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Mycobacterium simiae is an emerging nontuberculous mycobacterium (NTM) and an opportunistic pathogen which is described mainly in Asia and presents in the environment that can cause pulmonary infection. The objective of this study is to characterize M. simiae clinical isolates using mycobacterial interspersed repetitive unit variable-number tandem repeats (MIRU-VNTR) typing for the differentiation of the strains. A total of 169 clinical isolates of NTM were recovered from patients suspected of having tuberculosis (TB)-like and related infections. After isolation and identification of mycobacterial strains by conventional biochemical and PCR-based tests, M. simiae strains were confirmed using restriction fragment length polymorphism (RFLP)-based identification assay. Furthermore, drug susceptibility and MIRU-VNTR typing was performed using on the clinical isolates of M. simiae. Out of 169 NTM strains, 92 (54.4%) isolates were identified as M. simiae. Antibiotic susceptibility experiments indicated that all 92 M. simiae isolates were resistant to first line antimycobacterial agents. Moreover, 8 (8.6%) M. simiae isolates were resistant to ciprofloxacin; and 6 (6.5%) were resistant to both amikacin and kanamycin, while the remaining were susceptible to second line antimycobacterial agents. MIRU-VNTR analysis showed that the M. simiae isolates were classified in four distinct M. simiae clusters and two single types. The minimum spanning analysis revealed that the isolates were grouped in three complexes. The data suggested that MIRI-VNTR typing is useful for typing of M. simiae isolates, however, MIRU-16 locus was absolutely absent in M. simiae.

Mycobacterium tuberculosis has infected more than two billion individuals worldwide, of whom 5%-10% have clinically active disease and 90%-95% remain in the latent stage with a reservoir of viable bacteria in the macrophages for extended periods of time. The tubercle bacilli at this stage are usually called dormant, non-viable, and/or non-culturable microorganisms. The patients with latent bacilli will not have clinical pictures and are not infectious. The infections in about 2%-23% of the patients with latent status become reactivated for various reasons such as cancer, human immunodeficiency virus infection, diabetes, and/or aging. Many studies have examined the mechanisms involved in the latent state of Mycobacterium and showed that latency modified the expression of many genes. Therefore, several mechanisms will change in this bacterium. Hence, this study aimed to briefly examine the genes involved in the latent state as well as the changes that are caused by Mycobacterium tuberculosis . The study also evaluated the relationship between the functions of these genes.

Background : Daily intake of air is 30 Ib as compared with 2-Ib of food and 4½ of water. Thereby, breathing-contaminated air is as harmful as drinking or eating contaminated water or food, respectively. Recent research has highlighted the extent of outdoor air pollution in large cities and warranted high-quality studies to clarify the magnitude of the problem. Here, we evaluated the possible association between tuberculosis (TB) development and exposure to outdoor air pollution in a metropolitan city of Tehran. Methods: Extraction and analysis of relevant data. Investigation performed on TB patients (n = 1167) that were residing in Tehran for the past 10 years. The average concentration of sulfur dioxide (SO2), nitrogen dioxide, carbon monoxide (CO), and particles with an aerodynamic diameter of ≤ 2.5μm (PM2.5) and ≤ 10.0 (PM10) was measured from Tehran Air Quality Control Corporation (TAQCC). Patient and ecological informations were analyzed using geographical information system. Results: Based on TAQCC, Tehran had an average of 180–250 polluted days per year for the last 10 years. The high incidence of pulmonary TB (18 to 31/100,000) was detected in populations which were exposed to high concentration of CO (2.7 to 5.2 parts per million, 95% confidence interval [CI]; 1.10 to 1.90) and PM2.5(35 to 42μg/m3; 95% CI 1.03 to 1.80). The level of SO2,NO, and PM10was also high but not significantly related to TB (P > 0.05). Conclusion: The long-term exposure to PM2.5 and CO was positively associated with TB development.

Objectives Antituberculosis drug resistance is increasing among tuberculosis (TB) patients globally, particularly in those who are human immunodeficiency virus (HIV)-positive. The aim of this study was to determine the pattern of anti-TB drug resistance in these patients in an effort to improve successful treatment outcomes with a proper regimen. Methods A cross-sectional study was conducted on adult TB/HIV co-infected patients from 2005–2015. The pattern of anti-TB drug resistance was evaluated among HIV-positive patients with and without a history of TB treatment. Categorisation was made as follows: isoniazid (INH)-resistant; rifampicin (RIF)-resistant; or multidrug-resistant (MDR). Results A total of 52 patients were enrolled in this study (median age 38 years). Among the 52 patients, 18 (34.6%) were MDR-TB patients and the rest were monoresistant TB (resistant either to INH or RIF). INH resistance was the most common resistance pattern (36.5%) noted among patients and was significantly associated with new TB cases (69% vs. 31%; P = 0.01). During TB treatment, 3/48 patients (6.3%) failed treatment and 11/48 (22.9%) died. Patients with MDR-TB were more likely to die during treatment (44.4% vs. 10%; P = 0.011). Conclusions Any drug resistance in previously treated TB cases among HIV-infected patients remains high. The risk of death is increasing in MDR-TB/HIV co-infected patients.

Cystic fibrosis (CF) has been generally well defined throughout the world although its prevalence is very difficult to ascertain for a number of reasons, including the fact that the medical/scientific literature and patient registries vary in quality in different countries. In the present review literature (1938–2017), we found out the higher frequency of registered CF patients in the European Union. This could be due to strong clinical awareness and greater health facilities. In contrast, we found a very irregular report from Asian and African countries. In these countries, the national CF registration system is mostly lacking or it is individualized-based research. In this situation, the estimation of various risk factors such as ethnicity and/or races is remained to be resolved. Overall, this review outlines the urgent need for revitalization of national and global CF registration, worldwide.

The main aim of this chapter is to describe the informative steps to diagnose Mycobacterium other than tuberculosis (NTM). Although, the death rate from NTM may not be as high as tuberculosis and lepromatous diseases, it was described that the laboratory work engaged in mycobacteriology should follow the standard classification of methods to detect NTM. The information provided here are the standard protocols recommended by the European Society of Mycobacteriology, the American Society of Microbiology, and the World Health Organization.

