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Summary Background HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis. Methods We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection. Findings We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0–2·9) for all patients with HIV-infection, 1·8 (1·5–2·2) for HIV-positive patients on ART, and 4·2 (3·0–5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death. Interpretation Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued. Funding American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

We regret that this article is behind a paywall., BACKGROUND: Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens. METHODS: We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug. FINDINGS: 58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed. INTERPRETATION: Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.

Supplemental vitamin D can reduce the risk and mortality of viral pneumonia. The relationship between 25 hydroxyvitamin D [25(OH)D] levels and the severity and mortality of Coronavirus disease 2019 (COVID-19) was evaluated. In this cross-sectional study, the admitted patients with COVID-19 were categorized as mild, moderate, severe, and critical based on clinical and radiologic characteristics. Calcium, phosphorus, albumin, creatinine, and serum 25(OH)D were measured and their correlation with the severity of disease and mortality were analyzed. During 2 months, 508 patients (442 patients in general wards and 66 patients in the intensive care unit (ICU)) were included. The participants were 56 ± 17 years old (52% male, 37% with comorbidity). Concerning severity, 13%, 42%, 36%, and 9% had mild, moderate, severe, and critical diseases, respectively. The mortality rate was 10.8%. Admission to ICU, severity of disease and mortality decreased significantly across quartiles of 25(OH)D. According to multivariate logistic regression analysis, disease mortality had a positive correlation with age and had a negative correlation with the serum level of 25(OH)D, calcium, and albumin. In hospitalized patients with COVID-19, low 25(OH)D was associated with severe disease and increased ICU admission and mortality rate.

Considering the increasing prevalence and burden of coronavirus disease 2019 (COVID-19) disease and false-negative results in routine reverse transcription-polymerase chain reaction (RT-PCR) tests, additional diagnostic methods are needed to diagnose active cases of this disease. This prospective study was conducted on patients, in whom clinical and radiological symptoms/signs were in favor of COVID-19 while their first PCR test was negative. Later on, a second RT-PCR was performed and serological evaluation was carried out and results were compared with each other. Out of 707 patients who had been referred to the hospital and were clinically and radiologically suspicious of disease, 137 patients with negative RT-PCR tests entered the study. RT-PCR assay became positive for the second time in 45 (32.8%). Anti-COVID-19 IgM and IgG antibodies were positive in 83 (60.6%) and 86 (62.8%) patients, respectively. Finally, it was determined that serological test was diagnostic in 73% of patients and the diagnostic yield of serology was significantly higher after the first week of illness (54.8% in the first week and 88% after that). Taking advantage of both serological tests and RT-PCR helps in diagnosing 83.9% of cases. Based on the present study, the serology may be useful as a complementary test and in parallel to RT-PCR assay for diagnosis of COVID-19 among admitted symptomatic cases.

Highlights: • To date, there is not any specific agent to treat COVID-19. • Interferon-β1 can be used as a treatment of COVID-19. • Interferon-β1-a can reduce mortality rate in admitted patients with COVID-19. • Interferon-β1-a can improve oxygen support in hospitalized patients with COVID-19., Interferon Beta-1a (IFN-β1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-β1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-β1-a and Lopinavir 400mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-β1-a on outcome and all-cause mortality. 152 cases in IFN-β1-a group and 304 cases as control group were included. IFN-β1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p=0.001) and (34% vs. 24%, p=0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-β1-a (HR 5.12, 95% CI: 2.77- 9.45), comorbidity (HR 2.28, 95% CI: 1.13- 4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56- 4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-β1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-β1-a in COVID-19 treatment.

Highlights • The pathophysiology of severe SARS-CoV-2 infection may be attributed to cytokine release syndrome. • In this syndrome, inflammatory cytokines (especially interleukin 6) are released after the activation of the inflammatory cascade. • The mortality rate among patients receiving tocilizumab with severe or critical SARS-CoV-2 infection was reported 16% in the current study comparing to 49 % based on the recent studies. • Tocilizumab, as an interleukin 6 antagonist, may be a promising agent to decrease the mortality rate in severe or critical SARS-CoV-2 infection., Background The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. Methods In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. Results Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. Conclusions Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.

Background Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-β-1a administration in COVID-19. Methods In this prospective non-controlled trial, 20 patients included. They received IFN-β-1a at a dose of 44 µg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study. Results The mean age of the patients was 58.55 ± 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 ± 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period. Conclusions Our findings support the use of IFN-β-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19. Clinical trial registration number: IRCT20151227025726N12.

