Receiving Tuberculosis Treatment Research Articles

Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies.

India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.

Impact of Dolutegravir-based Regimen on Tolerance and Virologic Suppression, Compared to Non-dolutegravir Regimen among PLHIV in Southern Senegal

Background: In 2020, Senegal began a transition to a Dolutgravir-based treatment as a first-line regimen in all new ART initiators in accordance with WHO recommendations. Aims: To determine the virological suppression and the tolerance on patients under a dolutegravir-based regimen by comparison with patients on a regimen without dolutegravir after at least 6 months of treatment. Materials and Methods: A cross-sectional study based on retrospective data (from January 2nd, 2017 to June 30th; 2022) involving 469 patients, 219 people were initiated with Dolutegravir regimen ART between Jan 2nd, 2020, and June 30th, 2022, and 250 patients treated using the old protocol (non-dolutegravir regimen). Patients who had received both the old protocol then switched to a DTG based regimen were excluded from the study. A single questionnaire was used to collect data. Sociodemographic, clinical and virological parameters and the last control of the virological load were analyzed with Stata 16 software. Descriptive statistics and univaried analysis were also carried-out. Results: In the dolutegravir regimen ART group, 161 (73, 52%) of 219 were women and 58 (26.48) were men. The median participant age was 43·0 years (IQR 33·0–53·0) and the median time on ART was 28·0 months (23·0–36·0). The dolutegravir-based regimen combined tenofovir, lamivudine and dolutegravir. 15 (6, 85 %) were receiving tuberculosis treatment at the time of ART initiation. The proportion of patients screened at an advanced clinical stage of AIDS (WHO stage 3 or 4) were 63, 47%. People initiated on dolutegravir were more likely to be retained in care at 12 months (100% vs. 95.20%; p=0.075) and having viral suppression (96.80%vs. 96.40% ; p=0,810) compared with those initiated on non-dolutegravir-based regimens but the difference was not statistically significant. Fewer patients presented side effects due to triple therapy in the dolutegravir-based regimen group compared to the non-dolutegravir group (2.74% vs. 3.20%; p=0.77). In the dolutegravir based regimen the side effects were mainly vomiting, insomnia, and dizziness. The mean gain weight was 6,7± 8,2 kilograms. For the non-dolutegravir regimen group, 195 (78.00%) were women. The median participants age was 43·0 years (IQR 34·0–53·0) and the median time on ART was 55·0 years (48·0–65·0) months. 18 (7, 20%) were receiving tuberculosis treatment at time of ART initiation. The therapeutic protocol combined TDF, lamivudine, Efavirenz in 225 cases (90%). A percentage of 59.20% patients were screened at an advanced clinical stage of AIDS (WHO Stage 3 and 4). In this group the side effects were mainly nausea and insomnia and the mean gain weight was 7,2 ± 6,2 kilograms. Conclusion: The results of our study show a high rate of viral suppression, and good tolerance of the dolutegravir-based regimen in a decentralized setting.

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.

GeneXpert MTB/RIF Ultra vs Unstimulated Interferon γ (IRISA-TB) for the Diagnosis of Tuberculous Pericarditis in a Tuberculosis-Endemic Setting.

Tuberculous pericarditis (TBP) is a paucibacillary disease, where host biomarkers such as unstimulated interferon γ (IRISA-TB) have high diagnostic accuracy. However, DNA-based diagnostic tests (GeneXpert Ultra), more sensitive than an earlier versions, have recently become available. Given that the diagnosis of TBP is challenging, we performed a comparative diagnostic accuracy study comparing both assays. We recruited 99 consecutive patients with suspected TBP in Cape Town, South Africa. Definite TBP was defined by microbiological confirmation of tuberculosis (TB) on pericardial fluid culture or an alternative polymerase chain reaction-based test (GeneXpert MTB/RIF) or by use of sputum (polymerase chain reaction or culture). Probable TBP was defined as a high clinical suspicion of TB accompanied by anti-TB treatment, while non-TBP was defined as negative microbiological test results for TB without initiation of TB treatment and/or the presence of an alternative diagnosis. There were 39 patients with definite TBP, 35 with probable TBP, and 23 with non-TBP. Approximately 70% of participants who received TB treatment were HIV coinfected. Overall, IRISA-TB was more sensitive than Xpert Ultra (88.6% [95% CI, 74.1%-95.5%] vs 71.5% [55.0%-83.7%], n = 53) and significantly more sensitive in participants who were HIV uninfected (100% [95% CI, 72.3%-100.0%] vs 60% [31.3%-83.2%], P = .03). In patients with definite and probable TBP combined (n = 84), sensitivity was significantly higher with IRISA-TB (77.3% [95% CI, 65.9%-85.8%] vs 37.9 [27.2%-50.0%], P < .0001). A similar pattern was seen in persons who were HIV uninfected (88.3% vs 35.3%, P = .002). Specificity was high for both assays (>95%). Unstimulated interferon γ (IRISA-TB) was significantly more sensitive than Xpert Ultra for the diagnosis of TB pericarditis in a TB-endemic resource-poor setting.

