Worldwide, tuberculosis (TB) is still a serious and significant health concern, more so with the emergence of multidrug-resistant-TB. The inability of mankind to control this infection stems from the fact that the vaccines and drugs that were once effective against TB are no longer efficacious. This has led to a search for new antituberculous agents and adjuvant therapy. Vitamins are being revisited for their role in pathogenicity as well as for their antimycobacterial properties. Vitamins such as biotin and thiamin are essential for Mycobacterium tuberculosis and are required for establishment of infection. On the other hand, vitamins such as Vitamin C and Vitamin D have been shown to possess antimycobacterial properties. To combat M. tuberculosis, innovative strategies need to be devised, keeping in mind the efficacy of the agent to be used. Vitamins can prove to be useful agents capable of modifying the life cycle and biology of M. tuberculosis. We present here a brief overview of the available knowledge on thiamin, biotin, Vitamin C, and Vitamin D, keeping TB treatment and control in perspective.

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Background: Tuberculosis (TB) is one of the leading causes of morbidity and mortality in Pakistan. Assessment of TB treatment outcomes, monitoring and evaluation of its risk factors in Directly Observed Treatment Short Course (DOTS) are among the major indicators of the performance of a national TB control program. Even though Pakistan ranks 5^th among the 22 high-TB burden countries, there are no available data in this regard. Methods: Institution-based retrospective study was conducted to determine the treatment outcome of TB patients and investigate associated risk factors at District Head Quarter Hospital Shangla, Khyber-Pakhtunkhwa, Pakistan. Two-year record (January 2011 to December 2012) of TB clinic of the hospital was reviewed. A total of 493 patients' complete information was reviewed in the study period. Results: Of these, 42.19% were smear-positive pulmonary TB (PTB), 35.09% were smear-negative PTB, and 22.72% were extra-PTB (EPTB). The overall prevalence of smear-positive PTB was 42.19% (95% confidence interval [CI]: 37.9–46.2). Records of the treatment outcome showed that 192 (38.94%) were cured, 276 (55.98%) completed treatment, 13 (2.6%) defaulted, 9 (1.8%) died, 1 (0.2%) treatment failure, and 1 (0.2%) had transferred to other facilities. The overall mean treatment success rate of the TB patients was 94.93%. TB age and TB form or baseline smear were significantly associated with unsuccessful treatment outcome. The risk of unsuccessful outcome was significantly lower among TB patients age <14 years (Adjusted odds ratio [AOR] = 0.118, 95% CI: 0.022–0.644), and PTB (smear positive: AOR = 0.125, 95% CI: 0.023–0.669; Smear negative: AOR = 0.024, 95% CI: 0.003–0.205) compared to their counterpart. Conclusion: The treatment success rate was high and match the World Health Organization criteria. To sustain the effective implementation of DOTS in the area, effective management, and diagnosis should be given for EPTB.

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Background: To identify strains of Mycobacterium tuberculosis complex (MTBc) circulating in Bamako region during the past 10 years. Methods: From 2006 to 2016, we conducted a cross-sectional study to identify with spoligotyping, clinical isolates from tuberculosis (TB)-infected patients at different stages of their treatments in Bamako, Mali. Results: Among the 904 suspected TB patients included in the study and thereafter tested in our BSL-3 laboratory, 492 (54.4%) had MTBc and therefore underwent spoligotyping. Overall, three subspecies, i.e., MTB T1 (31.9%) and MTB LAM10 (15.3%) from lineage 4 and M. africanum 2 (16.8%) from lineage 6 were the leading causes of TB in Bamako region during the past 10 years. Other spoligotypes such as MTB T3, MTB Haarlem 2, MTB EAI3, and MTB family 33 were also commonly seen from 2010 to 2016. Conclusion: This study showed a high genetic diversity of strains isolated in Bamako region and highlights that M. tuberculosis T1 strain was the most prevalent. Furthermore, the data indicate an increasing proportion of primary drug resistance overtime in Bamako.