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.

Drug-induced hepatitis (DIH) is one of the major complications among the treatment of patients with tuberculosis (TB); it might even be fatal. This study tries to address the recurrence of DIH with 2 anti-TB regimens. In the retrospective study from 2007 to 2010, 135 TB patients with DIH who were older than 16 years were entered to study. The patients with DIH were randomly treated with a regimen, including isoniazid, rifampin, and ethambutol, plus either ofloxacin or pyrazinamide. The patients were reviewed for occurrence of recurrent DIH. Cure and completed treatment were considered as acceptable treatment outcomes, whereas default of treatment, treatment failure, and death were considered to be unacceptable outcomes. Therefore, 135 subjects with DIH were reviewed, and 23 patients (17%) experienced recurrence of hepatitis (19 cases in the ofloxacin group and 4 cases in the pyrazinamide group). There is no significant difference in recurrence of hepatitis between these 2 groups (P = 0.803). An acceptable outcome was observed in 95 patients (70.4%), and an unacceptable outcome was seen in 14 cases (10.3%). There was no significant difference in outcomes between these 2 regimens (P = 0.400, odds ratio = 1.62, 95% confidence interval, 0.524-4.98). The results of our study suggest that ofloxacin-based anti-TB regimen does not decrease the risk of recurrent DIH. Therefore, adding ofloxacin in the case of DIH is not recommended.

A significant link between diabetes mellitus (DM) and tuberculosis (TB) has been widely demonstrated. DM increases the risk of TB in all aspects. The aims of this study were to assess the prevalence of DM among newly diagnosed TB patients, to screen these patients for DM, and to determine the number needed to screen (NNS) to diagnose new cases of DM.A prospective cohort descriptive study was carried out in Iranian adults admitted to the National Research Institute of Tuberculosis and Lung Disease from 2012 to 2013 with a new diagnosis of TB. Glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) were measured for all patients.Of the 293 patients included, 101 (34.5%) had DM. DM was newly diagnosed in 45 (19%) patients. The number needed to screen was 5 to identify one new DM case. Age ≥ 40 years was associated with DM in this population (odds ratio (OR) = 3.91, 95% confidence interval (CI) = 1.47-10.38).Screening for DM should be performed routinely in patients with TB and may improve treatment outcomes.

Tuberculosis (TB) is still a major health problem and TB hospital readmission could increase health system costs. In a retrospective study in a tertiary referral hospital for TB in Tehran, Iran, TB patients with readmission were evaluated. These TB patients in the index year who were then readmitted were compared with TB patients in the same year who were not readmitted during the follow-up period. One hundred and forty-six patients had hospital readmission within three-year follow-up with mean age of 51.6 years old of whom 78 patients (53.5%) were men. Univariate analysis revealed married status, smoking, opium smoking, and medical comorbidities (chronic obstructive pulmonary disease [COPD], hypertension, and human immunodeficiency virus [HIV] infection) as risk factors. Final logistic regression model revealed married status and smoking values of (0.478 odds ratio [OR], 0.310–0.737; 95% confidence interval [CI], P = 0.001) and (1.932 OR, 1.269–2.941; 95% CI, P = 0.002), respectively. Readmission predicted probability was 37% for married patients and 31% for active smokers. The most common medical comorbidities in the first readmission were COPD and HIV infection. Dyspnea and anti-TB drug-induced hepatitis were a common cause of early readmission, while failure and default of treatment were more frequent causes of late readmission. Admission and discharge guidelines, outpatient follow-up, and smoking cessation intervention were proposed as important factors in decreasing the readmission rate.

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.

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.

The early definitive diagnosis of pulmonary tuberculosis (TB) is important for control of the disease in the community. We performed this study to evaluate the additional gain of post-bronchoscopy sputum in the diagnosis of pulmonary TB.Bronchoscopy and bronchoalveolar lavage were performed for 126 patients suspected of pulmonary TB who either had 3 negative sputum smears for acid-fast bacilli or could not expectorate. After bronchoscopy the patients were asked to give sputum samples for 3 consecutive days. All of the obtained specimens were investigated for Mycobacterium tuberculosis by smear and culture.Pulmonary TB was confirmed in 56 patients. Among all confirmed cases, the sensitivity of bronchoalveolar lavage smear was 57.1% (32 of 56), sensitivity of post-bronchoscopy smear was 76.7% (43 of 56), and the yield of a combination of the 2 methods was 83.9% (47 of 56). Results of post-bronchoscopy sputum smears were not significantly related to sex, age, human immunodeficiency virus (HIV) infection, presence of cavitary lesions on chest X-ray, or the ability to expectorate before bronchoscopy (p0.05).Evaluation of post-bronchoscopy sputum smears is helpful for earlier diagnosis of pulmonary TB and is an inexpensive and accessible assay.