Evaluation of the Xpert MTB Host Response assay for the triage of patients with presumed pulmonary tuberculosis: a prospective diagnostic accuracy study in Viet Nam, India, the Philippines, Uganda, and South Africa

Non-sputum-based triage tests for tuberculosis are a priority for ending tuberculosis. We aimed to evaluate the diagnostic accuracy of the late-prototype Xpert MTB Host Response (Xpert HR) blood-based assay. We conducted a prospective diagnostic accuracy study among outpatients with presumed tuberculosis in outpatient clinics in Viet Nam, India, the Philippines, Uganda, and South Africa. Eligible participants were aged 18 years or older and reported cough lasting at least 2 weeks. We excluded those receiving tuberculosis treatment in the preceding 12 months and those who were unwilling to consent. Xpert HR was performed on capillary or venous blood. Reference standard testing included sputum Xpert MTB/RIF Ultra and mycobacterial culture. We performed receiver operating characteristic (ROC) analysis to identify the optimal cutoff value for the Xpert HR to achieve the target sensitivity of 90% or more while maximising specificity, then calculated diagnostic accuracy using this cutoff value. This study was prospectively registered with ClinicalTrials.gov, NCT04923958. Between July 13, 2021, and Aug 15, 2022, 2046 adults with at least 2 weeks of cough were identified, of whom 1499 adults (686 [45·8%] females and 813 [54·2%] males) had valid Xpert HR and reference standard results. 329 (21·9%) had microbiologically confirmed tuberculosis. Xpert HR had an area under the ROC curve of 0·89 (95% CI 0·86-0·91). The optimal cutoff value was less than or equal to -1·25, giving a sensitivity of 90·3% (95% CI 86·5-93·3; 297 of 329) and a specificity of 62·6% (95% CI 59·7-65·3; 732 of 1170). Sensitivity was similar across countries, by sex, and by subgroups, although specificity was lower in people living with HIV (45·1%, 95% CI 37·8-52·6) than in those not living with HIV (65·9%, 62·8-68·8; difference of 20·8%, 95% CI 13·0-28·6; p<0·0001). Xpert HR had high negative predictive value (95·8%, 95% CI 94·1-97·1), but positive predictive value was only 40·1% (95% CI 36·8-44·1). Using the Xpert HR as a triage test would have reduced confirmatory sputum testing by 57·3% (95% CI 54·2-60·4). Xpert HR did not meet WHO minimum specificity targets for a non-sputum-based triage test for pulmonary tuberculosis. Despite promise as a rule-out test that could reduce confirmatory sputum testing, further cost-effectiveness modelling and data on acceptability and usability are needed to inform policy recommendations. National Institute of Allergy and Infectious Diseases of the US National Institutes of Health. For the Vietnamese and Tagalog translations of the abstract see Supplementary Materials section.

Two Difficult Pandemics: Tuberculosis and COVID-19.

