Decoding drug resistance in Mycobacterium tuberculosis complex: genetic insights and future challenges.

INTRODUCTION: Tuberculosis (TB), particularly its drug-resistant forms (MDR-TB and XDR-TB), continues to pose a significant global health challenge. Despite advances in treatment and diagnosis, the evolving nature of drug resistance in Mycobacterium tuberculosis (MTB) complicates TB eradication efforts. This review delves into the complexities of anti-TB drug resistance, its mechanisms, and implications on healthcare strategies globally. AREAS COVERED: We explore the genetic underpinnings of resistance to both first-line and second-line anti-TB drugs, highlighting the role of mutations in key genes. The discussion extends to advanced diagnostic techniques, such as Whole-Genome Sequencing (WGS), CRISPR-based diagnostics and their impact on identifying and managing drug-resistant TB. Additionally, we discuss artificial intelligence applications, current treatment strategies, challenges in managing MDR-TB and XDR-TB, and the global disparities in TB treatment and control, translating to different therapeutic outcomes and have the potential to revolutionize our understanding and management of drug-resistant tuberculosis. EXPERT OPINION: The current landscape of anti-TB drug resistance demands an integrated approach combining advanced diagnostics, novel therapeutic strategies, and global collaborative efforts. Future research should focus on understanding polygenic resistance and developing personalized medicine approaches. Policymakers must prioritize equitable access to diagnosis and treatment, enhancing TB control strategies, and support ongoing research and augmented government funding to address this critical public health issue effectively.

Effectiveness of bedaquiline containing all oral longer regimens in treating multidrug/rifampicin resistant tuberculosis in Pakistan.

BACKGROUND: Despite the introduction of bedaquiline (Bdq) containing all-oral regimens for treating patients with rifampicin resistant/multidrug resistant tuberculosis (MDR/RR-TB) in 2019, data on its effectiveness in Pakistan, which has the fifth highest MDR-TB burden, is lacking. This study evaluates treatment outcomes and identifies factors associated with unsuccessful outcomes among MDR/RR-TB patients treated with an all-oral longer treatment regimen (LTR). METHODS: This retrospective record review included all microbiologically confirmed pulmonary MDR/RR-TB patients treated with an all-oral LTR between August 2019 and February 2021 across nine PMDT centres in Pakistan. Sociodemographic and clinical data were retrieved from the Electronic Nominal Recording and Reporting System. Treatment outcomes, defined by WHO criteria, were analysed using SPSS and multivariate binary logistic regression to identify factors associated with unsuccessful outcomes. A p-value < 0.05 was considered statistically significant. RESULTS: The final analysis included 644 MDR/RR-TB patients (mean age 37.9 ± 17.6 years), mostly male (53.0 %), underweight (68.0 %), with TB treatment history (66.1 %), MDR-TB (84.9 %), lung cavitation (71.0 %), and no comorbidities (86.4 %). Fluoroquinolone resistance was found in 41.9 %, 16 % had used second-line drugs, and 9.8 % had previous MDR-TB treatment. A total of 400 (62.1 %) patients were declared cured, 53 (8.2 %) treatment completed, 117 (18.2 %) died, 37 (5.7 %) lost to follow-up (LTFU), and 37 (5.7 %) treatment failures. Overall treatment success rate was 70.3 % (n = 453). In multivariate analysis, history of TB treatment (OR:1.63, 95 %CI:1.09-2.64, p = 0.023), previous SLD use (OR:2.09, 95 %CI: 1.20-3.37, p = 0.012), resistance to Z (OR:0.43, 95 %CI: 0.20-0.81, p = 0.023), and resistance to > 5 drugs (OR:3.12, 95 %CI:1.36-11.64, p = 0.013) were significantly associated with death and treatment failure. Whereas, lung cavitation had statistically significant association with LTFU (OR:2.66, 95 %CI:1.10-7.32, p = 0.045). CONCLUSION: Treatment success rate (70.3 %) in this study fell below the WHO recommended target success rate (>90 %). Enhanced clinical management, coupled with special attention to patients exhibiting identified risk factors could improve treatment outcomes.

