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Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018-December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein-Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018-2019 and 5220 specimens (30.8%; from 2175 patients) in 2020-2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also. [ABSTRACT FROM AUTHOR]

Aims and objectives: Sarcoidosis and tuberculosis (TB) are two granulomatous inflammatory diseases with several common symptoms. The aim of the present study was to compare the serum levels of biomarkers including interleukin-4 (IL-4) and IL-13, calcium (Ca), hemoglobin, sedimentation rate, and lymphocyte-to-neutrophil ratio between patients with pulmonary TB, patients with sarcoidosis, and control group. Methods: This case–control study was performed on patients referred to the Masih Daneshvari Hospital, Tehran, from April 2017 to 2018. In this study, 24 newly diagnosed patients with active pulmonary TB, 34 patients with pulmonary sarcoidosis, and 30 healthy individuals as the control group were enrolled. Demographic data, erythrocyte sedimentation rate (ESR), the ratio of neutrophil-to-lymphocyte (NLR), serum Ca level, hemoglobin (Hb), and IL-4 and IL-13 were compared between the study groups. Receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity were also calculated using SPSS 16.0 software. Results: The mean age was 47.71 ± 10.88 and 55.25 ± 21.58 years in the sarcoidosis and TB. The mean ESR in sarcoidosis patients was 21.45 ± 13.37 mm/h and 41.4 ± 17 mm/h in the TB group. The percentage of peripheral blood lymphocytes in sarcoidosis and TB patients was 28.02 ± 12.20 and 21.41 ± 12.49, respectively, which was significantly higher among patients with sarcoidosis. NLR was also 2.4 ± 1.6 and 4.4 ± 2.9 in sarcoidosis and TB patients, respectively, which showed a significant difference among the groups. Regarding the evaluation of the level of IL-4 and IL-13 in patients, it is worth noting that IL-4 in patients with sarcoidosis was 90 pg/ml compared to 20 pg/ml for TB patients (P < 0.001). There was no significant difference in the levels of IL-13 in the TB and control groups, which varied between 20 and 80 pg/ml (P = 0.35). However, its value was significantly higher in patients with sarcoidosis (P = 0.01) than in the healthy control group and TB (P = 0.01). The ROC curves showed that the diagnostic cutoff of ESR level, Ca, NLR, and Hb could be valuable due to the area under the curves. The cutpoint of 34 mm/h for ESR had a sensitivity of 86% as well as 80% specificity to distinguish TB from the sarcoidosis. Conclusions: Serum levels of the biomarkers indicated a stronger immunological background in sarcoidosis using NLR, Ca, ESR, and Hb. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a significant global health concern and kills millions of people every year. While TB can affect any organ in the body, breast TB is relatively uncommon. This study presents a comprehensive review of literature spanning 23 years, with a focus on cases of breast TB in Iran. Among the 96 cases found, the majority (89.6%) fell within the age range of 20–60, with a striking prevalence among women (98.9%). Common symptoms included pain and palpable mass, each presenting in approximately 60.4% of cases. Notably, only a quarter of patients had a confirmed history of exposure to a known TB case. Left breast involvement was more prevalent (58.3%), with ipsilateral lymph node enlargement observed in 40.6% of cases. Given the clinical presentation of breast TB, which often leads to misdiagnosis, a significant proportion of cases (68.7%) were diagnosed through excisional biopsy. Following a standard 6-month regimen of anti-TB drugs, relapse occurred in only 4.2% of cases. This study highlights the need for heightened awareness and vigilance in diagnosing breast TB, especially in regions with a high burden. Although breast TB poses diagnostic challenges, with prompt identification and treatment, the prognosis is generally favorable, with a low incidence of relapse.

