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.

Artificial intelligence-based radiographic extent analysis to predict tuberculosis treatment outcomes: a multicenter cohort study.

Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management.

Impact of hyperglycemia on tuberculosis treatment outcomes: a cohort study.

Hyperglycemia is prevalent and closely associated with pulmonary tuberculosis (PTB). This study aimed to investigate the effects of hyperglycemia on the outcomes of PTB treatment. This study comprised 791 patients with PTB in total. Patients with fasting plasma glucose levels of ≥ 6.1 mmol/L were diagnosed with hyperglycemia. Anthropometric and baseline demographic data were also collected. The treatment response was assessed based on clinical symptoms (sputum production, cough, chest pain, fever, hemoptysis, night sweats, loss of appetite, and fatigue), sputum smear, chest computed tomography (CT), and adverse gastrointestinal responses (vomiting, nausea, abdominal distension, diarrhea, and constipation). A generalized estimating equation (GEE) was used to evaluate these relationships. Hyperglycemia affected 266 (33.6%) of the 791 patients with PTB. In GEE analyses, patients with hyperglycemia exhibited a greater incidence of elevated tuberculosis (TB) scores (odds ratio (OR) 1.569; 95% CI 1.040-2.369), cough (OR 1.332; 95% CI 1.050-1.690), and night sweats (OR 1.694; 95% CI 1.288-2.335). Hyperglycemia was linked with a higher risk of positive sputum smears (OR 1.941; 95% CI 1.382-2.727). During therapy, hyperglycemia was also associated with an increased incidence of vomiting (OR 2.738; 95% CI 1.041-7.198), abdominal distension (OR 2.230; 95% CI 1.193-4.171), and constipation (OR 2.372; 95% CI 1.442-3.902). However, the CT results indicated that hyperglycemia did not affect pulmonary lesions in patients with TB. Patients with TB and hyperglycemia are at a higher risk of severe clinical manifestations, positive sputum smears, and adverse gastrointestinal effects and, therefore, the special situation of hyperglycemic patients should be considered in the prevention and treatment of TB.

ED50 of ciprofol combined with sufentanil for fiberoptic bronchoscopy of different patient populations with pulmonary tuberculosis.

BACKGROUND: Ciprofol is a promising sedative. This study aims to explore the median effective dose (ED50) of ciprofol in inhibiting responses to fiberoptic bronchoscopy in patients with pulmonary tuberculosis (PTB) of different genders and ages when combined with 0.15 µg/kg sufentanil, and to evaluate its efficacy and safety, providing a reference for the rational use of ciprofol in clinical practice. METHODS: PTB patients who underwent bronchoscopy examination and treatment at The Third People's Hospital of Changzhou between May 2023 and June 2023 were selected and divided into four groups using a stratified random method. All patients received intravenous injection of 0.15 µg/kg sufentanil followed by injection of the test dose of ciprofol according to Dixon's up-and-down method. The initial dose of ciprofol in all four groups was 0.4 mg/kg, with an adjacent ratio of 1:1.1. The next patient received a 10% increase in the dose of ciprofol if the previous patient in the same group experienced positive reactions such as choking cough, frowning, and body movements during the endoscopy. Otherwise, it was judged as a negative reaction, and the next patient received a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study of the group was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points in all groups. The Probit regression analysis method was used to calculate the ED50 of ciprofol in the four groups and compare between the groups. RESULTS: The ED50 of ciprofol combined with 0.15 µg/kg sufentanil for bronchoscopy in the four groups were 0.465 mg/kg, 0.433 mg/kg, 0.420 mg/kg and 0.396 mg/kg, respectively. CONCLUSION: The ED50 of ciprofol used for fiberoptic bronchoscopy varied among PTB patients of different genders and ages. TRIAL REGISTRATION: The Chinese Clinical Trial Registry, ChiCTR2300071508, Registered on 17 May 2023.

Tuberculosis Treatment Compliance Under Smartphone-Based Video-Observed Therapy Versus Community-Based Directly Observed Therapy: Cluster Randomized Controlled Trial.