The coinfection of Mycobacterium tuberculosis and SARS-CoV-2 is called tuberculosis and COVID-19 coinfection (TB-COVID-19). We aimed to share the clinical, radiological, and laboratory findings and treatment processes of our patients with TB-COVID-19 coinfection in our tertiary reference hospital. Patients aged 18 years and over and hospitalized in the tuberculosis service between March 2020 and September 2022 were included. All coinfected patients whose COVID-19 polymerase chain reaction results were positive while receiving tuberculosis treatment or who were diagnosed with tuberculosis while receiving treatment for COVID-19 were included. The number of patients was 39; 61.6% of males; the mean age was 52 ± 17.1 years; 20% were foreign nationals; 92.5% were Asian; 69.5% had a bacteriological diagnosis; 84.6% had pulmonary tuberculosis; 10% had received antituberculosis treatment before; and 87.5% were sensitive to the first-line antituberculosis drugs. The most common comorbidities were diabetes and hypertension. 87.5% of the patients were diagnosed with tuberculosis and were superinfected with COVID-19 while receiving tuberculosis treatment. 49.5% of patients had received at least one dose of COVID-19 vaccine. The most common presenting symptom was cough and sputum; the prominent laboratory parameter was C-reactive protein increase, and thorax computed tomography finding was consolidation, tree-in-bud, and cavitation. While 45.9% of the patients were still under treatment, 1 (2.5%) patient also resulted in mortality. In this study, attention was drawn to two infectious diseases seen with respiratory tract symptoms. The mortality rate was found to be low. Neither disease was found to be a factor aggravating the course of each other.

Analysis of Adherence Factors to Tuberculosis Therapy at the PB Selayang II Health Center, Medan City

&lt;p class="Default"&gt;&lt;em&gt;Pulmonary tuberculosis disease in Indonesia is increasing every year.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;The percentage of people receiving tuberculosis treatment as of 1 November 2022 is still far below the goal set (90%) or 52%. The 2020-2024 national health development strategy and the national medium term development plan 2020-2024 call for eliminating tuberculosis in Indonesia by 2030. Many factors can affect the success of tuberculosis treatment, including patient factors, drug ingestion monitor factors, and drug factors. This study aimed to determine the factors that influence therapy compliance in tuberculosis patients at the PB Selayang II Public health center, Medan City. This research method is quantitative analytical with a cross-sectional research design. The research was conducted at the PB Selayang II Public health center, Medan City, which was carried out from May to June 2023. The population in the study was all 109 tuberculosis patients. The sampling technique was purposive sampling, so the sample for this study was 56 patients. Data collection uses questionnaires with interviews. Data analysis using bivariate analysis using the chi-square test. The results of this study show that internal factors, namely taking anti-tuberculosis drugs, are related to compliance with a sig value of 0.002 and external factors, namely the role of officers and motivation, are related to compliance with tuberculosis therapy at&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;PB Selayang II Public health center&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;with a sig value of 0.000. The conclusion from the results obtained that significantly influences compliance with tuberculosis therapy is external factors where there are 2 categories related to compliance, namely motivation and the role of officers.&lt;/em&gt;&lt;/p&gt;&lt;p class="Default"&gt;&lt;strong&gt;&lt;em&gt;Keywords: External factors, Internal factors, Public health center, Tuberculosis, Treatment compliance&lt;/em&gt;&lt;/strong&gt;&lt;/p&gt;

Costs incurred by people receiving tuberculosis treatment in low-income and middle-income countries: a meta-regression analysis

People accessing and completing treatment for tuberculosis can face large economic costs, even when treatment is provided free of charge. The WHO End TB Strategy targets the elimination of catastrophic costs among tuberculosis-affected households. While low-income and middle-income countries (LMICs) represent 99% of global tuberculosis cases, only 29 of 135 LMICs had conducted national surveys of costs for patients with tuberculosis by December, 2022. We estimated costs for patients with tuberculosis in countries that have not conducted a national survey, to provide evidence on the economic burden of tuberculosis in these settings and inform estimates of global economic burden. We extracted data from 22 national surveys of costs faced by patients with tuberculosis that were completed across 2015-22 and met inclusion criteria. Using a Bayesian meta-regression approach, we used these data and covariate data for all 135 LMICs to estimate per-patient costs (2021 US$) by cost category (ie, direct medical, direct non-medical, and indirect), country, drug resistance, and household income quintile. We also estimated the proportion of households experiencing catastrophic total costs (defined as >20% of annual household income) as a result of tuberculosis disease. Across LMICs, mean direct medical costs incurred by patients with tuberculosis were estimated as US$211 (95% uncertainty interval 154-302), direct non-medical costs were $512 (428-620), and indirect costs were $530 (423-663) per episode of tuberculosis. Overall, per-patient costs were $1253 (1127-1417). Estimated proportions of tuberculosis-affected households experiencing catastrophic total costs ranged from 75·2% (70·3-80·0) in the poorest quintile to 42·5% (34·3-51·5) in the richest quintile, compared with 54·9% (47·0-63·2) overall. Tuberculosis diagnosis and treatment impose substantial costs on affected households. Eliminating these economic losses is crucial for removing barriers to accessing tuberculosis diagnosis and completing treatment among affected households and achieving the targets set in WHO's End TB Strategy. World Health Organization.