Background: The overexpression of efflux pumps (Eps) was reported to contribute to multidrug resistant tuberculosis (MDR-TB). Increases in Eps that expel structurally unrelated drugs contribute to reduced susceptibility by decreasing the intracellular concentration of antibiotics. In the present study, an association of mycobacterial membrane protein (MmpS5-MmpL5) Ep and its gene regulator (Rv0678) was investigated in MDR-tuberculosis isolates. Methods: MTB strains were isolated from patients at two different intervals, i.e., once when they had persistent symptoms despite 3–15 ≥ months of treatment and once when they had started new combination therapy ≥2–3 months. Sputum specimens were subjected to Xpert MTB/rifampicin test and then further susceptibility testing using proportional method and multiplex polymerase chain reaction (PCR) were performed on them. The isolates were characterized using both 16S-23S RNA and hsp65 genes spacer (PCR-restriction fragment length polymorphism). Whole-genome sequencing (WGS) was investigated on two isolates from culture-positive specimen per patient. The protein structure was simulated using the SWISS-MODEL. The input format used for this web server was FASTA (amino acid sequence). Protein structure was also analysis using Ramachandran plot. Results: WGS documented deletion, insertion, and substitution in transmembrane transport protein MmpL5 (Rv0676) of Eps. Majority of the studied isolates (n = 12; 92.3%) showed a unique deletion mutation at three positions: (a) from amino acid number 771 (isoleucine) to 776 (valine), (b) from amino acid number 785 (valine) to 793 (histidine), and (c) from amino acid number 798 (leucine) to 806 (glycine).” One isolate (7.6%) had no deletion mutation. In all isolates (n = 13; 100%), a large insertion mutation consisting of 94 amino acid was observed “from amino acid number 846 (isoleucine) to amino acid number 939 (leucine)”. Thirty-eight substitutions in Rv0676 were detected, of which 92.3% were identical in the studied isolates. WGS of mycobacterial membrane proteins (MmpS5; Rv0677) and its gene regulator (Rv0678) documented no deletion, insertion, and substitution. No differences were observed between MmpS5-MmpL5 and its gene regulator in isolates that were collected at different intervals. Conclusions: Significant genetic mutation like insertion, deletion, and substitution within transmembrane transport protein MmpL5 (Rv0676) can change the functional balance of Eps and cause a reduction in drug susceptibility. This is the first report documenting a unique amino acid mutation (insertion and deletion ≥4–94) in Rv0676 among drug-resistant MTB. We suggest the changes in Mmpl5 (Rv0676) might occurred due to in-vivo sub-therapeutic drug stress within the host cell. Changes in MmpL5 are stable and detected through subsequent culture-positive specimens.

Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018–December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein–Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018–2019 and 5220 specimens (30.8%; from 2175 patients) in 2020–2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.

Background: The risk of death is significantly higher in TB/HIV-infected patients than in those patients with just one disease or the other. 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 TB tertiary center in Iran. Materials and methods: The study was conducted at Iran's National Referral Center for Tuberculosis. In total, 111 patients were recruited between 2004 and 2007. Mycobacteriology studies were performed for all patients. Demographic, clinical, and lab data of all patients were analyzed, and predictors of unsuccessful outcomes, as well as mortality, were determined. Results: The mean age for all 111 TB/HIV patients was 38±9 years (range 22–70) and 107 patients (96.3%) were male; 104 patients (93.7%) had a history of drug abuse, and 96 patients (86.4%) had a history of imprisonment. The route of transmission of HIV was intravenous drug use in 88 of the patients (79.3%); 23 patients (20.7%) had a history of Category 1 (CAT-1) (5.4%) and CAT-2 treatment. Highly Active Antiretroviral Therapy (HAART) was given to 48 patients (43.2%). There was no significant association found between treatment outcome or mortality with sex, smoking, drug and alcohol abuse, imprisonment, route of transmission, history of CAT-1 and CAT-2, cluster of differentiation 4 (CD4), and adverse effects (p > 0.05). Administration of HAART led to a significantly higher rate of good outcome (p < 0.001). Lower Albumin levels and body weight were significantly associated with mortality. Conclusion: Albumin levels and weight can be predictors of mortality and an unsuccessful outcome. Administration of HAART led to a better outcome.

Acute tubercular appendicitis has remained a rare disease despite frequent cases of tuberculosis. The following study reports a patient with multidrug-resistant (MDR) pulmonary tuberculosis that developed acute appendicitis. Histopathology of the appendix was compatible with tuberculosis. The patient had a good outcome after surgery and medical therapy.

