Household contact investigation for the detection of active tuberculosis and latent tuberculosis: A comprehensive evaluation in two high-burden provinces in Iran.

BACKGROUND: Systematic evaluation of household contacts of persons with pulmonary tuberculosis (TB) in low- and middle-income countries is recommended by the World Health Organization (WHO). This study recruited adult household contacts of diagnosed TB patients in two high burden provinces of Iran to estimate the prevalence and incidence of active disease and latent TB infection (LTBI) among individuals exposed to TB cases. METHODS: We conducted a cohort study among adults in household contact with a pulmonary TB index case. All subjects were assessed for active disease through evaluation of symptoms. Tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were used to define LTBI. These tests were performed at the time of the index TB case diagnosis and repeated if the previous result was negative, at three-, 12-, and 18-months post recruitment. In addition, interferon-γ-induced protein-10 (IP-10) concentrations were measured in QFT-Plus supernatants for all participants three months after diagnosing the index case. RESULTS: A total of 451 individuals who had close contact with 95 active TB patients were enrolled in this study. Five (1.1%) contacts were diagnosed with active TB and 285 (63.2%) were identified with LTBI during our study. The incidence rate of LTBI among adult household contacts of TB index cases was 0.44 per person per year. CONCLUSION: The overall rate of LTBI was high. Systematic screening of all household contacts of pulmonary TB should be expanded in Iran to make the timely achievement of the global end TB strategy feasible.

Demographics, laboratory parameters and outcomes of 1061 patients with coronavirus disease 2019: a report from Tehran, Iran.

We aimed to determine the characteristics of coronavirus disease 2019 (COVID-2019) among the Iranian population. In this study, we collected and analysed the demographics, laboratory findings and outcomes of patients with COVID-19 who were admitted to Masih Daneshvari Hospital in Tehran, Iran between 20 February 2020 and 2 April 2020. Among 1061 patients, 692 (65.2%) were male and the median age was 55 years (interquartile range (IQR), 44-66 years). Totally, 129 (12.2%) patients died during hospitalization in the ward or intensive care unit. From the remaining 932 individuals, 46 (5.0%) were admitted to the intensive care unit and 886 (95.0%) were hospitalized in the ward. Those patients who died were significantly older than those hospitalized in the ward (p < 0.001). The median absolute number of lymphocytes was 1.2 × 103/µL (IQR 0.9 × 103 to 1.6 × 103/µL) and 708 (66.7%) patients had lymphopenia (absolute lymphocyte count <1500/µL). Among the laboratory tests, D-dimer, serum ferritin and albumin had the strongest correlations with mortality (r = 0.455, r = 0.412, r = -0.406, respectively; p < 0.001 for each one). In conclusion, laboratory findings could provide useful information with regard to the management of individuals with COVID-19.

Molecular identification, phylogenetic analysis and antifungal susceptibility patterns of Aspergillusnidulans complex and Aspergillusterreus complex isolated from clinical specimens.

OBJECTIVE: Aspergillus sections Terrei and Nidulantes are the less common causes of invasive aspergillosis and pulmonary aspergillosis (PA) in immunocompromised patients when compared to A. fumigatus and A. flavus. Identifying these fungi as the infectious agent is crucial because of the resistance to amphotericin B (AMB) and increased lethality. The aim of this study was to identify the molecular status, evaluate the genetic diversity and examine the antifungal susceptibility profile of the uncommon Aspergillus species. Forty-five uncommon Aspergillus species were identified based on the microscopic and macroscopic criteria. Then, the molecular identification was performed using the sequencing beta tubulin (benA) gene. In vitro antifungal susceptibility to amphotericin B (AMB), itraconazole (ITC), ravuconazole (RAV), voriconazole (VRC), caspofungin (CFG) isavuconazole (ISA) and posaconazole (POS) test was performed according to the CLSI M38-A2 guidelines. RESULTS: A. terreus was the most species detected, followed by A. nidulans, A. latus, A.ochraceus, and A. citrinoterreus, respectively. The analysis of the benA gene showed the presence of 12 distinct genotypes among the A. terreus isolates. The other species did not show any intraspecies variation. CFG exhibited the lowest MEC50/MIC50 (0.007µg/mL), followed by POS (0.125µg/mL), VRC, ITC, ISA (0.25µg/mL), RAV (0.5µg/mL), and AMB (8µg/mL). Among all the isolates, only 15.5% (7/45) were susceptible to AMB. CONCLUSION: Antifungal susceptibility pattern of the uncommon Aspergillus species is useful to improve patient management and increase knowledge concerning the local epidemiology. Moreover, this information is necessary when an outbreak dealing with drug-resistant infections occurs.

