Mortality and associated factors among patients with TB-HIV co-infection in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection is a major public health problem in Ethiopia. Patients with TB-HIV co-infection have significantly higher mortality rates compared to those with TB or HIV mono-infection. This systematic review and meta-analysis aim to summarize the evidence on mortality and associated factors among patients with TB-HIV co-infection in Ethiopia. METHODS: Comprehensive searches were conducted in multiple electronic databases (PubMed/MEDLINE, Embase, CINAHL, Web of Science) for observational studies published between January 2000 and present, reporting mortality rates among TB/HIV co-infected individuals. Two reviewers performed study selection, data extraction, and quality assessment independently. Random-effects meta-analysis was used to pool mortality estimates, and heterogeneity was assessed using I² statistics. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity. RESULTS: 185 articles were retrieved with 20 studies included in the final analysis involving 8,113 participants. The pooled mortality prevalence was 16.65% (95% CI 12.57%-19.65%) with I2 : 95.98% & p-value < 0.00. Factors significantly associated with increased mortality included: older age above 44 years (HR: 1.82; 95% CI: 1.31-2.52), ambulatory(HR: 1.64; 95% CI: 1.23-2.18) and bedridden functional status(HR: 2.75; 95% CI: 2.01-3.75), extra-pulmonary Tuberculosis (ETB) (HR: 2.34; 95% CI: 1.76-3.10), advanced WHO stage III (HR: 1.76; 95% CI: 1.22-2.38) and WHO stage IV (HR: 2.17; 95% CI:1.41-3.34), opportunistic infections (HR: 1.75; 95% CI: 1.30-2.34), low CD4 count of < 50 cells/mm3 (HR: 3.37; 95% CI: 2.18-5.22) and lack of co-trimoxazole prophylaxis (HR: 2.15; 95% CI: 1.73-2.65). CONCLUSIONS: TB/HIV co-infected patients in Ethiopia experience unacceptably high mortality, driven by clinical markers of advanced immunosuppression. Early screening, timely treatment initiation, optimizing preventive therapies, and comprehensive management of comorbidities are imperative to improve outcomes in this vulnerable population.

TB prevention activities in the WHO European Region.

BACKGROUND: TB preventive treatment (TPT) is the primary available healthcare intervention to reduce the risk of progression from TB infection to TB disease. The WHO Regional Office for Europe established the European Prevention and Systematic Screening Initiative to End TB (PASS) to scale up activities related to the programmatic management of TPT. In the absence of a system to measure and monitor preventive activities, a baseline assessment survey was carried out to provide a reference to monitor the scale-up of the intervention. METHODS: This was a semi-structured survey including 52 questions that was developed, implemented in the WHO-hosted LimeSurvey data form and sent to focal points in the 55 countries and territories in the European Region between September and October 2023. The questions covered TPT, systematic screening and infection prevention and control. RESULTS: A total of 28 questionnaires were returned, corresponding to an overall 51% response rate. Most national policies for TPT and TB screening are in line with the latest WHO guidelines. However, implementation of TB screening, prevention, and infection control activities is lagging. Results are presented separately for high-priority and low-priority countries. CONCLUSION: The survey identified several important areas that the PASS initiative will focus on to accelerate efforts towards reaching the targets set at the 2027 UN High-Level Meeting on TB for preventive therapy in the European Region. This will require a massive scale-up of efforts and larger investments, as well as coordinated approaches and interventions across the 'cascade' of prevention, from the identification of target populations to the completion of treatment.