Pediatric tuberculosis in a high burden setting: Socio-spatial distribution, blood elements features, and outcomes.

Background: The childhood tuberculosis (TB) epidemic has been long neglected. Data on pediatric tuberculosis is needed to develop effective strategies against TB. Methods: We retrospectively reviewed 200 medical records from children aged 0-15 years who suffered from tuberculosis between 2011 and 2021 in Libreville, Gabon. We collected and analyzed socio-demographic data and clinical data. Results: 141 children files were selected (43 % girls and 57 % boys). The mean age of the patients was 9.2 years (CI: 8.5-10). Sixty per cent (60 %) of cases were from precarious housing areas, 35.34 % from mixed housing areas, and 4.51 % from residential. The cure rate was 75.24 %, 9.52 % relapsed, and 15.24 % died. Deaths were significantly higher in older children (Dunn's post-test p < 0.01). Children who recovered had higher haemoglobin and platelet counts than those who died (Dunn's test: haemoglobin p < 0.0001; thrombocytes p < 0.05). The haemoglobin threshold value of 5.5 g/dL identified children death with up to 80 % sensitivity and 86 % specificity. Thrombocytes count identified children's death with a sensitivity of 80 % and a specificity of 51 %. Conclusion: Precariousness is associated with childhood tuberculosis. The directly observed therapy (DOTS) in older children should be reinforced to limit tuberculosis-associated deaths. Haemoglobin concentration and platelet are vital prognosis markers in pediatric tuberculosis.

Savings from the introduction of BPaL and BPaLM regimens at the country level.

BACKGROUND: In 2022, the WHO recommended the 6-month regimens BPaL (bedaquiline + pretomanid + linezolid) and BPaLM (BPaL + moxifloxacin) as treatment options for most forms of drug-resistant TB. SLASH-TB estimates the cost-saving and cost-effectiveness for the healthcare system and patients when a country switches from current standard-of-care treatment regimens to BPaL/BPaLM. METHODOLOGY: Country data from national TB programmes (NTP) are used to calculate the costs for all regimens and treatment outcomes. Where BPaL/BPaLM is not currently used, clinical trial outcomes data are used to estimate cost-effectiveness. DALYs are calculated using the Global Burden of Disease (GBD) database. RESULTS: We present the results of four countries that have used the tool and shared their data. When shorter and longer regimens are replaced with BPaL/BPaLM, the savings per patient treated in Pakistan, the Philippines, South Africa, and Ukraine are $746, $478, $757, and $2,636, respectively. An increased number of patients would be successfully treated with BPaL/BPaLM regimens, with 411, 1,025, 1,371 and 829 lives saved and 20,179, 27,443, 33,384 and 21,924 DALYs averted annually in the four countries, respectively. CONCLUSION: Through BPaL/BPaLM regimens, drug-resistant TB treatment has become more effective, shorter, less burdensome for patients, cheaper for both health systems and patients, and saves more lives.