Implementation and outcomes of dolutegravir-based first-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study

There are few data assessing the uptake of first-line dolutegravir among men and women living with HIV in low-income and middle-income countries, and subsequent clinical outcomes in non-trial settings. We aimed to determine dolutegravir uptake in women, and the effect of dolutegravir on clinical outcomes in routine care in South Africa. In this cohort study, we analysed deidentified data from adults receiving first-line antiretroviral therapy (ART) at 59 South African clinics from Dec 1, 2019, to Feb 28, 2022, using two distinct cohorts. In the initiator cohort, we used Poisson regression models to assess the outcome of initiation with dolutegravir-based ART by gender, and associations between dolutegravir use and the outcomes of 12-month retention in care and viral suppression at less than 50 copies per mL. In the transition cohort, comprising adults who received non-dolutegravir-based first-line ART in December, 2019, we used Cox proportional hazards models to assess the outcome of transition to first-line dolutegravir by gender. We then used time-dependent propensity score matching to compare the outcomes of subsequent 12-month retention in care and viral suppression between people who transitioned to dolutegravir and those who had not yet transitioned at the same timepoint. In both the initiation and transition cohort, the primary viral load analysis was an intention-to-treat analysis, with a secondary as-treated analysis that excluded people who changed their ART regimen after baseline. In the initiator cohort, between Dec 1, 2019, and Feb 28, 2022, 45 392 people were initiated on ART. 23 945 (52·8%) of 45 392 were non-pregnant women, 4780 (10·5%) were pregnant women, and 16 667 (36·7%) were men. The median participant age was 31·0 years (IQR 26·0-38·0) and 2401 (5·3%) were receiving tuberculosis treatment at time of ART initiation. 31 264 (68·9%) of 45 392 people were initiated on dolutegravir, 14 102 (31·1%) on efavirenz, and 26 (0·1%) on nevirapine. In a univariable Poisson regression model, pregnant women (risk ratio [RR] 0·57, 95% CI 0·49 to 0·66; risk difference -35·4%, 95% CI -42·3 to -28·5) and non-pregnant women (RR 0·78, 0·74 to 0·82; risk difference -18·4%, -21·6 to -15·2) were less likely to be initiated on dolutegravir than were men. In Poisson models adjusted for age, gender (including pregnancy), time, tuberculosis status, and initiation CD4 count, people initiated on dolutegravir were more likely to be retained in care at 12 months (adjusted RR 1·09, 95% CI 1·04 to 1·14; adjusted risk difference 5·2%, 2·2 to 8·4) and virally suppressed (adjusted RR 1·04, 95% CI 1·01 to 1·06; adjusted risk difference 3·1%, 1·2 to 5·1) compared with those initiated on non-dolutegravir-based regimens. For the transition cohort, on Dec 1, 2019, 180 956 people were receiving non-dolutegravir-based first-line ART at the study clinics, of whom 124 168 (68·6%) were women. The median age was 38 years (IQR 32-45), and the median time on ART was 3·9 years (2·0-6·4) years, with most people receiving efavirenz (178 624 [98·7%] people) and tenofovir (178 148 [98·4%]). By Feb 28, 2022, 121 174 (67·0%) of 180 956 people had transitioned to first-line dolutegravir at a median of 283 days (IQR 203-526). In a univariable Cox regression model the hazard of being transitioned to dolutegravir was lower in women than in men (hazard ratio 0·56, 95% CI 0·56 to 0·57). Among 92 318 propensity score matched people, the likelihood of retention in care was higher among the dolutegravir group compared with matched controls (adjusted RR 1·03, 95% CI 1·02 to 1·03; risk difference 2·5%, 95% CI 2·1 to 2·9). In the dolutegravir group, 33 423 (90·5%) of 36 920 people were suppressed at less than 50 copies per mL compared with 31 648 (89·7%) of 35 299 matched controls (adjusted RR 1·01, 95% CI 1·00 to 1·02; risk difference 0·8%, 95% CI 0·3 to 1·4). Women were less likely to receive dolutegravir than men. As dolutegravir was associated with improved outcomes, roll-out should continue, with a particular emphasis on inclusion of women. Wellcome Trust, Africa Oxford Initiative, International Association of Providers of AIDS Care, and Bill & Melinda Gates Foundation. For the isiZulu translation of the abstract see Supplementary Materials section.

