Background: Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2017, the World Health Organization (WHO) estimated that only 2% of the TB patients in Indonesia had only been tested with rapid diagnostics at the time of diagnosis, resulting in largely underdetected rifampicin-resistant TB (RR-TB). Utilization of GeneXpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay as a point-of-care molecular assay to detect TB and RR-TB and serving its purpose in accordance with the first pillar of the WHO End-TB Strategy. Objective: This study investigated the use of GeneXpert MTB/RIF assay to determine the molecular epidemiology of RR-TB in an urban setting of Indonesia. Methods: All molecular epidemiological and microbiological databases were retrospectively examined from GeneXpert MTB/RIF assay results in Siloam Hospital Lippo Village. The sociodemographic characteristics and results of microbiological examinations consisting of Ziehl–Neelsen staining and GeneXpert MTB/RIF assay were analyzed. Results: During the study period, 600 cases were registered, and GeneXpert MTB/RIF tests were done in which the tests yielded 597 (99.5%) valid results; 62.0% were male and adult of age category; of whom 29 samples (4.9%) were found to be RR-TB, 186 samples (31.2%) were RIF sensitive, and remainders were negative. Conclusions: The results of GeneXpert MTB/RIF to be a fundamental diagnosis of RR-TB and subsequently to notify MDR-TB were satisfying and valuable in this study. This further increased and reinforced TB surveillance and national TB program to finally bring about WHO end-TB strategy one step closer in Indonesia.

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Background: Despite effort to diagnose tuberculosis (TB) in the Human Immunodeficiency Virus (HIV) infected population, 45% of adults with HIV that had a previously unknown reason for death, demonstrated TB was the cause by autopsy examination. We aimed to assess the clinical outcomes of implementation a new algorithm for diagnosis and treatment of tuberculosis (TB) related sepsis among PLHIV presenting with life-threatening illness. Methods: This study is a prospective cohort conducted in three-referral hospitals in Kilimanjaro, recruited 97 PLHIV from February through June 2018. Patients provided urine and sputum samples for testing lateral flow – lipoarabinomannan (LF-LAM) and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assays, respectively. Anti-TB was prescribed to patients with positive LF-LAM or Xpert MTB/RIF or received broad-spectrum antibiotics but deteriorated. Results: Of 97 patients, 84 (87%) provided urine and sputa, and 13 (13%) provided only urine. The mean age (95% confidence interval) was 40 (38–43) years and 52 (54%) were female. In 84 patients, LF-LAM increased TB detection from 26 (31%) by Xpert MTB/RIF to 41 (55%) by both tests. Of 97 patients, 69 (71%) prescribed anti-TB, 67% (46/69) and 33% (23/69) had definitive and probable TB respectively. Sixteen (16.5%) patients died, of which one died before treatment, 73% (11/15) died within 7 days of admission. The 30-day survival was similar in both treatment groups (log rank = 0.1574). Mortality was significantly higher among hospitalized patients compared to outpatients (P ≤ 0.027). Conclusion: Implementation of new algorithm increased TB case detection in patients that could have been missed by Xpert MTB/RIF assay. Survival of PLHIV with confirmed or probable TB was comparable to those of PLHIV that were treated with broad-spectrum antibiotics alone. Further work should focus on the optimal timing and content of the immediate antimicrobial regimen for sepsis among PLHIV in TB-endemic settings.

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Background: Tuberculosis (TB) control is challenging due to poor drug compliance and emerging resistance. The need of the hour is to determine the prediction of disease cure and relapse. Patients' immune response is crucial to the disease outcome. This study was designed to study the immune profile of TB patients during treatment and cure. Methods: The cross-sectional study included newly diagnosed pulmonary TB patients and healthy controls. Levels of serum cytokines/chemokines (Th1/Th2/Th17) were measured by BD cytometric bead array. The cell surface markers assessed in the study were CD3, CD4, CD8, CD16, CD56, and BD human regulatory T cell cocktail (CD4/CD25/CD127). Results: Data analysis observed statistically significant differences in CD3dim/CD56 + natural killer T (NKT) among TB patients with significantly low levels in healthy controls and after treatment completion (P < 0.0001). The analysis also revealed a high percentage of CD3dim/CD56 + NKT in fast responders. The percentage of T regulatory was found to be high in patients when compared with healthy controls; the values were statistically significant (0.0002). Interleukin-6 was significantly associated with the disease (P < 0.0485). Discussion: A comprehensive understanding of role of CD3dim/CD56+ NKT in antimycobacterial immunity may enable new possibilities for NK cell-based prophylactic and/or therapeutic strategies against TB.