Mycobacterium simiae pulmonary disease in Iran: systematic review and meta-analysis.

Mycobacterium simiae is one of the most common nontuberculous mycobacteria (NTM) microorganisms causing lung disease in many countries in the world. A reliable estimate of the extent of M. simiae pulmonary disease has not been well investigated in Iran. We systematically searched multiple databases to identify relative studies. Studies were excluded if they did not use the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) diagnostic criteria for NTM diseases. Data were extracted independently and in duplicate. We assessed pooled estimate by using a random model effect, and sources of heterogeneity were assessed by using Cochran's Q and the I 2 statistic. The potential for publication bias was explored by using Begg's and Egger's tests. All analyses were conducted with Stata 14.0 (StataCorp, College Station, TX, USA). Of 172 articles identified, seven met the inclusion criteria. Of 355 patients who were culture positive for NTM, 82 had M. simiae pulmonary disease according to the ATS/IDSA diagnostic criteria. The pooled frequency of M. simiae pulmonary disease among patients with NTM was 25.0% (95% confidence interval, 16.8-33.2). No evidence of publication bias was observed among the included studies (p >0.05 for Begg's and Egger's tests). Clinical isolates of M. simiae are increasingly being recognized as a cause of pulmonary disease in Iran and need further attention by health authorities.

The effects of smoking on treatment outcome in patients newly diagnosed with pulmonary tuberculosis.

SETTING: Smoking is reported to be associated with tuberculosis (TB), but its effect on sputum smear conversion remains a matter for discussion. OBJECTIVE: To assess the effects of smoking and smoking cessation on treatment outcomes in patients newly diagnosed with TB in Iran. DESIGN: Newly diagnosed smear-positive TB patients were included in the study. All smokers participated in a smoking cessation programme. Sputum smear status was evaluated at the end of month 2, 5 and 6 of treatment, and smoking status was evaluated at the end of month 2. Differences in smear conversion rates were compared between the three groups, i.e., non-smokers, smokers and quitters. RESULTS: A total of 183 smokers and 151 non-smokers were included. When smoking cessation was assessed after 2 months, 42.6% (78/183) of the smokers were found to have quit. The cure rate at the end of 6 months, precisely compatible with the conversion rate, was significantly higher among non-smokers (P = 0.004) and quitters at 2 months (P = 0.049) than among persisting smokers (83.4%, 80.8% and 67.6%, respectively). CONCLUSION: Cure rates in patients newly diagnosed with pulmonary TB were higher in non-smokers and quitters at 2 months than in smokers. Smoking cessation advice should be included in TB control programmes.

Cigarette smoking in patients newly diagnosed with pulmonary tuberculosis in Iran.

BACKGROUND: The association between pulmonary tuberculosis (PTB) and tobacco smoke has been verified by most studies on the subject; figures from different countries for the prevalence of smoking among PTB patients vary. OBJECTIVE: To assess the prevalence of and factors associated with smoking among TB patients in Iran. DESIGN: In this cross-sectional study, subjects were included on a first-come, first-served basis from among newly diagnosed PTB patients using a multistage cluster sampling method during 2012-2014. Data were collected during face-to-face interviews and a questionnaire was used to gather information on smoking habits. RESULTS: Of 1127 newly diagnosed PTB patients included in the study (mean age 50.0 ± 19.8 years), 228 (20.2%) were daily smokers, 20 (1.8%) were occasional smokers and 93 (8.9%) had quit before diagnosis. Simultaneous drug use (P < 0.001, OR 75.21), increasing age (P = 0.001), being single (P < 0.001, OR 16.95), being an Iranian national (P < 0.001, OR 6.26) and living in a rural area (P < 0.001, OR 5.85) were found to be independent risk factors for smoking in study patients. CONCLUSION: The prevalence of smoking among PTB patients in Iran is relatively high. It is therefore necessary to include smoking cessation interventions in the National TB Programme.

Impact of chronic renal failure on anti-tuberculosis treatment outcomes.