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

Background: Pleural tuberculosis (TB) is common among HIV-infected patients. In the absence of HIV infection, the yield of mycobacteriological study is low and usually invasive procedures, including pleural fluid analysis and pleural biopsy, are necessary. The present study aimed to determine the yield of mycobacteriological study of sputum and pleural fluid among HIV-infected patients. Methods: This retrospective case–control study involved HIV-positive and HIV-negative patients with new pleural TB admitted to the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran, for 5 years. The results of sputum and pleural fluid smear for acid-fast bacilli (AFB) and mycobacterium culture were extracted and compared between the two groups. Results: In the study period, 343 patients were admitted due to pleural TB, of which 42 were HIV-positive patients. We randomly selected 132 HIV-negative patients as controls. In total, 57.1% of HIV-infected patients had positive sputum smear for AFB compared with 38.6% of controls (p = 0.04). Positive culture of pleural fluid was more frequent among the HIV-positive patients than among the controls (63.6% vs. 29.5%, p = 0.001). There was no significant correlation between CD4 cell count and sputum or pleural fluid results. Mycobacteriological assay was enough for diagnosis in 66.6% of HIV-positive patients compared with 49.2% in controls. After adjusting for other factors and multivariate analysis, HIV remained independently and significantly associated with positive culture of pleural fluid. Conclusion: The diagnostic yield of mycobacteriological studies is higher among HIV-infected patients with pleural TB than among HIV-negative patients. This may decrease the need for pleural biopsy among them. Therefore, a diagnostic approach to pleural TB may be different among HIV-infected patients. In this group of patients, it is prudent to perform sputum and pleural analysis for the detection of AFB before pleural biopsy.

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.

Objective/background: Pulmonary hypertension (PH) can be a complication of patients with severe pulmonary tuberculosis (TB). We aimed to study the correlation between pulmonary artery (PA) diameter (PAD) as measured by computed tomography (CT) and mean PA pressure (mPAP) as measured by echocardiography. We also aimed to determine the accuracy of PAD in diagnosing PH in patients with pulmonary TB. Methods: We retrospectively investigated the correlation between PAD measured using CT and mPAP measured using echocardiography in 132 patients with TB and PH, and 68 patients with TB but without PH, admitted to the TB intensive care unit at Masih Daneshvari Hospital in Tehran, Iran. We used logistic regression analysis to determine the relationships between PAD, PA diameter to ascending aorta (AA) ratio, and area of PA to area of AA ratio with mPAP. Using receiver operating characteristic analysis, we examined the utility of the PAD in predicting PH (mPAP ≥25 mmHg). Results: PAD had a significant correlation with mPAP (p

Background and objective: Diabetes mellitus (DM) has an effect on many aspects of tuberculosis (TB). The aim of this study is to determine the impact of DM on anti-tuberculosis drug resistance in new cases of TB patients. Materials and Methods: 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 hospitalized and treated at the National Research Institute of Tuberculosis and Lung Disease (NRITLD) from May 2013 to October 2013. A molecular resistance test for rapid detection of resistance to isoniazid and rifampin was done for all smear-positive TB patients. A multivariate analysis was performed to determine the impact of DM on any anti-TB drug resistance. Results: 45TB cases with DM and 45TB cases without DM were included. TB cases with DM were more likely to be older (61 vs. 47 years, p = 0.001). Two TB–DM patients had multidrug-resistant TB (MDR-TB) (4.4%) compared with zero cases of MDR-TB in the control group, and TB–DM cases were resistant to at least one drug (11.1% vs. 4.4%, p = 0.43). DM remained significantly associated with any drug resistance (OR: 6.32, 95% CI: 1–40.72) in multivariate analysis. Conclusion: New TB patients with DM are at increased risk of anti-TB drug resistance. More studies are needed to confirm these results.

Introduction: Nontuberculous mycobacterium (NTM) has clinical and radiological manifestations that are indistinguishable from Mycobacterium tuberculosis (MTB). In an endemic area for tuberculosis (TB), limited data about prevalence and outcome of treatment of these patients is available. In this study the prevalence of different types of mycobacterium and response to treatment in a tertiary referral center in Iran will be evaluated. Materials and method: All NTM cases from 2004 to 2013 at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) in Iran were extracted from the database. All NTM patients who were treated for NTM diseases entered this study, and the outcome of treatment was evaluated. Results: A total of 104 cases were detected. The mean age was 56.34±15.77 years. Half of the patients were male. Most of the patients had a history of prior TB treatment. The most common types of NTM were Mycobacterium simiae (44 [42.3%]), Mycobacterium kansasii (18 [17.3%]), Mycobacterium abcessus (15 [14.4%]), and Mycobacterium chelonea (14 [13.5%]), respectively. The outcome of treatment was as follows: cure 61 (58.7%), failure 17 (16.3%), relapse 3 (2.9%), default 13 (12.5%) and death in 10 (9.6%) patients. Conclusion: Treatment of NTM had a low cure rate despite low mortality.

