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Background and Objectives : There is a lack of information regarding the effective duration of treatment necessary to prevent the development of acquired resistance when fluoroquinolones (FQ), and/or pyrazinamide (Z) resistance has occurred in patients with polydrug-resistant tuberculosis and isoniazid resistance. The management of these kinds of patients should be carried out in experienced centers according to drug susceptibility test results, clinical status of the patient and the extensity of the disease. Materials and Methods : We evaluated treatment regimens, treatment outcomes, and drug adverse effects in seven patients with polydrug-resistant tuberculosis, including those with Z and/or FQ resistance in a retrospective analysis Results : Regarding the patients with polydrug-resistant tuberculosis in addition to isoniazid (H) resistance, three had Z, two had FQ, and the remaining two had both Z and FQ resistance. In the intensive phase of the treatment, the patients were given at least four drugs according to drug susceptibility tests, and at least three drugs in the continuation phase. The duration of treatment was 9-12 months. Two of the patients were foreign nationals, and could not be followed up with due to returning to their home countries. Regarding the remaining five patients, three of them were terminated as they completed treatment, and two as cured. No recurrence was observed in the first year of the treatment. The most common, and serious drug side effect was seen for amikacin. Conclusions : In patients with polydrug-resistant TB, if Z and/or FQ resistance is detected in addition to H resistance, the treatment of these patients should be conducted on a case-by-case basis, taking into account the patient's resistance pattern, clinical condition, and disease prognosis. Close monitoring of the side effects will increase the success rate of the treatment.

Indoor air pollution (IAP) is a recognized risk factor for various diseases. This paper examines the role of indoor solid fuel exposure in the risk of mycobacterium tuberculosis (TB) in Delhi Metropolitan, India. Using a cross-sectional design, subjects were screened for a history of active TB and lifelong exposure to IAP sources, such as solid fuel burning and kerosene. The TB prevalence rate in the study area was 1117 per 100 000 population. Every year, increase in solid fuel exposure was associated with a three percent higher likelihood of a history of active TB. Subjects exposed to solid fuel and kerosene use for both heating home and cooking showed significant associations with TB. Age, household expenditure (a proxy of income), lung function, and smoking also showed significant associations with TB. Smokers and solid fuel-exposed subjects were four times more likely to have a history of active TB than non-smoker and unexposed subjects. These finding calls strategies to mitigate solid fuel exposure, such as use of clean cookstove and ventilation, to mitigate the risk of TB which aligns with the United Nations' goal of "End TB by 2030.", (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diagnostic accuracy of Xpert MTB/RIF assay for pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB) has not been investigated in Iran. This study was aimed to assess the diagnostic accuracy of Xpert MTB/RIF assay for both PTB and EPTB. A total of 2111 clinical samples (1218 pulmonary and 838 extra-pulmonary) were collected from 16 medical centers during the study period and were analyzed for detection of PTB and EPTB by both Xpert MTB/RIF assay and standard conventional methods (culture and direct smear microscopy). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Xpert MTB/RIF assay for PTB were found to be 95.5%, 96.7%, 83.8%, and 99.1% respectively. For EPTB, the sensitivity, specificity, PPV and NPV of Xpert MTB/RIF assay counted for 76.5%, 95.9%, 62%, and 97.9% respectively. Xpert MTB/RIF assay found to be highly sensitive, specific and comparable to standard conventional methods for the diagnosis of PTB. However, the sensitivity and specificity of Xpert MTB/RIF for EPTB specimens were highly variable; thus, Xpert MTB/RIF cannot be recommended to replace standard conventional tests for diagnosis of EPTB.