BACKGROUND: There are no recent studies comparing the compliance rates of both patients and observers in tuberculosis treatment between the video-observed therapy (VOT) and directly observed therapy (DOT) programs. OBJECTIVE: This study aims to compare the average number of days that patients with pulmonary tuberculosis and their observers were compliant under VOT and DOT. In addition, this study aims to compare the sputum conversion rate of patients under VOT with that of patients under DOT. METHODS: Patient and observer compliance with tuberculosis treatment between the VOT and DOT programs were compared based on the average number of VOT and DOT compliance days and sputum conversion rates in a 60-day cluster randomized controlled trial with patients with pulmonary tuberculosis (VOT: n=63 and DOT: n=65) with positive sputum acid-fast bacilli smears and 38 observers equally randomized into the VOT and DOT groups (19 observers per group and n=1-5 patients per observer). The VOT group submitted videos to observers via smartphones; the DOT group followed standard procedures. An intention-to-treat analysis assessed the compliance of both the patients and the observers. RESULTS: The VOT group had higher average compliance than the DOT group (patients: mean difference 15.2 days, 95% CI 4.8-25.6; P=.005 and observers: mean difference 21.2 days, 95% CI 13.5-28.9; P<.001). The sputum conversion rates in the VOT and DOT groups were 73% and 61.5%, respectively (P=.17). CONCLUSIONS: Smartphone-based VOT significantly outperformed community-based DOT in ensuring compliance with tuberculosis treatment among observers. However, the study was underpowered to confirm improved compliance among patients with pulmonary tuberculosis and to detect differences in sputum conversion rates. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR) TCTR20210624002; https://tinyurl.com/3bc2ycrh. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/38796.

A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis.

OBJECTIVE: To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance. METHODS: 122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score. RESULTS: The TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579-0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756-1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6-98.2%) and specificity was 81.3% (95% CI: 70.0-88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2. CONCLUSION: Xpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.

Concomitant osimertinib and antituberculosis therapy in an elderly patient with EGFR-mutated lung cancer and pulmonary tuberculosis: A case report.

The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well-established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89-year-old female, diagnosed with epidermal growth factor receptor (EGFR)-mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient.

BACKGROUND: Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. CASE PRESENTATION: The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient's condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. CONCLUSION: Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Tuberculosis treatment delay and associated factors among pulmonary tuberculosis patients at public health facilities in Dale District and Yirgalem Town administration, Sidama Region, South Ethiopia.

BACKGROUND: Tuberculosis (TB) treatment delay is one of the major challenges of TB care in many low-income countries. Such cases may contribute to an increased TB transmission and severity of illness. The aim of this study was to determine the magnitude of patient delay in TB treatment, and associated factors in Dale District and Yirgalem Town administration of Sidama Region, Southern Ethiopia. METHODS: Between January 1-Augst 30/ 2022, we studied randomly selected 393 pulmonary TB cases on Directly Observed Treatment Short course (DOTS) in Dale District and Yirgalem Town Administration. After conducting a pretest, we interviewed participants on sociodemographic, health seeking behavior and clinical factors and reviewed the TB registry. Trained enumerators interviewed to collect data. We entered data in to EPI-info 7 version 3.5.4 and then exported to the Statistical Package for Social Science (SPSS) version 23 for analysis. Multivariable logistic regression was used to identify associated factors of TB and statistical significance was defined using the 95% confidence interval. RESULT: A total of 393 (98%) participants involved in the study. The magnitude of delay in TB treatment among the study participants was 223 (56.7%) (95% CI (51.8 - 61.6%)). Distance of the health facility from home, (adjusted odds ratio (AOR) = 2.04, 95% CI (1.3, 3.2)), seeking antibiotic treatment before being diagnosed for TB (AOR = 2.1, 95% CI (1.3, 3.5)) and the knowledge of TB prevention and treatments (AOR = 5.9, 95% CI (3.6, 9.8)), were factors associated with delay in TB treatment. CONCLUSION: The prevalence of TB treatment delay among pulmonary TB patients in the study setting was high. Delay in TB treatment was associated with knowledge, behavioral and accessibility related factors. Providing health education and active case finding of TB would help in minimizing the delay.