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Background: Mycobacterium tuberculosis induces cellular necrosis that could promote spread of infection. The aim of this study is to analyze the effects of Vitamin D3 supplementation to improve the effectiveness of 2^nd-line anti-tuberculosis (TB) drug therapy, especially in relation with cell death pathways. Methods: Mus musculus C3HeB/FeJ was randomly divided into four groups containing eight animals each. The 1^st group (G1), consisting of mice that were intratracheally infected with multidrug-resistant strain of M. tuberculosis and sacrificed on 2-week postinfection to confirm successful infection. (G2) was a group of TB mice without therapy. Then, (G3) was a group of mice with the 2^nd-line anti-TB therapy. The last group (G4) was a group of mice receiving not only the 2^nd-line anti-TB therapy but also daily oral Vitamin D3 supplementation. Immunohistochemistry was used to measure expression of nuclear Vitamin D receptor, apoptosis marker cleaved caspase-3, cathelin-related antimicrobial peptide (CRAMP) and LC3B autophagy markers, necrosis marker RIPK3, and collagenase matrix metalloproteinase-1 (MMP1). The number of bacteria in the lung was calculated by colony forming units. The partial least square structural equation modeling with SmartPLS 3.2.6 software was used to analyze structural models among the variables. Results: Supplementation of Vitamin D3 on the 2^nd-line anti-TB therapy increases Vitamin D3 receptor, CRAMP, LC3B, caspase-3 (P = 0.026, P = 0.000, P= 0.001), presses MMP1, and the number of bacteria (P = 0.010 and P= 0.000, respectively). The structural equation modeling analysis shows that increasing autophagy pathways reduces necrosis by lowering MMP1, whereas apoptosis reduces necrosis by decreasing the number of bacteria (each with indirect effects − 0.543 and − 0.544). Conclusion: A comprehensive analysis with the partial least square structural equation modeling shows decreasing necrosis requires increasing autophagy and apoptosis.

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The literature on tuberculous dactylitis is poor, and most literature consists of isolated case reports. The aim of this case series is to study the particularities and the epidemiological aspects of tuberculous dactylitis in Tunisian patients. Google and Medline search was done using key words “tuberculous dactylitis” and “spina ventosa.” Only Tunisian reports in adult patients were included. Eleven cases including this mentioned case were included in this review. There was a female predominance, high frequency of trauma before disease installation, rarity of predisposing factors, and less inflammation in blood tests when comparing with other cases in literature.

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Background: Mortality from tuberculosis (TB) remains high despite its declining global incidence. Host risk factors of TB death have not been fully identified. The aim of this study is to explore some of the host risk factors associated with TB mortality. Methods: We conducted a retrospective cross-sectional review of patients with TB admitted to Sultan Qaboos University Hospital in Oman from July 2006 to February 2016. Multivariate logistic regression analyses were used to evaluate the risk factors for TB mortality. Results: Of the 205 TB cases reviewed, we identified 31 (15%) TB deaths during TB treatment. The median time of death from starting TB drugs was 30 days. Fifty-one percent of the TB deaths occurred in the 1^st month of TB diagnosis. The main risk factors for TB mortality were advanced age, low body weight, negative sputum TB smear, pulmonary involvement, human immunodeficiency virus infection, and noncitizen status. Conclusion: To improve TB outcome in this high-risk group, abrupt clinical management approaches should be applied when TB is suspected. Public health measures that increase community awareness of TB mortality and reduce barriers to TB care are crucial to reducing TB mortality.

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Sweet's syndrome is reportedly associated with preceding nontuberculous mycobacterial infections (NTMIs). Here, we report on a systemic Mycobacterium intracellulare infection in a patient on corticoid therapy for Sweet's syndrome. Literature searches show that 69.1% of patients with Sweet's syndrome and NTMIs developed this syndrome later than NTMIs and 89.3% of them developed during the clinical course of a rapidly growing mycobacterial infection. The residual cases were associated with slow-growing mycobacteria (14.3%), but only three cases of Mycobacterium avium complex (MAC) infections before the onset of Sweet's syndrome have been reported, and all of them were caused by disseminated MAC disease. One of these cases developed during corticoid therapy for Sweet's syndrome, while another case had underlying diabetes mellitus. Hence, the occurrence of systemic MAC disease may be an inevitable consequence of long-term steroid use and underlying diseases. Literature searches also show that cervical lymphadenitis was a predominant symptom in NTMIs (90.5%). The present case did not have cervical lymphadenitis although the previously reported MAC cases did experience it. Therefore, lymphadenitis from NTMIs may be related to the pathogenesis of Sweet's syndrome. Hence, should a patient have systemic infection without lymphadenitis, it will be more difficult to clinically confirm that MAC disease is a predisposing factor for Sweet's syndrome.

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Symmetrical peripheral gangrene (SPG) is a rare clinical syndrome characterized by ischemic necrosis of 2 or more limbs, without involvement of large vessels. It is often associated with disseminated intravascular coagulation and septic shock. Usually caused by Gram-positive and Gram-negative organisms, tuberculosis as a cause is extremely rare. We present the case of a 46-year-old man, who initially presented with signs and symptoms suggestive of tuberculosis but later developed SPG along with septic shock after his initial visit. The case highlights the progression of this dreaded complication and touches upon recent developments in its etiology as well as pathogenesis.