CONTEXTE: En 2022, l'OMS a préconisé l'utilisation des schémas thérapeutiques (bedaquiline + pretomanid + linezolid) et BPaLM (BPaL + moxifloxacin), d'une durée de 6 mois, comme alternatives pour traiter la plupart des formes de TB résistante aux médicaments. SLASH-TB a réalisé une estimation des économies et de la rentabilité pour le système de santé et les patients lorsqu'un pays décide de passer des schémas thérapeutiques standards actuels au BPaL/BPaLM. MÉTHODOLOGIE: Les programmes nationaux de lutte contre la TB (NTP) utilisent les données nationales pour évaluer les coûts des différents schémas thérapeutiques et des résultats des traitements. Si le BPaL/BPaLM n'est pas utilisé actuellement, les données des essais cliniques sont utilisées pour estimer le rapport coût-efficacité. Les années de vie ajustées sur l'incapacité (DALYs, pour l'anglais « disability-adjusted life-years ¼) sont calculées à l'aide de la base de données Global Burden of Disease (GBD). RÉSULTATS: Nous présentons les résultats de quatre pays qui ont utilisé l'outil et partagé leurs données. Lorsque les schémas plus courts et plus longs sont remplacés par BPaL/BPaLM, les économies par patient traité au Pakistan, aux Philippines, en Afrique du Sud et en Ukraine sont respectivement de 746, 478, 757 et 2 636 dollars. L'utilisation des schémas BPaL/BPaLM permettrait de traiter un plus grand nombre de patients avec succès, ce qui sauverait respectivement 411, 1 025, 1 371 et 829 vies et éviterait 20 179, 27 443, 33 384 et 21 924 DALYs par an dans les quatre pays. CONCLUSION: Les schémas BPaL/BPaLM ont révolutionné le traitement de la tuberculose pharmacorésistante en le rendant plus efficace, plus rapide, moins contraignant pour les patients, plus économique pour les systèmes de santé et les patients, et en sauvant un plus grand nombre de vies.

Adverse drug reactions due to linezolid in the programmatic management of drug-resistant tuberculosis in India: A retrospective multicenter study.

BACKGROUND: Monitoring and managing adverse drug reactions (ADR) are critical for treating drug-resistant tuberculosis (TB). OBJECTIVE: To study symptomatic, linezolid-attributable ADRs in TB patients initiated on all oral longer bedaquiline-based treatment regime for multidrug-resistant/rifampicin-resistant (MDR/RR)-TB under programmatic conditions. METHODS: It was a multicenter, retrospective study of people with MDR/RR-TB in nine TB units in Nagpur, India, from March 2020 to April 2022. RESULTS: The study consisted of a sample size of 106 individuals with multidrug-resistant and rifampicin-resistant tuberculosis out of a total of 110 individuals with the disease. Of these, 45 (42.45%) experienced linezolid ADRs, with an incidence of 11.37 cases per 1000 person-weeks. These patients were significantly younger (31.24 ± 11.13 years) and more likely to be female (27, 50%) than those without ADRs. ADR severity was mild in 20 (44.45%), moderate in 15 (33.33%), and severe in 10 (22.22%) patients. The most common ADR was peripheral neuropathy (42, 93.33%), followed by lactic acidosis (3, 6.67%), anemia (2, 4.44%), and optic neuritis (2, 4.44%). Dosing was reduced in 17 (37.78%) patients, and linezolid was withdrawn entirely in 19 (42.22%) patients. Only 9 (20%) patients continued linezolid unmodified. For mild to moderate linezolid-associated symptomatic peripheral neuropathy, symptom management with or without dose reduction is an effective strategy; however, immediate linezolid withdrawal is necessary in severe or life-threatening peripheral neuropathy cases. After a mean follow-up of 41 ± 21.33 weeks, ADR symptoms resolved completely in 4 (6.67%) patients and decreased in 42 (93.33%) patients. CONCLUSION: Linezolid ADRs, often neuropathy, frequently occur in patients on an all-oral bedaquiline-based treatment regime for MDR/RR-TB. Women and younger patients are more likely to experience these ADRs, usually mild to moderate in severity. Management of symptomatic linezolid-associated peripheral neuropathy should be based on ADR severity. These ADRs often affect linezolid dosing, so it is important to identify and manage them early.

Metformin reduces the risk of poor treatment outcomes among individuals with rifampicin-resistant tuberculosis and type-2 diabetes mellitus.

We conducted a retrospective cohort study among individuals with rifampicin-resistant tuberculosis and diabetes to determine the association between metformin use and tuberculosis treatment outcomes. We found that individuals with metformin use had a significantly lower risk of poor tuberculosis treatment outcomes (adjusted RR=0.25, 95%CI 0.06 - 0.95) compared to those without.