Qualitative study exploring the feasibility of using medication monitors and a differentiated care approach to support adherence among people receiving TB treatment in South Africa

ObjectivesThe tuberculosis (TB) MATE study evaluated whether a differentiated care approach (DCA) based on tablet-taking data from Wisepill evriMED digital adherence technology could improve TB treatment adherence. The DCA entailed...

Mortality among persons receiving tuberculosis treatment in Itezhi-Tezhi District of Zambia: A retrospective cohort study.

Itezhi-Tezhi District in southern Zambia has been reporting tuberculosis (TB) mortality rates that are fourfold higher than the national average of six percent. We conducted a retrospective cohort study to establish the demographic and clinical characteristics associated with mortality among persons under treatment for TB in Itezhi-Tezhi District, as well as the likely causes and time to death. We reviewed medical records for persons with TB registered in 19 public health facilities in Itezhi-Tezhi District between January 2015 and December 2018. Of the 506 persons with TB registered in the study period, 426 were included in the analysis. Of these, 71 (16.7%) died before completing treatment. The overall mortality rate was 31.8 per 1,000 person-months of observation. Most of the deaths (53 [74.7%]) occurred in the first month of treatment (median: 16 days; interquartile range: 5-52 days). In a multivariate Cox regression model, type of TB was found to be an independent predictor of mortality while on TB treatment. The risk of dying was more than twice higher for persons with clinically diagnosed PTB compared to those with bacteriologically confirmed PTB (adjusted hazard ratio = 2.2, 95% CI: 1.4-3.6). In a sub-analysis of persons with clinically diagnosed PTB, persons with TB who were on a community-based DOT plan were more than twice more likely to die compared to those on facility-based DOT plan (adjusted hazard ratio = 2.21, 95% CI: 1.1-4.8). Common likely causes of death were pulmonary TB disease (66.0%), anemia (12.8%), cardiac failure (4.3%), pneumocystis jiroveci pneumonia (4.3%), and gastroenteritis (4.2%). These findings show that most deaths occurred during the first month of treatment. Clinical evaluation at initiation of anti-TB treatment and during follow-up care, especially in persons with clinically diagnosed PTB, should include screening and treatment of other conditions.

Nontuberculous mycobacteria isolation from sputum specimens: A retrospective analysis of 1061 cases.