Objective: To investigate the prevalence of non-tuberculosis mycobacteria (NTM) among the samples deposited from the National Tuberculosis Reference Laboratory of Iran between 2011 and 2018. Methods: The study evaluated the prevalence of NTM among specimens from patients with pulmonary tuberculosis symptoms (n=15 771) deposited at the National Tuberculosis Reference Laboratory of Iran from 2011 to 2018. Detection of Mycobacterium (M.) tuberculosis was based on presence of a 190-bp amplicon from IS6110 insertion sequence using Tb1 and Tb2 primers, and amplicon-negative specimens were tested for NTM and M. tuberculosis (refractory to IS6110 amplification) using restriction fragment length polymorphism PCR of hsp65 amplicon fragment. Results: A total of 7 307 (46.33%) M. tuberculosis and 658 (4.17%) NTM specimens were found, the latter mainly comprising M. abscessus (10.18%), M. avium (2.28%), M. chelonae (8.97%), M. intracellulare (10.49%), M. kansasii (4.71%), and M. simiae (56.08%). Conclusions: As treatment for NTM differs from that for M. tuberculosis, accurate detection of Mycobacterium sp. is of public health significance.

Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

This chapter briefly reviews drug resistance in Mycobacterium tuberculosis . The difference of cell wall thickness in M. tuberculosis was demonstrated using atomic and electron micrographs.

This chapter briefly reviews the architecture of the Mycobacterium tuberculosis cell envelope and the compounds that surround the cytoplasm and protect M. tuberculosis from the environment. In addition, it demonstrates the fine structures that transfer the materials in and out of tubercle bacilli.

This chapter demonstrates the morphology of latent Mycobacterium tuberculosis . The cell was isolated from an in vitro and in vivo model of latency. Atomic force micrographs show the nonacid-fast bacilli.

This chapter briefly reviews the variable cell shape in Mycobacterium tuberculosis . The tubercle bacillus does not always manifest itself in the classical rod shape. They can appear as a granular rod, round, Y-, V-, ovoid, and club shapes. These variable shapes can be seen as a marker of virulence, of biological defense against specific immune responses, or of cell division. However, the possible significance of such variant forms with respect to etiology, control, and prognosis of tuberculosis infection is not very clear and needs future investigations.

Background and objectives:Isoniazid (INH) is one of the most potent anti-tuberculosis (TB) drugs. The spread and transmission of INH- resistant bacilli are likely to pose a significant problem for National TB control Program (NTP). In this study, we aimed to determine the trend of INH-monoresistant TB in Iran.Methods:The susceptibility patternsof Mycobacterium tuberculosis(MTB) strains that were isolated from clinical samples were retrospectively analyzed (January 2003-December 2011). Identification and drug susceptibility testing (DST) were performed using both conventional and molecular methods. The associated risk factors were assessed using the Chi-square test.Results:Out of 4825 culture-positive isolates, 6.1% were resistant to INH, with an increasing trend over the study period. The INH-monoresistance from 4.4 in 2003 reached to 9.4% in 2011. Among the studied risk factors, age was significantly associated with INH-monoresistance (p < 0.05).Conclusions:The increased trend in INH-monoresistance underlines the need for greater enforcement of national TB control programs. In this regard, better management of TB cases, establishing advanced diagnostic facilities and use of standard treatment regimens are recommended to avoid further emergence of INH resistant cases.

Objective/background: The risk of mortality and morbidity among tuberculosis (TB) and human immunodeficiency virus (HIV) coinfected patients is significantly higher than that of patients infected with TB alone. The aim of this study was to evaluate the survival of TB-HIV patients in a TB-referral center during a 10-year follow-up. Methods: All TB-HIV patients in our referral center were enrolled in the study from 2003 to 2014, and patients were divided into two groups: HIV-TB patients without a history of TB treatment (new cases of TB) and HIV-TB patients with a history of TB treatment. Both groups were treated based on World Health Organization TB-treatment guidelines, and multivariate analysis was performed to evaluate risk factors of all-cause mortality. Results: During the study, 22 HIV-TB patients with a history of TB treatment and 263 HIV-TB patients with newly diagnosed TB were included. Baseline demographic and clinical characteristics were similar, except that miliary TB (98% vs. 2%) and mortality (97% vs. 3%; p = 0.06) were more likely in HIV patients with newly diagnosed TB. During TB treatment and subsequent follow-up, two patients did not respond to treatment and 92 (32.3%) patients died, whereas the cure rate was 60%. Pneumothorax [hazard ratio (HR): 3.17], coinfection (herpes zoster, toxoplasmosis, cytomegalovirus infection, Pneumocystis jiroveci, candidiasis, and other opportunistic infection; HR: 1.75), CD4

There is little information on atypical mycobacterium and human T lymphothropic virus Type I (HTLV-I) co-infection. We present the first case of pulmonary M. simiae infection in co-infection with HTLV-1, confirmed by ELISA antibody test and Western Blot. We discuss the clinical characteristics and laboratory tests of the patient and presumptive immunological relation. We propose that in patients with the HTLV infection and pulmonary symptoms and signs compatible with tuberculosis, evaluation for atypical mycobacteriosis may be recommendable.

The risk of death is significantly higher in HIV-infected patients with tuberculosis (TB). This study aims to evaluate the impact of demographic, clinical and laboratory characteristics on the treatment outcome and mortality of TB/HIV co-infected patients in a tertiary TB centre in Iran. In total, 111 patients were recruited from 2004 to 2007. Mycobacteriological studies and demographic, clinical, and laboratory data from all patients were analysed and predictors of unsuccessful outcomes as well as mortality were determined. The mean age for all 111 TB-HIV patients was 38 ± 9 years (range 22–70) and 107 (96.3%) were men; 104 (93.7%) had a history of drug abuse and 96 (86.4%) had a history of imprisonment. The method of HIV transmission was intravenous drug use in 88 (79.3%). Twenty-three (20.7%) had a history of Category 1 (CAT I) TB treatment and six (5.4%) Category 2 (CAT II) treatment. Combination antiretroviral therapy (cART) was given to 48 (43.2%). No significant associations were found between treatment outcomes or mortality and gender, smoking, drug and alcohol abuse, imprisonment, method of transmission, history of CAT I and CAT II treatments, CD4 counts or adverse effects ( P > 0.05). Administration of cART led to significantly better outcomes ( P < 0.001). Lower serum albumin levels and low body weight were significantly associated with mortality.

We describe the efficacy and outcome of standardised second-line anti-tuberculosis (TB) medications during pregnancy. Treatment outcomes of five pregnant women with documented multidrug-resistant TB (MDR-TB) referred to the National Research Institute of Tuberculosis and Lung Diseases from 2003 to 2009 were analysed in two categories, maternal and neonatal. Patients became pregnant during treatment for MDR-TB without any changes in their anti-tuberculosis regimen. None of them had any adverse effects during pregnancy and delivery. No adverse effects were observed in mothers or neonates. The treatment of MDR-TB during pregnancy with a standardised second-line regimen in this study population was safe, with an acceptable rate of treatment success.