Understanding the Spectrum and Management of Post-Tuberculosis Lung Disease: A Comprehensive Review.

Post-tuberculosis lung disease (PTLD) poses a significant clinical challenge in regions with a high burden of tuberculosis (TB). This review provides a comprehensive overview of PTLD, encompassing its pathogenesis, clinical manifestations, diagnostic modalities, management strategies, long-term outcomes, and public health implications. PTLD arises from residual lung damage following TB treatment and is characterized by a spectrum of pathological changes, including fibrosis, bronchiectasis, and cavitation. Clinical presentation varies widely, from chronic cough and hemoptysis to recurrent respiratory infections, which are oftentimes a diagnostic dilemma. Radiological imaging, pulmonary function tests, and careful consideration of patient history play pivotal roles in diagnosis. Management strategies involve pharmacological interventions to alleviate symptoms and prevent disease progression, which are influenced by the extent of lung damage, comorbidities, and access to healthcare. Rehabilitation programs and surgical options are available for select cases. Prognosis is influenced by the extent of lung damage, comorbidities, and access to healthcare. Prevention efforts through a TB control program and early detection are crucial in reducing the burden of PTLD. This review stresses the importance of understanding and addressing PTLD to mitigate its impact on individuals and public health systems worldwide.

A mixed-methods study on impact of active case finding on pulmonary tuberculosis treatment outcomes in India.

BACKGROUND: Tuberculosis (TB) remains a significant public health burden in India, with elimination targets set for 2025. Active case finding (ACF) is crucial for improving TB case detection rates, although conclusive evidence of its association with treatment outcomes is lacking. Our study aims to investigate the impact of ACF on successful TB treatment outcomes among pulmonary TB patients in Gujarat, India, and explore why ACF positively impacts these outcomes. METHODS: We conducted a retrospective cohort analysis in Gujarat, India, including 1,638 pulmonary TB cases identified through ACF and 80,957 cases through passive case finding (PCF) from January 2019 to December 2020. Generalized logistic mixed-model compared treatment outcomes between the ACF and PCF groups. Additionally, in-depth interviews were conducted with 11 TB program functionaries to explore their perceptions of ACF and its impact on TB treatment outcomes. RESULTS: Our analysis revealed that patients diagnosed through ACF exhibited 1.4 times higher odds of successful treatment outcomes compared to those identified through PCF. Program functionaries emphasized that ACF enhances case detection rates and enables early detection and prompt treatment initiation. This early intervention facilitates faster sputum conversion and helps reduce the infectious period, thereby improving treatment outcomes. Functionaries highlighted that ACF identifies TB cases that might otherwise be missed, ensuring timely and appropriate treatment. CONCLUSION: ACF significantly improves TB treatment outcomes in Gujarat, India. The mixed-methods analysis demonstrates a positive association between ACF and successful TB treatment, with early detection and prompt treatment initiation being key factors. Insights from TB program functionaries underscore the importance of ACF in ensuring timely diagnosis and treatment, which are critical for better treatment outcomes. Expanding ACF initiatives, especially among hard-to-reach populations, can further enhance TB control efforts. Future research should focus on optimizing ACF strategies and integrating additional interventions to sustain and improve TB treatment outcomes.

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

Introduction: 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. Methodology: 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. Results: 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. Conclusion: 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.

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

Background: The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). Methods: This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. Results: Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. Conclusions: TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

Effect of Metformin on systemic chemokine responses during anti-tuberculosis chemotherapy.