Currently, the Category (CAT) II regimen is recommended for patients who have failed the CAT I regimen. We have determined before that prevalence of multidrug-resistant tuberculosis (MDR TB) is relatively high among these patients. On the other hand, the retreatment success rate with CAT II in CAT I treatment failures and defaults is nearly 50%. Therefore, we tried to find another strategy with a higher success rate. From January 2004 to November 2007, 105 patients with pulmonary TB, who failed a prior CAT I regimen or with more than one course of irregular anti-TB treatment, were included in this study, whereas five cases with nontuberculous mycobacteria were excluded. Drug susceptibility testing (DST), for first line anti-TB drugs, and polymerase chain reaction were performed. By the time of availability of DST that took 3 to 4 months, a pilot protocol consisted of isoniazid, rifampin, ethambutol, ofloxacin, cycloserine, and amikacin was started. Then therapeutic regimen was adjusted based on four categories of DST pattern: sensitive, non-MDR pattern, MDR pattern, and culture-negative. Sensitive patients received the standard CAT I regimen, non-MDR patients an individualized regimen based on DST, MDR patients a standard second-line regimen, and culture-negatives a standard CAT I plus a 6-month injectable agent. Treatment outcomes were categorized and analyzed. Forty-eight patients with prior CAT I treatment failure and 52 with more than one irregular treatment courses were included in the analysis. Six percent of subjects had confirmed HIV infection. Seventy-two percent of subjects were assigned to a good outcome and 28% were assigned to a poor outcome group. Seventeen percent were culture-negative. Regarding DST pattern, 13% isolated strains were completely sensitive to first-line drugs. 53% strains were MDR, 10% monodrug-resistant, and 7% polydrug-resistant. There was no significant association between DST pattern and outcome (P = 0.13). The irregular regimen was associated with MDR TB as twice as CAT I regimen failure (69.2% versus 35.4%, P = 0.004). Patients with MDR TB significantly experienced more side effects than non-MDR-TBs (47% versus 27%, P = 0.102). Of 100 patients, 72% were cured, 5% abandoned treatment, 12% died, 6% were classified as treatment failures, 1% relapsed, and 5% were transferred out. Of 53 patients with MDR TB, 33 subjects were cured and seven died. All together, successful outcome was achieved in 62.2%, 76%, and 76% of MDR TB, non-MDR TB, and completely sensitive cases, respectively. A retreatment strategy based on DST and replacing the Category II regimen with an intermediate regimen called revised CAT II may improve clinical outcomes among Category I treatment failures and defaults who found to have active, infectious MDR TB. This strategy significantly reduces delays to MDR TB diagnosis and to the initiation of MDR TB therapy. Success rate of this strategy is 62.2% and 72% in MDR TB and overall CAT I failure cases and defaulters, respectively.

Compared with the treatment of drug-sensitive tuberculosis, the treatment of multidrug-resistant tuberculosis (MDR-TB) is more difficult. This study was conducted at the national referral center of tuberculosis in Tehran, Iran, to evaluate adverse drug reactions of treatment of MDR-TB. From 2006 to 2009, all patients admitted into Masih Daneshvari Hospital in Tehran, Iran, for MDR-TB were considered for this study. The standard treatment for MDR-TB consisted of amikacin, prothionamide, ofloxacin, and cycloserine. Ethambutol and pyrazinamide were added to treatment if mycobacterium was sensitive to them. All adverse effects observed in patients were recorded in our registry. Eighty patients were considered in the study; of this cohort, 44 were male and 36 were female. The mean age of patients was 40.64 ± 17.53 years (range, 14-81 years). All patients received standardized therapy for MDR-TB. The major adverse effects included neurologic side effects (depression, convulsions, consciousness, psychosis, suicide; 7.5%), hepatitis (5%), rash (1.3%), renal toxicity (3.8%), and auditory toxicity (14.5%). Those with neurologic side effects had less favorable outcome (P value = 0.038) and risk of death was increased among them (odds ratio, 13.8; 95% confidence interval, 2.2-86.77). Other adverse effects did not show statistical significance in our analysis. A major adverse effect such as neurologic side effects (depression, convulsions, consciousness, and psychosis) can result in an increased chance of death among patients with MDR-TB.

