BACKGROUND: Digital adherence technologies (DATs) are being studied to determine their potential to support tuberculosis (TB) treatment and address the shortcomings of directly observed therapy. Previous research has shown inconclusive results on whether DATs can enhance medication adherence among persons with TB.
OBJECTIVE: This study aims to understand the acceptability of DATs, namely, medication labels and smart pillboxes, among persons with TB, health care workers (HCWs), and key informants (KIs) in the Philippines. The objective is to gain valuable insights that can inform the design and implementation of DATs in the Southeast Asian region, which meet the needs and preferences of end users.
METHODS: Persons with TB, HCWs, and KIs were recruited from intervention facilities to participate in in-depth interviews conducted between March 2022 and January 2023. These interviews were transcribed and translated into English. A thematic analysis was carried out using NVivo software (Lumivero) to identify and analyze themes. Themes were then structured within a modified social-ecological model.
RESULTS: A total of 25 persons with drug-sensitive TB and 20 HCWs or KIs were interviewed. Both groups emphasized that users\' technology literacy level, financial conditions, and motivation to be cured determined how they interacted with the DAT. They also acknowledged that DATs helped foster their relationship with HCWs and enabled efficient treatment support. Concerning technology, persons with TB found DATs easy to use and able to reduce clinic visits. HCWs mentioned that DATs added to their workload but also allowed them to support users who missed doses. However, both groups experienced technical challenges with DATs. Regarding program implementation, users appreciated the clear explanations and demonstrations provided by HCWs. Yet, some users reported inconsistencies between DAT settings and the information provided. HCWs stressed the importance of comprehensive training and sufficient resources for effective program implementation in the future. At the community level, both groups noted that DATs and program design protected users\' privacy and reduced the risk of stigma. Finally, users and HCWs shared various contextual factors that influenced their experience with DAT, including infrastructure challenges and the impact of the COVID-19 pandemic.
CONCLUSIONS: In the Philippines, persons with TB and HCWs showed a high level of acceptance and satisfaction with the impact of DAT and program design. They expressed a desire for the continuation of DATs. The challenges encountered underscore the need for ongoing technological development to minimize malfunctions, enhance the capacity of health facilities, and improve infrastructure. DATs have demonstrated their ability to strengthen user-HCW relationships and protect users from stigmatization. Additional efforts are required to scale up the DAT program in the Philippines.

BACKGROUND: Rifampicin (RIF) is considered the backbone of TB treatment, but adverse effects often limit its use.
METHODS: This retrospective cohort study examined patients treated for TB disease at our institution, and compared those who received RIF to those who were intolerant to RIF.
RESULTS: A total of 829 patients were included. Seventy-six patients (9%) were intolerant to RIF. Patients with RIF intolerance were significantly older (median age: 67 years, IQR 50-78 vs. 48 years, IQR 31-70; P < 0.0001), and were more likely to be female (57% vs. 41%; P = 0.01) and have concurrent diabetes mellitus (37.3% vs. 19%; P < 0.0001) compared to those who tolerated RIF. RIF intolerance was most commonly due to transaminitis (25%), cytopenia (14.5%), rash (17.1%) and gastro-intestinal intolerance (7.8%). Twenty patients were subsequently challenged with rifabutin, and this was successful in 70%. The mean treatment duration was significantly longer in patients who were intolerant to RIF (335 vs. 270 days; P < 0.001). There was no significant difference in treatment outcomes.
CONCLUSIONS: RIF intolerance is more common in older patients, females, and those with concurrent diabetes mellitus. Patients who could not tolerate RIF had a longer duration of therapy, but no difference in treatment outcomes. When attempted, rifabutin was well tolerated in most patients with a previous RIF-related adverse event.
BACKGROUND: La rifampicine (RIF) est généralement considérée comme le pilier du traitement de la TB, cependant, ses effets indésirables limitent fréquemment son utilisation.
UNASSIGNED: Dans cette étude de cohorte rétrospective nous avons examiné les patients traités pour la TB dans notre institution et avons comparé ceux qui ont reçu la RIF à ceux qui n\'ont pas pu la tolérer.
UNASSIGNED: Au total, 829 patients ont été inclus. Soixante-seize patients (9%) étaient intolérants au RIF. Les patients intolérants au RIF étaient significativement plus âgés (âge médian : 67 ans, IQR 50–78 vs. 48 ans, IQR 31–70 ; P < 0,0001), et étaient plus susceptibles d\'être des femmes (57% vs. 41% ; P = 0,01) et d\'avoir un diabète sucré concomitant (37,3% vs. 19% ; P < 0,0001) par rapport à ceux qui toléraient le RIF. L\'intolérance au RIF était principalement due à une transaminite (25%), une cytopénie (14,5%), une éruption cutanée (17,1%) et une intolérance gastro-intestinale (7,8%). Vingt patients ont ensuite été soumis à un test de provocation à la rifabutine, avec un taux de succès de 70%. La durée moyenne du traitement était significativement plus longue chez les patients intolérants au RIF (335 vs. 270 jours ; P < 0.001). Aucune différence significative n’a été observée dans les résultats du traitement.
CONCLUSIONS: L\'intolérance au RIF est plus courante chez les patients plus âgés, les femmes et les patients atteints de diabète sucré. Les patients qui n\'ont pas pu tolérer le RIF ont suivi un traitement plus long, mais cela n’a pas entrainé de différence dans les résultats du traitement. Lorsqu\'elle a été tentée, la rifabutine a été bien tolérée par la plupart des patients ayant déjà présenté un effet indésirable lié au RIF.