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Context: The risk of antituberculosis (TB) drug-induced liver injury could be determined by patients' genotype polymorphism of the xenobiotic-metabolizing enzymes. To find the meaning of cytochrome P-4502E1 (CYP2E1) polymorphism in TB patients. Corresponding of CYP2E1 polymorphism in TB patients with the level of isoniazid and rifampicin as well as for the outcome and toxicity development during inpatient TB treatment. Methods: CYP2E1 genotype was detected with the help of polymerase chain reaction and endonuclease analysis. The level of rifampicin, isoniazid, diene conjugates (DC), and catalase activity in the blood was determined spectrophotometrically. We have considered medical records at the beginning and at the end of inpatient treatment. Statistical Analysis Used: Kruskal–Wallis, ANOVA, and Chi-square tests were used in this study. Results: The concentration of rifampicin 6 h after its intake was 17.6% higher in carriers of slow metabolizer (SM) CYP2E1 genotype than in patients with rapid metabolizer (RM) genotype that proved a participation of hepatic enzyme CYP2E1 in metabolism of rifampicin. According to obtained results in TB patients with RM genotype, the indexes of cytolysis (alanine aminotransferase, aspartate aminotransferase) and bile stasis (gamma-glutathione transferase) were higher comparatively to SM genotype both before and after inpatient treatment. This correlated with a higher concentration of DC in the blood (+8.6%) and lower plasma catalase activity (−50.0%) in the patients with RM genotype comparatively with the patients with SM genotypes. Conclusion: Polymorphism of CYP2E1 genotype is an important criterion for the development of hepatotoxicity before and during TB treatment while increased rifampicin level has no influence on it.

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Background: Rapidly growing mycobacterial species (RGM) are increasingly being recognized as the cause of various superficial and deep infections in humans. Two of the species most frequently isolated from clinical specimens are Mycobacterium abscessus and Mycobacterium fortuitum. Both species are associated with antibiotic resistances that may complicate therapy. This paper describes the pattern of resistance to five antibiotics commonly prescribed for RGM infections, in M. abscessus and M. fortuitum isolated from Malaysian patients. Methods: The bacterial strains studied were examined with Etest strips to determine their minimum inhibitory concentrations (MICs) toward amikacin, ciprofloxacin, clarithromycin, imipenem, and linezolid. Results: Among 51 M. abscessus isolates examined by the Etest, the overall MICs of ciprofloxacin, imipenem, amikacin, clarithromycin, and linezolid showed resistance rates of 33.3%, 31.4%, 2.0%, 5.9%, and 21.6%, to the five antibiotics, respectively. M. abscessus subspecies abscessus was more resistant than M. abscessus subsp. massilience to ciprofloxacin, imipenem, and linezolid but was more susceptible to clarithromycin and amikacin. M. fortuitum isolates were significantly less resistant than M. abscessus to ciprofloxacin (3.6%) and imipenem (7.1%) but more resistant to clarithromycin (42.9%) and linezolid (39.3%). Conclusion: A suitable combination therapy for Malaysian patients would be amikacin plus clarithromycin and ciprofloxacin, to cover infections by all three M. abscessus subspecies and M. fortuitum.

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Background: Survival of Mycobacterium leprae, the causative bacteria for leprosy, in the human host is dependent to an extent on the ways in which its genome integrity is retained. DNA repair mechanisms protect bacterial DNA from damage induced by various stress factors. The current study is aimed at understanding the sequence and functional annotation of DNA repair genes in M. leprae. Methods: T he genome of M. leprae was annotated using sequence alignment tools to identify DNA repair genes that have homologs in Mycobacterium tuberculosis and Escherichia coli. A set of 96 genes known to be involved in DNA repair mechanisms in E. coli and Mycobacteriaceae were chosen as a reference. Among these, 61 were identified in M. leprae based on sequence similarity and domain architecture. The 61 were classified into 36 characterized gene products (59%), 11 hypothetical proteins (18%), and 14 pseudogenes (23%). All these genes have homologs in M. tuberculosis and 49 (80.32%) in E. coli. A set of 12 genes which are absent in E. coli were present in M. leprae and in Mycobacteriaceae. These 61 genes were further investigated for their expression profiles in the whole transcriptome microarray data of M. leprae which was obtained from the signal intensities of 60bp probes, tiling the entire genome with 10bp overlaps. Results: It was noted that transcripts corresponding to all the 61 genes were identified in the transcriptome data with varying expression levels ranging from 0.18 to 2.47 fold (normalized with 16SrRNA). The mRNA expression levels of a representative set of seven genes ( four annotated and three hypothetical protein coding genes) were analyzed using quantitative Polymerase Chain Reaction (qPCR) assays with RNA extracted from skin biopsies of 10 newly diagnosed, untreated leprosy cases. It was noted that RNA expression levels were higher for genes involved in homologous recombination whereas the genes with a low level of expression are involved in the direct repair pathway. Conclusion: This study provided preliminary information on the potential DNA repair pathways that are extant in M. leprae and the associated genes.