Background Extensively drug-resistant tuberculosis (XDR-TB) has recently been identified as a major threat to global health. XDR-TB poses a risk of higher failure rates and death during TB treatment. We report herein the outcomes of XDR-TB in patients treated with the standardized regimen in Iran. Patients and methods Between 2002 and 2006, seven patients were diagnosed with XDR-TB. All patients were treated with the standardized second-line regimen containing cycloserine, prothionamide, amikacin, and ofloxacin. First-line drugs, such as ethambutol and pyrazinamide, were added to the regimen if drug susceptibility testing showed sensitivity to these drugs. Results Four (57.1%) patients were male. All seven patients were HIV-negative. The patient age range was 22–79 years. Of the seven cases, the final outcome was ‘cure' in two (28.6%), ‘relapse' in one, ‘treatment failure' in one, and ‘death' in two; the outcome for one patient was unknown. Conclusion Our study shows a poor prognosis in patients with XDR-TB. This indicates the necessity of detecting XDR-TB cases earlier, as well as the need to gain access to more second-line agents. This is particularly important in resource-limited settings in order to administer individualized regimens.

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.

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

To screen for Tuberculosis (TB) in human immunodeficiency virus (HIV) people in an effort to improve early TB diagnosis and reduce TB transmission.A prospective study was conducted on adult HIV people from 2008 to 2011. Three samples of sputum, cell blood count, tuberculin skin test (TST) and chest X-ray were obtained from all patients. The characteristics of HIV patients with TB and HIV patients without TB were compared to each other.Of the 154 HIV patients included, 58 (38%) had tuberculosis with a mean CD4 cell count of 68 cells/mmThere was a high prevalence of TB within the HIV population. Screening for TB among these patients can be carried out at every clinic or health facility using a combination of symptoms, TST, chest X-ray and smear sample.

The nature of tuberculosis (TB), being one of the most common opportunistic infections, is different among HIV-infected patients than HIV-negative patients. A retrospective study was conducted on HIV-positive and HIV-negative patients with new TB pleural effusion who were admitted to the National Research Institute of Tuberculosis and Lung Diseases in Tehran, Iran from 2005 to 2012. The two groups were compared with respect to clinical, imaging, mycobacteriologic and histopathologic characteristics of TB pleural effusion. In all, 42 HIV-positive and 132 HIV-negative cases of TB pleural effusion were included. Bilateral pleural effusion was statistically more common in the HIV-positive group ( p = 0.004, OR = 3.81, 95% CI: 1.46–9.94) without any correlation with CD4 cell count. Pulmonary infiltration was found in 81% of HIV-positive and 49.2% of HIV-negative patients ( p = 0.001, OR = 4.38, 95% CI: 1.88–10.1). Mycobacteriologic studies led to the diagnosis of TB in 66.6% of HIV-infected and 49.2% of HIV-negative patients. In 23.8% of HIV-positive and 50.7% of HIV-negative patients TB was ultimately diagnosed by pleural biopsy. HIV remained significantly associated with positive culture of pleural fluid in multivariate analysis. The diagnostic approach to TB pleural effusion in HIV-infected patients may be different. The diagnostic yield of mycobacteriologic studies was higher among HIV-positive patients, which may help in reducing the need for invasive procedures like pleural biopsy.

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.

Background: This study performed at the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran, aimed to evaluate the effect of concomitant pulmonary hypertension on the outcome of pulmonary tuberculosis. Methods: New cases of pulmonary tuberculosis were recruited for the study. Pulmonary hypertension was defined as systolic pulmonary arterial pressure ≥35 mm Hg estimated by transthoracic Doppler echocardiography. We assessed the relationship between pulmonary hypertension and mortality during the six-month treatment of tuberculosis. Results: Of 777 new cases of pulmonary tuberculosis, 74 (9.5%) had systolic pulmonary arterial pressure ≥35 mm Hg. Ten of them (13.5%) died during treatment compared to 5% of cases with pulmonary arterial pressure less than 35 mm Hg (p = 0.007). Logistic regression analysis showed that pulmonary hypertension and drug abuse remained independently associated with mortality (OR = 3.1; 95% CI: 1.44–6.75 and OR = 4.4; 95% CI: 2.35–8.17, respectively). Conclusion: A significant association was found between mortality and presence of pulmonary hypertension and drug abuse among new cases of pulmonary tuberculosis. Keywords: Tuberculosis, Pulmonary hypertension, Echocardiography, Survival