The aim of this study was to analyze mutations occurring in the rpoB gene of Mycobacterium tuberculosis (MTB) isolates from clinical samples of extrapulmonary tuberculosis (EPTB). Seventy formalin-fixed, paraffin-embedded samples and fresh tissue samples from confirmed EPTB cases were analyzed. Nested PCR based on the rpoB gene was performed on the extracted DNAs, combined with cloning and subsequent sequencing. Sixty-seven (95.7%) samples were positive for nester PCR. Sequence analysis of the 81 bp region of the rpoB gene demonstrated mutations in 41 (61.2%) of 67 sequenced samples. Several point mutations including deletion mutations at codons 510, 512, 513 and 515, with 45% and 51% of the mutations in codons 512 and 513 respectively were seen, along with 26% replacement mutations at codons 509, 513, 514, 518, 520, 524 and 531. The most common alteration was Gln → His, at codon 513, presented in 30 (75.6%) isolates. This study demonstrated sequence alterations in codon 513 of the 81 bp region of the rpoB gene as the most common mutation occurred in 75.6% of molecularly confirmed rifampin-resistant strains. In addition, simultaneous mutation at codons 512 and 513 was demonstrated in 34.3% of the isolates., (© 2018 APMIS. Published by John Wiley & Sons Ltd.)

Recurrent tuberculosis (TB) continues to be a significant problem and is an important indicator of the effectiveness of TB control. Recurrence can occur by relapse or exogenous reinfection. Recurrence of TB is still a major problem in high-burden countries, where there is lack of resources and no special attention is being given to this issue. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 47%. This variability is related to differences in regional epidemiology of recurrence and differences in the definitions used by the TB control programs. In addition to treatment failure from noncompliance, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include gender differences, malnutrition; comorbidities such as diabetes, renal failure, and systemic diseases, especially immunosuppressive states such as human immunodeficiency virus; substance abuse; and environmental exposures such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being identified. Information on temporal and geographical trends of TB cases as well as studies with whole-genome sequencing might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and an understanding of host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence., Competing Interests: There are no conflicts of interest.

The mixed strains infection phenomenon is a major problem posing serious challenges in control of tuberculosis (TB). In patients with mixed infection, several different strains of Mycobacterium tuberculosis can be isolated simultaneously. Although different genotyping methods and various molecular approaches can be employed for detection of mixed infection in clinical samples, the MIRU-VNTR technique is more sensitive with higher discriminative power than many widely used techniques. Furthermore, the recent introduction of whole genome sequencing (WGS) promises to reveal more details about mixed infection with high resolution. WGS has been used for detection of mixed infection with high sensitivity and discriminatory, but the technology is currently limited to developed countries. Mixed infection may involve strains with different susceptibility patterns, which may alter the treatment outcome. In this report, we review the current concepts of mixed strains infection and also infection involving strains with a different susceptibility pattern in TB. We evaluate the importance of identifying mixed infection for diagnosis as well as treatment and highlight the accuracy and clinical utility of direct genotyping of clinical specimens., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Recent studies using molecular epidemiological techniques have demonstrated mixed infection with multiple strains of Mycobacterium tuberculosis especially in countries with high tuberculosis (TB) burden. We aimed to determine the prevalence of mixed infection among patients with TB in the capital of Iran as a country with moderate incidence rate., Methods: Samples were collected randomly from January 2011 to December 2013 in Tehran, capital of Iran. A total of 75 M. tuberculosis isolates were genotyped by 24 loci mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-VNTR) for screening the mixed infection., Results: Twenty patients (20/75) were identified with mixed infection, and the estimated rate of mixed infection was 26.6%. Thirteen out of the 24 loci were able to detect the mixed infection in our study., Conclusions: Mixed infections occur at high prevalence among studied Iranian TB patients. Further research is inevitable to evaluate the association of mixed infection and disease progression and treatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The potential role of environmental Mycobacterium tuberculosis in the epidemiology of TB remains unknown. We investigated the transmission of M tuberculosis from humans to the environment and the possible transmission of M tuberculosis from the environment to humans., Methods: A total of 1,500 samples were collected from three counties of the Tehran, Iran metropolitan area from February 2012 to January 2014. A total of 700 water samples (47%) and 800 soil samples (53%) were collected. Spoligotyping and the mycobacterial interspersed repetitive units-variable number of tandem repeats typing method were performed on DNA extracted from single colonies. Genotypes of M tuberculosis strains isolated from the environment were compared with the genotypes obtained from 55 patients with confirmed pulmonary TB diagnosed during the study period in the same three counties., Results: M tuberculosis was isolated from 11 of 800 soil samples (1%) and 71 of 700 water samples (10%). T family (56 of 82, 68%) followed by Delhi/CAS (11 of 82, 13.4%) were the most frequent M tuberculosis superfamilies in both water and soil samples. Overall, 27.7% of isolates in clusters were related. No related typing patterns were detected between soil, water, and clinical isolates. The most frequent superfamily of M tuberculosis in clinical isolates was Delhi/CAS (142, 30.3%) followed by NEW-1 (127, 27%). The bacilli in contaminated soil (36%) and damp water (8.4%) remained reculturable in some samples up to 9 months., Conclusions: Although the dominant M tuberculosis superfamilies in soil and water did not correspond to the dominant M tuberculosis family in patients, the presence of circulating genotypes of M tuberculosis in soil and water highlight the risk of transmission.

