Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) remain the leading causes of lung disease and mortality worldwide. Interferon-gamma (IFN-γ) and its receptor (IFN-γR) play a key role in mediating immunity against Mtb and NTM. This study was conducted as a systematic review; all information was collected from databases such as: PubMed, Scopus, Medline, SID, and medical databases. Finally, all the collected data were reviewed, and all content was categorized briefly. There is growing evidence that IFN-γ plays an important role in host defense against these two intracellular pathogens by activating macrophages. In addition, IFN-γ has been shown to be an integral part of various antibacterial methods such as granuloma formation and phagosome-lysosome fusion, both of which lead to the death of intracellular Mycobacterium. As a result, its absence is associated with overgrowth of intracellular pathogens and disease caused by Mtb or Mycobacterium nontuberculosis. We also look at the role of IFN-γR in Mtb or NTM because IFN-γ acts through IFN-γR. Finally, we introduce new approaches to the treatment of M. tuberculosis complex (MTC) and NTM disease, such as cell and gene-based therapies that work by modulating IFN-γ and IFN-γR.

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Background : Tuberculosis (TB) is common form of communicable disease in India. Abdominal TB is one of the most common yet misdiagnosed forms of extrapulmonary TB. It is missed due to its similarity to other conditions such as Crohn's disease and nonspecific clinical presentation. Methods: Medical records of 317 patients who were diagnosed with abdominal TB from August 2015 to December 2020 were reviewed retrospectively from our prospectively maintained database. Results: Among 317 patients, 167 (52.7%) were male. Median age of presentation was 45 (8–85) years. Luminal involvement was seen in most of the patients (n = 157, 49.5%), followed by peritoneal (n = 63, 19.8%), mixed (n = 42, 13.2%), solid visceral (n = 30, 9.4%), and nodal (n = 25, 7.8%) involvement. Two hundred and sixty-one (82.3%) showed complete response. Seven (2.2%) patients died and 5 (1.6%) patients lost to follow-up. Median duration of treatment was 28 (25–52) weeks. Drug-induced liver injury was identified in 30 (9.5%) patients. Median follow-up duration was 32 (1–70) months. Conclusion: Abdominal TB is quite a diagnostic challenge due its vague clinical symptoms, nonspecific radiological features, and poor sensitivity and specificity of diagnostic tests. Hence, clinicians should have a high index of suspicion to diagnose and treat this treatable yet lethal condition promptly. Most cases respond very well to medical management and a small fraction requires surgical intervention if diagnosed early.

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Background: The diagnosis of leprosy is based on the characteristic signs and symptoms of the disease, subsidized by laboratory tests. When positive, the bacilloscopy closes the diagnosis for leprosy. Phenolic glycolipid-I, or PGL-I, is a molecule in the bacillus cell wall that confers a greater immune response. The ML Flow test is an immunochromatographic test for the detection of anti-PGL-I IgM in human blood or serum. Methods: A prospective study with data collection and biological materials in patients with suspected leprosy from August 2020 to May 2021. For microscopy, intradermal smears were stained with Auramine O, and after reading under a fluorescence microscope, reviewed by Ziehl–Neelsen. The ML flow test was performed according to the Bührer-Sékula protocol. To assess the agreement between the methods, the Kappa index was estimated. Results: Of the 94 suspected leprosy patients, 31 (32.9%) were diagnosed with leprosy. There was moderate agreement between the results of the ML Flow and Auramine O tests (Kappa = 0.58) and substantial agreement between the ML Flow and Ziehl–Neelsen microscopy (Kappa = 0.72). In paucibacillary cases, serology was positive in 100% of patients. Conclusions: This study concluded that the Ziehl–Neelsen technique remains the best option for standard leprosy staining, and the ML flow test is more positive among the three techniques evaluated and can be an effective tool in the early diagnosis of leprosy cases.