Summary: The objectives of this study were to determine drug resistance pattern in new and previously treated tuberculosis (TB) patients, to assess function of TB control program, and to characterize multidrug resistant TB (MDR-TB) by molecular fingerprinting methods. Anti-micorbial susceptibility testing (AST) to the first line anti-TB drugs was performed on Löwenstein–Jensen (middlebrook 7H10) medium according to the proportion method. Molecular fingerprinting of all MDR strains was performed by spoligotyping and MIRU-VNTR. Mycobacterium tuberculosis strains were isolated from 53 Iraqi patients with pulmonary TB. Thirty eight patients (71.7%) tested cases, and 15 (28.3%) were previously treated. Four of the 38 new cases (10.5%) had resistant, of which 3 (7.9%) were MDR. Eight (53.3%) of the 15 previously treated patients had resistant strains, of which 7 (46.7%) were MDR. Spoligotyping of MDR strains showed CAS family (40%) as the predominant genotype. Using MIRU-VNTR typing, all isolates had a unique profile. MDR-TB prevalence is higher among previously treated patients than among the new cases. The many drug resistant strains, in absence of evidence of recent transmission and in combination with the many previously treated cases, highlight the need for an improved control program, coupled with a need to improve detection rate and early diagnosis of MDR-TB. Keywords: Tuberculosis, Multidrug resistant, Iraq, Drug susceptibility testing, Molecular genotyping

We report a case of pulmonary infection caused by Mycobacterium branderi, a slow growing non-tuberculosis mycobacteria, in a patient with acute myelogenous leukemia. The pulmonary disease was treated successfully with the combination of Ciprofloxacin, Doxycycline and Clarithromycin. M. branderi may be considered as an opportunistic pathogen, especially among immunologically compromised patients.

Background: Medical geographic information systems (Medical GIS) has a pronounced capacity to help us understand infectious disease epidemiology, and the transmission of pathogens in a defined geographical area over time. This could not only help us increase the understanding of public health, but also be a most useful base for medical intervention as improved infection control where it is most needed. In this study, we applied GIS to characterize Tuberculosis (TB) epidemiology in Iran. TB, caused by Mycobacterium tuberculosis, is a severe bacterial infection that can be transmitted among humans and more than 10 million people develop active TB every year and with a mortality of 1.4 million. Methods: In this cross-sectional study carried out on 3710 tuberculosis patients who had been diagnosed in 2013 to 2017 at the National Tuberculosis Reference Laboratory, we aimed to explore the geographic and gender patterns of tuberculosis in Iran using GIS. Results: Results showed that the number of patients with tuberculosis was highest in Tehran city, despite the fact that it is the richest and most developed city of Iran and that the tuberculosis dispersion reflected by GIS revealed a significant geographical heterogeneity. Conclusion: These results could be useful to establish and implement new guidelines for effective control strategies in geographic areas with the highest prevalence of tuberculosis.

Background: The aim of this study was to identify prevalent spoligopatterns of Mycobacterium tuberculosis (MTB) strains within Iran and its neighboring countries. Methods: The spacer oligonucleotide typing (spoligotyping) was performed on 1,742 MTB strains isolated from Iranian and Afghan patients. Subsequently, these results were compared with published results of Pakistan and Turkey. Results: Based on the international spoligotyping database T, Central Asian Strain (CAS), East African-Indian and Latin American and Mediterranean families were prevalent in the region. T was dominant amongIranian (32.3%) and Turkish (36.5%), whereas CAS was more prevalent among Pakistani (61.3%) and Afghan-immigrant (27.4%) TB patients. Conclusion: The majority of strains isolated from Pakistan and Afghanistan belonged to ancient MTB genotypes (principal genetic group, PGG, I). In contrast, in Turkey there was prevalence of modern TB (PGG II and III), whereas in Iran, the prevalence of ancient and modern TB was almost equal. Therefore, Iran may be considered as the connecting geographical location between ancient and modern TB.

Pyrazinamide (PZA) is an important first-line drug used for the short-course treatment of tuberculosis in combination with isoniazid and rifampin. It has been reported that mutations in pncA gene correlate well with PZA resistance depending on the geographic area. On the other hand, different genotypes of Mycobacterium tuberculosis show different affinities to acquire resistance-related mutations. To determine the relative significance of various mutations in the pncA gene in Iranian PZA-resistant M. tuberculosis isolates and to analyze the association of different genotypes of M. tuberculosis with PZA resistance, 34 PZA-resistant M. tuberculosis isolates were analyzed for their pncA mutations using direct sequencing. These isolates were genotyped by IS6110 fingerprinting and spoligotyping methods. Mutations in the pncA gene were identified in 24 of 34 of these isolates (70.58%). No mutations were found in 10 PZA-resistant isolates, which implied that alternative mechanisms of resistance existed in these strains. PZA resistance was strongly (41.2%) associated with multidrug-resistant tuberculosis. Genotyping revealed the Central Asian (CAS) and East-African Indian families as the most prevalent families between PZA-monoresistant isolates versus the Beijing and Haarlem families which were the most frequent families between PZA including multidrug-resistant isolates.

Purpose : The purpose of this study was to understand the molecular epidemiology of tuberculosis in Khorasan province of Iran was studied by spoligotyping 113 Mycobacterium tuberculosis isolates. The spoligotyping results were in comparison to the word Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4). Spoligotyping data from Iran has rarely been described and there is limited information on the major circulating clades of M. tuberculosis in Iran. Materials and Methods: Spoligotyping was performed on 113 M. tuberculosis isolates from Mashhad patients between November 2004 and September 2005. Results: The study found 57 spoligopatterns. 17 clusters and 32 true orphan genotype. The biggest cluster with 13 isolates had not been previously reported. The Beijing genotype was seen in eight (7.1%) isolates. Conclusions: Genotyping and Spoligotyping gives a unifying framework for both epidemiology and evolutionary analysis of M. tuberculosis populations.