In recent years, with the development of laboratory methods, the frequency of nontuberculosis mycobacteria (NTM) infections has increased. The primary aim of this study was to evaluate the clinical significance of therapeutic drug monitoring (TDM) growths in respiratory samples, and the secondary aim was to evaluate the treatment regimens and treatment outcomes of treatment for TDM disease. This study was a retrospective cohort study. Persons with NTM growth in respiratory samples admitted to the reference hospital between 2009 and 2020 were included in this study. Samples detected as NTM by the immunochromatographic rapid diagnostic test, those requested by the clinicians, species were determined by the hsp65PCRREA method. The subjects were classified into 3 groups: patients with NTM infection who received treatment (135, 12.7%), those followed up without treatment (690, 65.1%), and a last group of patients with Mycobacterium tuberculosis (TB) complex strains were isolated and received TB treatment (236, 22.2%). Initiating NTM treatment was decided in accordance with the American Thoracic Society recommendations. The mean ± standard deviation age of patients was 53.8 ± 16.5 years, and 749 (70.6%) were male. In total, 278 (26.2%) out of 1061 cases had identified, and the most frequent species were MAC (81; Mycobacterium avium: 39, Mycobacterium intracellulare: 39, and MAC: 3), Mycobacterium abscessus (67), Mycobacterium kansasii (48), Mycobacterium fortuitum (23), Mycobacterium chelonae (12), Mycobacterium gordonae (11), and Mycobacterium szulgai (11). In the NTM treatment group, 116 (85.9%) of 135 patients had multiple culture positivity. Previous TB treatment history had 51 (37.8%) of 135 patients, respiratory comorbidities were evident in 37 (27.4%) of 135 patients. Thorax computed tomography imaging in 84 patients revealed nodule 38 (45.2%), consolidation 46 (54.8%), cavity 52 (61.9%), and bronchiectasis 27 (32.1%). Treatment results in the NTM treatment group were as follows: ongoing treatment 14 (10.4%), cure 64 (47.4%), default 33 (24.4%), exitus 19 (14.1%), recurrence 3 (2.2%), and refractory disease 2 (1.5%). This is a large case series evaluating the clinical significance of NTM growths and NTM treatment in Turkey. The clinical significance of NTM growth in respiratory samples is low. Treatment success rates of NTM patients who are treated are low. Treatment defaults and mortality rates are high. New drugs and new regimens are needed.

Lost to Follow-Up among Tuberculosis Patients during the Public-Private Mix Era in Rural Area of Indonesia.

Indonesia's national Tuberculosis (TB) strategy is public-private mix (PPM). The PPM aims to treat patients who have lost sight during TB treatment as these patients are TB carriers and at risk of transmitting TB. The purpose of this study was to identify predictive factors for loss to follow-up (LFTU) among TB patients receiving treatment when the PPM was at place in Indonesia. The design of this study was a retrospective cohort study. The data used in this study was sourced from the Tuberculosis Information System (SITB) of Semarang which was recorded routinely during 2020-2021. Univariate analysis, crosstabulation, and logistic regression were performed on 3434 TB patients meeting the minimum variables. The participation of health facilities in reporting TB during the PPM era in Semarang reached 97.6% consisting of 37 primary healthcare center (100%), 8 public hospitals (100%), 19 private hospitals (90.5%), and a community-based pulmonary health center (100%). The regression analysis reveal that the predictive factors of LTFU-TB during the PPM are the year of diagnosis (AOR=1.541; p-value=<0.001; 95% CI=1.228-1.934), referral status (AOR=1.562, p-value=0.007; 95% CI=1.130-2160), healthcare and social security insurance ownership (AOR=1.638; p-value=<0.001; 95% CI=1.263-2.124), drugs source (AOR=4.667; p-value=0.035; 95% CI=1.117-19.489). The PPM strategy in dealing with LTFU patients should focus on TB patients without Healthcare and Social Security Insurance and who receive TB treatment rather than program drugs.

Diagnostic accuracy of two confirmatory tests for diabetes mellitus in adult Ugandans with recently diagnosed tuberculosis.

The optimal confirmatory tests for diabetes mellitus (DM) in patients with tuberculosis (TB) vary across populations. This study aimed to evaluate the performance of two confirmatory tests for DM against the oral glucose tolerance test (OGTT) as the reference test in adult Ugandans with recently diagnosed TB. A total of 232 adult participants receiving TB treatment underwent initial screening for DM with random blood glucose (RBG) measurement. Participants with a RBG level ⩾6.1 mmol/l received additional screening with fasting blood glucose (FBG), laboratory-measured glycated haemoglobin (HbA1c) and an OGTT. Using the latter as the gold standard and reference test, we evaluated the diagnostic accuracy of laboratory-measured HbA1c and FBG. Of the 232 participants initially screened for DM using RBG measurement, 117 participants (50.4%) had RBG level ⩾6.1 mmol/l and were scheduled to return for additional blood glucose testing. Of these, 75 (64.1%) participants returned for FBG and HbA1c measurements. A diagnosis of DM was made in 32 participants, corresponding to a prevalence of 13.8% [95% CI 9.9-18.9].The areas under the curve (AUC) for FBG and laboratory-measured HbA1c were 0.69 [95% CI 0.47-0.90] and 0.65 [95% CI 0.43-0.87], respectively. The sensitivity and specificity of a FBG level of ⩾7 mmol/l were 57.1% [95% CI 18.4-90.1] and 74.6% [95% CI 62.5-84.5], respectively, whereas the sensitivity and specificity for laboratory-measured HbA1c of ⩾6.5 mmol/l (48 mmol/mol) were 14.3% [95% CI 0.40-57.9] and 95.3% (86.9-99.0%), respectively. FBG may be better than laboratory-measured HbA1c in confirming DM in adult Ugandans with recently diagnosed TB. However, because of the small study sample size, larger studies evaluating the diagnostic utility of these diabetes screening tests in adult Ugandans with TB are needed to confirm these findings.