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Background: Extra pulmonary manifestations of tuberculosis (TB) are rare in developed countries. TB is the main etiology of chronic pericarditis in developing countries, but it's epidemiology is not unknown in the United States. Methods: This retrospective study used the Healthcare Utilization Projects/Nationwide Inpatient Sample (HCUPS/NIS) database from 2002-2014 to evaluate the characteristics, risk factors, trends over time and region of tuberculous pericarditis in the United States. Results: The data during the study period consists of 100,790,900 discharges accounting for 482,872,274 weighted discharges. The data showed 744 weighted discharges with indication of both tuberculosis and pericarditis. A co-ocurrence of TB pericarditis and malignancy or chronic kidney disease was more common than in patients without TB pericarditis. The frequency of co-ocurrence of TB pericarditis and HIV infection, obesity, alcohol abuse and organ transplant was not elevated. Conclusion: TB pericarditis is rare disease in the USA and the classical risk factors for lung tuberculosis may not be associated with TB pericarditis. CKD and malignancy appear to be associated with TB pericarditis, further studies are required to determine causality.

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Tuberculous (TB) encephalopathy is a rare presentation of the central nervous system tuberculosis. Its pathophysiology is believed to have an immune mechanism without any direct invasion by the tubercular bacilli. The clinical presentation is highly variable from mild illness to a potentially fatal one. The characteristic signs of meningitis and cerebrospinal fluid findings are mild or absent. Diffuse white matter edema and demyelination have been noted. This clinical entity has been reported mainly from the pediatric population. In the adult population, it has been reported only in very few case reports. We report here a rare case of TB encephalopathy in a 21-year-old female with disseminated tuberculosis, without meningitis, responding to antitubercular therapy.

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Background: Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach. Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome. Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits. Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.

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Background: Bedaquiline (BDQ) is a new antituberculosis (TB) drug effectively used for the treatment of multidrug-resistant and extensively drug-resistant TB. However, the reports on drug-susceptibility testing (DST) for BDQ are scarce. The study aimed to validate and standardize BDQ DST by BACTEC MGIT 960 system for Mycobacterium tuberculosis. Methods: A panel of ten M. tuberculosis isolates comprising 8 BDQ sensitive and 2 BDQ resistant strains were used to test accuracy, repeatability, and reproducibility of BDQDST by MGIT 960. BDQ DST by Middlebrook 7H11 agar method using polystyrene tubes was used as a standard method to calculate the accuracy of the validation. Results: DST by MGIT for BDQ showed 100% accuracy, repeatability, and reproducibility, although variations were observed in the growth units of the “test” MGIT tubes between technologist and drug stocks while testing for reproducibility. Conclusion: BDQ DST by MGIT 960 system is accurate, repeatable, and reproducible and hence can be implemented in certified laboratories routinely performing DST by MGIT 960 system.