Background The study documented the emergence of new forms of resistant bacilli (totally drug-resistant [TDR] or super extensively drug-resistant [XDR] tuberculosis [TB] strains) among patients with multidrug-resistant TB (MDR-TB). Methods Susceptibility testing against first- and second-line drugs was performed on isolated Mycobacterium tuberculosis strains. Subsequently, the strains identified as XDR or TDR M tuberculosis were subjected to spoligotyping and variable numbers of tandem repeats (VNTR). Results Of 146 MDR-TB strains, 8 XDR isolates (5.4%) and 15 TDR isolates (10.3%) were identified. The remaining strains were either susceptible (67%) or had other resistant patterns (20%). Overall, the median of treatments and drugs previously received by MDR-TB patients was two courses of therapy of 15 months' duration with five drugs (isoniazid [INH], rifampicin [RF], streptomycin, ethambutol, and pyrazinamide). The median of in vitro drug resistance for all studied cases was INH and RF. The XDR or TDR strains were collected from both immigrants (Afghan, 30.4%; Azerbaijani, 8.6%; Iraqi, 4.3%) and Iranian (56.5%) MDR-TB cases. In such cases, the smear and cultures remained positive after 18 months of medium treatment with second-line drugs (ethionamide, para-aminosalicylic acid, cycloserine, ofloxacin, amikacin, and ciprofloxacin). Spoligotyping revealed Haarlem (39.1%), Beijing (21.7%), EAI (21.7%), and CAS (17.3%) superfamilies of M tuberculosis . These superfamilies had different VNTR profiles, which eliminated the recent transmission among MDR-TB cases. Conclusions The isolation of TDR strains from MDR-TB patients from different regional countries is alarming and underlines the possible dissemination of such strains in Asian countries. Now the next question is how one should control and treat such cases.

The ultrastructure of the cell wall of extensively drug-resistant (XDR), multidrug-resistant (MDR) and susceptible tuberculosis (TB) bacilli was viewed under transmission electron microscopy (TEM). Under the TEM, marked differences were observed in the thickness of their cell wall: 20.2 ±1.5 and 17.1 ±1.03 nm for the XDR and MDR TB bacilli, respectively, and 15.6 ± 1.3 nm for the susceptible isolates (p < 0.05). In MDR bacilli, thickening of the cell wall was observed in the intermediate electron-transparent layer (ETL) and outer electron-opaque layer, whereas in XDR TB cells the basal peptidoglycan layer was denser and almost fused with the ETL. Five to seven percent of XDR TB bacilli had the appearance of the stationary phase with cell wall thickness ranging from 21 to 26 nm (p < 0.001). Information provided in this study is of significant importance in terms of drug selection for effective treatment of resistant strains.

The objectives of this study were to determine the impact of diabetes mellitus (DM) on antituberculosis drug resistance in new cases of tuberculosis (TB). A case-control study was conducted on all newly diagnosed pulmonary TB adult patients with DM as cases and without DM as controls who were hospitalised from May 2013 to October 2013 in Iran. A molecular resistance test for rapid detection of resistance to isoniazid and rifampicin was done. Multivariate analysis was performed to determine the impact of DM on any anti-TB drug resistance. In total, 62 TB cases with DM and 64 TB cases without DM were included. TB cases with DM were more likely to be older (59 years vs. 43 years; P=0.001). Two TB-DM patients had multidrug-resistant TB (MDR-TB) (3.2%) compared with no cases of MDR-TB in the control group, and more TB-DM cases had isolates that were resistant to at least one drug (12.9% vs. 10.9%). DM [odds ratio (OR)=4.82, 95% confidence interval (CI) 1-23.57], age

Background Scaling-up in treatment for Mycobacterium tuberculosis (MTB) is a health priority. Currently, treatment regimens are long with complications, and default rates are very high. Tuberculosis (TB) patients who do not complete treatment pose a potential public health risk and are categorized as default to follow-up (DFU). Methods In 2014, an anti-TB drug-resistance survey in Tehran, Iran, enrolled 1718 new and re-treatment patients who were TB, MDR-TB (multidrug-resistant) and old TB. TB was detected in these patients with positive acid fast bacilli (AFB) in smear and culture of sputum. Results All patients received treatment with standardized first-line or second-line regimens (based on the type of TB infection). Patients are followed from the time of registration and treatment until the completion of treatment. This study reports the treatment outcomes of the retrospective study which was assessed from 2004 up to 2014. The reported cure rate for TB patients was 97.5% among new and old cases; 85.9% of patients ( n = 1476) had no relapse; 13.7% of them ( n = 236) had two or less than two relapses, and only 6 cases (0.4%) had more than two relapses; 10.5% of patients ( n = 183) defaulted from anti-TB treatment and have not come back for follow-up after 52 weeks. Conclusions These results showed the achievement of the National Tuberculosis Control Program implementation. It can be concluded that the treatment plans and appropriate follow-up of therapy have the greatest success in improving TB treatment outcomes.

Background and objective: One third of the world population is currently infected with Mycobacterium tuberculosis (MTB), but only between 5% and 10% of them show signs of tuberculosis (TB). Factors such as aging, drinking alcohol, and smoking can be involved in contributing to TB progress, but host genetic factors have the most important role in the progression of this disease. Cytokine polymorphisms are among the most important genetic factors influencing an individual's susceptibility and development of the disease. The present study is designed to evaluate the association of interferon-γ (IFN-γ) and p2x7 polymorphisms in pulmonary TB patients. Material and Methods: Single-nucleotide polymorphisms in IFN-γ and p2x7 genes in patients [n = 100] were analyzed and compared with controls [n = 100]. The genotypes of the above-mentioned genes were investigated by the PCR-RFLP method. Statistical analysis was performed using chi-square test to determine statistical associations between cases and controls. Results: The results indicated that there is a significant association between control and patient in IFN-γ −611 allele (p 0.05). Discussion: The presence of polymorphisms in the region-611 of IFN-γ-R1 gene and p2x7 1513/−762 alleles may increase the host susceptibility to MTB infections. Consequently, genotype determination of these special alleles can be regarded as important tools to identify infected persons at high risk of TB.