暂无摘要。

Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alternatives that are better tolerated but equally or more effective. Therefore, this review aims to identify and explore the novel alternative oxazolidinones to potentially replace linezolid in the management of TB. The keywords tuberculosis and oxazolidinones were searched in PubMed to identify eligible compounds. The individual drug compounds were then searched with the term tuberculosis to identify the relevant in vitro, in vivo and clinical studies. The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. An additional search resulted in 32 preclinical and 21 clinical studies. All novel oxazolidinones except posizolid and eperezolid resulted in positive preclinical outcomes. Sutezolid and delpazolid completed early phase 2 clinical studies with better safety and equal or superior efficacy. Linezolid is expected to continue as the mainstay therapy, with renewed interest in drug monitoring. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens.

UNASSIGNED: Eswatini is one of the countries affected by malnutrition and tuberculosis (TB) and some cases remained untreated. These two conditions are major public health problems.
UNASSIGNED: This study aimed to explore and describe caregivers\' experiences and practices of children\'s nutrition during treatment.
UNASSIGNED: Baylor College of Nursing Children\'s Foundation - Eswatini (BCMCF-SD).
UNASSIGNED: A qualitative study following a narrative design used purposive sampling to identify 12 caregivers of malnourished children and informed consent obtained. In-depth interview used semi-structured interview guide and digital voice recorder. Field notes were taken, transcribed, translated and analysed using NVivo version 11.
UNASSIGNED: Two themes emerged as home\'s nutritional situation and health facility\'s nutritional support. The study found that most of the caregivers gave children unbalanced diet, while those less than a year were mixed-fed. Some caregivers reported experience of lost breadwinners, unemployment and high number of children than what the family could afford. The caregivers\' practices around food by prescription included inadequate supply of the ready-to-use therapeutic food and sharing of prescribed food supplies with other healthy children.
UNASSIGNED: During treatment, children\'s caregivers need short health education and support. The Ministry of Health in Eswatini should consider using some comic books to guide that. Moreover, upscale vocational training promotes entrepreneurship and agricultural activities.
UNASSIGNED: Association of malnutrition and TB outcomes has provided evidence-based information for more comprehensive integration between nutrition programmes and tuberculosis programmes. The study\'s findings contributed to the growing body of knowledge about the association between malnutrition and diagnosed drug-susceptible TB among children aged from 0 - 15 years.

BACKGROUND: 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.
OBJECTIVE: This study aims to investigate the role of glycemic control in improving TB treatment outcomes among patients with DM.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: PROSPERO CRD42023427362; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=427362.