Objective: Resistance to anti-tuberculosis (anti-TB) drugs is becoming a major and alarming threat in most regions worldwide., Methods: This was a descriptive cross-sectional study at a tertiary hospital in Iran, using patient medical records for 2000-2003. The findings were analyzed following the same framework as that used for previous reports from this center., Results: Among 1556 TB patients, drug susceptibility testing (DST) was performed for 548 culture-positive cases. Anti-TB drug resistance to both isoniazid and rifampin was identified in 10 (2.8%) of the new TB cases (multidrug-resistant TB; MDR-TB). Any resistance was detected in 228 (41.6%), showing an increasing trend in both new and retreatment cases. The data analysis revealed that drug-resistant TB had a statistically significant association with Afghan ethnicity, age>65 years, and the type of disease (retreatment vs. new TB case) (p<0.05). Also, assessment of the drug resistance trends showed a significant increase in resistance to any anti-TB agent, to isoniazid, and to streptomycin in new cases, and to all of the first-line anti-TB drugs in retreatment patients., Conclusions: There has been an increasing trend in drug resistance in recent years, particularly in retreatment cases. Hence, revision of the national TB control program, reevaluation of the role of the World Health Organization category II (CAT II) regimen, as well as the conducting of a nationwide drug resistance survey, are recommended.

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN-gamma axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN-gamma circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN-gamma receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12Rbeta1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN-gamma circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN-gamma circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil.  NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as they can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in human immunodeficiency virus (HIV)-infected patients or those with severely compromised immune system. NTM are also found in many subjects without any known risk factors.  Although the recent advances in imaging and microbiologic techniques including gene sequencing have provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections. [ABSTRACT FROM AUTHOR]

Background Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases at the national level. The purpose of this study is to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM cases in the United States from 2001 through 2012. Methods This study is a retrospective, community-based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of Health and Human Services. The statistical significance of observed trends of NTM and TB national hospital costs was calculated using Poisson log-linear regression. Results 20,049 hospital discharges were reported for pulmonary NTM and 69,257 for pulmonary TB in the US from 2001 through 2012. The total associated cost of these discharges was $903,767,292 for pulmonary NTM and $2,078,113,317 for pulmonary TB. During the study period, the national hospital costs of pulmonary NTM increased at a statistically significant rate in the US over each year ( P = 0.001). However, no such increase was found for national hospital costs of pulmonary TB. Conclusions The national hospital cost of NTM management is increasing. These results emphasize the importance of continued research in pulmonary NTM in order to improve current guidelines in prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Until recently, the study of mycobacterial diseases was trapped in culture-based technology that is more than a century old. The use of nucleic acid amplification is changing this, and powerful new technologies are on the horizon. Metabolomics, which is the study of sets of metabolites of both the bacteria and host, is being used to clarify mechanisms of disease, and can identify changes leading to better diagnosis, treatment, and prognostication of mycobacterial diseases. Metabolomic profiles are arrays of biochemical products of genes in their environment. These complex patterns are biomarkers that can allow a more complete understanding of cell function, dysfunction, and perturbation than genomics or proteomics. Metabolomics could herald sweeping advances in personalized medicine and clinical trial design, but the challenges in metabolomics are also great. Measured metabolite concentrations vary with the timing within a condition, the intrinsic biology, the instruments, and the sample preparation. Metabolism profoundly changes with age, sex, variations in gut microbial flora, and lifestyle. Validation of biomarkers is complicated by measurement accuracy, selectivity, linearity, reproducibility, robustness, and limits of detection. The statistical challenges include analysis, interpretation, and description of the vast amount of data generated. Despite these drawbacks, metabolomics provides great opportunity and the potential to understand and manage mycobacterial diseases. [ABSTRACT FROM AUTHOR]

