomes among people in care for tuberculosis in the Lake Victoria region of East Africa: A multi-site prospective cohort study.

Geographic mobility may disrupt continuity of care and contribute to poor clinical outcomes among people receiving treatment for tuberculosis (TB). This may occur especially where health services are not well coordinated across international borders, particularly in lower and middle income country settings. In this work, we describe mobility and the relationship between mobility and unfavorable TB treatment outcomes (i.e., death, loss to follow-up, or treatment failure) among a cohort of adults who initiated TB treatment at one of 12 health facilities near Lake Victoria. We abstracted data from health facility records for all 776 adults initiating TB treatment during a 6-month period at the selected facilities in Kenya, Tanzania, and Uganda. We interviewed 301 cohort members to assess overnight travel outside one's residential district/sub-county. In our analyses, we estimated the proportion of cohort members traveling in 2 and 6 months following initiation of TB treatment, explored correlates of mobility, and examined the association between mobility and an unfavorable TB treatment outcome. We estimated that 40.7% (95% CI: 33.3%, 49.6%) of people on treatment for TB traveled overnight at least once in the 6 months following treatment initiation. Mobility was more common among people who worked in the fishing industry and among those with extra-pulmonary TB. Mobility was not strongly associated with other characteristics examined, however, suggesting that efforts to improve TB care for mobile populations should be broad ranging. We found that in this cohort, people who were mobile were not at increased risk of an unfavorable TB treatment outcome. Findings from this study can help inform development and implementation of mobility-competent health services for people with TB in East Africa.

CO105 The Association of Sars-Cov-2 Infection and Tuberculosis Disease with Unfavorable Treatment Outcomes: A Systematic Review

We synthesized evidence on the influence of SARS-CoV-2 coinfection (Coinfection Review ) and its management (Clinical Management Review ) on treatment outcomes among people with tuberculosis (TB) disease. We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable TB treatment outcomes (Coinfection and Clinical Management Review ) and/or severe or critical COVID-19 or death (Clinical Management Review ). Study quality was assessed with Newcastle Ottawa Scale. We included 11 studies and 7305 participants. Evidence was low quality, and no study was designed to answer our research questions. Eight studies of 5749 people (286 [5%] with SARS-CoV-2) treated for TB were included in the Coinfection Review , and five addressed the primary outcome. There was no significant association between SARS-CoV-2 coinfection and unfavorable TB outcomes. Four studies of 1572 people treated for TB (291 [19%] received corticosteroids) were included in the Clinical Management Review , and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies with vs. without statistical adjustment. It remains unclear whether SARS-CoV-2 and its management are associated with unfavorable outcomes among people with TB. High-quality research is required to address the key knowledge gap.

A mixed-methods study on impact of silicosis on tuberculosis treatment outcomes and need for TB-silicosis collaborative activities in India

Globally, silicosis and tuberculosis (TB) have been targeted for elimination by 2030. The study’s objectives were to determine the association of silicosis with unfavorable TB treatment outcomes, as well as to explore experts’ perspectives on improving treatment outcomes among silico-tuberculosis patients. A retrospective cohort study evaluated TB treatment outcomes in Khambhat block, the western part of India, between 138 patients with silico-tuberculosis and 2610 TB patients without silicosis in February–March 2022. ‘Unfavorable TB treatment outcomes’ was defined as a patient stopping treatment for at least one month, a positive sputum smear at the end of treatment, or, a patient dying while on treatment. During April–July 2022, fifteen in-depth interviews with experts in the field of silicosis/tuberculosis were audio-recorded, transcribed, and analyzed to generate codes (thematic analysis). On multivariable logistic regression analysis, patients with silico-tuberculosis had a 2.3 (95% CI 1.6–3.4) times higher odds of unfavorable treatment outcomes. The experts recommended collaborative TB-silicosis activities for improving treatment outcomes of patients with silico-tuberculosis. I conclude from the study’s findings that silicosis is associated with unfavorable TB treatment outcomes in this study setting. All patients with silicosis should be screened for TB and treated according to national TB program guidelines. All patients with TB who have a history of occupational dust exposure should be evaluated for silicosis and provided appropriate pulmonary/vocational rehabilitation.