BACKGROUND: Metformin (MET), by boosting immunity, has been suggested as a host-adjunctive therapy to anti-tuberculosis treatment (ATT). METHODS: We evaluated whether adding MET to the standard ATT can alter the host chemokine response. We investigated the influence of metformin on the plasma levels of a wide panel of chemokines in a group of active tuberculosis patients before treatment, at 2nd month of ATT and at 6-months of ATT as part of our clinical study to examine the effect of metformin on ATT. RESULTS: Our results demonstrated that addition of metformin resulted in diminished CC (CCL1 and CCL3) and CXC (CXCL-2 and CXCL-10) chemokines in MET arm as compared to non-MET arm at the 2nd month and 6th month of ATT. In addition to this, MET arm showed significantly diminished chemokines in individuals with high bacterial burden and cavitary disease. CONCLUSION: Our current data suggest that metformin alters chemokines responses that could potentially curb excessive inflammation during ATT.

Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.

BACKGROUND: Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together. OBJECTIVES: The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens. DESIGN: A prospective observational cohort study. METHODS: From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine. RESULTS: A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens (p < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine. CONCLUSION: Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.

Study about the impact of rapid resistance detection on the treatment of patients with tuberculosis in Ukraine written by healthcare and biomedical professionals to better understand how we can improve the results of treatment and to prevent spreading of resistant bacteriaWhy was the study done? Ukraine has over 4000 patients with tuberculosis (TB) resistant to at least one drug (rifampicin) - five times that of all 30 European Union/European Economic Area countries combined. Unfortunately, only about 60% of such patients have been successfully treated in 2019. At that time, the majority of people suffering from tuberculosis in Ukraine, after checking resistance to rifampicin, initially received standard combinations of the first-line or second-line anti-TB medicines before the result of traditionally used tests (usually few weeks later) became available to individualize the treatment. Alternatively, the sputum could be transported to some overloaded reference laboratories located hundreds of km away from the treatment places.What did the researchers do? The INNOVA4TB team implemented rapid diagnostics of drug resistance in routine practice, guiding key antibiotics use in TB patients. A total of 181 samples from 126 individuals were tested during 2019-2020.What did the researchers find? This new diagnostic technology accurately detected resistance to 9 anti-TB drugs in sputum samples. It could be helpful to select appropriate TB treatment regimens, reducing time for decision from 1 month up to 2 days. Recommended at the study time 9-month shorter standardized treatment regimen with injectable agent was suitable only for 5% of patients for whom it was indicated in Vinnytsia region of Ukraine.What do the findings mean? The study has demonstrated successful implementation of the new molecular diagnostic technology from scratch in a country with restricted resources and limited TB laboratory capacity. This test can facilitate optimal distribution of available wards among patients with different profiles of resistance and correct choice between treatment options.

A ten-year experience of musculoskeletal tuberculosis at a tertiary care hospital in South India.

Background: The delayed identification and management of musculoskeletal tuberculosis (MSTB) poses substantial health challenges and leads to significant morbidity. This study aimed to collate ten years of hospital data and provide valuable insights into the clinical, diagnostics, and outcomes of the patients diagnosed with MSTB. Methods: A retrospective study was undertaken to review clinic records from 2013 to 2022 for all individuals diagnosed with MSTB in a tertiary care hospital in South India. Results: Over a decade, 400 cases of MSTB were diagnosed, revealing 57 % males and 43 % females with a mean age of 43.2 ± 18.9 years. Spinal TB constituted 72 % of cases, with the most common involvement of thoracic vertebrae (50.9 %). Extra-spinal MSTB accounted for 28 %, prevalent more in the pediatric age group (p < 0.05). Surgical intervention was required for 80 % of spinal TB cases and 58 % of extra-spinal MSTB cases. The average follow-up duration was two years, with 73 % completing treatment. Unfortunately, seven patients died, and three experienced relapse. Conclusion: Spinal TB is the most common type of MSTB and is predominant in young and middle-aged adults, while extra-spinal MSTB is more frequently observed in children. Where use of MRI facilitates early detection of spinal TB; histopathological and microbiological examination confirm the diagnosis. Combining anti-tubercular drugs with modern surgical approaches is essential for obtaining favorable outcomes and improving the quality of life of such patients. It is crucial to have advanced and affordable diagnostic facilities, along with increased public awareness, to reinforce tuberculosis control strategies.