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Background: Early prediction of tuberculosis (TB) cases is very crucial for its prevention and control. This study aims to predict the number of TB cases in Gombak based on sociodemographic and environmental factors. Methods: The sociodemographic data of 3325 TB cases from January 2013 to December 2017 in Gombak district were collected from the MyTB web and TB Information System database. Environmental data were obtained from the Department of Environment, Malaysia; Department of Irrigation and Drainage, Malaysia; and Malaysian Metrological Department from July 2012 to December 2017. Multiple linear regression (MLR) and artificial neural network (ANN) were used to develop the prediction model of TB cases. The models that used sociodemographic variables as the input datasets were referred as MLR1 and ANN1, whereas environmental variables were represented as MLR2 and ANN2 and both sociodemographic and environmental variables together were indicated as MLR3 and ANN3. Results: The ANN was found to be superior to MLR with higher adjusted coefficient of determination (R²) values in predicting TB cases; the ranges were from 0.35 to 0.47 compared to 0.07 to 0.14, respectively. The best TB prediction model, that is, ANN3 was derived from nationality, residency, income status, CO, NO₂, SO₂, PM₁₀, rainfall, temperature, and atmospheric pressure, with the highest adjusted R² value of 0.47, errors below 6, and accuracies above 96%. Conclusions: It is envisaged that the application of the ANN algorithm based on both sociodemographic and environmental factors may enable a more accurate modeling for predicting TB cases.

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Background: Non-tuberculous Mycobacteria (NTM) cause different forms of diseases. According to recent guideline by ATS/ERS/ESCMID/IDSA, drug susceptibility test (DST) is an important requirement to choose adequate treatment. The minimum inhibitory concentration (MIC) test is the recommended method. Sensititre SLOMYCO and RAPMYCO commercial panels were developed to perform mycobacteria DST easier. However, there are only two comparative studies between SLOMYCO and the MIC method and none for the RAPMYCO panel. The present study aimed to evaluate the Sensititre SLOMYCO and RAPMYCO plates in determining drug susceptibility compared to the gold standard method (MIC). Methods: The tests were carried out with clinical isolates received in the diagnostic routine of the Tuberculosis Laboratory at Institute Adolfo Lutz from the most frequent species in the state of São Paulo, Brazil. Reference strains were tested for repeatability and reproducibility analyses. MIC and Sensititre plates readings were compared with and without resazurin stain. Agreement between results was defined as MIC within the same dilution or dilution variation resulting the same category in both tests. Results were classified by categorical errors. Results: The RAPMYCO panel had 100% agreement for the drugs amikacin, doxycycline, ciprofloxacin and trimethoprim/sulfamethoxazole, 83.3% for clarithromycin and moxifloxacin and 60% for cefoxitin. The SLOMYCO panel had 80% agreement for amikacin and moxifloxacin and 60% for clarithromycin, rifabutin, rifampicin and ciprofloxacin. The repeatability and reproducibility with RAPMYCO and SLOMYCO plates showed a high level of agreement for the drugs tested, being higher with the use of resazurin. However, an evaluation on routine condition is needed. Conclusions: The present study found that the fewer steps in the tests with Sensititre plates and reading with resazurin allow its use with greater safety and efficiency in the laboratory routine. The results presented here will facilitate the execution of a validation for complete incorporation of Sensititre plates into a diagnostic routine.