Background: Based on the authors’ knowledge, there is no study on the co-infection of opportunistic agents such as Mycobacterium tuberculosis and Pneumocystis jirovecii in the lungs of Iranian patients with immunosuppression. Objectives: The current study aimed to show the rate of co-infection of M. tuberculosis and P. jirovecii in patients with Human Immunodeficiency Virus (HIV). Patients and Methods: Forty-five pulmonary samples were collected from 30 patients with HIV who also infected with Tuberculosis and Pneumonia. All of the patients were admitted to two university hospitals of Mycobacteriology and the Iranian HIV/AIDS research centers. DNA of P. jirovecii was detected using nested-Polymerase Chain Reaction (nested-PCR) assay. Results: All of the patients were male with the mean age of 32.95 ± 7.15 years. The mean of CD4 cell count was 109.25 cell/mm3. Of 30 patients with HIV, three (10%) were co-infected with M. tuberculosis and P. jirovecii. No other causes of pneumonia were found in those three patients and CD4 cell counts less than 50 cell/mm3 was reported. Conclusions: The results of the current study showed a high rate of co-infection of M. tuberculosis and P. jirovecii in the Iranian patients with HIV. As the immune system condition worsened, the probability of occurrence of Pneumocystis Pneumonia (PCP) increased. Therefore, more specific, most rapid and sensitive tests should be utilized for diagnosis of PCP in this group of patients.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms that are highly prevalent in the environment. The evidence that these organisms originate in the environment is overwhelming; and there is no significant evidence for animal-to-human or human-to-human transmission. NTM were first recognized as human pathogens in 1950s [1] and since then more than 150 NTM species have been recognized [2]. Humans may be exposed to NTM on a regular basis through showering, bathing, and other activities using water, soil, or aerosols [3]. How, when, why, and in which population NTM infection might occur are largely unknown. The incidence rate of NTM infections appears to have increased during the last decade globally resulting in a significant mortality and morbidity [4, 5]. Studies have shown a high incidence rate of NTM in elderly population and increasing susceptibility in very elderly people. It has been estimated that NTM incidence will continue to rise due to increasing elderly population by 2050 [6]. Little is known about the diseases caused by the NTM and only limited data are available showing its prevalence and associated factors [7, 8]. Bronchiectasis, chronic lung diseases, pulmonary fibrosis, and decreased lung immunity are some of known risk factors for pulmonary NTM diseases. NTM disease has also gained increasing attention in countries with high incidence of tuberculosis due to risk of misdiagnosis with multidrug resistant tuberculosis (MDR-TB) [9]. A recently published study showed the frequency of NTM misdiagnosis in up to 30% of patients with suspected MDR-TB [10]. The disease caused by NTM forms a broad clinical spectrum from asymptomatic infection to fatal disseminated disease in human. While many of NTM patients have underlying pulmonary diseases, NTM symptoms are undifferentiated from symptoms of patients with chronic pulmonary structural diseases such as bronchiectasis. Therefore, routine screening and having high suspicion for NTM disease are highly recommended. Diagnosis of infection by NTM is another challenging issue. The diagnosis of NTM with conventional microbiologic methods may be misleading and molecular approaches are advised [11]. Increased knowledge and understanding of this type of mycobacterial disease could improve patient care of affected persons worldwide. We also highly recommend continuing translational studies to develop precision medicine in mycobacterial diseases [12]. In this special issue, a series of original articles as well as expert reviews on NTM are published to stimulate a greater understanding of NTM infections. Suggested areas of research are included: microbiologic and molecular diagnostic tools, drug susceptibility tests, human genetic susceptibility, prevalence and incidence studies, clinical presentations, and clinical trials for antibiotic therapy. We were particularly interested in studies describing new laboratory diagnostic tools for NTM, modalities for clinical characterization of NTM diseases in patients with and without underlying diseases, and measuring outcomes of treatment trials. In conclusion, the incidence of NTM disease is increasing and needs urgent attention by health policy makers and international societies. Better molecular tools for rapid diagnosis of NTM, understanding of immunopathogenesis, and host pathogen interactions are needed. In the last years, we have seen an explosion in NTM researches. Consequently, we hope to see more publications from basic and traditional research to answer our questions about NTM in coming years.

The aim of this study was to determine the prevalence of drug-resistant tuberculosis (TB) and its associated risk factors. The susceptibilities of Mycobacterium tuberculosis isolates were tested against four first-line antituberculous drugs and were typed by spoligotyping. Spoligotyping of M. tuberculosis strains resulted in 95 different patterns that were divided into three evolutionary groups (1–3). Eighty-six (90%) of the isolates had unique patterns that were reported for the first time. Interestingly, 9.4% of the strains belonged to the Beijing family. Multidrug resistance (MDR) was seen in group 1 of the evolutionary scenario. All M. tuberculosis isolates belonging to the Beijing family were associated with a resistance pattern. MDR was much higher in bacteria isolated from Afghan TB patients residing in Iran.

Objectives. To evaluate the DNA polymorphism among Mycobacterium tuberculosis (MTB) strains isolated from new smear positive tuberculosis (TB) patients residing in Tehran capital city of Iran, during the year 2001. Methods. IS6110-restriction fragment length polymorphism (RFLP) and spoligotyping analyses were performed on 129 M. tuberculosis strains. Additional patient's information was collected for further epidemiological analyses. Patients whose isolates had identical RFLP and spoligotyping patterns were considered a cluster. Results. The results show that the IS6110 were polymorphic and the strains with 8 or 9 IS6110 copy number were more frequently defected (42%). Out of 129 available isolates, 56 (43%) belonged to clusters and 72 (57%) did not. The risk factors like age, sex, family history or close contact and intravenous drug abuse were associated with clustering. Whereas, unemployment (61%) and poor living conditions (83%) contributed to diseases development in both groups. Spoligotyping of M. tuberculosis strains resulted in 46 different patterns, out of which 38 patterns were unique and reported for the first time. We found one M. tuberculosis strains with a pattern characteristic of the Beijing family. Conclusion. In the studied time period both reactivation (57%) and recent transmission (43%) were contributing to annual new TB cases in Tehran.

Objective/background Tuberculosis (TB) remains the leading cause of AIDS-related deaths among adults in countries with resource limitations. The emergence of the Xpert MTB/RIF rapid molecular assay and its subsequent World Health Organization endorsement in 2010 transformed the TB-diagnostic landscape. Xpert provided diagnostic accuracy that was far superior to that of the sputum-smear microscopy test previously used. The detection of mycobacterial lipoarabinomannan (LAM) antigen in urine has emerged as a potential point-of-care test for TB. LAM antigen is a lipopolysaccharide present in mycobacterial cell walls which is released from metabolically active or degenerating bacterial cells and appears to be present only in people with active TB. Urine-based testing has advantages over sputum-based testing because urine is easy to collect and store and lacks the infection control risks associated with sputum collection. A previously study reported that urinary-LAM testing is a rapid, low-cost, ante-mortem diagnosis for human immunodeficiency virus (HIV)-associated TB. The objective of this study was to investigate the levels of LAM in HIV patients referred to the Mashih Daneshvari Hospital Tehran, Iran. Methods Urine from 31 HIV patients without TB, 33 HIV patients with pulmonary TB, and eight HIV patients with extrapulmonary TB was analyzed for LAM using enzyme-linked immunosorbent assay kits (Mybiosource, San Diego, CA, USA). Results The plasma levels of LAM in pulmonary TB/HIV patients was 7.67 ± 2.3 ng/ml compared with 4.5 ± 1.6 ng/ml in extrapulmonary TB/HIV and 6.7 ± 1.2 ng/ml in HIV patients without TB. There was no significant difference in urine LAM levels between the three groups. Conclusion Our results highlight the limitations of using urine LAM levels for differentiating HIV-associated TB patients in Iran.