Pneumothorax is a well known complication of pulmonary tuberculosis (TB), particularly in patients with advanced TB.At our national TB-referral hospital, we compared the medical records of 53 TB patients with pneumothorax and 106 TB patients without pneumothorax, seen in 2003 to 2008. We analyzed data on demographics; TB type (smear-positive, smear-negative, extrapulmonary); patient type (new patient, relapse, treatment default, treatment failure); clinical and radiological manifestations; surgeries; and outcomes.Of the 53 pneumothorax patients, 34 (64%) were male. The pneumothorax group's mean age was 34 y (range 14-76 y). Thirty-six (68%) of the pneumothorax patients were new TB cases (ie, TB undiagnosed before they presented with pneumothorax). Pneumothorax was not significantly associated with sex, smoking, or drug use. Pneumothorax was significantly more common in patients30 years old (P.001). In terms of radiological manifestations, 20 pneumothorax patients (38%) had cavitary lesions, and pulmonary infiltration and effusion were present in 19 (36%) and 17 (32%) patients, respectively. Cavitary lesion was significantly more common among the pneumothorax patients (P = .006). Overall, 47 (89%) of the pneumothorax patients were relieved with chest-tube insertion; the other pneumothorax patients were only observed.In patients30 years old or with cavitary lesions, worsening of the patient's respiratory condition should prompt consideration of pneumothorax.

The limited experience in treating patients with extensively drug-resistant tuberculosis (XDR-TB) shows a therapeutic success rate under 50-60% and there are no publications regarding the outcome of these patients treated with standardized regimens. All multidrug-resistant tuberculosis (MDR-TB) patients hospitalized at the Masih Daneshvari Hospital in Tehran, Iran, during 2004-2007 were recruited. Drug susceptibility testing to 14 drugs (including eight second-line drugs) was performed and a standardized regimen with ofloxacin, cycloserine, prothionamide, and amikacin was administered for all patients. Outcome of the patients was studied, comparing between the MDR-TB non-XDR-TB and the XDR-TB. Fifty-one patients were included, 12 with XDR-TB criteria. Of 51, 48 were HIV negative and HIV status was unknown in three cases. All 12 were HIV negative. XDR-TB infection was significantly associated only with age (p = 0.039). The success rates for the total 51 MDR-TB, the 39 MDR-TB non-XDR-TB, and the 12 XDR-TB patients were 76.5% (39 patients), 87.2% (34 patients), and 41.7% (5 patients), respectively. Resistance to ofloxacin, ciprofloxacin, and amikacin were found to be significantly associated with unsuccessful outcome. In this setting, a standardized second-line drugs regimen produces high treatment success rates in MDR-TB patients unless XDR-TB is present.

Drug-induced hepatitis (DIH) is an important issue in tuberculosis (TB) treatment. We intend to assess the incidence, risk factors, and outcome of hepatitis due to anti-TB drugs. The study is carried out at the national TB referral center 2006-2008 including all documented new cases of TB. All patients received standard anti-TB treatment. If DIH occurred, all drugs were discontinued and reinitiated after liver function tests (LFT) normalization in a stepwise way. Of total 761 patients, 99 (13.0%) patients developed DIH during anti-TB treatment. There was no difference in sex, nationality, smoking, or opium use history between the hepatitis group and the control group (P > 0.05). DIH was significantly higher in patients older than 65 years (P = 0.019). The mean duration of DIH from the beginning of treatment was 17.53 +/- 19.42 days (median = 12; 1-125 days). Also, the mean of the time elapsed from DIH till the (LFT) normalization was 10.26 +/- 5.95 (median = 9; 0-32 days). Anorexia, nausea, vomiting, abdominal pain, jaundice, diarrhea, decreased level of consciousness, and fever were significantly higher in patients with DIH. In DIH group, 13 patients (13.4%) died, whereas in the control group, death occurred just in 21 cases (3.2%) (P < 0.001, 95% confidence interval = 2.26-9.70, odds ratio = 4.7). After adjusting with logistic regression, all the anticipated factors retained the statistical significance. Our study indicated that DIH most often occurs during the first 2 weeks of anti-TB treatment. DIH development is associated with old age, certain clinical manifestations, and higher death rates.