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Background: Tuberculosis (TB) remains a major cause of morbidity and mortality in Ethiopia despite the increased availability of effective treatments. Trend analysis of issues and priorities affecting TB programs across different regions of the country is critical to ensure equitable and sustainable TB outcomes. We aimed to analyze the trends of TB in Bahir Dar, Northwest Ethiopia, over 5 years from 2015 to 2019. Methods: An institution-based, retrospective cross-sectional study was conducted in Bahir Dar, the capital city of the Amhara Region in Ethiopia. Five-year data and records of individual TB cases were reviewed from all public and private health-care facilities and health bureaus in Bahir Dar. Using a standard checklist adapted from the World Health Organization, data were abstracted relevant to sociodemographic characteristics of the patients, year and type of TB infection, and HIV status. SPSS version 20 software was used for data analysis. Results: Data of 4275 patients with TB were identified, of which 929 (21.7%) were smear-positive pulmonary TB, 1195 (28%) were smear-negative pulmonary TB, and 2151 (50.3%) were extrapulmonary TB patients. TB was more prevalent in the age group 15–34 years (51.2%), and females (55.5%). In the years from 2015 to 2019, the prevalence of all forms of TB was 922 (21.6%), 812 (19.0%), 843 (19.7%), 876 (20.5%), and 822 (19.2%), respectively, demonstrating a decreasing trend though inconsistent. The variables sex (adjusted odds ratio [AOR]: 1.734, 95% confidence interval [CI] [1.390–2.187]), HIV co-infection (AOR: 1.875, 95% CI [1.553–2.265]), and age <15 years (AOR: 1.372, 95% CI [1.121–1.680]) showed a significant association with TB infection. Conclusions: The prevalence of TB in Bahir Dar, Northwest Ethiopia, demonstrated a decreasing trend over the years from 2015 to 2019 but with inconsistencies. HIV co-infection significantly increased the risk of developing TB, and productive age groups and females were at the greater prevalence of TB, highlighting the importance of strengthening sustainable TB care and prevention interventions toward these groups of people.

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Background: One-third of tuberculosis (TB) cases are missed each year and delays in the diagnosis of TB are hampering the whole cascade of care. Early chest X-ray (CXR) in patients with cough irrespective of duration may reduce TB diagnostic and treatment delays and increase the number of TB patients put into TB care. We aimed to evaluate the impact of CXR on delay in the diagnosis of pulmonary tuberculosis (PTB) among people with cough of any duration. Methods: A facility-based cross-sectional study was conducted in four selected health facilities from two regions and two city administrations of Ethiopia. Patients who sought health care were screened for cough of any duration, and those with cough underwent CXR for PTB and their sputum specimens were tested for microbiological confirmation. Delays were followed up and calculated using median and inter-quartile range (IQR) to summarize (first onset of cough to first facility visit, ≥15 days), diagnosis delay (first facility visit to date of PTB diagnosis, >7 days), and total delay (first onset of cough to date of PTB diagnosis, >21 days). Kruskal–Wallis and Mann–Witney tests were used to compare the delays among independent variables. Results: A total of 309 PTB cases were consecutively diagnosed of 1853 presumptive TB cases recruited in the study that were identified from 2647 people who reported cough of any duration. The median (IQR) of patient delay, diagnosis delay, and the total delay was 30 (16–44), 1 (0–3), and 31 (19–48) days, respectively. Patients' delay contributed a great role in the total delay, 201/209 (96.2%). Median diagnosis delay was higher among those that visited health center, diagnosed at a facility that had no Xpert mycobacterium tuberculosis (MTB)/RIF assay, radiologist, or CXR (P < 0.05). Factors associated with patients delay were history of previous TB treatment (adjusted prevalence ratio [aPR] = 0.79, 95% confidence interval [CI]: 0.63–0.99) and history of weight loss (aPR = 1.12; 95% CI: 1.0–1.25). Early CXR screening for cough of <2 weeks duration significantly reduced the patients' delay and thus the total delay, but not diagnostic delay alone. Conclusion: Early screening using CXR minimized delays in the diagnosis of PTB among people with cough of any duration. Patients' delay was largest and contributed great role in the delay of TB cases. Screening by cough of any duration and/or CXR among people seeking healthcare along with ensuring the availability of Xpert MTB/RIF assay and skilled human power at primary healthcare facilities are important to reduce patient and diagnostic delays of PTB in Ethiopia.