Abstract: The incidence of nontuberculous mycobacteria (NTM) has increased over the last decades. Elderly people are more susceptible to NTM and experience increased morbidities. NTM incidence is expected to rise due to an increasing elderly population at least up to 2050. Given the importance of NTM infection in the elderly, an increasing interest exists in studying NTM characteristics in the aged population. In this review, we summarize the characteristics of NTM infection among elderly patients. We focus on epidemiology, clinical presentation, and treatment options of NTM in this age group. We highlight the differences in the diagnosis and treatment between rapid and slow growing mycobacterial infections. The current recommendation for treatment of NTM is discussed. We debate if in vitro susceptibility testing has a role in the treatment of NTM. Drug–drug interaction between antibiotics used to treat NTM and other medications, particularly warfarin, is another important issue that we discuss. Finally, we review the prognosis of NTM disease in elderly patients. [Copyright &y& Elsevier]

Background: Environmental nontuberculous mycobacteria (NTM) are ubiquitous organisms with which humans commonly interact. The epidemiologic characteristics of NTM diseases including mortality rate and its associated factors remain largely unknown. In this study, we explored the geographical area of exposure and mortality and comorbid conditions of affected persons to determine environment, host, and host-pathogen interactive factors. Methods: We analyzed mortality related to nontuberculous mycobacterial infections from 1999 through 2010 by examining multiple-cause-of-death data from the National Center for Health Statistics. Among those who died with these diseases, we analyzed age-adjusted mortality rates, trends, associations with demographic variables, and comorbid conditions and correlated this information with similar data for tuberculosis-related mortality during the same time. Measurements and Mean Results: From 1999 through 2010, nontuberculous mycobacterial disease was reported as an immediate cause of death in 2,990 people in the United States with a combined overall mean age-adjusted mortality rate of 0.1 per 100,000 person-years. A significant increase in the number of NTM related deaths was seen from 1999 through 2010 (R2 = 0.72, p<0.0001), but it was not significant after adjustment for age. Persons aged 55 years and older, women, those living in Hawaii and Louisiana, and those of non-Hispanic, white ethnicity had higher mortality rates. Compared to tuberculosis-related mortality, chronic obstructive pulmonary disease, bronchiectasis, HIV, interstitial lung diseases, and tobacco use were significantly more common in persons with nontuberculous mycobacteria-related deaths. Conclusions: Nontuberculous mycobacteria-related death numbers are rising and are unevenly distributed. The strong association of nontuberculous mycobacterial disease with age suggests that its prevalence will increase as the United States population ages. [ABSTRACT FROM AUTHOR]