Baseline IL-6 is a biomarker for unfavourable tuberculosis treatment outcomes: a multisite discovery and validation study.

BackgroundBiomarkers of unfavorable tuberculosis treatment outcomes are needed to accelerate new drug and regimen development. Whether plasma cytokine levels can predict unfavorable tuberculosis treatment outcomes is unclear.MethodsWe identified and internally validated the association between 20 a-priori selected plasma inflammatory markers and unfavorable treatment outcomes of failure, recurrence and all-cause mortality among adults with drug-sensitive pulmonary tuberculosis in India. We externally validated these findings in two independent cohorts of predominantly diabetic and HIV coinfected tuberculosis patients in India and South Africa, respectively.ResultsPre-treatment IFN-γ, IL-13 and IL-6 were associated with treatment failure in the discovery analysis. Internal validation confirmed higher pre-treatment IL-6 concentrations among failure cases compared to controls. External validation among predominantly diabetic tuberculosis patients found an association between pre-treatment IL-6 concentrations and subsequent recurrence and death. Similarly, external validation among predominantly HIV coinfected tuberculosis patients found an association between pre-treatment IL-6 concentrations and subsequent treatment failure and death. In a pooled analysis of 363 tuberculosis cases from the Indian and South African validation cohorts, high pre-treatment IL-6 concentrations were associated with higher risk of failure (adjusted odds ratio [aOR]=2.16, 95%CI 1.08-4.33, p=0.02), recurrence (aOR=5.36, 95%CI 2.48-11.57, p<0.001) and death (aOR=4.62, 95%CI 1.95-10.95, p<0.001). Adding baseline IL-6 to a risk-prediction model comprising of low BMI, high smear grade and cavitation improved model performance by 15 percent (C-statistic of 0.66 versus 0.76, p=0.02).ConclusionPre-treatment IL-6 is a biomarker for unfavorable tuberculosis treatment outcomes. Future studies should identify optimal IL-6 concentrations for point-of-care risk prediction.

Tuberculosis Burden and Determinants of Treatment Outcomes According to Age in Brazil: A Nationwide Study of 896,314 Cases Reported Between 2010 and 2019.

Approximately 1.4 million people die annually worldwide from tuberculosis. Large epidemiologic studies can identify determinants of unfavorable clinical outcomes according to age, which can guide public health policy implementation and clinical management to improve outcomes. We obtained data from the national tuberculosis case registry; data were reported to the Brazilian National Program (SINAN) between 2010 and 2019. Clinical and epidemiologic variables were compared between age groups (child: <10 years, young: 10–24years, adult: 25–64years, and elderly: ≥65years). Univariate comparisons were performed together with second-generation p-values. We applied a backward stepwise multivariable logistic regression model to identify characteristics in each age group associated with unfavorable TB treatment outcomes. There were 896,314 tuberculosis cases reported during the period. Tuberculosis incidence was highest among adult males, but the young males presented the highest growth rate during the period. Directly observed therapy (DOT) was associated with protection against unfavorable outcomes in all age groups. The use of alcohol, illicit drugs, and smoking, as well as occurrence of comorbidities, were significantly different between age groups. Lack of DOT, previous tuberculosis, race, location of tuberculosis disease, and HIV infection were independent risk factors for unfavorable outcome depending on the age group. The clinical and epidemiological risk factors for unfavorable tuberculosis treatment outcomes varied according to age in Brazil. DOT was associated with improved outcomes in all age groups. Incidence according to age and sex identified adults and young males as the groups that need prevention efforts. This supports implementation of DOT in all populations to improve tuberculosis outcomes.