Treatment outcome and its associated factors among HIV-MTB co-infected patients in Sichuan, China: A retrospective study

Human immunodeficiency virus (HIV)-Mycobacterium tuberculosis (MTB) co-infection has become a pressing global public health problem. Although tuberculosis (TB) is both treatable and curable, it has been exacerbated by the HIV/acquired immune deficiency syndrome (AIDS) epidemic. HIV-MTB co-infected patients have a variety of disease-specific, and treatment-related factors that can adversely affect their treatment outcomes. This study was conducted to assess the outcomes of TB treatment and its associated factors among HIV-MTB co-infected patients in Sichuan, Southwest China. A retrospective study was performed on HIV-MTB co-infected patients who were diagnosed and registered in TB designated hospitals in Sichuan from January 1, 2016, to December 31, 2020. Data were collected from patients' electronic medical records regarding their demographic, clinical, and social support information, and categorical data, such as sex, were reported using numbers and percentages. χ2 and t-tests were conducted to compare groups in relation to different levels of medical institutions. A binary logistic regression model was used to identify the factors associated with unsuccessful TB treatment outcomes. For logistic regression analysis performed using an α of 0.05, odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for various risk factors. A total of 3677 registered HIV-MTB co-infected patients were enrolled. After adjusting for other variables, male, advanced age, receiving TB treatment at the municipal medical institution, being diagnosed with external pulmonary TB, referral or tracing, being sputum smear positive, not initiating antiretroviral therapy (ART) and not using fixed-dose combinations were the main risk factors for treatment failure of HIV-MTB co-infected patients in Sichuan province. Sex, age, hospital level, patient source, other diagnostic factors (e.g., sputum smear results, anatomical site of TB), and factors of therapeutic schemes (e.g., antiretroviral therapy, fixed-dose combinations) may serve as risk factors to estimate the likely treatment outcome of HIV-TB co-infection.

Implementing tuberculosis patient cost surveys in resource-constrained settings: lessons from Tanzania

Tuberculosis (TB) disproportionally affects persons and families who are economically and socially disadvantaged. Therefore, a patient cost survey was conducted in Tanzania to evaluate the costs incurred by patients and their households before and after the diagnosis of TB. It was the first survey in Tanzania to ascertain baseline information and experience for subsequent surveys. This paper aims to share the experience encountered during the survey to ensure a standardized approach and elimination of potential barriers for the implementation of future surveys. A total of 777 TB patients from 30 clusters selected based on probability proportional to the size were interviewed during the study period. As the sample size was calculated based on notification data from the previous year, some health facilities experienced an inadequate number of TB patients during the study to meet the allocated cluster size for the survey. Most facilities had poor recording and recordkeeping in TB registers where deaths were not registered, and some patients had not been assigned district identification numbers. Fixed days for TB drug refills in health facilities affected the routine implementation of the survey as the interviews were conducted when patients visited the facility to pick up the drugs. Tablets used to collect data failed to capture the geographic location in some areas. The households of TB patients lost to follow-up and those who had died during TB treatment were not included in the survey. When planning and preparing for patient costs surveys, it is important to consider unforeseen factors which may affect planned activities and findings. During the survey in Tanzania, the identified challenges included survey logistics, communications, patient enrollment, and data management issues. To improve the quality of the findings of future surveys, it may be reasonable to revise survey procedures to include households of TB patients who were lost to follow-up and those who died during TB treatment; the households of such patients may have incurred higher direct and indirect costs than households whose patient was cured as a result of receiving TB treatment.