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Background: Extra-pulmonary TB(EPTB) accounts for 15-20% of total TB cases in India. Many cases remain undiagnosed due to poor sensitivity/long turn-around-time of conventional diagnostic tests. Molecular tests offer rapidity, improved sensitivity and exquisite specificity, but are expensive, require skilled manpower and enhanced laboratory infrastructure. Loop-mediated isothermal amplification (LAMP) assay is a unique, temperature-independent DNA amplification test facilitated by visual optic-readout. WHO has recommended use of LAMP for pulmonary TB diagnosis in 2016. For END-TB strategy to succeed, its necessary to capture all forms of TB. The aim of the study was to determine the sensitivity and specificity of LAMP assay against culture, Xpert MTB/RIF assay and Composite Reference Standard(CRS) for diagnosis of EPTB. Methods: In a cross-sectional study hundred consecutive EPTB specimens were processed for microscopy, culture, Xpert and LAMP assay. Standard formulae of sensitivity and specificity and McNemar chi square test of significance was applied. Results: Hundred specimens included in the study were fluids(65), pus(19) and tissue(16). TB was detected in 38 specimens by any of the four methods. Positivity of microscopy-5%, culture-28%, Xpert-25% and LAMP-32%. Sensitivity and specificity of LAMP against culture was 85.71% and 88.89%; against Xpert was 88% and 86.67%; against CRS was 80% and 88.6% respectively. LAMP detected TB in 32 patients of which 28 were put on anti-TB treatment (ATT). Of the 62 patients with negative results in all the tests, 22 were put on ATT. Conclusions: LAMP has good sensitivity for EPTB diagnosis. Further studies are required to establish utility of LAMP as EPTB diagnostic tool.

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Type 2 lepra reaction (or erythema nodosum leprosum [ENL]) is an immune complex-mediated reaction which has been reported to occur for up to 8 years after successful completion of multibacillary multidrug therapy. The management of ENL is a challenge with the patient often becoming steroid dependent; predisposing to recurrent episodes in 39%–77% of cases on attempted steroid withdrawal. Here, we present a case of recalcitrant recurrent type 2 reaction which responded promptly to treatment with colchicine.

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Background: The objective of this study was to evaluate the residual parenchymal and pleural lesions on chest X-ray posttherapy in new tuberculosis (TB) cases. Methods: This prospective study was done from January 2018 to December 2020, which involved the evaluation of medical records of 60 pulmonary or pleural TB patients who underwent successful treatment. Chest X-rays of the patients at the start and end of treatment were studied as per the guidelines by Revised National Tuberculosis Control Program. The primary outcome measures were residual chest X-ray lesions after the complete treatment of new cases of TB. Secondary outcomes measures were significant factors affecting the chest X-ray clearance. Results: Chest X-ray showed clearing in 48.33% of cases. Residual chest X-ray findings were present in 31 cases which mainly included fibrosis in 23.33% and pleural thickening in 20%. None of the clinical and demographic characters and biochemical parameters showed significant association with chest X-ray clearance (P > 0.05). Sputum microscopy was done in 45 cases of which 25 (41.66%) were positive for acid-fast bacilli. Sputum positivity showed no significant correlation with chest X-ray clearance (odds ratio [OR]: 0.734, confidence interval [CI]: 0.224–2.411, P = 0.592). Compared to nonstandardized regimen, standardized regimen showed no significant correlation with chest X-ray clearance (OR: 0.664; CI: 0.233–1.892, P = 0.426). Conclusion: Residual radiological sequelae were seen in more than half of the study subjects who were successfully treated for TB (51.67%). Demographic, clinical characteristics, sputum positivity, and treatment regimen showed no significant association with chest X-ray clearance.

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Intestinal tuberculosis (TB) is a diagnostic challenge and can closely mimic Crohn's disease (CD) and colon cancer. These disease entities very closely resemble each other in symptomatology, imaging, appearance, and pathology. We present a case of colonic TB where the initial diagnostic workup was suggestive of CD. However, the detection of Mycobacterium tuberculosis in biopsy specimens confirmed the diagnosis.