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

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

Treatment Outcomes of Tuberculosis and Associated Factors Among Tuberculosis and Human Immunodeficiency Virus Co-infected Patients in Public Health Facilities in Jigjiga, Somali Region, Ethiopia.

BACKGROUND: Worldwide, tuberculosis (TB) is a serious public health issue, especially in low-income countries, including Ethiopia. For those who are HIV-positive, TB poses a major risk to their health. The development of chemotherapy and the effectiveness of treatment have resulted in notable increases in patient survival. The evaluation of TB treatment outcomes is an essential metric for determining the success of TB and HIV co-morbidity control strategies. PURPOSE: This study aims to identify TB treatment outcomes and associated factors among TB/HIV co-infected patients in public health facilities in Jigjiga, Somali Region, Ethiopia, in 2021. PATIENTS AND METHODS: A hospital-based cross-sectional study design was done on three facilities (Karamara, Hasan Yabare Referral Hospital, and Jigjiga Health Center) with a total of 194 study participants. Data were extracted using a checklist, entered into EpiData version 3 (The EpiData Association, Odense, Denmark), and analyzed using SPSS Statistics version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) for descriptive and inferential analysis of the study objectives. Variables in the bivariate logistic regression analysis with p-values less than 0.25 were entered into a multivariate logistic regression to identify the independent factors of TB treatment outcome. Associations were computed using an adjusted odds ratio with a 95% CI. P-values less than 0.05 were finally considered statistically significant. RESULTS: The following TB treatment outcomes were observed among all TB/HIV co-infected patients enrolled in this study: 126 (67.4%) completed treatment, three (1.8%) died, 42 (22.5%) were cured, and 16 (8.6%) were transferred out; 168 (89.8%) had a successful treatment outcome. Category of the patient (AOR = 0.194, 95% CI: 0.041, 0.923), sex of the patient (AOR = 1.490, 95% CI: 1.449, 4.951), and cotrimoxazole preventive therapy (CPT) initiation (AOR = 0.073, 95% CI: 0.021, 0.254) were found to be significant predictors for successful TB treatment outcome at a p-value less than 0.05 with a 95% CI. CONCLUSION: Overall, 89.8% of TB treatments were successful among TB/HIV co-infected patients. This study has found sex, socioeconomic status, and CPT initiation were significant factors for a successful TB treatment outcome. Based on these findings, governmental and non-governmental organizations should facilitate the implementation and enforce the availability of all TB/HIV co-infected patients.

Pangenomic analyses of tuberculosis strains to identify resistomes using computational approaches.

Objective: To locate resistomes in tuberculosis strains, to determine the severity of drug resistance, and to infer its implications with respect to high tuberculosis prevalence in a Third World setting. METHODS: The pangenomic study was conducted from October 2022 to January 2023 in Sir Syed University of Engineering and Technology, Karachi, and comprised 2012-22 data on multiple sequence alignment to assess the genetic evolution of tuberculosis strains. Antibiotic resistance drug classes were identified using the Canadian Antibiotic Resistance Database, which entailed multidrug-resistant and extremely drug-resistant strains. Also, GenBank was used for tuberculosis genome FASTA (fast-all; nucleotide and protein sequence representation) files, prediction of resistome sequences on the basis of Canadian Antibiotic Resistance Database, and multiple sequence alignment was done in Mauve. RESULTS: Evolutionarily, the 6 strains identified were structurally similar with polymorphisms in their core chromosomal regions. Their resistome genes showed perfect hits for isoniazid, rifamycin, cephalosporin, fluoroquinolone, aminoglycosides, penem, penam and cephamycin. Conclusion: Drugs discovered in antibiotic resistance genes are now less effective in treatment, and have the potential to develop into more dangerous bacteria, if not monitored. For treatment, staying long durations in hospitals for quality healthcare and supervision in third world countries is unaffordable.