Risk Factors for Unfavorable Treatment Outcomes among the Human Immunodeficiency Virus-Associated Tuberculosis Population in Tashkent City, Uzbekistan: 2013–2017

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection poses a growing clinical challenge. People living with HIV have a higher chance of developing TB, and once the disease has progressed, are at greater risk of having unfavorable TB treatment outcomes. Data on TB treatment outcomes among the HIV-associated TB population in Uzbekistan are limited. Thus, we conducted a cohort study among 808 adult patients with HIV-associated TB registered at the Tashkent TB referral hospital from 2013–2017 to document baseline characteristics and evaluate risk factors for unfavorable TB treatment outcomes. The data were collected from medical records and ambulatory cards. About 79.8% of the study population had favorable treatment outcomes. Antiretroviral therapy (ART) coverage at the admission was 26.9%. Information on CD4-cell counts and viral loads were largely missing. Having extrapulmonary TB (aOR 2.21, 95% CI: 1.38–3.53, p = 0.001), positive sputum smear laboratory results on admission (aOR 1.62, 95% CI: 1.07–2.40), diabetes (aOR 5.16, 95% CI: 1.77–14.98), and hepatitis C (aOR 1.68, 95% CI: 1.14–2.46) were independent risk factors for developing unfavorable TB treatment outcomes. The study findings provide evidence for targeted clinical management in co-infected patients with risk factors. Strengthening the integration of TB/HIV services may improve availability of key data to improve co-infection management.

Factors associated with unfavourable treatment outcomes in people with HIV-associated tuberculosis in Armenia, 2015 to 2019.

To evaluate factors associated with tuberculosis (TB) treatment outcomes in human Immunodeficiency Virus-Associated (HIV) TB patients in Armenia, we conducted a nation-wide cohort study using routine programmatic data of all HIV-associated TB patients receiving TB treatment with first- or second-line drugs from 2015 to 2019. Data were obtained from the TB and HIV electronic databases. We analysed occurrence of the combined unfavourable outcome (failure, lost to follow-up, death and not evaluated) and death separately, and factors associated with both outcomes using Cox regression. There were 320 HIV-associated TB patients who contributed a total of 351 episodes of TB treatment. An unfavourable TB treatment outcome was registered in 155 (44.2%) episodes, including 85 (24.2%) due to death, 38 (10.8%) lost to follow up, 13 (3.7%) failure and 19 (5.4%) not evaluated. Multivariable analysis showed that receipt of Antiretroviral Treatment (ART) [ART start before TB treatment: adjusted hazard ratio (aHR)=0.3, 95% confidence interval (CI): 0.2-0.5, aHR=, 95% CI:, 95% CI:, 95% CI:TB meningitis (aHR=4.4, 95% CI: 1.6-11.9) increased the risk. The risk of death was affected by the same factors as above in addition to the low BMI (aHR=2.5, 95% CI: 1.3-4.5) and drug resistance (aHR=2.3, 95% CI: 1.0-5.4). In the subsample of episodes receiving ART, history of interruption of ART during TB treatment increased the risk of unfavourable outcome (aHR=2.1 95% CI: 1.2-3.9), while ART start during TB treatment was associated with lower risk of both unfavourable outcome (within first 8 weeks: aHR: 0.5, 95% CI: 0.3-0.9; after 8 weeks: aHR: 0.4, 95% CI: 0.2-1.0) and death (within first 8 weeks: aHR: 0.2, 95% CI: 0.1-0.4; after 8 weeks: aHR: 0.1, 95% CI: 0.01-0.3). The rates of unfavourable TB treatment outcomes, and death in particular, among HIV-associated TB patients in Armenia are high. Our findings emphasize the protective effect of ART and the importance of proper management of cases complicated by drug resistance or meningitis.

Do catastrophic costs impact treatment outcomes in people with rifampicin-resistant tuberculosis in the Republic of Moldova?