Objectives/background The region of differences (RDs) polymorphisms is a potential molecular epidemiology method to distinguish origins of Mycobacterium tuberculosis. To date, 68 RDs have been identified in M. tuberculosis. This study was designed to determine the frequency of RD deletions in M. tuberculosis strains that were isolated from patients with pulmonary tuberculosis who were referred to the National Research Institute of Tuberculosis and Lung Disease for diagnosis and treatment. Therefore, highly polymorphic regions (RD1, RD150, and RD181) among M. tuberculosis strains isolates were investigated. Methods A total of 250 M. tuberculosis isolates were identified by conventional and molecular methods. Subsequently, spoligotyping and RD typing (RD1, RD150 and RD181) were performed to genotype these strains. Results The most frequent spoligotype belonged to Haarlem (n = 85, 34.0%) followed by CAS (n = 54, 21.6%), T1 (n = 27, 10.8%), and Beijing (n = 28, 11.2%) lineages. Deletion in RD181 was identified only among the Beijing lineage ( Fig. 1 ). Conclusion As we found a deletion in RD181 in the Beijing strains only, we propose to use this marker as an identification tool for genotyping of the Beijing strain.

1 Mycobacteriology Research Centre(MRC), National Research Institute of Tuberculosis and Lung Disease (NRITLD), WHO; UNION Collaborating Centre for TB and Lung Diseases, Shahid Beheshti University (Medical Campus), Darabad, Tehran, Iran. 2 The Republican Research and Practical Centre for Epidemiology and Microbiology, Minsk, Belarus. 3 Institute for Chemistry of New Materials, Belarus National Academy of Sciences, Minsk, Belarus. 4 Experimental & animal research Laboratory, NRITLD, Shahid Beheshti University (Medical Campus), Darabad, Tehran, Iran

The six major lineages of Mycobacterium tuberculosis [MTB] are found to be strongly associated with specific geographical outbreaks. But whether these bacterial lineages influence the host genetic polymorphism is uncertain. The present study was designed to evaluate the relevance of strain diversity and host genetic polymorphisms in susceptibility to pulmonary tuberculosis [PTB]. For this reason, single –nucleotide polymorphisms [SNPs] in interferon- γ [IFN-γ] receptor-1[G-611A], IFNG [G+ 2109A] and tumor necrosis factors [TNF-α] genes [at -238, 308,-857position] in patients [n=151] were analyzed and compared with controls [n=83]. The genetic diversity of M. tuberculosis isolates were performed using spacer oligonucleotide typing. Thereafter, the profile of IFN-γ and TNF-α allele frequency were investigated in each subtype of M .tuberculosis. The results showed C allele of TNF 857 and A allele of TNF 238 were more frequent in PTB cases [[TNF 857 C allele OR [CI95%] 0.6[0.4-0.9], p= 0.02] for TNF 238 A allele OR [CI95%] 5.5[3.4-9.0], p= 0.00]]. Similarly, G allele in IFNG+ 2109 A/G polymorphism were significantly more in patients than control subject[OR[CI95%] 0.3; p< 0.05]. The major identified clinical isolates of M. tuberculosis were EAI[42; 27.8% ], Haarlem[ 31; 20.5% ], CAS [ 23;15.2% ], Beijing[14; 9.2%], and T [11; 7.2% ] lineages. No correction was observed between strains diversity and frequency of SNPs in studied PTB cases. In conclusions, we exclude the possibility of genetic mutation in IFN-γ and TNF-α gene by different subtypes of M .tuberculosis. Although, our results supports a positive correlation between host SNPs and susceptibility to PTB.

We determined the prevalence of rifampin-monoresistant tuberculosis (RMR-TB) in Iran. Because development of RMR-TB is not common, we also identified the major risk factors associated with RMR-TB reported from different provinces of Iran. Data for 3,020 TB patients who remained or became smear positive after two, four, six, and nine months of standard first-line chemotherapy were retrospectively analyzed. Of 3,020 patients, 1,242 patients (41.1%) were culture and DNA positive for Mycobacterium tuberculosis. Of these patients, 73 (7.4%) patients had monoresistant isolates to rifampin, which was significantly higher than that for multidrug-resistant TB (5.8%). The average rate of RMR-TB in the studied population ranged from 5% to 10%. Classical investigation showed that 33.6% of patients had either a previous or family history of TB. Molecular epidemiology methods (i.e., spoligotyping and Mycobacterium interspersed repetitive unit-variable number tandem repeat), defined transmission link in three clusters (13%). These results outline the urgent need for a comprehensive plan for detection and treatment of RMR-TB cases.

Background: Pneumocystis jirovecii (formerly known as P. carinii) is one of the most opportunistic agents, which frequently leads to hospitalization and death in immunocompromised patients, especially in HIV-infected individuals. Objectives: The current study is the first report on the rate of the infection in Iranian HIV-infected individuals. Patients and Methods: We used two nested PCR and PCR-RFLP assays to amplify mt LSU rRNA and DHPS genes in 126 samples obtained from the respiratory systems of Iranian HIV-patients with CD4 count < 200 cells/μL, who were referred to two Research Centers from August 2010 to March 2011. Results: In the group of studied patients, 112 were male (88.9%). The mean age of the patients was 35.12 ± 9.75 years. Median CD4 T cell count of the patients was 93 cells/μL. Thirty nine patients (31%) were hospitalized, and 24 patients (18.9%) tested positive for Mycobacterium tuberculosis. In spite of receiving Pneumocystis pneumonia prophylaxis and highly active anti-retroviral therapy, P. jirovecii was detected in 15 samples (11.9%). Just one patient (0.8%) was co-infected with Mycobaterium tuberculosis. The mortality rate due to Pneumocystis pneumonia (PCP) was 26.6%. None of the isolates showed any mutation in codons 55 and 57, which are associated with resistance to sulfa/sulfon drugs. The sequencing results showed that the genetic patterns of Iranian isolates were similar to Indian and Spanish isolates (99% identity). Conclusions: The study indicated that the rate of P. jirovecii infection is similar to those reported from Asian, Indian and African countries. The similarity of the genetic pattern between Iranian and Indian isolates is probably due to their close geographical proximity.