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Background: To study the effectiveness of antituberculosis chemotherapy in patients with relapse pulmonary tuberculosis (RTB) compared with patients with the newly diagnosed process. Methods: We examined 285 TB patients, including 126 individuals with RTB (Group 1) and 159 patients with newly diagnosed pulmonary tuberculosis (NDPTB) (Group 2). All patients were diagnosed with infiltrative PTB. Effectiveness of the basic course of antimycobacterial treatment was assessed in accordance with the following data: time required for the normalization of clinical manifestations, smear conversion, cavity healing, disappearance of infiltrative and focal changes in the pulmonary tissue, as well as the final clinical effectiveness of therapy. Results: Disappearance of clinical symptoms was statistically significantly faster in Group 2 compared with RTB patients in 2.25 ± 0.11 and 3.40 ± 0.15 months, respectively (P < 0.001). Sputum culture conversion was observed after 6 months of treatment in 138 (86.79%) patients with NDPTB and 89 (72.22%) patients from Group 1 (P = 0.0023). Closure of cavities and disappearance of infiltrative and focal changes in the lungs occurred within 6 months of chemotherapy only in 55 (43.65%) patients with RTB and 93 (58.49%) patients with NDPTB (P = 0.0133). Conclusions: Standard treatment for patients with NDPTB is considered successful in case of faster health improvement and stabilization, less pronounced rates of toxic adverse reactions to antiTB drugs, faster sputum smear and culture conversion and cavity healing, signs of clinical and radiological convalescence, and the reduced number of large residual changes after the treatment compared with RTB.

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After a steady decline throughout the 20^th century, the incidence of tuberculosis (TB) in industrialized countries has started to rise again. However, in developing countries like India, the menace of TB had never been controlled. Gastrointestinal (GI) TB is rare, and the GI tract is considered only the sixth most frequent site of extrapulmonary TB. Esophageal TB (ET) is still rarer. This is a case report of a rare form of ET in a patient presenting with dysphagia. The patient was subjected to upper GI endoscopy, which revealed an ulcerative growth in the distal esophagus. Histopathology revealed ET. The patient was managed conservatively with anti-TB treatment (ATT). In spite of the rare nature of the disease, it can be managed effectively with ATT to avoid complications (fistula, stricture, and esophageal perforation), which might warrant surgery.

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A 59-year-old male, who had Mycobacterium abscessus lung disease and chronic obstructive pulmonary disease, visited our hospital because of dyspnea. Chest computed tomography showed ground-glass opacity and consolidation mainly in the left upper lobe. Antibiotics treatment with levofloxacin and tazobactam/piperacillin was not effective. He underwent bronchoscopy and based on pathological findings, organizing pneumonia (OP) was diagnosed. No other underlying factors causing OP, such as collagen vascular diseases, drug, or inhalation were detected. He had the diagnosis of secondary OP due to M. abscessus lung disease. Oral predonizolone with 30 mg was initiated, and the opacity improved rapidly. Secondary OP due to M. abscessus lung diseases should be considered during M. abscessus lung diseases when antibiotics and/or antimycobacterial drugs are not effective.

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Mycobacterium fortuitum is ubiquitous in nature and can cause a wide variety of lesions in humans with immunocompromised or antecedent chronic illness. Clinical diagnosis is difficult and relapses are seen. This is due to the fact that they are not critically investigated and are not responded to traditional antitubercular treatment and other antibiotics. Herewith, we report a case of M. fortuitum causing laparotomy port infection-causing repeated multiple abscess on the anterior abdominal wall and treated with amikacin and clarithromycin. The wound healed completely and the patient recovered after administering a combination of amikacin and clarithromycin. We conclude that strict standard operating procedures should be followed to prevent mycobacteria other than tuberculosis (MOTT) infections during and after surgical procedures. Any postoperative, chronic infection which is not responding to conventional antibiotics should be highly suspected for such MOTT infections. Antibiotic susceptibility testing should be performed so as to identify the required antibiotic combination and treated accordingly to prevent further complications and to reduce the cost of treatment.

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Muscle's tuberculosis (TB) without coexistent active skeletal involvement is very rare. We presented a case of tuberculous abscess of longissimus muscle in a young immunocompetent female. Magnetic resonance imaging showed a well-circumscribed lesion in the longissimus muscle. No bony abnormality was noticed. An ultrasound-guided biopsy revealed the presence of granulomatous features on cytological pathology. A good response was seen with antitubercular treatment. TB should be considered in the differential diagnosis of any unexplained soft-tissue swelling in people born in tubercular endemic areas. To the best of our knowledge, our observation is the third reported case in immunocompetent patient.