Baseline and end-of-treatment host serum biomarkers predict relapse in adults with pulmonary tuberculosis.

BACKGROUND: There is a need for new tools for monitoring of the response to TB treatment. Such tools may allow for tailored treatment regimens, and stratify patients initiating TB treatment into different risk groups. We evaluated combinations between previously published host biomarkers and new candidates, as tools for monitoring TB treatment response, and prediction of relapse. METHODS: Serum samples were collected at multiple time points, from patients initiating TB treatment at research sites situated in South Africa (ActionTB study), Brazil and Uganda (TBRU study). Using a multiplex immunoassay platform, we evaluated the concentrations of selected host inflammatory biomarkers in sera obtained from clinically cured patients with and without subsequent relapse within 2 years of TB treatment completion. RESULTS: A total of 130 TB patients, 30 (23%) of whom had confirmed relapse were included in the study. The median time to relapse was 9.7 months in the ActionTB study (n = 12 patients who relapsed), and 5 months (n = 18 patients who relapsed) in the TBRU study. Serum concentrations of several host biomarkers changed during TB treatment with IL-6, IP-10, IL-22 and complement C3 showing potential individually, in predicting relapse. A six-marker signature comprising of TTP, BMI, sICAM-1, IL-22, IL-1ß and complement C3, predicted relapse, prior to the onset of TB treatment with 89% sensitivity and 94% specificity. Furthermore, a 3-marker signature (Apo-CIII, IP-10 and sIL-6R) predicted relapse in samples collected at the end of TB treatment with sensitivity of 71% and specificity of 74%. A previously identified baseline relapse prediction signature (TTP, BMI, TNF-ß, sIL-6R, IL-12p40 and IP-10) also showed potential in the current study. CONCLUSION: Serum host inflammatory biomarkers may be useful in predicting relapse in TB patients prior to the initiation of treatment. Our findings have implications for tailored patient management and require prospective evaluation in larger studies.

A critical analysis of the decreasing trends in tuberculosis cure indicators in Brazil, 2001-2022.

OBJECTIVE: To analyze the temporal trend of tuberculosis cure indicators in Brazil. METHODS: An ecological time-series study using administrative data of reported cases of the disease nationwide between 2001 and 2022. We estimated cure indicators for each federative unit (FU) considering individuals with pulmonary tuberculosis, tuberculosis-HIV coinfection, and those in tuberculosis retreatment. We used regression models using joinpoint regression for trend analysis, reporting the annual percentage change and the average annual percentage change. RESULTS: For the three groups analyzed, we observed heterogeneity in the annual percentage change in the Brazilian FUs, with a predominance of significantly decreasing trends in the cure indicator in most FUs, especially at the end of the time series. When considering national indicators, an average annual percentage change of -0.97% (95% CI: -1.23 to -0.74) was identified for the cure of people with pulmonary tuberculosis, of -1.11% (95% CI: -1.42 to -0.85) for the cure of people with tuberculosis-HIV coinfection, and of -1.44% (95% CI: -1.62 to -1.31) for the cure of people in tuberculosis retreatment. CONCLUSIONS: The decreasing trends of cure indicators in Brazil are concerning and underscore a warning to public authorities, as it points to the possible occurrence of other treatment outcomes, such as treatment discontinuity and death. This finding contradicts current public health care policies and requires urgent strategies aiming to promote follow-up of patients during tuberculosis treatment in Brazil.

Prior COVID-19 infection among newly diagnosed tuberculosis patients in a tertiary care center in Tehran: A case-control study.