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Tuberculosis is a common clinical problem which can involve virtually any organ and mimic a multitude of clinical conditions. Colonic tuberculosis is a type of intestinal tuberculosis which involves the colon and mimics inflammatory bowel disease. Occasionally, it is also confused with colonic malignancy. We report the case of a young female who presented with abdominal pain, bleeding per rectum. Abdominal X-ray showed evidence of thumb-printing. A possibility of ischemic colitis was entertained. However, further investigation unraveled the presence of tubercular colitis. The patient improved with anti-tubercular therapy. Colonic tuberculosis can mimic a number of clinical entities and should be considered in differential diagnosis of colonic lesions in endemic areas.

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Background: There is a progressive increase in nontuberculous mycobacteria (NTM) in pulmonary and extrapulmonary infections that might cause confusion with the Mycobacterium tuberculosis complex. To determine the frequency of finding NTM in clinical samples from patients diagnosed with active tuberculosis, with negative acid-alcohol-resistant bacilli (acid-fast bacillus [AFB]) in a third-level specialty hospital's mycobacterial laboratory between January 2013 and December 2014. Methods: This is a prospective, descriptive study where isolated strains of biological material were studied in Lowenstein–Jensen and BACTEC MGIT 960 cultures. Results: Clinical samples of 120 patients were studied, with pulmonary samples of 99/120 (82%) and extrapulmonary samples of 21/120 (18%). We identified NTM in 37/120 samples (30.8%), of which 16 in pulmonary, 13 in genitourinary, 3 in bone marrow, and 5 in various specimens. Mycobacterium avium was isolated in 20 samples, Mycobacterium intracellulare in seven samples, and various other species of NTM in the other 10 samples. Conclusion: To establish adequate treatment, we point out the importance of identifying the presence of NTM in the clinical samples of active tuberculosis patients with negative AFB, as possibly becoming confused with M. tuberculosis and which is essential in deciding which treatment is the most adequate.

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Background: Nontuberculous mycobacteria (NTM) form a heterogeneous group regarding their ability to cause disease. To further understand their clinical relevance, the characteristics of patients who had positive cultures for NTM at a tertiary hospital in Portugal were reviewed. Methods: Retrospective analysis of patients assessed at the Infectious Diseases (ID) Department of the São João Hospital Center, from January 2007 to December 2014, from whom at least one biological sample was tested culture positive for NTM. Results: A total of 74 patients with at least one positive culture for NTM were identified. Forty-nine (66.2%) were infected by the human immunodeficiency virus, 4 (5.4%) had cancer, and 7 (9.5%) were under immunosuppressive medication. A total of 13 patients (17.6%) fulfilled the American Thoracic Society/ID Society of America criteria for pulmonary NTM disease and treatment was initiated in 12 other patients (16.2%), all of which were immunocompromised. Mycobacterium avium complex was more frequently associated with disease, responsible for 56% of the patients treated. Patients were treated with antituberculosis drugs adjusted for the species isolated, and cure was achieved in 13 patients (52%). Conclusion: The present study highlights the importance of understanding the epidemiology of NTM to better comprehend their clinical impact.

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Improved molecular diagnostic techniques have resulted in increased reporting of nontuberculous mycobacterial infections. A 40-year-old male immunocompetent individual presented with cough and fever of 2-week duration. His chest X-ray showed cavities in the left upper zone and fibrosis in the right upper zone. His sputum was positive for AFB on Ziehl–Neelsen staining and showed slow-growing mycobacteria in mycobacteria growth indicator tube. The isolate was identified as Mycobacterium interjectum using GenoType^® Mycobacterium CM assay (Hain Lifescience, GmBH, Nehren, Germany). At the end of a year's treatment, this first case from India has shown good progress.

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Isolated bilateral inguinal tubercular lymphadenitis is a very rare presentation. A 59-year-old male, on treatment for Carcinoma rectum (T3 N1 M0) presented with bilateral inguinal lymphadenopathy. Metastasis and tuberculosis were considered for differentials. FNAC of the lesion showed Necrotizing granulomatous lymphadenitis. There was regression of the lesion on both sides after two months of Anti-tubercular Therapy. Even though Metastasis is the commonest cause of inguinal lymphadenopathy in a case of carcinoma rectum, Tuberculosis needs to be considered in the differential diagnosis in our country. FNAC/Biopsy can be considered in those patients to confirm the diagnosis.

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