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Background: The aim of the present study was to isolate and characterize nontuberculous mycobacteria (NTM) on Lowenstein–Jensen media supplemented with glycerol or pyruvate on two different temperatures from soil samples from leprosy endemic tribal areas of Purulia. Methods: Mycobacterium leprae DNA was isolated from these samples followed by polymerase chain reaction (PCR) amplification using RLEP gene target specific to M. leprae. DNA was extracted from NTM cultures by lysis method. The presence of Mycobacterial DNA was confirmed by PCR using universal mycobacterial primer as 16S rRNA. NCBI nBlast was used for the authentication of NTMs, and phylogenetic tree was constructed using M. leprae and NTM species. Statistical Analysis Used: The percentile method and phylogenetic tree were used as stastical tool in this research article. Results: The rapid-growing mycobacteria (RGM) species, 4 (80%) was obtained more than that of slow growing mycobacteria (SGM) 1 (20%) supplemented on glycerol at 30°C followed by SGM species 8 (62%) were recovered more than RGM at 37°C. Similarly, SGM species 2 (100%) were recovered on supplemented with pyruvate at 30°C and no RGM growth when supplemented with pyruvate. Further, the recovery of RGM species 3 (60%) was better on supplemented with pyruvate than SGM species at 37°C. Mycobacterium timonense was first time isolated from Indian soil samples. Highest numbers of NTM were isolated from bathing place than washing and sitting places along with M. leprae PCR positivity. Phylogenetic tree showed a close genetic evolutionary association between Mycobacterium simiae and M. leprae in the leprosy endemic environment. Conclusion: Several NTM was isolated from soil of leprosy endemic area which might have role in susceptibility of leprosy. Phylogenetic tree revealed a closed association of M. simiae with M. leprae in the environment and might be maintaining the leprosy endemicity in north block of Purulia.

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Background: Ubiquitous presence of Mycobacterium fortuitum and ability to cause infections in human beings, hints toward its integral resistance against environmental and host stress conditions. With an aim to identify genes responsible for adapting in vitro acidic stress of M. fortuitum, in the previous study, TnphoA random mutagenesis identified acid susceptible mutant MT727, with mutation in ribosomal maturation factor encoding gene rimP, to be mutated. The present study was conducted to explore virulent behavior as well as growth behavior under in vitro stress conditions. Methods: Acid susceptible transposon mutant MT727 was injected intravenously in female BALB/c mice and kidney tissue was analyzed for the bacillary load as well as pathological characterization. Cytokine profiling of MT727-infected mice serum was done. MT727 was also subjected to various in vitro stress conditions, including detergent stress, heat stress, and hypoxic stress. The viable count of bacteria under different stress conditions was determined at regular time interval. Results: Mutant MT727 showed slight variation in bacillary load in vivo; however, defective growth behavior under detergent and hypoxic stress was observed when compared to wild type strain. Conclusion: Results conclude probable involvement of rimP gene in survival of M. fortuitum under hypoxic stress and detergent stress conditions.

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Background: Tuberculosis is an important infection that can be seen in several countries. The occurrence of disease in the remoted setting is an interesting issue that is an actual challenge for management. Here, the authors present and discuss on the newly registered tuberculosis cases in two island districts of Thailand, a tropical endemic country in Southeast Asia. Methods: The authors hereby retrospectively analyzed registered data of newly registered tuberculosis cases in two island districts with different in accessibility of transportation in Thailand. A comparison of rate and success of management was made. Results: According to the statistical analysis, there is a significant difference of incidence rates of newly registered tuberculosis cases between the two island districts (0.13% vs. 0.04%). There is also a significant difference of successful antituberculosis drug management rates between the two island districts (72.7% vs. 100%). Conclusion: The island district with easier accessibility by transportation has a more number of newly registered tuberculosis case and a less success rate of antituberculosis drug treatment.