CONTEXTE: Le traitement préventif de la TB (TPT) est une intervention majeure en santé publique pour réduire le risque de progression de l'infection TB vers la maladie TB. L'initiative européenne de prévention et de dépistage systématique pour mettre fin à la TB (PASS) a été lancée par le bureau régional de l'OMS pour l'Europe afin de renforcer les activités liées à la gestion programmatique du traitement préventif de la TB. Une enquête d'évaluation de base a été menée en l'absence d'un système de mesure et de suivi des activités de prévention, afin de fournir une référence pour suivre l'intensification de l'intervention. MÉTHODES: Il s'agit d'une enquête semi-structurée composée de 52 questions, conçue, mise en place dans le formulaire de données LimeSurvey hébergé par l'OMS, et envoyée aux points focaux dans les 55 pays et territoires de la Région européenne entre septembre et octobre 2023. Les questions abordaient le TPT, le dépistage systématique, ainsi que la prévention et le contrôle des infections. RÉSULTATS: Au total, 28 questionnaires ont été retournés, ce qui équivaut à un taux de réponse global de 51%. La plupart des politiques nationales en matière de TPT et de dépistage de la TB sont conformes aux dernières directives de l'OMS. Cependant, la mise en œuvre des activités de dépistage de la TB, de prévention et de lutte contre l'infection est en retard. Les résultats de l'initiative PASS sont présentés de manière distincte pour les pays hautement prioritaires et les pays faiblement prioritaires. CONCLUSION: L'enquête a révélé plusieurs domaines clés sur lesquels l'initiative PASS se concentrera pour accélérer les efforts visant à atteindre les objectifs de 2027 de l'UN High-Level Meeting en matière de traitement préventif dans la Région européenne. Cela exigera une intensification massive des efforts et des investissements accrus, ainsi que des approches et des interventions coordonnées tout au long de la « cascade ¼ de la prévention, depuis l'identification des populations cibles jusqu'à l'achèvement du traitement.

No increased risk of tuberculosis-related immune reconstitution inflammatory syndrome with integrase inhibitor-based antiretroviral therapy in people with HIV with profound immunosuppression.

INTRODUCTION: The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis-related immune reconstitution inflammatory syndrome (TB-IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB-HIV initiating antiretroviral therapy (ART) in Hong Kong. METHODS: This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. RESULTS: Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0-32.7) and 14 of 63 patients (22.2%; 95% CI 12.0-32.5) from the INSTI and non-INSTI groups experienced TB-IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0-7.8] vs. 4 weeks [IQR 2.0-5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS-related death in either group. The risk of TB-IRIS with INSTI versus non-INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 µL (10/33 [30.3%; 95% CI 14.6-46.0] vs. 10/22 [45.5%; 95% CI 24.7-66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti-TB treatment (10/26 [38.5%; 95% CI 19.8-57.2] vs. 10/23 [43.5%; 95% CI 23.2-63.7], p = 0.721). CONCLUSION: Our cohort study did not offer support for an increased risk of TB-IRIS with INSTIs compared with non-INSTIs, even in severely immunocompromised people with HIV.

[Differential diagnosis of coccidioidomycosis manifested by peripheral pulmonary lesion]. / Differentsial'naya diagnostika koktsidioidomikoza, manifestirovannogo perifericheskim obrazovaniem legkogo.

We present this clinical case as a demonstration of difficulties in differential diagnosis of pulmonary coccidioidomycosis. Differential diagnostics of peripheral pulmonary lesion performed using bronchoscopy with BAL and TBCB and video-assisted thoracic surgery (VATS) biopsy. Diagnostic specimens were tested using microbiological (luminescent microscopy, culture for M. tuberculosis (BACTEC MGIT960 and Lowenstein-Jensen Medium), RT-PCR, cytological and morphological (hematoxylin-eosin, Ziehl-Neelsen, PAS, Grocott methenamine silver (GMS) stainings) examinations. A diagnosis was verified correctly In Russia the country is not endemic for coccidioidomycosis and patient was treated accordingly. Diagnostics of peripheral pulmonary lesions requires of multidisciplinary approaches. Morphological examination, based on detection of only granulomatous inflammation in lung biopsy cannot be used for finally DS and requires microbiological confirmation for TB or other infections, and dynamic monitoring of the patient with concordance their anamnesis vitae and morbi.

Targeted next-generation sequencing of Mycobacterium tuberculosis from patient samples: lessons learned from high drug-resistant burden clinical settings in Bangladesh.