Background In this study, we intended to find the prevalence of nontuberculosis mycobacteria (NTM) among patients who are referred as suspected multidrug-resistant tuberculosis (MDR-TB) cases to the only referral center in Iran. Methods All patients referred to our center in 2002–2006 as MDR-TB with histories of treatment with standard and CAT II World Health Organization regimens were included in the study. Sputum smear and culture for acid-fast bacilli were performed for all patients 3 times. Sputum polymerase chain reaction was also performed for all patients. Mycobacterial identification was performed via polymerase chain reaction and routine identification tests for all culture-positive cases. Results Of the 105 patients in the study, 12 (11.43%) were identified to have NTM infection. The identified mycobacteria were classified in order of prevalence as Chelonae (8 cases), Simiae (2 cases), Aloei (1 case), and Farcinogen (1 case). Based on radiologic findings, most of the cases demonstrated bilateral nodularity (83.3%) and also multifocal bronchiectasis (75%). Notably, cavitary lesions were present in 41.7% of the cases. Conclusion Based on the findings of this study, it is essential that such cases be identified before commencing MDR-TB treatment.

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

An approved treatment regimen for multi-drug resistant tuberculosis (MDR-TB) patients during pregnancy does not exist to this day. The main reason for the lack of information in this area is the small number of patients and insufficient studies regarding the safety of the second-line drugs during pregnancy on the mother and the fetus [1]. This case report highlights the difficulties associated with MDR-TB. In December 2003, an 18-year-old Afghan woman was admitted to our center on complaints of cough, sputum, and dyspnea. The patient had a history of two periods of anti-TB treatments (Cat I and Cat II) in the past two years. Despite two years of anti-TB treatment the patient’s mother died secondary to TB. The patient’s chest X-ray demonstrated opacity accompanied by a cavity in the middle-upper lobe of the right lung, and alveolar infiltration together with nodular densities in the lower lobe of the left lung. Sputum smear was positive for Koch’s Bacillus (BK). An empirical regimen for MDR-TB was commenced because of a positive smear of sputum for BK (Ofloxacin, high-dose Isoniazid, Amikacin, Clofazimin, Pyrazinamid, and B6). After completion of five months of therapy, sputum smear and culture results were negative again. The performed chest X-ray at this stage demonstrated a decrease in the size of the right cavitary lesion. Considering the results of the patient’s drug susceptibility test, which demonstrated resistance to the four drugs Isoniazid, Rifampin, Ethambutol, and Streptomycin, and sensitivity to Pyrazinamid, the treatment regimen was continued. Earlier in the treatment the patient was advised to refrain from becoming pregnant and educated regarding the potential teratogenic side effects of anti-TB medications on the fetus and the need for up to 18 months