It is more than 100 years since the first Mycobacterium was isolated by Hansen (1874). That was leprosy bacillus, Mycobacterium leprae, which even today is still resisting all attempts to cultivate it in the laboratory. The tubercle bacillus, M. tuberculosis was discovered eight years later by Robert Koch (1882). The Koch discovery was confirmed by more efficient staining models of Ehrlich (1887) and ZiehlNeelsen (1883). Under Light microscope, the tubercle bacilli typically appear as straight or slightly curved rods. According to growth conditions and age of the culture, bacilli may vary in size and shape from coccobacilli to long rods. The dimensions of the bacilli have been reported to be 1-10 μm in length (usually 3-5 μm), and 0.2 -0.6 μm width. The possibility of morphological variations in tubercle bacilli was suggested by few investigators like Malassez and Vignal (1883), Nocard and Roux (1887), Metschnikoff (1888), Lubarsch(1899), Fischel(1893), and Vera and Rettger (1939). They showed under unfavorable conditions, i.e., a limited food supply, or oxygen deprivation, Mycobacterium assumed a swollen appearance without forming the vacuolar or globoid bodies (Vera and Rettger, 1939). These early reports were based on stained preparations and were subjected of severe criticism (Porter and Yegian, 1945). Today with advances in microscopic technique i.e., transmission electron microscope (TEM), scanning electron (SEM) and atomic force microcopy (AFM), almost all of investigators have been agreed that the Koch bacillus does not always manifest itself in the classical rod shape (figure 1). They become shorter in older cultures, filametous within macrophages and ovoid during starvation (Young et al., 2005; Farnia et al., 2010; Shleeva et al., 2011) and they may produce buds (Chauhan et al., 2006) and branches in extensively drug resistance strains (XDR-TB) (Velayati et al 2010; Farnia et al 2010). In the following parts the underlying mechanisms that may help the bacilli to change its morphology was highlighted.

Introduction: This study aimed to determine first-line anti-tuberculosis drug resistance rates in new and previously treated cases and to identify risk factors associated with multidrug resistant tuberculosis (MDR-TB) at the National Reference Tuberculosis Laboratory of Iran. Methodology: This was a retrospective analysis of all confirmed TB patients from December 2000 to June 2005. Drug susceptibility testing to isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide was performed on Löwenstein-Jensen (LJ) medium according to the proportion method. Results: Mycobacterium tuberculosis strains were isolated from 1,742 patients with TB, of whom 935 (53.7%) were male. The mean age of patients was 44.2 ± 17.4 years (SD). A total of 1,074 patients were native Iranians while 668 (38.3%) were immigrant patients. Out of 1,139 (65.4%) new cases, 340 (29.9%) had at least one drug resistance. Of 603 (34.6%) previously treated cases, 416 (69.0%) had resistant strains. There were 263 patients (15.1%) with MDR-TB, 72 of whom were new (6.3% of all new cases) and 191 were previously treated (31.7% of all previously treated cases). Factors associated with MDR-TB included age under 45 years, male sex, previous TB treatment, immigration, poor living conditions, and unemployment. Conclusions: The high rate of initial resistance in MDR-TB cases and the high rate of MDR-TB in a young age group were indicators of recent transmission. Therefore, closer monitoring of transmission trends of drug resistant strains should be considered as priority, to ensure a successful TB control programme.

The objective of this study was to determine the drug resistance prevalence and its pattern among tuberculosis (TB)–HIV patients in Iran. In this retrospective study, all admitted TB/HIV patients presenting to our tertiary centre during 2005–2007 were considered. After confirmation for TB–HIV, first-line DST was performed for culture-positive patients. The drug resistance patterns and the treatment outcomes were analysed. Of the total 92 TB/HIV patients, 27 were culture negative, and DST were available in 65. Intravenous drug abuse was seen in 59 (90.8%). Thirty-seven (57%) were ‘sensitive’ cases and 28 (43%) were ‘any drug resistance’ cases. Twenty-one (32.3%) were mono-drug, three (4.6%) poly-drug and four (6.1%) were multidrug-resistant TB patients. Previous anti-TB medication was significantly associated with any drug resistance ( P = 0.041; 95% confidence interval =0.086–0.984); however, having any drug resistance did not affect the treatment outcome ( P = 0.56). Streptomycin showed the highest resistance rate (27%) followed by isoniazid (20%), pyrazinamide (9.8%), rifampin (9.2%) and ethambutol (3%). Drug resistance to antitubercular agents in TB–HIV co-infected patients in Iran is high compared with other reports. Drug resistance is higher among those who have had prior anti-TB medication.

The malachite green microtube (MGMT) susceptibility assay was performed directly on sputum specimens ( n = 80) and indirectly on Mycobacterium tuberculosis clinical isolates ( n = 60). The technique is based on the malachite green dye, which changes color in response to M. tuberculosis growth. The MGMT assay is simple and rapid and does not require expensive instruments.

Background Limited evidence showed the persistence of Mycobacterium tuberculosis (MTB) in soil and water of TB sanatoriums or hospitals, but no reports suggest the occurrence of MTB in nature. Here, this study investigates the probability of isolating MTB from the environment with no clear source of contamination. To further highlight the transmission vehicle from human to nature and vice versa, the typing patterns of isolated MTB strains from the environment was compared with clinical MTB isolates. Additionally, the viability of MTB after 3 and 6 months of contamination was investigated. Methods The soil ( n = 700) and water ( n = 800) from different locations of suburban towns of Tehran was examined for the presence of MTB. The digested and decontaminated samples were inoculated in three LJ (Lowenstein Jensen) mediums and incubated at 37 °C, 25 °C and 42 °C for 12 weeks. Spoligotypes and MIRU-VNTR typing methods were performed on DNA extracted from single colonies. Thereafter, the obtained typing patterns were compared with the genotyping of TB patients that were residents of Robat Karim ( n = 25), Firuzkuh ( n = 10), Shahr-e-Ray ( n = 20) and Tehran ( n = 413). Result MTB accounts for 14.4% of total mycobacterium that was isolated from soil and water in suburban towns of Tehran. Based on polymerase chain reaction (PCR) typing methods, T family (56/82; 68%) followed by Delhi/CAS (11/82; 13.4%) were the most frequent MTB super families in both water and soil samples. Overall, 27.7% of isolates in clusters were intra-connected strains, i.e., found in different regions; however, no similar typing pattern between soil, water and clinical isolates was observed. The most frequent super family of MTB in clinical isolates was Delhi/CAS (142; 30.3%) followed by NEW-1 (127; 27.1%). The environment and clinical isolates had a minimum of 2 and a maximum of 10 loci difference (5–7 difference on average). The bacilli in contaminated soil (36%) and damp water (8.4%) remained alive for a considerable period of time, i.e., up to 9 months . Conclusion Persistence of MTB in soil and water highlights the risk of transmission, which needs further investigation. This study was supported by the National Research Institute of Tuberculosis and Lung Disease of Iran, Iran.