Background: Pulmonary tuberculosis (TB) is an important disease with various manifestations in intensive care units (ICU). Despite the availability of effective treatments for TB, the mortality for patients admitted with TB to an ICU remains high. Additionally, the history of exposure to TB may not be present, and evidence of active TB is present in less than 50% of cases. Therefore, understanding the typical distribution, patterns, and imaging manifestations of TB is crucial. Methods: In this retrospective study, all patients admitted to ICU with clinical and laboratory-confirmed TB were enrolled. The classic information, i.e., chest X-ray (CXR) and computed tomography (CT), for each patient was analyzed. Likewise, the presence of a cavity, involved segments and patterns of parenchymal lesion were assessed. Finally, tentative diagnosis and disease activity, bronchogenic spread of the lesion with CT and bronchiectasis were recorded. Results: Among the studied cases, 146 were laboratory-confirmed TB patients. The majority of patients had acute respiratory distress syndrome (ARDS) (16.0%, n = 24), followed by interstitial involvement (13.0%, n = 19), parenchymal nodular infiltration (12.0%, n = 18), alveolar consolidations (11.6%, n = 17), cavitary TB (11.0%, n = 16), pleural effusion (10.0%, n = 15), calcified parenchymal masses (9.0%, n = 13), ground glass opacities (8.0%, n = 12) and other manifestations (8.0%, n = 12). Radiographic evidence of lymphadenopathy was seen in up to 43% of adults and 96% of children. In the 73% of cases with parenchymal infiltration, more than one pulmonary segment was involved. Miliary TB was also observed in 5% of studied patients. Conclusion: Different features of TB patients in the ICU may be easily misled, and internists should have a comprehensive knowledge of various radiologic manifestations of TB in order to use this information and not ignore it.

Objectives: HIV patients are prone to tuberculosis (TB) disease, and screening these patients for TB is important. The aim of this study is to analyze the prevalence of active and latent TB and the sensitivity, specificity, negative (NPV) and positive predictive value (PPV) of clinical signs and symptoms for the diagnosis of active TB in HIV-infected subjects. Method: From April 2008 to March 2011, 154 consecutive HIV-infected patients attending the HIV clinic at Masih Daneshvari Hospital were enrolled in the study. For the diagnosis of active TB, two sputum samples (one on presentation and another early morning) were collected from each subject and examined by Ziehl–Neelsen (ZN) microscopy for identification of acid-fast bacilli (AFB). Mycobacterial culture sputum specimens were inoculated on Lowenstein–Jensen (LJ) slants for 4–8 weeks to detect colonies. In those patients with a negative sputum sample for AFB, a polymerase chain reaction (PCR) was performed. Active TB was defined as positive sputum smear or culture for mycobacterium TB or positive polymerase chain reaction (PCR). Also, patients with signs and symptoms compatible with TB who responded to anti-tuberculous medications were classified as having active TB. Results: The mean of age was 36±8 (ranged, 22–62) and 127 (82%) were male. The antiretroviral therapy (ART) had been started in 40 (26%) patients, with 15 (10%) receiving trimethoprim/sulfamethoxazole as a prophylaxis; 119 (77%) were intravenous drug users. Among these patients, 58 (38%) individuals were diagnosed with active TB, of which 48 (83%) had smear-positive pulmonary TB. The mean of the baseline CD4 cell count in HIV patients with and without active TB was 67cells/ μl and 180cells/ μl, respectively (P-value=0.018). The multivariable regression analyses found that CD4

Objectives: Pulmonary hypertension is a serious disorder with catastrophic outcomes. This study aimed to evaluate the effect of pulmonary arterial hypertension on the outcome among new cases of pulmonary tuberculosis. Novel modalities are available as therapeutic options, so early diagnosis of pulmonary arterial hypertension may be important. Methods: In a cross-sectional study, 777 new cases of pulmonary tuberculosis were recruited in the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran. Pulmonary arterial pressure was measured by resting transthoracic echocardiography on the beginning of tuberculosis treatment. Echocardiography was performed by a cardiologist expert in the field. Patients with systolic pulmonary arterial pressure more than 35 mmHg were defined as pulmonary hypertensive. The relationship between pulmonary arterial hypertension and mortality was assessed during six months of tuberculosis treatment. Results: Seventy-four (9.5%) of 777 new cases of pulmonary tuberculosis had pulmonary arterial hypertension. Among them, 10 (13.5%) died during the treatment period. In comparison with 5% mortality among cases without pulmonary arterial hypertension, death was significantly associated with pulmonary hypertension (p = 0.007). Logistic regression analysis showed that pulmonary arterial pressure more than 35 mmHg is an independent predictor of death among tuberculosis patients. Conclusion: Among new cases of pulmonary tuberculosis, a significant association between mortality and pulmonary arterial pressure >35 mmHg was found. Therapeutic intervention may change the outcome of these patients.