Prediction Models for Adverse Drug Reactions During Tuberculosis Treatment in Brazil.

BACKGROUND: Tuberculosis (TB) treatment-related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates. METHODS: We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk. RESULTS: There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74-.83) and fit (optimism-corrected slope and intercept of -0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75-4.09]) and CM use (HR, 5.26 [95% CI, 2.63-10.52]) increased TB-ADR risk. CONCLUSIONS: The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs.

Factors associated with tuberculosis treatment outcomes among TB patients aged 15 years and older at chawama level one hospital in Lusaka, Zambia.

Tuberculosis is a global health concern n impacting communities, health systems, and economies This study assessed the TB treatment outcomes among individuals aged 15+ at Chawama first level hospital in Lusaka, Zambia, using a retrospective design focussing on individuals notified in 2020. The sample was described using descriptive statistics. The Pearson Chi-square test and logistics regression were used to analyse the characteristics of the patients influencing the treatment outcomes at 5% significant level. Out of 404 participants, 83.4% of them had successful treatment outcomes. Varied outcomes were noted in sex, patient type, TB type, HIV status, and DOT plan, but lacked significance. Odds of success were lower by 72.4% for those aged 65+ compared to those aged 15-24 years (OR (95% CI): 0.276 (0.086-0.881), p = .030). Similarly, after adjusting for other variables, the odds of success were lower by 72.9% (AOR (95% CI): 0.271 (0.083-0.882), p = .030). This study yielded an encouraging 83.4% TB success rate highlighting the potential for improvement to meet WHO targets. Notably, individuals aged 65+ showed a distinct pattern with lower treatment success odds, suggesting a need for focussed interventions. Special attention to elderly patients and targeted TB program interventions are recommended.

Assessment of Comorbidity in Patients with Drug-Resistant Tuberculosis.

A wide range of comorbidities, especially in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients, markedly complicates selecting effective treatment of tuberculosis (TB) and preventing the development of adverse events. At present, it is impossible to assess the severity of comorbid pathologies and develop indications for the administration of accompanying therapy in TB patients. The aim of this study was to identify the difference in the range of comorbidities between patients with MDR-TB and XDR-TB and assess the impact of comorbidities on TB treatment. Materials and Methods: A retrospective, prospective study was conducted where 307 patients with MDR-TB and XDR-TB pulmonary tuberculosis aged 18 to 75 years who received eTB treatment from 2016 to 2021 in St. Petersburg hospitals were analyzed. The analysis showed that the comorbidity level in MDR-TB and XDR-TB patients with TB treatment success and treatment failure was comparable with the use of the Charlson Comorbidity Index (CCI). The CCI demonstrated declining data in terms of TB treatment outcome period in both groups. A slight predominance of CCI score (3 to 4 points) in XDR-TB (22.7%) vs. MDR-TB (15.4%) patients was found. In the case of an TB treatment failure, the CCI level in MDR-TB vs. XDR-TB patients was characterized by a significantly higher rate of low magnitude (ranging from 1 to 2 points) in 21.1% vs. 4.5% (p < 0.05), which was higher in XDR-TB patients (ranging from 4 to 5 points, in 10.0% vs. 0, χ2 = 33.7 (p < 0.01)). Chronic viral hepatitis B and C infection, cardiovascular pathology, chronic obstructive pulmonary disease, and chronic alcoholism were found to be significant comorbidity factors that influenced the TB treatment success. Conclusions: It is evident that XDR-TB patients comprise a cohort with the most severe disease course due to comorbidities impacting TB treatment efficacy. The obtained data pointed to the need to determine comorbidity severity in patients with drug-resistant Mbt prior to administering TB treatment schemes.