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Context: Treatment of the patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection in a state of severely suppressed immune system remains under efficient. Aims: The aim of this study was to assess the effectiveness of adjuvant immunoglobulin therapy in TB/HIV patients. Settings and Design: The relationship between biochemical indexes in the patients with MDR-TB/HIV co-infection and adjuvant immunoglobulin therapy. Materials and Methods: The study involved 52 HIV-positive patients with MDR-TB and CD4+ lymphocyte cells below 50 cells/μCL. Patients in control group (Group 1) and in basic group (Group 2) received standard treatment with second-line antituberculosis agents and antiretroviral agents. In addition patients in basic group were treated by immunoglobulin G intravenously. The evaluation of biochemical parameters such as bilirubin level, thymol test, the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) was carried out on automatic analyzer HumaStar 300 at the beginning and after 0.5–8 months of treatment. Statistical analysis was performed using the Statistica 10.0 software (Stat. Soft Inc., USA). Kruskal–Wallis, ANOVA, and Chi-square tests were used in this study. Results: After 8 months of treatment, studied biochemical indexes were lower in Group 2 than in patients from Group 1. For example, the number of patients in Group 2 with increased bilirubin level was 1.7 times more than in Group 1 (p < 0.05), with increased ALT, AST, or GGT activity in 2.5 times (p < 0.01), 2.7 times (p < 0.01), or 2.4 times (p < 0.05) correspondently, comparatively with Group 1. Conclusion: The usage of immunoglobulins intravenously in the group of patients with MDR-TB associated with HIV infection, with CD4+ level <50 cells/μCL, is appropriate and essential because it improves treatment outcome.

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Background: Tuberculosis (TB) is a preventable and treatable chronic disease. Afghanistan is among the high-TB-burden countries. The aim of this study is to find the determinants of treatment failure among TB patients in Kandahar City, Afghanistan. Methods: This was a retrospective cohort study conducted in Kandahar City during a period of 5 years (August 2014–July 2019). For data analysis; descriptive statistics, Chi-square test, and logistic regression were used. Results: Among 1416 TB patients, 894/1416 (63.1%) had pulmonary TB (PTB), whereas 522/1416 (36.9%) had extrapulmonary TB (EPTB). Mean age in these patients was 34.7 years while most of them were females in PTB (530/894 [59.3%]) and EPTB (340/522 [65.1%]) patients. Sputum smear was positive in 618/860 (71.9%) and 16/404 (4%) of PTB and EPTB patients, respectively. TB treatment failure was more in PTB (56/894 [6.3%]) than EPTB (4/522 [0.8%]). Chi-square test of TB cases showed that statistically significant determinants that may cause the treatment failure were re-treatment cases (crude odds ratio [COR] 7.7, P < 0.001), absence of fever (COR 5.2, P < 0.001), absence of cough (COR 1.7, P = 0.004), living in rural areas (COR 1.4, P = 0.035), and no weight loss (COR 1.3, P = 0.033). Binary logistic regression of the statistically significant variables revealed only absence of fever (adjusted odds ratio 6.0, P < 0.001) as the risk factor for treatment failure in TB patients. Conclusion: TB is still a major threat for Kandahar City. Low treatment success rate and increased number of defaulted cases are the major threats.

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Background: Strains of the Beijing sublineage of Mycobacterium tuberculosis have caused large outbreaks of tuberculosis, often involving multidrug resistance strains and this genetically highly conserved family of strains predominates in some geographic areas. For most of the countries of Latin America, no country-wide studies about the prevalence of the Beijing lineage are available. Methods: In this study, we determine the prevalence of the Beijing sublineage in Ecuador, using a large nation-wide sample of 991 isolates from the years 2014–2016 and with the strains, in case-related-proportional representation, emerging from most of the provinces of the country. The isolates were genotyped with asinglenucleotidespecific polymorphism (SNP) polymerase chain reaction for the Beijing sublineage. SNPpositive strains were confirmed as belonging to this lineage with 24 mycobacterial interspersed repetitive unitvariable number of tandem repeat and DNA sequencing. Results: We identified only four Beijing isolates in this collection of 991 strains and calculated a prevalence rate of 0.43%. Conclusions: Our study shows a limited dissemination of the Beijing strains in the Ecuadorian population. This in contrast with the neighbor countries of Peru and Colombia were locally a prevalence of up to 16% has been reported.

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