Objectives: Drug-resistant tuberculosis (TB) is a major challenge in controlling TB. HIV-positive patients are vulnerable to TB 100 times more than the general population. Drug-resistant TB leads to high morbidity and mortality in this population. In this study, the outcome of treatment of drug-resistant TB among HIV positive patients from 2003 to 2013 in a tertiary center in Iran will be reviewed. Materials and Methods: All HIV-positive patients with any drug-resistant TB from 2003 to 2013 were selected. The outcome of treatment was extracted from patients’ charts. Results: Out of 269 TB-HIV patients, 34 patients were recruited. All patients were male and the mean age was 37.38±7.03. Isoniazid (INH) resistant, rifampin (RIF) resistant and multi-drug resistant (MDR) was diagnosed in 11 (32.4%), 7 (20.6%) and 16 (47.1%), respectively. Mean CD4 count was 91.61±23.55. Outcome of treatment in the INH-resistant cases was cured in 5 (45.5%), failure in 2 (18.2%) and death in 4 (36.4%). In the RIF-resistant group, outcome was as follows: cured 5 (71.4%) and failure in 2 (28.6%). In the MDR-TB patients’ group, cured, failure and death were 12 (75%), 2 (12.5%) and 2 (12.5%), respectively. Conclusion: Treatment of drug-resistant TB can be achieved despite considerable mortality.

Background: The overexpression of efflux pumps (Eps) was reported to contribute to multidrug resistant tuberculosis (MDR-TB). Increases in Eps that expel structurally unrelated drugs contribute to reduced susceptibility by decreasing the intracellular concentration of antibiotics. In the present study, an association of mycobacterial membrane protein (MmpS5-MmpL5) Ep and its gene regulator (Rv0678) was investigated in MDR-tuberculosis isolates., Methods: MTB strains were isolated from patients at two different intervals, i.e., once when they had persistent symptoms despite 3-15 ≥ months of treatment and once when they had started new combination therapy ≥2-3 months. Sputum specimens were subjected to Xpert MTB/rifampicin test and then further susceptibility testing using proportional method and multiplex polymerase chain reaction (PCR) were performed on them. The isolates were characterized using both 16S-23S RNA and hsp65 genes spacer (PCR-restriction fragment length polymorphism). Whole-genome sequencing (WGS) was investigated on two isolates from culture-positive specimen per patient. The protein structure was simulated using the SWISS-MODEL. The input format used for this web server was FASTA (amino acid sequence). Protein structure was also analysis using Ramachandran plot., Results: WGS documented deletion, insertion, and substitution in transmembrane transport protein MmpL5 (Rv0676) of Eps. Majority of the studied isolates (n = 12; 92.3%) showed a unique deletion mutation at three positions: (a) from amino acid number 771 (isoleucine) to 776 (valine), (b) from amino acid number 785 (valine) to 793 (histidine), and (c) from amino acid number 798 (leucine) to 806 (glycine)." One isolate (7.6%) had no deletion mutation. In all isolates (n = 13; 100%), a large insertion mutation consisting of 94 amino acid was observed "from amino acid number 846 (isoleucine) to amino acid number 939 (leucine)". Thirty-eight substitutions in Rv0676 were detected, of which 92.3% were identical in the studied isolates. WGS of mycobacterial membrane proteins (MmpS5; Rv0677) and its gene regulator (Rv0678) documented no deletion, insertion, and substitution. No differences were observed between MmpS5-MmpL5 and its gene regulator in isolates that were collected at different intervals., Conclusions: Significant genetic mutation like insertion, deletion, and substitution within transmembrane transport protein MmpL5 (Rv0676) can change the functional balance of Eps and cause a reduction in drug susceptibility. This is the first report documenting a unique amino acid mutation (insertion and deletion ≥4-94) in Rv0676 among drug-resistant MTB. We suggest the changes in Mmpl5 (Rv0676) might occurred due to in-vivo sub-therapeutic drug stress within the host cell. Changes in MmpL5 are stable and detected through subsequent culture-positive specimens., (Copyright © 2024 Copyright: © 2024 International Journal of Mycobacteriology.)