AbstractLack of appropriate early diagnostic tools for drug-resistant tuberculosis (DR-TB) and their incomplete drug susceptibility testing (DST) profiling is concerning for TB disease control. Existing methods, such as phenotypic DST (pDST), are time-consuming, while Xpert MTB/RIF (Xpert) and line probe assay (LPA) are limited to detecting resistance to few drugs. Targeted next-generation sequencing (tNGS) has been recently approved by WHO as an alternative approach for rapid and comprehensive DST. We aimed to investigate the performance and feasibility of tNGS for detecting DR-TB directly from clinical samples in Bangladesh. pDST, LPA and tNGS were performed among 264 sputum samples, either rifampicin-resistant (RR) or rifampicin-sensitive (RS) TB cases confirmed by Xpert assay. Resistotypes of tNGS were compared with pDST, LPA and composite reference standard (CRS, resistant if either pDST or LPA showed a resistant result). tNGS results revealed higher sensitivities for rifampicin (RIF) (99.3%), isoniazid (INH) (96.3%), fluoroquinolones (FQs) (94.4%), and aminoglycosides (AMGs) (100%) but comparatively lower for ethambutol (76.6%), streptomycin (68.7%), ethionamide (56.0%) and pyrazinamide (50.7%) when compared with pDST. The sensitivities of tNGS for INH, RIF, FQs and AMGs were 93.0%, 96.6%, 90.9%, and 100%, respectively and the specificities ranged from 91.3% to 100% when compared with CRS. This proof of concept study, conducted in a high-burden setting demonstrated that tNGS is a valuable tool for identifying DR-TB directly from the clinical specimens. Its feasibility in our laboratory suggests potential implementation and moving tNGS from research settings into clinical settings.

Characterising the urinary acylcarnitine and amino acid profiles of HIV/TB co-infection, using LC-MS metabolomics.

INTRODUCTION: The human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection presents significant challenges due to the complex interplay between these diseases, leading to exacerbated metabolic disturbances. Understanding these metabolic profiles is crucial for improving diagnostic and therapeutic approaches. OBJECTIVE: This study aimed to characterise the urinary acylcarnitine and amino acid profiles, including 5-hydroxyindoleacetic acid (5-HIAA), in patients co-infected with HIV and TB using targeted liquid chromatography mass spectrometry (LC-MS) metabolomics. METHODS: Urine samples, categorised into HIV, TB, HIV/TB co-infected, and healthy controls, were analysed using HPLC-MS/MS. Statistical analyses included one-way ANOVA and a Kruskal-Wallis test to determine significant differences in the acylcarnitine and amino acid profiles between groups. RESULTS: The study revealed significant metabolic alterations, especially in TB and co-infected groups. Elevated levels of medium-chain acylcarnitines indicated increased fatty acid oxidation, commonly associated with cachexia in TB. Altered amino acid profiles suggested disruptions in protein and glucose metabolism, indicating a shift towards diabetes-like metabolic states. Notably, TB was identified as a primary driver of these changes, affecting protein turnover, and impacting energy metabolism in co-infected patients. CONCLUSION: The metabolic profiling of HIV/TB co-infection highlights the profound impact of TB on metabolic pathways, which may exacerbate the clinical complexities of co-infection. Understanding these metabolic disruptions can guide the development of targeted treatments and improve management strategies, ultimately enhancing the clinical outcomes for these patients. Further research is required to validate these findings and explore their implications in larger, diverse populations.

Expanding Xpert MTB/RIF Ultra® and LF-LAM testing for diagnosis of tuberculosis among HIV-positive adults admitted to hospitals in Tanzania and Mozambique: a randomized controlled trial (the EXULTANT trial).

INTRODUCTION: Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries. METHODS: This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment. DISCUSSION: The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention. TRIAL REGISTRATION: Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020-09-29.

Understanding the role of video direct observed therapy for patients on an oral short-course regimen for multi-drug resistant tuberculosis: findings from a qualitative study in Eswatini.

BACKGROUND: Improving treatment success rates among multi drug-resistant tuberculosis (MDR-TB) patients is critical to reducing its incidence and mortality, but adherence poses an important challenge. Video-based direct observed therapy (vDOT) may provide adherence benefits, while addressing the time and cost burden associated with community treatment supporter (CTS)-DOT. This study explored experiences of patients, family members and healthcare workers with different DOT modalities for adherence support in Eswatini. METHODS: Between April 2021 and May 2022, thirteen men and five women with MDR-TB, ten healthcare workers, and nine caregivers were purposively sampled to include a range of characteristics and experiences with DOT modalities. Data were generated through individual in-depth interviews and a smartphone messaging application (WhatsApp). Data coding was undertaken iteratively, and thematic analysis undertaken, supported by Nvivo. RESULTS: Four themes emerged that reflected participants' experiences with different DOT modalities, including stigma, efficiency, perceived risks of TB acquisition, and patient autonomy. vDOT was appreciated by patients for providing them with privacy and shielding them from stigmatisation associated with being seen in TB clinics or with community treatment supporters. vDOT was also seen as more efficient than CTS-DOT. Health workers acknowledged that it saved time, allowing them to attend to more patients, while many patients found vDOT more convenient and less expensive by removing the need to travel for in-person consultations. Health workers also appreciated vDOT because it reduced risks of TB acquisition by minimising exposure through virtual patient monitoring. Although many patients appreciated greater autonomy in managing their illness through vDOT, others preferred human contact or struggled with making video recordings. Most family members appreciated vDOT, although some resented feeling removed from the process of supporting loved ones. CONCLUSIONS: vDOT was generally appreciated by MDR-TB patients, their family members and health workers as it addressed barriers to adherence which could contribute to improved treatment completion rates and reduced workplace exposure. However, patients should be offered an alternative to vDOT such as CTS-DOT if this modality does not suit their circumstances or preferences.