UNASSIGNED: Acquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients.
UNASSIGNED: PLWH who developed ARR 2001-2023 were identified from the NYC TB registry.
UNASSIGNED: Sixteen PLWH developed ARR; 15 were diagnosed 2001-2009 and the 16th was diagnosed in 2017. Median CD4 count was 48/mm3. On initial presentation, 14 had positive sputum cultures; of these, 12 culture-converted prior to developing ARR. Ten patients completed a course of TB treatment but subsequently relapsed; in six of these cases, ARR was discovered upon relapse, triggering treatment with a non-rifamycin-containing regimen, while in the other four, ARR was discovered during a second round of rifamycin-containing treatment. Three patients were lost to follow-up during their initial course of TB treatment and later returned to care; after being restarted on a rifamycin-containing regimen, ARR was discovered. Finally, three patients culture-converted during their first course of treatment but subsequently had cultures that grew rifamycin-resistant Mycobacterium tuberculosis prior to treatment completion, leading to changes in their treatment regimens. Among the 16 patients, eight died before being cured of TB, seven successfully completed treatment, and one was lost to follow-up.
UNASSIGNED: PLWH should be monitored closely for the development of ARR during treatment for TB, and sputum culture conversion should be interpreted cautiously in this group. Collecting a final sputum sample may be especially important for PLWH, as treatment failure and relapse were common in this population. The decrease in the number of cases of ARR among PLWH during the study period may reflect the decrease in the total number of PLWH diagnosed with TB in NYC in recent years, improved immune status of PLWH due to increased uptake of antiretroviral drugs, and improvements in the way anti-TB regimens are designed for PLWH (such as recommending daily rather than intermittent rifamycin dosing).

Global tuberculosis (TB) eradication is undermined by increasing prevalence of emerging resistance to available drugs, fuelling ongoing demand for more complex diagnostic and treatment strategies. Early detection of TB drug resistance coupled with therapeutic decision making guided by rapid characterisation of pre-treatment and treatment emergent resistance remains the most effective strategy for averting Drug-Resistant TB (DR-TB) transmission, reducing DR-TB associated mortality, and improving patient outcomes. Solid- and liquid-based mycobacterial culture methods remain the gold standard for Mycobacterium tuberculosis (MTB) detection and drug susceptibility testing (DST). Unfortunately, delays to result return, and associated technical challenges from requirements for specialised resource and capacity, have limited DST use and availability in many high TB burden resource-limited countries. There is increasing availability of a variety of rapid nucleic acid-based diagnostic assays with adequate sensitivity and specificity to detect gene mutations associated with resistance to one or more drugs. While a few of these assays produce comprehensive calls for resistance to several first- and second-line drugs, there is still no endorsed genotypic drug susceptibility test assay for bedaquiline, pretomanid, and delamanid. The global implementation of regimens comprising these novel drugs in the absence of rapid phenotypic drug resistance profiling has generated a new set of diagnostic challenges and heralded a return to culture-based phenotypic DST. In this review, we describe the available tools for rapid diagnosis of drug-resistant tuberculosis and discuss the associated opportunities and challenges.

UNASSIGNED: Completion of tuberculosis (TB) treatment presents several challenges to patients, including long treatment duration, medication adverse-effects and heavy pill burden. WHO emphasize the need for patient-centered TB care, but such approaches require understanding of patient experiences and perceptions.
UNASSIGNED: In 2020, we nested a qualitative study within a clinical trial that recruited 128 HIV-TB co-infected adults in Kampala receiving rifampicin-based TB treatment, alongside anti-retroviral therapy. A purposively selected sub-sample of 46 trial participants contributed to nine gender segregated focus group discussions. Of these, 12 also participated in in-depth interviews. Sessions were recorded, transcribed verbatim and translated from local languages into English. Thematic analysis focused on drug adverse-effects, use of self-prescribed medications and barriers to treatment adherence.
UNASSIGNED: Patients seemed more concerned about adverse effects that clinicians sometimes overlook such as change in urine color. Those who remembered pre-treatment counselling advice were disinclined to manage adverse-effects by self-prescription. Difficulty in accessing a medical practitioner was reported as a reason for self-medication. Obstacles to adherence included stigma (especially from visible adverse-effects like \"red urine\"), difficulties with pill size and number, discomfort with formulation and medication adverse effects.
UNASSIGNED: Tailored pre-treatment counselling, improved access to clinical services, and simpler drug administration will deliver more patient-centered care.

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.