Introduction In many developing countries, like Iran, newborns receive the BCG vaccination for prophylaxis against mycobacterial infections. Although in many children or infants BCG infection after BCG vaccination is rare, children with primary immunodeficiency are at high risk of developing BCG-osis. According to many studies, some cytokines such as IL-12 play a major role in immunological responses in dealing with mycobacterial infections. Therefore, this research studies the relationship between polymorphism of genes encoding this cytokine and BCG-osis in Iranian children. Method Thirty-four children up to 7 years old with BCG-osis and 34 healthy children vaccinated with BCG during the first two days of life were chosen for this analysis. DNA samples were extracted from both groups. Single nucleotide polymorphisms (SNPs) in IL-12 (at +705, +1158, +1196 and +1637) genes were assessed using PCR-RFLP. Allele and genotype frequencies in cases and controls were compared using the Pearson Chi-Square test. Result The prevalence of IL-12 705 AG (heterozygote mutant) genotype was 50% in patients, but in the control group this rate was 38.2%. Likewise, AA (frequent hemozygote) genotypes were 52.9% and 38.2% in patients and control groups, respectively ( p -Value >0.05). It was observed only homozygote alleles for 1158, 1196, 1637 and 1664 positions in both patients and control groups. However, there was no significant association between case and control groups. Conclusions BCG vaccination in infants can cause protective immunity, and IL-12 plays an important role in immune responses. However, this study did not show any significant association between polymorphisms in IL-12 (at +705, +1158, +1196 and +1637) and risk of developing BCG-osis.

Introduction This study was conducted to assess the rate of human P2X7 and TNF-α gene polymorphisms among Iranian pulmonary tuberculosis (TB) cases. P2X7 gene is highly polymorphic, and it is up-regulated by an inflammatory cytokine. Recently, a correlation between the expression of the P2X7 receptor and the elevated levels of TNF-α have been shown, but the apparent clinical correlation could not be demonstrated. Methodology This study included 80 confirmed pulmonary tuberculosis (PTB) cases. Fifty control subjects were selected from the TB patients (clinical and laboratory) who had positive tuberculin tests (10–15 mm) and showed no sign of diseases (laboratory, radiological and clinical parameter). Single nucleotide polymorphisms (SNPs) in P2X7 (+1513, −762) and TNF-α (at −238, −308, −244, −857, −863) genes were assessed using PCR-RFLP and allele-specific PCR. Thereafter, haplotype and diplotype variability were compared and analyzed. Results For 1513 loci, the heterozygosity was higher in patients (35%; 44.3%) than control subjects (12%; 24%) [(p = 0.026) ORS; 2.45 CI 95% (1.13–5.33)]. For −762 loci, the frequency of mutant alleles between patients and controls were not statistically significant. No statistical difference was observed in allele frequencies of TNF −308 and −857. However, the frequency of −238 allele were more in TB cases (72.1%) (P = 0.000)[ORs: 5.85(2.70–12.64). Data analysis showed more frequencies of haplotypes, i.e., TGGA-CA and CGGA-TA in patients (21.5%; 14.6%) than the control group (2.0%; 6.0%), respectively. Additionally, the diplotype “CCGGGGGG-CCAA” was significantly associated with susceptibility to PTB (1.9 [0.08–48.3]). Conclusions In the studied population, polymorphisms in P2X7 (1513) and TNF-α (−238) gene was associated with the risk of developing PTB. Additionally, distribution of haplotype and diplotype variables did appear to be more specific than SNPs.

This survey identified the spoligopatterns of Mycobacterium tuberculosis strains with an international designation responsible for transmission and prevalence of TB (2000 to 2005) among native and immigrant populations of Tehran. The spacer oligonucleotides typing was performed on 1742 Mycobacterium tuberculosis strains isolated from verified cases of TB. Clinical and demographic data of patients were collected using traditional methods. A total of 133 distinct spoligopatterns was observed. 1679 clinical isolates were clustered in 70 clusters (52.5%) and 63 isolates were defined as orphans pattern (47.3%). Based on an international spoligotype database, the east African-Indian (EAI, 24%), central Asian (CAS, 20.8%), T clade (20.7%), Haarlem I (4.4%), Beijing (3.2%) and shared type 253 (3.1%) were the major identified M. tuberculosis superfamilies. Our results showed that the intra-community TB transmission was 13.7%, whereas the inter-community transmission was 39.3% for Afghanis and 20.3% for Iranians. The study highlighted the epidemic potential of specific genotypes (EAI, CAS, T clades) among tuberculosis cases in the Tehran territory. We also confirmed that the impact of transmission through immigration is low.

Extensively drug-resistant (XDR) tuberculosis (TB) is a cause of concern because it renders patients untreatable with available drugs. In this study we documented the existence and transmission of XDR TB among patients with multidrug-resistant TB. These patients were referred to the National Research Institute of Tuberculosis and Lung Diseases (Tehran Iran) for treatment and diagnosis from 2003 to 2005. The sputum specimens from a total of 2030 patients with TB were digested examined microscopically for acid-fast bacilli and inoculated into Lowenstein-Jensen slants by standard procedures. Testing of susceptibility to first-line drugs was performed for 1284 Mycobacterium tuberculosis isolates. Subsequently the strains that were identified as multidrug-resistant M. tuberculosis (113 isolates) were subjected to susceptibility testing for secondline drugs. Spoligotyping and restriction fragment--length polymorphism were performed for strains that were identified as XDR M. tuberculosis. A total of 12 (10.9%) of 113 multidrug-resistant M. tuberculosis strains were resistant to all 8 second-line drugs tested and therefore were denoted as XDR M. tuberculosis. Retrospective analysis of the cases of XDR TB showed that all of them belonged to 1 of 2 epidemiological clusters either a single-family cluster (4 cases) or a cluster of close contacts (8 cases). The strains were identified as belonging to the M. tuberculosis super-families Haarlem 1 and East African Indian 3. The emergence of XDR TB cases in Iran highlights the need to reinforce the Iranian TB policy with regard to control and detection strategies. (authors)