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Background: In recent studies, it has been established that countries having Bacillus Calmette-Guerin (BCG) vaccination programs reported less COVID-19 cases and deaths per population Preliminary studies suggest that BCG vaccination could upregulate the vaccine-induced immunity against SARS-CoV-2. Hence, the recent study was aimed to determine the association of BCG vaccine with the development of COVID-19 in health care workers. Methods: The participants included in the study were healthcare workers (doctors, paramedics, and other supporting staff) working in the high and low-risk zones of COVID-19 in the hospital. The Graph Pad statistical analysis tool was used to determine the association of preliminary BCG vaccination with their COVID-19 status. Results: A total of 200 health care workers working in different departments of the hospital were enrolled in the study. The relative risk of COVID-19 positivity in BCG vaccinated versus unvaccinated was 0.79 (0.50–1.25). There was also a significant negative correlation between two groups. The relative risk of COVID-19 positivity in those with a BCG scar was 0.63 (0.44–0.92). The relative risk of COVID-19 infection in those with a history of tuberculosis was 1.08 (0.56–2.09). Conclusion: The present study did not support the beneficial effect of BCG vaccine in protection against the development of COVID-19 disease.

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Background: From the time vaccines were introduced, their impact has been beyond measurable. Mycobacteria are pathogens increasingly isolated from postvaccination abscess. Identification of these pathogens plays a very crucial role in the management of these babies. We aimed to determine Mycobacterial spp occurrence from vaccination abscess, draw local antibiogram, and guide management of babies with vaccination abscess. Methods: Babies with postvaccination abscess from 2016 to 2020 were included. Pus collected during incision and drainage was processed as per the standard guidelines. Mycobacterium isolates were identified by conventional methods, and all samples were confirmed by polymerase chain reaction. All babies underwent incision and drainage, and all were started with amoxicillin and clavulanic acid and changed later as per the sensitivity report. Results: Mycobacterium abscessus was isolated from 17% (12) pus samples from 71 postdiphtheria pertussis and tetanus vaccination, and Mycobacterium bovis was isolated from 83.3% (10) babies with post-Bacillus Calmette–Guérin vaccination. The mean interval between injection and abscess formation was 32.75 days in case of M. abscessus, whereas it was 50.4 days in case of M. bovis. All the M. abscessus were sensitive to linezolid, amikacin, and clarithromycin, whereas no treatment except incision and drainage was required for M. bovis. Conclusion: There is an increased incidence of Mycobacterial spp infection in postvaccination abscess. All babies with M abscessus responded well with combination antibiotic therapy plus drainage of abscesses, whereas M. bovis was treated by incision and drainage, and no further antibiotics were given.