SETTING: National Referral Centre for Tuberculosis (TB), Tehran, Iran. OBJECTIVE: To determine the impact of chronic renal failure (CRF) on TB treatment outcomes. DESIGN: A retrospective study was conducted among adult TB patients with CRF and age- and sex-matched TB controls without CRF treated at the National Research Institute of Tuberculosis and Lung Disease from 2004 to 2011. Multivariate analysis was performed to determine the impact of CRF on drug-induced hepatitis (DIH), treatment failure and all-cause mortality. RESULTS: A total of 55 TB cases with CRF and 165 TB cases without CRF were included in the study. Baseline demographic and clinical characteristics were similar, except that TB cases with CRF were more likely to be of Iranian nationality (94.5% vs. 83%, P = 0.04). During anti-tuberculosis treatment, 40 (18.2%) patients developed DIH, none failed treatment and 15 (6.8%) died. Patients with CRF were more likely to develop DIH (27.3% vs. 15.2%, P = 0.04) and to die during treatment (16.4% vs. 3.6%, P = 0.001). CRF remained significantly associated with all-cause mortality (HR 4.87, 95%CI 1.73-13.65) in multivariate analysis, whereas the relationship with DIH was not. CONCLUSION: TB patients with CRF are at increased risk of death. More intensive monitoring of patients with CRF should be considered by the National TB Programme.

Isoniazid, rifampicin and pyrazinamide plasma concentrations 2 and 6 h post dose in patients with pulmonary tuberculosis.

BACKGROUND: Low concentrations of anti-tuberculosis drugs are related to drug resistance and treatment failure. OBJECTIVE: To determine the prevalence of low plasma concentrations of anti-tuberculosis drugs. METHODS: The study was performed among 60 pulmonary tuberculosis (TB) in-patients at a tertiary care university-affiliated hospital in Tehran, Iran. Drug samples were drawn 2 and 6 h post dose for isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA); related concentrations were determined using high-performance liquid chromatography. Plasma drug concentrations, duration of treatment, age, sex, liver enzyme levels, administered doses and smoking status were evaluated and recorded. RESULTS: Among 60 patients recruited to the study, the mean (±SD) age was 54.2 (±20.9) years; 39 were female. The median peak plasma concentrations (C(max)) of INH, RMP and PZA were respectively 2.5, 4.0 and 43.6 µg/ml; 81% of the patients had drug plasma concentrations lower than the target ranges for at least one administered drug. Respectively 49.1%, 92.5% and 8.7% of the patients had low concentrations of INH, RMP and PZA. CONCLUSION: The results indicate that RMP concentrations are below the reference range in most patients, while PZA is within the target range of the standard doses.

Treatment outcome, mortality and their predictors among HIV-associated tuberculosis patients.

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.

Drug resistance pattern and outcome of treatment in recurrent episodes of tuberculosis.

Patterns of drug resistance in recurrent cases of tuberculosis may be different than in those without a history of treatment. In this retrospective study, the drug resistance pattern and outcome of treatment with DOTS category I (CAT I) regimen was compared in 63 recurrent cases and 872 new cases of pulmonary tuberculosis from April 2003 to January 2008 at the National Research Institute of Tuberculosis and Lung Disease in Tehran, Islamic Republic of Iran. Resistance to isoniazid and ethambutol was significantly more common in recurrent cases, but there were no differences in rates of resistance to rifampin, pyrazinamide, streptomycin or the rate of multi-drug resistant strains. Resistance to streptomycin was the most common. No significant differences in treatment outcome and deaths were found between the 2 groups. Due to the low frequency of multi-drug resistance in the recurrent cases, a CAT I regimen may be suitable for empirical therapy before drug sensitivity results become available.

Drug resistance pattern and outcome of treatment in recurrent episodes of tuberculosis

Patterns of drug resistance in recurrent cases of tuberculosis may be different than in those without a history of treatment. In this retrospective study, the drug resistance pattern and outcome of treatment with DOTS category I [CAT I] regimen was compared in 63 recurrent cases and 872 new cases of pulmonary tuberculosis from April 2003 to January 2008 at the National Research Institute of Tuberculosis and Lung Disease in Tehran, Islamic Republic of Iran. Resistance to isoniazid and ethambutol was significantly more common in recurrent cases, but there were no differences in rates of resistance to rifampin, pyrazinamide, streptomycin or the rate of multi-drug resistant strains. Resistance to streptomycin was the most common. No significant differences in treatment outcome and deaths were found between the 2 groups. Due to the low frequency of multi-drug resistance in the recurrent cases, a CAT I regimen may be suitable for empirical therapy before drug sensitivity results become available

Standardised second-line treatment of multidrug-resistant tuberculosis during pregnancy.

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.

Concomitant cryptococcosis and burkholderia infection in an asymptomatic lung transplant patient with cystic fibrosis.

Concomitant pulmonary infections with Cryptococcus neoformans and Burkholderia cepacia in lung transplant recipients are very rare and create unique diagnostic and therapeutic dilemmas. Herein, we present a double lung transplant patient with cystic fibrosis who was found to have coinfection with these two rare organisms, though he was completely asymptomatic.