Background: There are number of patients who are unable to expectorate sputum specimens. In this study, we used gastric lavage (GL) test for diagnosis of tuberculosis (TB) in patients who were unable to produce sputum. Materials and Methods: Patients who were unable to produce sputum specimens were included in the study to confirm TB disease. Gastric lavage sampling was performed and sent for acid fast bacillus smear and culture under special laboratory conditions and sterilized methods. Further bronchoscopy for broncho-alveolar lavage was done on patients with negative GL smear results. Drug susceptibility tests were performed on 48 GL culture positive cases. Results: Eighty-five patients were included in the study; who were hospitalized at our referral center for suspected TB. GL smears were reported to be positive in 37 cases (66.07%) and culture in 85.7%. The total number of smear and culture-positive cases in this study was 48 (85.7%). Forty cases (87%) of drug-sensitive, 1 case (2.2%) of isoniazid and rifampin-resistant TB (multi-drug resistant; MDR), and 5 cases of resistant to one drug were detected. There have not been observed any complications after the GL method. Conclusion: It seems that regarding the high number of positive GL cultures (85.7%), GL can be effective for diagnosis of patients who have suspicious tuberculosis symptoms and are unable to produce sputum especially in resource limited areas. [ABSTRACT FROM AUTHOR]

Background and objective: The prevalence of multidrug-resistant tuberculosis (MDR-TB) has increased substantially in the past 20 years, however, there are no data specific to Iran. This study investigated patients suspected to have MDR-TB, attending the TB referral hospital in Iran. Methods: All patients suspected of having MDR-TB on hospital admission in the period 2003–2005 were included in this study. Sputum from all patients was tested for smear and culture, and drug sensitivity testing was performed using the proportion method. Patients were categorized into three groups based on their history of medical treatment. Group I consisted of patients with CAT I regimen failure; Group II consisted of patients with a history of CAT II regimen failure and Group III comprised patients with a history of more than two courses of irregular CAT I anti-TB regimen. Results: There were 105 patients recruited; 32 in Group I, 53 in Group II and 20 in Group III. There were no significant differences between the three groups in their resistance to first-line anti-TB drugs. Fifty-five patients were diagnosed with MDR-TB. The prevalence of MDR-TB was 56% (18 cases) in group I, 49% (26 cases) in group II and 55% (11 cases) in group III. No significant difference in the pattern of drug resistance was observed between the three groups. Conclusion: The prevalence of MDR-TB was high in this study. The lack of response of MDR-TB patients to CAT II treatment indicates that antibiotic sensitivity testing is essential in patients with CAT I treatment failure. [ABSTRACT FROM AUTHOR]

Background and objectives: Mitochondrial DNA has a unique role in ATP production and subsequent mitochondrial reactive oxygen species (ROS) production in eukaryotic cells and there is a potential role for ROS and oxygen burst against Mycobacterium tuberculosis, an intracellular pathogen. This study aimed to determine whether the frequency of different mitochondrial haplogroups was significantly different in patients with tuberculosis (TB) compared with a normal population. Methods: Mitochondrial DNA haplogroups M, N, J and K were studied by PCR-restriction fragment length polymorphism and sequencing. Cases were 54 patients with confirmed smear positive pulmonary TB. Controls were 256 healthy persons. Results: There were no statistically significant differences between those with TB and the control group. Conclusions: There was no statistically significant association between mtDNA haplogroups and the presence of TB infection. [ABSTRACT FROM AUTHOR]

Summary: Background: Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Cystic fibrosis (CF) patients are susceptible to NTM, but data about NTM in patients with non-CF bronchiectasis are limited. Methods: We conducted a retrospective, descriptive study at the University of Illinois Medical Center. All patients diagnosed with bronchiectasis (code 494) using the International Classification of Diseases, ninth revision (ICD-9), between 1999 and 2006, were identified. Clinical data including lung function, radiology studies, and presence of NTM in sputum were abstracted for those who met the study criteria. Results: One hundred eighty-two patients were enrolled in the study. Patients were divided into two groups: bronchiectasis with NTM isolates (n = 68) and bronchiectasis without isolates (n =114), and compared for clinical characteristics and underlying diseases. Mycobacterium avium complex (MAC) was the most common isolate. Fifty-five patients (30%) met the American Thoracic Society criteria for diagnosis of NTM disease. Gram-negative rods were commonly co-isolated. The probability of NTM isolation was significantly higher in elderly female patients (p = 0.04). Moreover, the probability of NTM isolation was significantly higher in the female group with low body mass index (BMI) (p = 0.002). Conclusions: NTM infections are common in non-CF bronchiectasis. MAC is the most frequently isolated NTM in these patients. There is also great variability in age and sex characteristics for NTM in non-CF bronchiectasis patients. Female patients with a low BMI are a high risk group for NTM infection in non-CF bronchiectasis. Routine screening for NTM is strongly recommended in this patient population. [Copyright &y& Elsevier]