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Background: Establishing the etiology of exudative pleural effusions in the setting of an unrewarding pleural fluid analysis often requires biopsies from the parietal pleura. However, it may be noted that diagnosis such as pulmonary embolism and connective tissue diseases can result in an exudative pleural effusion where a pleural biopsy can yield nonspecific results. Medical thoracoscopy (MT) is a minimally invasive procedure performed under local anesthesia or moderate sedation with excellent yield and favorable safety profile. We analyzed the diagnostic yield of MT for exudative pleural effusions after employing a rigid diagnostic algorithm. The study was undertaken to ascertain the yield of MT in establishing the diagnosis in diagnosis of exudative pleural effusions, to find out the relative contribution of pleural tuberculosis (TB) as a cause of undiagnosed exudative pleural effusion, to describe the etiology of undiagnosed exudative pleural effusion in patients undergoing MT and to determine the correlation between pleural fluid adenosine deaminase (ADA) levels and TB pleuritis in patients undergoing MT. Methods: This was a retrospective study. Patients with undiagnosed exudative pleural effusion were included in the study. MT was performed with semirigid thoracoscope (Olympus LTF 160) under local anesthesia and conscious sedation. Gross appearance and ADA level of pleural fluid were noted. Pleural biopsy material was subjected to histopathology examination and culture for mycobacteria along with cartridge-based nucleic acid amplification test for TB. The yield of MT for establishing the etiology of pleural effusion and the relative contribution of tuberculous pleuritis as a cause of undiagnosed pleural effusion was ascertained. Correlation of pleural fluid ADA levels was done with a final diagnosis of TB pleuritis in patients undergoing MT. Results: Twenty-five patients with undiagnosed exudative pleural effusion underwent thoracoscopy of which 16 were male and 9 were female. MT was able to establish the diagnosis in all cases, providing a diagnostic yield of 100%. Histopathological examination of biopsy specimens yielded a diagnosis of malignant involvement of pleura in 10 patients and granulomatous pleuritis consistent with TB in 14 patients. Pleural TB contributed to 60% of undiagnosed pleural effusions in the present study. The mean ADA value among those who turned positive was 56.338 and 35.300 among those who turned negative using genexpert, which was found to be statistically significant. A value of 31 IU/L showed a sensitivity of 93.3% and specificity of 99.8% and hence can be taken as a cut off value for the diagnosis of pleural TB based on receiver-operating characteristic analysis. Conclusion: TB contributed to 60% of undiagnosed exudative pleural effusions in the present study. MT had 100% yield in the diagnosis of undiagnosed exudative effusions. Pleural fluid ADA levels may help in differentiating TB versus malignant effusion.

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Background: An adverse drug event (ADE) is an injury resulting from medical intervention associated with a drug. This study assesses the incidence of ADEs among participants on second-line drugs for tuberculosis (TB) in Cameroon. Methods: This was a longitudinal observational study including 65 participants and carried out from January 2017 to December 2017. Markers of ADEs were obtained from creatinine, transaminase audiogram, and clinical data. Multivariate analysis was used to determine the association between predictors and ADEs. Results: Forty-eight (73.8%) of the 65 participants developed 72 ADEs. Fifty-four (75%), 11 (15.3%), and 7 (9.7%) of the 72 ADEs were classified as Grades 1, 2, and 3, respectively. Gastrointestinal disorders were most common (35 [46.6%]) followed by auditory injuries (16 [22.2%]), hepatotoxicity (11 [15.3%]), neurological disorders (6 [8.3%]), and kidney disorders (4 [5.6%]). The follow-up duration of this study was 11,250-person day (PDY). The incidence rate for ADEs was 4.3/1000 PDY and that for gastrointestinal disorders, auditory injuries, hepatotoxicity, neurological disorders, and kidney disorders was 3.1, 1.4, 1.0, 0.5, and 0.2 (/1000PDY), respectively. Kanamycin (65 [90.3%]), isoniazid (4 [5.6%]), and ethambutol (3 [4.2%]) were incriminated with ADEs. Most (29 [60.4%]) of the ADEs occurred during the first 2 months of drug initiation. There was an association between poor treatment outcome and ADEs (P = 0.04, odds ratio = 1.20, 95% confidence of interval = 0.21–6.80]. Conclusions: The incidence of ADEs is associated with several factors and most of them occurred during the intensive phase of treatment. Kanamycin was the most associated drug linked to ADEs requiring its replacement with a less toxic one.

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Cutaneous tuberculosis (TB) known as tuberculid forms 1%–1.5% of all extrapulmonary manifestation of TB. Tuberculids result from a hypersensitivity reaction to an extracutaneous source of Mycobacterium tuberculosis in individuals with high immunity and can be difficult to diagnose. Lichen scrofulosorum (LS) is a rare form of tuberculid predominantly seen in children and young adults; we report a case of an 8-year-old boy evaluated for fever and mediastinal lymphadenopathy in whom the skin lesions, LS, served as an important clue for the diagnosis of tuberculous lymphadenitis.