Epidemiology of Pediatric Tuberculosis and Factors Associated with Unsuccessful Treatment Outcomes in the Centre Region of Cameroon: A Three-Year Retrospective Cohort Study.

Background In Cameroon, there are limited data on treatment outcomes of pediatric tuberculosis (TB). We sought to identify the factors associated with unsuccessful treatment outcomes and the risk factors for mortality among children receiving TB treatment in the Centre Region of Cameroon. Methods This was a multicentre facility-based retrospective cohort study using routinely collected programmatic data. All children <15 years old treated for TB between 2018 and 2020 in 21 health facilities were included. We assessed risk factors for experiencing an unsuccessful treatment outcome and mortality through multivariable logistic regression analysis. Results Of the 610 children with TB, 307 (50.3%) were females and the median age was 6 years (IQR = 2–12). One hundred and fifty-three (25.1%) of the children were TB/HIV co-infected patients. TB treatment success (cases categorized as cured and completed treatment) was observed in 488 (80.0%) of the patients. Unsuccessful treatment outcomes were experienced by 122 (20.0%) children. Of these, 73 (12.0%) died, 4 (0.6%) had treatment failure, 25 (4.1%) were lost to follow-up, and the outcomes of 20 (3.3%) children were not evaluated. In multivariable analysis, HIV-positive status (adjusted odds ratio [AOR] = 2.43; 95% CI, 1.55–3.80, p < 0.001) and clinical method of TB diagnosis (AOR = 2.46; 95% CI, 1.55–3.91, p < 0.001] were associated with unsuccessful treatment outcomes. HIV-positive status (AOR = 4.23; 95% CI, 2.44–7.33, p < 0.001) and clinical method of TB diagnosis (AOR = 2.22; 95% CI, 1.25–3.91, p=0.006) were the risk factors for mortality among children on TB treatment. Conclusion The study found that HIV-TB co-infected children and those clinically diagnosed with TB were significantly more likely to have had unsuccessful TB treatment outcomes and mortality. Our findings underscore the need for healthcare workers to closely monitor and support HIV-TB co-infected children on TB treatment. TB/HIV collaborative activities should be strengthened by implementing TB preventive interventions among HIV-infected children.

Epidemiology and Control of diabetes - tuberculosis comorbidity in Eswatini: protocol for the prospective study of tuberculosis patients on predictive factors, treatment outcomes and patient management practices

IntroductionPrevious studies indicate people with diabetes mellitus (DM) may have varying treatment outcomes when receiving treatment for tuberculosis (TB) and that TB infection or its treatment may predispose them to...

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy

BackgroundSome tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described.MethodsWe conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan–Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation.Results2303 patients met inclusion criteria: 2003(87%) received TB treatment 5–7 days/week and 300(13%) 2–3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5–7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5–7 vs. 2–3 days/week (HR = 0.68; 95% CI = 0.51—0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5–7 days/week vs. 2–3 days/week (HR 0.75, 95%CI 0.55–1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83–2.45; P = 0.20).ConclusionsTB treatment 5–7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2–3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

Diagnostic Challenges in Childhood Pulmonary Tuberculosis-Optimizing the Clinical Approach.

The management of childhood tuberculosis (TB) is hampered by the low sensitivity and limited accessibility of microbiological testing. Optimizing clinical approaches is therefore critical to close the persistent gaps in TB case detection and prevention necessary to realize the child mortality targets of the End TB Strategy. In this review, we provide practical guidance summarizing the evidence and guidelines describing the use of symptoms and signs in decision making for children being evaluated for either TB preventive treatment (TPT) or TB disease treatment in high-TB incidence settings. Among at-risk children being evaluated for TPT, a symptom screen may be used to differentiate children who require further investigation for TB disease before receiving TPT. For symptomatic children being investigated for TB disease, an algorithmic approach can inform which children should receive TB treatment, even in the absence of imaging or microbiological confirmation. Though clinical approaches have limitations in accuracy, they are readily available and can provide valuable guidance for decision making in resource-limited settings to increase treatment access. We discuss the trade-offs in using them to make TB treatment decisions.