Introduction: Pyrazinamide (PZA) susceptibility testing plays a critical role in determining the appropriate treatment regimens for multidrug-resistant tuberculosis. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of sequencing PZA susceptibility tests against culture-based susceptibility testing methods as the reference standard. Methods: We searched the MEDLINE/PubMed, Embase, and Web of Science databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (version 1.4, Cochrane Colloquium, Barcelona, Spain), STATA (version 14, Stata Corporation, College Station, TX), and RevMan (version 5.3, The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark) software. Results: A total of 72 articles, published between 2000 and 2019, comprising data for 8,701 isolates of Mycobacterium tuberculosis were included in the final analysis. The pooled sensitivity and specificity of the PZA sequencing test against all reference tests (the combination of BACTEC mycobacteria growth indicator tube 960 (MGIT 960), BACTEC 460, and proportion method) were 87% (95% CI: 85–88) and 94.7% (95% CI: 94–95). The positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve estimates were found to be 12.0 (95% CI: 9.0–16.0), 0.17 (95% CI: 0.13–0.21), 106 (95% CI: 71–158), and 96%, respectively. Deek's test result indicated a low likelihood for publication bias (p = 0.01). Conclusions: Our analysis indicated that PZA sequencing may be used in combination with conventional tests due to the advantage of the time to result and in scenarios where culture tests are not feasible. Further work to improve molecular tests would benefit from the availability of standardized reference standards and improvements to the methodology. [ABSTRACT FROM AUTHOR]

Toll-like receptors are transmembrane glycoproteins predominantly expressed in tissues with immune function. They are considered one of the most important pattern recognition receptor families discovered at the end of 20th century and a key aspect of the innate immune system response to infectious disease. Here we present a review of the current knowledge of individual Toll-like receptors, 1 through 13, with a focus on their role in the immune system response to mycobacterial infection. We present literature to date about the Toll-like receptors structure, localization and expression, signaling pathways, and function. The Toll-like receptor family may have proven an important role in the immune system response to mycobacterial infections, including M. tuberculosis and non-tuberculous (NTM) organisms. [ABSTRACT FROM AUTHOR]

Introduction Multidrug resistant tuberculosis (MDR-TB) presents a great challenge to public health, especially for developing countries. Some nontuberculous mycobacteria (NTM) cause the similar clinical and radiological characteristics with tuberculosis. We aimed to identify the frequency of NTM infections among subjects who were suspected to have MDR-TB due to lack of response to anti-TB treatment. Methods This retrospective study evaluated patients with suspected MDR-TB due to lack of sputum conversion after 2–3 month therapy with first line anti-TB treatment from 2009 through 2014. Cultures for mycobacteria were performed and identification was done to species level by phenotypic and molecular tests. The outcome of the patients with NTM disease and related risk factors for poor outcome were evaluated. Results Out of 117 consecutive strains isolated from suspected MDR-TB subjects, 35 (30%) strains were identified as NTM by using conventional and molecular approaches. Of these patients with positive NTM cultures, 32 (27%) patients met ATS/IDSA diagnostic criteria. Out of 32, 29 (90%) individuals with confirmed NTM diseases had underlying disorders including 8 subjects with malignancy, 5 with organ transplantations, and 4 with the human immunodeficiency virus. No known underlying disorder was found in 3 (9%) subjects. Treatment outcomes were available for 27 subjects, 17 (63%) of whom were cured and 10 (37%) had poor outcome including 6 (60%) who failed and 4 (40%) who died during treatment. Conclusion The high costs to the patient and society should lead health care providers to consider NTM in all patients suspected of having TB. [ABSTRACT FROM AUTHOR]