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Background: Pulmonary tuberculosis (PTB) is still a major health problem worldwide. The espD has a potential to be a new biomarker because it is important for the espA, espC, and ESX-1 protein secretion system that are actively expressed in active multiplication of Mycobacterium tuberculosis complex. Methods: A total of 55 sputum samples and 41 culture isolates from newly diagnosed PTB patients at Dr. Soetomo Academic Hospital were collected from September 2016 to April 2019. The tested samples using polymerase chain reaction targeted 555 bp of espD gene and sequencing. Clone Manager Version 6 and NCBI BLAST were used to align the gene sequence against wild-type M. tuberculosis. The prediction of T-cell epitope in espD gene was detected by GENETYX. The three-dimensional (3D) structure of espD was modeled by SWISS-MODEL and I-TASSER and was visualized with PyMOL. Results: From 55 sputum samples, 43 (78.18%) showed positive results, and all culture isolates showed positive results. In addition, all sequenced samples showed 100% homolog with M. tuberculosis H37Rv gene without detected variant or mutation. There were four T-cell epitopes that could be obtained. The 3D model had a I-TASSER confidence score of 3.91 with estimated RMSD of approximately 14.5 Å. The structure consists of a main fold of a three-stranded antiparallel β-sheet and a long α-helix surrounded by several minor secondary structures. Conclusions: This study provides a brief information about the sequence, epitope prediction, and 3D structure of EspD protein from M. tuberculosis strains in Indonesia.

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Background: Suboptimal drug exposure in patients with drug-susceptible tuberculosis (DS-TB) can drive treatment failure. Pharmacodynamics (PD) biomarkers such as the plasma TB drug-activity (TDA) assay may guide dose finding studies and predict microbiological outcomes differently than conventional indices. Methods: A study was nested from phase 2b randomized double-blind controlled trial of Tanzanian patients who received a 600 mg, 900 mg, or 1200 mg with a standard dose for DS-TB. Serum at 6 weeks collected over 24-h at 2-h intervals was collected for rifampin area under the concentration–time curve relative to minimum inhibitory concentration (AUC_0-24/MIC) or peak concentration and MIC (C_max/MIC). TDA was the ratio of time-to-positive growth of the patient's Mycobacterium tuberculosis isolates with and without coculture of patient's plasma collected at C_max. Spearman's rank correlation (r) between PD parameters and culture convention on both liquid and solid culture media. Results: Among 10 patients, 600 mg (3), 900 mg (3), and 1200 mg (4) of rifampin dosages. The mean ± standard deviation (SD) of AUC_0-24/MIC for patients on 600 mg was 168 ± 159 mg·h/L, on 900 mg was 169 ± 166 mg·h/L, and on 1200 mg was 308 ± 238 mg·h/L. The mean-TDA (SD) was 2.56 (±0.75), 1.5 (±0.59), and 2.29 (±1.08) for patients on 600 mg, 900 mg, and 1200 mg rifampin doses, respectively. Higher TDA values correlated with faster time to culture convention on both liquid (r = −0.55, P = 0.099) and solid media (r = −0.65, P = 0.04). Conclusions: TDA and rifampin AUC_0-24/MIC did not trend as expected with rifampin dose, but TDA better predicted the time to sputum culture conversion. TDA may provide additional discrimination in predicting treatment response for some regimens distinct from plasma exposure relative to MIC or mg/kg dose.

