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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.

BACKGROUND: The potential role of environmentalMycobacterium tuberculosisin the epidemiology of TB remains unknown. We investigated the transmission ofM tuberculosisfrom humans to the environment and the possible transmission ofM tuberculosisfrom 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 ofM tuberculosisstrains 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 tuberculosiswas 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 frequentM tuberculosissuperfamilies 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 ofM tuberculosisin 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 dominantM tuberculosissuperfamilies in soil and water did not correspond to the dominantM tuberculosisfamily in patients, the presence of circulating genotypes ofM tuberculosisin soil and water highlight the risk of transmission.

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

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.

Background and objective Nontuberculosis mycobacteria (NTM) are free-living saprophytes that are found in water, soil, animals and dairy products. During recent years, advances in molecular biology improved the recovery and accuracy of NTM identification. In the present study, similar approaches were used to differentiate environmental NTM. For this reason, the prevalence of environmental NTM in soil and water in two densely populated areas of Tehran were investigated. Material and methods A total of 2,540 samples were collected from soil (n = 1237) and water (n = 1303) resources. For the soil sample: digestion and decontamination were performed using modified Engbaeks method, and for the water sample: decontamination followed with ethylpyridinium chloride (CPC; final concentration of 0.05%) and standard protocol. The phenotypic and genotyping tests were performed on all positive cultures. For molecular tests, both 16S-23S RNA and hsp65 genes spacer PCR-RFLP were used. Results Of the 2,540 collected samples, 285 (12%) were positive for mycobacterium. One hundred and sixty-nine (169; 60%) belonged to a slow growing mycobacteria (SGM) and 116 (41%) were rapid growing mycobacteria (RGM). The most frequent NTM were identified as Mycobacterium farcinogenes (51/485; 10.5%) and Mycobacterium fortuitum (38/485; 7.8%). However, M. farcinogenes is found to be dominant in both studied areas, but the frequency of RGM was different. In Shahre-ray, Mycobacterium senegalense was identified as the most frequent RGM (22/65; 34%), while in Varamin, M. fortuitum (20/51; 40%) had the most frequency. Conclusion The molecular genotyping methods facilitate the rapid identification of environmental NTM. As the higher prevalence of NTM within a region increases the risk of human infection, this study outlines the importance of further investigation.

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 During recent years, the World Health Organization (WHO) proposed new software for improving the tuberculosis (TB) laboratory services. The protocol is known as “quality stepwise implementation tool” and is based on enforcement of quality assurance services through accreditation by the International Organization for Standardization (ISO) 15189. As a national reference TB laboratory (NRL) of Iran, the benefit and challenges of implementing this standard were analyzed. Material and methods The investigation was a cross-sectional study and was underlined by the committee of the Quality Management System (QMS) in the NRL. The required information was collected in two steps: first, the QC form that contains 334 quality questions (designed by WHO) was filled out. These questions determine 12 main organizational blocks of laboratory (facilities and safety1¸ organization and personnel2¸ documents and records3¸ management reviews4¸ client management and customer service5¸ equipment6¸ internal audit7¸ purchasing and inventory8¸ information management9¸ process control and internal / external quality management10¸ corrective actions occurrence11, and incident management and process improvement12). The minimum rating of laboratories is stated to be from 55% to a maximum of 95%. In the second step, using the quality stepwise implementation tool, these blocks were in four phases, and 41 steps were analyzed. The data were compared using Fisher’s Exact test and Pearson Chi-Square. Results In the period 2013–2014, the rate of OMS in three focal points (pre-analytical¸ analytical¸ and post-analytical) in the NRL was in the range of 80–100%; whereas in previous years the rate ranged from 48% to 79%. Therefore, through QMS the NRL scores had reached a higher level. Based on available results, the NRL-assigned score was a 5-star rating. Conclusions As the internal score of NRL reaches 5, an international evaluation of accreditation scheme is sought. This is the first investigation that used the quality stepwise implementation tool in Iran.

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.

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.

The capacity of three proinflammatory cytokines, interferon-gamma (rhifn-gamma), tumour-necrosis factor-alpha (rHTNF-alpha) and interleukin-1 (rHIL-1), to induce release of nitric oxide (NO) from human mononuclear phagocytes were investigated. Peripheral blood monocytes were either used immediately or after culturing in vitro to develop into monocyte-derived macrophages (macrophages). Lipopolysaccharide (LPS) was used as second signal in all experiments. The three cytokines tested had significantly high enhancing influence on the production of nitric oxide by monocytes as well as by macrophages. However production was significantly higher by the monocytes matured in vitro to macrophages (P0.01). In our experimental system LPS had only marginal synergistic influence on production of NO2, and IFN-gamma demonstrated to be the most efficient of the three cytokines tested. Addition of L-arginine in the monocytes/macrophages culture further amplified production of NO2, whereas addition of NG-monomethylarginine abrogated this amplification. We conclude that human mononuclear phagocytes are capable of using inducible nitric oxide synthase pathway to produce nitric oxide.

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