OBJECTIVE: To assess the risk of developing pulmonary tuberculosis (TB) in accordance with prior history of COVID-19 infection. BACKGROUND: Since the advent of the COVID-19 pandemic much discussion has been had on the possible role it might play on global efforts to combat TB; most, focusing on the pandemic's impact on health care systems' capabilities to manage TB cases. Mechanisms have also been proposed by which the COVID-19 infection may directly affect individuals' chance of developing TB infection. Cases have been reported with a history of COVID-19 infection preceding a diagnosis of TB, evidencing its possible role as a risk factor for the disease. METHODS: A case-control study was conducted enrolling patients diagnosed with pulmonary TB in the absence of major risk factors previous history of TB, (HIV) human immunodeficiency virus infection), end-stage renal disease, organ transplants, and use of immunosuppressive agents) for developing TB. Each patient was age and sex matched with one healthy control. Data regarding prior COVID-19 infection, diabetes, and smoking status as well as the use of corticosteroids and Tocilizumab for the treatment of COVID-19 infection was obtained. Bivariate analysis was conducted and variables with a likely association with TB status were entered in a multivariate model. RESULTS: Bivariate analysis demonstrated a significant relationship between prior COVID-19 infection and TB (95% confidence interval = 1.1-22.8, odds ratio [OR] = 5). Among other variables the severity of COVID-19 infection was found to have a likely association with TB status (p = .125). In a multivariate model, prior COVID-19 infection per se, was not found to be significantly associated with TB (p = .12, OR = 4.5). CONCLUSIONS: There seems to be an association between prior history of COVID-19 and a future diagnosis of TB partially linked to the severity of disease. The findings of the current study may serve as a basis for further studies to determine the need for and efficacy of measures to follow-up COVID-19 patients at an increased risk for developing TB.

Two Difficult Pandemics: Tuberculosis and COVID-19.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Norwegian scabies in human immunodeficiency virus and tuberculosis-infected child: A case report.

Norwegian scabies is a rare scabies with the manifestation of thick crusts of the extremities of the skin that contain eggs and mites. Several conditions in which scabies infection is easily transmitted include immunocompromised, home nursing, and severe neurological disorder. The aim of this case report was to present a thorough analysis of a comprehensive resource for the management of Norwegian scabies patients, with a specific focus on individuals who also have HIV or other immunocompromising diseases. A 1-year-and-7-month-old boy was presented to the hospital with a chief complaint of a thick crust that he had experienced for four months. It began as a red papule in the lower extremity, then crusted and spread to the whole body. The patient kept scratching due to itching, had a recurrent fever and diarrhea for three months, and cough for one month. The patient was diagnosed with human immunodeficiency virus (HIV) and pulmonary tuberculosis at three months, suspected to get the infection from the parents. Sarcoptes scabiei was found from microscopy examination of skin scraping. The patient received holistic treatment, including antiretroviral drugs, antituberculosis medication, scabies treatment, and malnutrition treatment. Appropriate scabies treatment aimed at peeling crusted skin, relieving itching, and increasing the patient ability to use the extremities. Comorbidity conditions caused by HIV and pulmonary tuberculosis should also be treated to optimize the outcome. The patient was discharged in good condition with sanitation education and regular follow-up at the outpatient clinic. This case highlights that Sarcoptes scabiei infestation may be a clue to an immunocompromised condition. Holistic therapy aiming to cure underlying infection, infestation and underlying nutrition and psychosocial problems must be addressed to fully cure this high-burden case.

Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.

BACKGROUND: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. METHODS: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined "subclinical" or "asymptomatic" pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. RESULTS: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002-2022) using "absence of cough of any duration" criteria reported higher subclinical TB prevalence than those using the stricter "completely asymptomatic" threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. CONCLUSION: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

Genotypic and phenotypic drug resistance patterns of Mycobacterium tuberculosis isolated from presumptive pulmonary tuberculosis patients in Ethiopia: A multicenter study.