Prevalence and associated factors of TB and HIV coinfections among adult inmates with presumptive pulmonary TB in a Kenyan prison.

BACKGROUND: Tuberculosis (TB) is more than ten times higher in prisons compared to the general population, and HIV-infected persons are at increased risk of developing active TB and death. In the World Health Organization (WHO) African region, however, where the TB and HIV coinfections are highest, and prisons rarely factored in national disease surveillance, epidemiological data to inform TB control interventions in correctional facilities is limited. In this study, we assessed the prevalence of TB and HIV coinfections, as well as the factors associated with coinfections in our study setting. METHODS: This was a prospective cross-sectional study among 157 adult (≥ 18 years) prisoners presenting with symptoms of pulmonary TB at Shimo La Tewa Prison, Kenya, between January and June 2023. The study excluded those with a history of anti-TB drugs use or on treatment follow-up and collected demographic and clinical characteristics data using a questionnaire. Sputum samples were collected and processed immediately using Xpert® MTB/RIF assay or stored at 4 °C for three (3) days in case of delay. RESULTS: The overall prevalence of TB among inmates with presumptive pulmonary TB was 10.2%, 95% CI 6.37-16.91% (16/157), HIV 19.1%, 95% CI 13.73-25.97% (30/157). All the TB cases were positive for HIV (16/16, 100%), translating to TB/HIV coinfection of 10.2%, 95% CI 6.37-16.91% (16/157), and there was no rifampicin resistance. TB and HIV coinfection cases were found among underweight (100%, 16/16) prisoners. The independent factors associated with TB and HIV coinfections were education level (adjusted OR = 0.17, p = 0.007), smoking history (adjusted OR = 3.01, p = 0.009) and illegal drug use history (adjusted OR = 4.55, p = 0.044). CONCLUSION: We report a high prevalence of pulmonary TB and HIV coinfections among adult inmates with presumptive pulmonary TB in Kenya, with education level, smoking status, and illegal drug use as the independent factors associated with the coinfection. The authority should take measures to protect HIV-positive prisoners from TB, focusing on education, nutrition, smoking, and illegal drug use.

N-Acyl phenothiazines as mycobacterial ATP synthase inhibitors: Rational design, synthesis and in vitro evaluation against drug sensitive, RR and MDR-TB.

The mycobacterial F-ATP synthase is responsible for the optimal growth, metabolism and viability of Mycobacteria, establishing it as a validated target for the development of anti-TB therapeutics. Herein, we report the discovery of an N-acyl phenothiazine derivative, termed PT6, targeting the mycobacterial F-ATP synthase. PT6 is bactericidal and active against the drug sensitive, Rifampicin-resistant as well as Multidrug-resistant tuberculosis strains. Compound PT6 showed noteworthy inhibition of F-ATP synthesis, exhibiting an IC50 of 0.788 µM in M. smegmatis IMVs and was observed that it could deplete intracellular ATP levels, exhibiting an IC50 of 30 µM. PT6 displayed a high selectivity towards mycobacterial ATP synthase compared to mitochondrial ATP synthase. Compound PT6 showed a minor synergistic effect in combination with Rifampicin and Isoniazid. PT6 demonstrated null cytotoxicity as confirmed by assessing its toxicity against VERO cell lines. Further, the binding mechanism and the activity profile of PT6 were validated by employing in silico techniques such as molecular docking, Prime MM/GBSA, DFT and ADMET analysis. These results suggest that PT6 presents an attractive lead for the discovery of a novel class of mycobacterial F-ATP synthase inhibitors.

Risk of tuberculosis after initiation of antiretroviral therapy among persons with HIV in Europe.