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Background: This study aimed to validate the value of tuberculostearic acid (TBSA) whether it could implicate the existence of Mycobacterium tuberculosis (Mtb) and assist for the clinical diagnosis of tuberculous meningitis (TBM). Methods: The patient's cerebrospinal fluid (CSF) specimen was collected through the lumbar puncture and detected for TBSA with gas chromatography/mass spectrometry. At the same time, gold standard tests, i.e., CSF direct culture, CSF smear microscopy, or nucleic acid amplification tests, for Mtb were routinely performed. Furthermore, we evaluated all patients by the Lancet consensus scoring system, which classifies suspected patients to “Definite (depend on gold standard results only),” “Probable (>10 pts without imaging or >12 pts with imaging information),” “Possible (6–9 pts without imaging or 6–11 pts with imaging),” and “Not (<6 pts or with alternative diagnoses)” TBM. Results: In total, 140 patients were admitted for our study included 27 confirmed TBM patients and 50 TBSA-positive patients. Sensitivity (0.7407, confidence interval [CI] 95%: 0.5372–0.8889) and specificity (0.7345, CI 95%: 0.6432–0.8132) were calculated. The Lancet consensus scoring system was also applied to evaluate the possibility of TBM in suspected patients, finding that TBSA-positive patients showed a similar grouping distribution as the definite TBM patients. Conclusions: Our study implicates that the prospective utilization of TBSA is worth combining into a scoring system for characterizing the features of Mtb, showing a great potential of TBM diagnosis by TBSA in future.

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Background: Sputum smear microscopy examination and culture for tuberculosis (TB) remain a fundamental tool of diagnosis but may be negative up to 50% case of active pulmonary TB. Bronchoscopy to obtain sputum is invasive and not readily available. Alternative methods of obtaining sputum specimens are crucial in suspected pulmonary TB cases who are unable to expectorate. In this context, it may be beneficial to stimulate sputum production by administering a mist of hypertonic saline produced by ultrasonic nebulization. The aims of the study are to describe the experience of a tertiary center in Saudi Arabia with sputum induction (SI) for the investigation of patients suspected to have sputum scare TB. Methods: A retrospective cohort study was performed. All patients suspected of sputum scare TB and investigated with SI were included. Standard descriptive statistics were used. Categorical data presented as frequency were compared using the Chi square test. Continuous data presented as mean ± standard deviation were compared using Student's t test. Sensitivity, specificity, and predictive values were calculated. Results: Of 252 patients with suspected TB who underwent SI, 78 (31%) were ultimately diagnosed to have TB. Culture of induced sputum confirmed the diagnosis of TB in 44 (56.4%) of these patients. However, the diagnosis of TB would have been missed in 13.5% of the cohort if no further investigations were done. The incidence of complications was low. No patients required hospitalization or specialist intervention. Conclusions: SI is safe well tolerated and inexpensive. It may reduce the need for bronchoscopy in patients with suspected sputum scare TB. However, around 20% of TB can be missed by SI unless further investigations are performed. Hence, patients suspected to have sputum scare TB in whom the risk of bronchoscopy is high, a clinical decision on the appropriateness of empirical therapy is often required.

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Background: The fusion protein H65, composed of Mycobacterium tuberculosis (TB) ESX-secreted antigens, has improved the bacillus Calmette–Guerin-induced immune protection in a mouse model of bovine TB when formulated in the liposomal adjuvant CAF01. In this study, we aimed to evaluate the protective efficacy of an attenuated Mycobacterium bovis strain – a mutant in mce2 and phoP genes – combined with H65+CAF01 immunization. We evaluated the protection of MbΔmce2-phoP alone or combined with H65+CAF01 against M. bovis challenge in mice. Methods: Groups of BALBc mice were inoculated with the vaccine candidates or phosphate buffered saline (PBS), and 6 weeks after the last immunization, the animals were aerogenically challenged with virulent M. bovis. Bacterial load in organs was counted after 45 days of the challenge. One-way analysis of variance and Bonferroni's posttest were used for statistical analysis. Results: All vaccinated mice showed reduced bacterial loads in lungs compared to unvaccinated animals. However, the protection level was similar between vaccinated groups. Conclusions: The MbΔmce2-phoP strain combined with three doses of H65+CAF01 induced equivalent protection than the MbΔmce2-phoP strain alone. Thus, the use of combined vaccination strategies requires a careful analysis of the potential interactions of each of their components with the host's immune system.

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