The Republic of Moldova is among the 30 Rifampicin-Resistant and/or Multidrug-Resistant (RR/MDR) Tuberculosis (TB) high burden countries in the world. Despite free TB diagnostics and treatment, TB patients face substantial economic losses and this may impact overall treatment outcomes. We assessed if there is an association between TB-related catastrophic costs and TB treatment outcomes. We conducted a cohort study using data from patient records and a survey that quantified catastrophic costs among RR/MDR-TB affected households in the Republic of Moldova in 2016. We included adult patients (age ≥18 years) with RR/MDR-TB who had been in inpatient (intensive phase) or outpatient (continuous phase) treatment for at least 2 months. Unfavourable treatment outcome, such as failure, death or lost to follow-up, was the primary outcome variable. The definition of catastrophic TB-related costs followed the World Health Organisation (WHO) guidelines: costs due to TB ≥20% of annual household income. Log-binomial regression was used to assess association between the outcome and catastrophic TB-related costs adjusting for other socio-demographic, behavioural and clinical covariates. In total 287 RR/MDR-TB patients (78% males, mean age 42 years) were included. Of them, 30% experienced catastrophic TB-related costs. Overall, one in five patients (21%) had unfavourable treatment outcome, such as treatment failure (5%), death (8%) or lost to follow-up (8%). The experience of catastrophic TB-related costs was not associated with unfavourable treatment outcome [adjusted relative risk (aRR)=0.88, 95% CI: 0.50–1.50]. Major factors independently associated with unfavourable TB treatment outcomes were poverty (aRR=2.07; 95% CI: 1.06-4.07), urban residence (aRR=1.99; 95% CI: 1.12-3.52) and positive HIV (Human Immunodeficiency Virus) status (aRR=2.61; 95% CI: 1.31-4.89). As a result, we failed to find an association between catastrophic costs and treatment outcomes of RR/MDR-TB patients in the Republic of Moldova. However, we found that patients from poor households and urban areas were twice more likely to achieve unfavourable TB treatment outcomes disregarding whether they experienced catastrophic costs or not. Also, TB/HIV patients and urban residents were identified as the most vulnerable groups with higher risk of unfavourable treatment outcome and TB-related costs.

Tuberculosis Burden and Determinants of Treatment Outcomes According to Age in Brazil: A Nationwide Ecological Study of 896,314 Cases Reported between 2010 and 2019

Background: Approximately 1·4 million people die annually worldwide from tuberculosis. Large epidemiologic studies can identify determinants of unfavorable clinical outcomes according to age, which can guide implementation of public health policies and clinical management to improve outcomes. Methods: We obtained data from the national tuberculosis case registry: cases reported to the Brazilian National Program (SINAN) between 2010-2019. Clinical and epidemiologic variables were compared between age groups (child:<10 years, young:10-24years, adult:25-64years and elderly:≥65years). Univariate comparisons were performed together with second-generation p-values. We applied a backward stepwise multivariable logistic regression model to identify characteristics in each age group associated with unfavorable TB treatment outcomes. Findings: There were 896,314 tuberculosis cases reported during the period. The tuberculosis incidence was highest among adult males, but the young males presented the highest growth rate between the period. Directly observed therapy (DOT) was associated with protection against unfavorable outcomes in all age groups. The use of alcohol, illicit drugs, and smoking, as well as occurrence of comorbidities were significantly different between age groups. Lack of DOT, previous tuberculosis, race, location of tuberculosis disease, and HIV infection were independent risk factors for unfavorable outcome depending on the age group. Interpretation: The clinical and epidemiological risk factors for unfavorable tuberculosis treatment outcomes varied according to age in Brazil. DOT was associated with improved outcomes in all age groups. Incidence according to the age and sex identified adults and young males as the groups that need prevention efforts. This supports implementation of DOT in all population to improve tuberculosis outcomes. ​ Funding Statement: This study was supported by the National Institutes of Health (NIH U01 AI069923 and NIAID 1 P30AI110527-03), CCASAnet, RePORT-Brazil Tennessee Center for AIDS Research (TNCFAR), BB-D and MA-P received a research fellowship from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) (Finance code: 001). MBA received a fellowship from the Fundacao de Amparo a Pesquisa da Bahia (FAPESB). The work of BBA is supported by the Intramural Research Program of the Oswaldo Cruz Foundation (FIOCRUZ) and the National Council for Scientific and Technological Development (CNPq), Brazil. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.