BACKGROUND: The emergence of drug-resistant tuberculosis (DR-TB) has been a major obstacle to global tuberculosis control programs, especially in developing countries, including Ethiopia. This study investigated drug resistance patterns and associated mutations of Mycobacterium tuberculosis Complex (MTBC) isolates from the Amhara, Gambella, and Benishangul-Gumuz regions of Ethiopia. METHODS: A cross-sectional study was conducted using 128 MTBC isolates obtained from patients with presumptive tuberculosis (TB). Phenotypic (BACTEC MGIT 960) and genotypic (MTBDRplus and MTBDRsl assays) methods were used for drug susceptibility testing. Data were entered into Epi-info and analyzed using SPSS version 25. Frequencies and proportions were determined to describe drug resistance levels and associated mutations. RESULTS: Of the 127 isolates recovered, 100 (78.7%) were susceptible to four first-line anti-TB drugs. Any drug resistance, polydrug resistance, and multi-drug resistance (MDR) were detected in 21.3% (27), 15.7% (20), and 15% (19) of the isolates, respectively, by phenotypic and/or genotypic methods. Mono-resistance was observed for Isoniazid (INH) (2, 1.6%) and Streptomycin (STR) (2, 1.6%). There were two genotypically discordant RIF-resistant cases and one INH-resistant case. One case of pre-extensively drug-resistant TB (pre-XDR-TB) and one case of extensively drug-resistant TB (XDR-TB) were identified. The most frequent gene mutations associated with INH and rifampicin (RIF) resistance were observed in the katG MUT1 (S315T1) (20, 76.9%) and rpoB (S531L) (10, 52.6%) genes, respectively. Two MDR-TB isolates were resistant to second-line drugs; one had a mutation in the gyrA MUT1 gene, and the other had missing gyrA WT1, gyrA WT3, and rrs WT1 genes without any mutation. CONCLUSIONS: The detection of a significant proportion of DR-TB cases in this study suggests that DR-TB is a major public health problem in Ethiopia. Thus, we recommend the early detection and treatment of DR-TB and universal full first-line drug-susceptibility testing in routine system.

Antimycobacterial and healing effects of Pranlukast against MTB infection and pathogenesis in a preclinical mouse model of tuberculosis.

It is essential to understand the interactions and relationships between Mycobacterium tuberculosis (Mtb) and macrophages during the infection in order to design host-directed, immunomodulation-dependent therapeutics to control Mtb. We had reported previously that ornithine acetyltransferase (MtArgJ), a crucial enzyme of the arginine biosynthesis pathway of Mtb, is allosterically inhibited by pranlukast (PRK), which significantly reduces bacterial growth. The present investigation is centered on the immunomodulation in the host by PRK particularly the activation of the host's immune response to counteract bacterial survival and pathogenicity. Here, we show that PRK decreased the bacterial burden in the lungs by upregulating the population of pro-inflammatory interstitial macrophages (IMs) and reducing the population of Mtb susceptible alveolar macrophages (AMs), dendritic cells (DCs), and monocytes (MO). Additionally, we deduce that PRK causes the host macrophages to change their metabolic pathway from fatty acid metabolism to glycolytic metabolism around the log phage of bacterial multiplication. Further, we report that PRK reduced tissue injury by downregulating the Ly6C-positive population of monocytes. Interestingly, PRK treatment improved tissue repair and inflammation resolution by increasing the populations of arginase 1 (Arg-1) and Ym1+Ym2 (chitinase 3-like 3) positive macrophages. In summary, our study found that PRK is useful not only for reducing the tubercular burden but also for promoting the healing of the diseased tissue.

Disseminated tuberculosis in PLWHIV presenting as primary adrenal insufficiency.

A woman in her 40s presented with a history of fatigue, symptoms of light-headedness on getting up from a sitting position and hyperpigmentation of the skin and mucous membranes. During the evaluation, she was diagnosed with primary adrenal insufficiency. Radiological imaging and microbiological evidence revealed features of disseminated tuberculosis involving the lungs and the adrenals. She was found to have an HIV infection. This patient was prescribed glucocorticoid and mineralocorticoid replacement therapy and was administered antituberculous and antiretroviral treatment.