Bilateral diffuse pulmonary infiltration in a heart transplant recipient.

Pulmonary complications are not infrequent after heart transplantation. Kaposi sarcoma is a vascular tumor that can involve the skin as well as visceral organs. We describe a case of visceral and cutaneous Kaposi sarcoma that presented with diffuse bilateral pulmonary infiltration and breathlessness 6 month after heart transplantation. Following modulation of the immunosuppressive regimen and addition of chemotherapy, the patient had an excellent response and has had an uneventful 1-year follow-up.

Human infections due to Mycobacterium lentiflavum: first report in Iran.

Non-tuberculosis mycobacteria (NTM), as certain species of mycobacteria, can affect human in several ways. In the preceding years, the rate of NTM detection has risen in both immunocompromised and immunocompetent patients. On the other hand, several reports have debated the possibility of co-infection of both Mycobcateriu tuberculosis (MTB) and NTM in individuals that puts the role of NTM in disease manifestations under question. Moreover, it is now proven that some of the cases that are identified as anti-TB treatment failure or suspected for drug resistance are actually NTM.

Eight years of lung transplantation: experience of the National Research Institute of Tuberculosis and Lung Diseases.

BACKGROUND: Lung transplantation has evolved from an experimental procedure to a viable therapeutic option in many countries. In Iran, the first single-lung transplantation was performed in the year 2000, more than 3 decades after the first successful procedure in the world, and the first double-lung transplantation was performed in the year 2006. OBJECTIVE: To describe our 8-year experience in lung transplantation. PATIENTS AND METHODS: During 8 years, we performed 24 lung transplantation procedures. Underlying lung diseases were pulmonary fibrosis in 16 patients (66.6%); chronic obstructive pulmonary disease in 2 (8.3%); bronchiectasis in 5, including 2 patients with cystic fibrosis (20.8%), and alveolar microlithiasis in 1 (4.16%). Data for all patients were collected and analyzed. Procedures were carried out using standardized methods. The induction suppression regimen consisted of cyclosporine and methylprednisolone. Maintenance immunosuppression drugs were cyclosporine and mycophenolate mofetil, and tapering dosage of prednisolone. Patients were followed up with physical examinations, 3 times a week, as well as and cycle ergometry 3 times a week and spirometry and laboratory tests once a week and chest radiography per needed for up to 3 months posttransplantation. RESULTS: The longest survival time was 7.2 years, in a 60-year-old patient with idiopathic pulmonary fibrosis. Fourteen patients died, 8 as a result of hemodynamic instability and/or hemorrhage, 1 as a result of bone and fat emboli, 3 after cessation of drug and 2 of them after infection. CONCLUSION: Although lung transplantation is a complex procedure it can be performed in developing countries such as Iran.

First-line antituberculosis drug resistance prevalence and its pattern among HIV-infected patients in the national referral tuberculosis centre, Iran.

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.

Drug abuse profile - patient delay, diagnosis delay and drug resistance pattern - among addict patients with tuberculosis.

Socioeconomic problems limit the access of drug users to health-care services. This descriptive cross-sectional study was carried out by making use of the medical records of new case tuberculosis (TB) patients hospitalized at Masih Daneshvari Hospital, the national referral centre in Iran, from 2003 to 2006. Demographic and personal characteristics of the patients and type of disease were collected and categorized. Of the 944 patients with confirmed TB, 143 (15.1%) were drug users, among whom 140 (97.9%) were men with just three women drug users. The mean age of the drug users group was 43.04 +/- 13.81 years. The type of drug used was opium in 100 cases (69.9%), heroin in 29 (20.3%), opium and heroin together in four (2.8%) and all three, opium, heroin and crack, in two (1.4%). For 238 high-risk patients, an HIV test was performed and HIV infection was confirmed in 33 cases. Patient delay was longer in drug users (P = 0.000) against other patients, whereas diagnosis delay was shorter (P = 0.007). Drug susceptibility tests were performed for 515 patients with positive cultures. One hundred and thirty-three (14.1%) were found to have 'any resistance' to anti-TB drugs, and 10 (1.1%) individuals had multidrug-resistant TB. Twenty-six (19.5%) of the individuals who showed resistance to first-line agents were drug users. There was no significant relation between drug resistance and drug use (P = 0.4). In conclusion, it seems that active case finding for TB and HIV in addict cases must be contained in harm reduction packages. Moreover, the manifestations of the disease should be considered seriously regardless of attributing them to drug use.