OBJECTIVES: Tuberculosis (TB) risk after initiation of antiretroviral treatment (ART) is not well described in a European setting, with an average TB incidence of 25/105 in the background population. METHODS: We included all adult persons with HIV starting ART in the RESPOND cohort between 2012 and 2020. TB incidence rates (IR) were assessed for consecutive time intervals post-ART initiation. Risk factors for TB within 6 months from ART initiation were evaluated using Poisson regression models. RESULTS: Among 8441 persons with HIV, who started ART, 66 developed TB during 34,239 person-years of follow-up [PYFU], corresponding to 1.87/1000 PYFU (95% confidence interval [CI]: 1.47-2.37). TB IR was highest in the first 3 months after ART initiation (14.41/1000 PY (95%CI 10.08-20.61]) and declined at 3-6, 6-12, and >12 months post-ART initiation (5.89 [95%CI 3.35-10.37], 2.54 [95%CI 1.36-4.73] and 0.51 [95%CI 0.30-0.86]), respectively. Independent risk factors for TB within the first 6 months after ART initiation included follow-up in Northern or Eastern Europe region, African origin, baseline CD4 count <200 cells/mm3, HIV RNA >100,000 copies/mL, injecting drug use and heterosexual transmission. CONCLUSIONS: TB IR was highest in the first 3 months post-ART initiation and was associated with baseline risk factors, highlighting the importance of thorough TB risk assessment at ART initiation.

Effect of structure on sensing performance of nitro explosives with high sensitivity and mechanism of two Tb(III) coordination polymers.

The use of a conjugate N-containing ligand resulted in the decreasing of structural dimensions from 2D network of [Tb(2-pyia)(Ac)(H2O)] (CP1) to 1D chain [Tb(2-pyia)(Ac)(IDP)] (CP2) (2-H2pyia = 5-(pyridin-2-ylmethoxy) isophthalic acid and IDP=imidazo[4,5-f]-[1,10] phenanthroline). Both of them exhibit the characteristic luminescence of Tb ions and could have high fluorescence sensing properties for cefixime and fluridine. The different sensing properties for nitro explosives are manifested as CP1 for nitrobenzene and CP2 for 4-nitrophenol due to the difference in structure. Furthermore, CP2 exhibits the ratiometric fluorescence sensing for Fe3+ ion with a low detection limit of 0.405 µM. The fluorescence sensing mechanism of the two Tb complexes for different analytes was investigated using experimental methods and theoretical calculations. CP1 was used for the detection of Flu residues in the actual system and better results were obtained. The work shows the introduction of the chelated ligand might affect the structural and sensing performance changes of coordination polymers.

Machine learning investigation of tuberculosis with medicine immunity impact.

Tuberculosis (T.B.) remains a prominent global cause of health challenges and death, exacerbated by drug-resistant strains such as multidrug-resistant tuberculosis MDR-TB and extensively drug-resistant tuberculosis XDR-TB. For an effective disease management strategy, it is crucial to understand the dynamics of T.B. infection and the impacts of treatment. In the present article, we employ AI-based machine learning techniques to investigate the immunity impact of medications. SEIPR epidemiological model is incorporated with MDR-TB for compartments susceptible to disease, exposed to risk, infected ones, preventive or resistant to initial treatment, and recovered or healed population. These masses' natural trends, effects, and interactions are formulated and described in the present study. Computations and stability analysis are conducted upon endemic and disease-free equilibria in the present model for their global scenario. Both numerical and AI-based nonlinear autoregressive exogenous NARX analyses are presented with incorporating immediate treatment and delay in treatment. This study shows that the active patients and MDR-TB, both strains, exist because of the absence of permanent immunity to T.B. Furthermore, patients who have recovered from tuberculosis may become susceptible again by losing their immunity and contributing to transmission again. This article aims to identify patterns and predictors of treatment success. The findings from this research can contribute to developing more effective tuberculosis interventions.

Skin-attachable Tb-MOF ratio fluorescent sensor for real-time detection of human sweat pH.

The pH of human sweat is highly related with a variety of diseases, whereas the monitoring of sweat pH still remains challenging for ordinary families. In this study, we developed a novel dual-emission Tb-MOF using DPA as the ligand and further designed and constructed a skin-attachable Tb-MOF ratio fluorescent sensor for real-time detection of human sweat pH. With the increased concentration of H+, the interaction of H+ with carbonyl organic ligand leads to the collapse of the Tb-MOF crystal structure, resulting in the interruption of antenna effect, and correspondingly increasing the emission of the ligand at 380 nm and decreasing the emission of the central ion Tb3+ at 544 nm. This Tb-MOF nanoprobe has a good linear response in the pH range of 4.12-7.05 (R2 = 0.9914) with excellent anti-interference ability. Based on the merits of fast pH response and high sensitivity, the nanoprobe was further used to prepare flexible wearable sensor. The wearable sensor can detect pH in the linear range of 3.50-6.70, which covers the pH range of normal human sweat (4.50-6.50). Subsequently, the storage stability and detection accuracy of the sensors were evaluated. Finally, the sensor has been successfully applied for the detection of pH in actual sweat samples from 21 volunteer and the real-time monitoring of pH variation during movement processing. This skin-attachable Tb-MOF sensor, with the advantages of low cost, visible color change and long shelf-life, is appealing for sweat pH monitoring especially for ordinary families.

Burden of drug-resistant tuberculosis by the GeneXpert MTB/RIF assay and its clinico-epidemiological aspects at a tertiary care hospital in West Bengal.

Multidrug -resistant tuberculosis (MDRTB) is a serious threat to mankind. India has the highest number of MDRTB cases, although majority remain undiagnosed due to inadequate diagnostic infrastructure, leading to increased community transmission and mortality. This one-year observational retrospective study highlighted the effectiveness of the National Tuberculosis Elimination Program (NTEP) for prompt detection of drug-resistant TB by GeneXpert MTB/RIF assay and revealed its associated clinico-epidemiological factors. The overall detection rates of MTB and RRTB were 20.70 % and 20.86 % respectively. The pediatric population had 7.69 % rifampicin resistance, and HIV was strongly associated with the development of TB and RRTB (P < 0.01).

Trends of drug resistance in M. tuberculosis in a reference laboratory in Central India: Forging ahead towards TB elimination.

PURPOSE: The National Tuberculosis Elimination Programme (NTEP) of the Government of India has strived to control tuberculosis (TB) in the country through various interventions. Understanding the trends of resistance patterns may provide insights into the effectiveness of TB control activities in the country. METHODS: A total of 31,144 clinical samples were received from 2013 to 2022 from presumptive drug-resistant TB patients. All the specimens were decontaminated and subjected to the line probe assay for detection of resistance to rifampicin and isoniazid. Mycobacterium tuberculosis (MTB) was detected in 28,814 samples. Autoregressive integrated moving average model (ARIMA) was fitted to assess the trend over time. RESULTS: A decreasing trend in multi-drug resistant TB from 19 % in 2013 to 4 % in 2022 was seen. A decreasing trend in rifampicin monoresistance from 11.2 % in 2013 to 1.5 % in 2022 was seen, though there was an increase in resistance in 2017. No significant decreasing trends were seen in the proportion of isoniazid monoresistance from 8.3 % in 2013 to 7 % in 2022. CONCLUSION: The findings are encouraging, and to a considerable extent, affirm that India is well on track with regard to the goal of TB elimination.

Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis.

Linezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB). We conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992-2018. Data was collected from medical records. ADRs were classified according to Common Terminology Criteria for Adverse Events (version 5.0). Of all participants (n=132), 43.2% were female and the median age 28 years. The median linezolid treatment was 6.5 months (IQR 3.0-12.7) with a median daily dose of 9.6 mg/kg/day. Any ADR was seen in 58.3% (n=77) of participants, with 35.6% having peripheral neuropathy (n=47), 27.3% anaemia (n=36), 22.0% leukopenia (n=36) while 6.1% (n=8) had optic neuritis. The median time for peripheral neuropathy was 3.6 months (IQR 2.1-5.9) and 8.3 months (6.2-10.7) for optic neuritis. A >2.0 mg/L trough concentration (n=40) was associated with anaemia (p=0.0038) and thrombocytopenia (p=0.009) but not with peripheral neuropathy. In multivariable analysis, a dose ≥12 mg/kg/day was associated with time to peripheral neuropathy (HR 2.89, 95%CI 1.08-7.74, p=0.035), anaemia (HR 6.62, 95%CI 2.22-19.8, p=0.001) and leukopenia (HR 5.23, 95% CI 1.48-18.5, p=0.010). Linezolid ADRs were frequent in a high-resource setting. Structured, regular follow-up for ADRs and adjusting dosing according to body weight followed-up by monitoring of drug concentrations early may reduce toxicity.