⁎ Corresponding author. Masih Daneshvari Hospital, Darabad, Niavaran Tehran, Iran. E-mail address: s.mirzendehdel@gmail.com (S. Mirzendehdel). Understanding the prevalence of HIV and HPV infection among drug-addictedwomen and detecting high-risk HPV types could lead to integration of prevention and treatment into public health planning. This cross-sectional study of HPV and HIV prevalence was performed between 2007 and 2008 among women attending a drop-in center in Southern Tehran, Iran, that provides food and methadone to drugaddictedwomen.All addictedwomenattending the centerwere included in the study. All study participants were interviewed and their method of drug use was determined. After obtaining consent, a gynecological exam was conducted and a cervical swab sample was obtained for laboratory studies. If participants had vaginal discharge or there was clinical suspicion of pelvic infection, appropriate tests and treatment were provided. A 2 mL-sample of blood was obtained from the study participants and tested for HIV using an ELISA test (Adaltis Inc, Montreal, Canada). Positive screens were followed by western blot for confirmation. If test results were positive for HIV, referral was made to specialty clinics for further evaluation and possible treatment. Cervical swabs and scrapes obtained for HPV detection in all cases were transferred into tubes and transported at 8°C to the Virology Research Center of the National Research Institute of Tuberculosis and Lung Disease, Tehran. At the laboratory the cervical samples were resuspended in 500 μL of phosphate-buffered saline, immediately centrifuged, and the pellet was stored at −70 °C until further processing. For detection of HPV genotypes, nested polymerase chain reaction (PCR) analysis was performed using MY09/MY11 as the outer primers and GP5+/GP6+ as the inner primers, as previously described and with minor modification [1]. The positive samples were genotyped using a GP-E6/E7 nested multiplexPCRassay [1].HPVgenotypesweredivided into3groups: highrisk genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68); lowrisk genotypes (6–11, 42, 43, 44); and genotypes that could not be identified. The study protocol was approved by the scientific and ethics committee of the National Research Institute of Tuberculosis and Lung disease, Tehran. Data were analyzed using SPSS version 15.0 (SPSS, Chicago, IL, USA). Continuous variables were expressed as group means±SD. The χ test without Yates correction and a Fisher exact test were used as appropriate. All reported P values are two-sided. Pb0.05was considered statistically significant. Multivariate logistic regression was used to determine the independent risk factors for HPV and high-risk genotypes. A total of 118 women were included in the study. The average age of the participants was 35.06±1.16 years (range, 15–61 years). There were 15participantswithahistoryof intravenousdruguse.A total of 91 (77.1%) women had a history of crack cocaine use. Ten (8.5%) participants had a history of crack cocaine abuse and intravenous drug use. A total of 29 (24.6%) women had multiple sexual partners. Five (4.2%) women were unmarried, 51 (43.2%) were married, 51 (43.2%) were divorced, and 11 (9.3%) were widowed. Seventeen (14.4%) women were illiterate, 89 (75.4%) had a level of education below diploma level, and 12 (10.2%) participants had a diploma or higher level of education. Vaginal discharge was reported by 64 (54.2%) women. Candidiasis was found in 22 (18.6%) women and discharge caused by other infection was found in 44 (35.6%) participants. A total of 8 participants (6.8%) tested positive for HIV. The vaginal swab samples of 59 (50%)women testedpositive forHPV. More than one type of HPV virus was identified in 16 (13.6%) women. There were 26 (22%) cases of high-risk HPV, 9 (7.6%) cases of both high

We report the case of a 23-year-old asthmatic woman who had clinical and radiological deterioration due to Mycobacterium szulgai infection and good response to anti-mycobacterial treatment without any structural abnormalities in previous lung imaging studies. M. szulgai may be considered a pathogen able to cause deterioration of respiratory health even in patients with previously normal lungs.

Tuberculosis (TB) is a frequently encountered infection among organ transplant recipients in developing countries, and the incidence of infection after the first year of transplantation is considerably high. In this study, the impact of rifabutin treatment on organ transplant recipients with TB infection was evaluated with respect to the trend of infection, management and outcome. The medical records of 26 post-transplant patients who received an organ transplant between 2004 and 2012 and later diagnosed with TB of different organs were reviewed retrospectively. We retrieved data regarding clinical features as well as treatment and outcomes. The median time interval between transplantation and TB was 36 months (IQR 12-101 months). The most common form of infection was pulmonary/pleural TB. All our subjects received rifabutin instead of rifampin in the anti-TB treatment regime as rifabutin is a less-potent inducer of cytochrome P-450. All patients responded satisfactorily to the treatment and maintained excellent allograft function. Moreover, we did not have any mortality among our recipients. Drug-induced hepatitis was observed in nine (35%) patients. Rifabutin is an excellent alternative medication to rifampin in the setting of TB management. Hepatotoxicity is a potential risk for treatment because of the potential additive toxicity of immunosuppressive drugs.

Introduction: Several species of non-tuberculosis mycobacteria (NTM) can affect humans and can cause either symptomatic or asymptomatic infection. This study aimed to determine the clinical and radiological manifestation, as well as the treatment, of M. simiae in patients in Masih Daneshvari Hospital, a TB referral hospital in Iran. Methodology: This retrospective study involved all patients presenting to our referral center from 2002 to 2009, with confirmation of M. simiae pulmonary infection. For all patients, sputum smear and culture for identification was performed, as was drug susceptibility testing. Additionally, PCR identification methods for NTM, and high-resolution CT scan were conducted. All patients were treated according to American Thoracic Society recommendations.Results: In total, 26 cases of M. simiae were identified in our center. The mean age of the patients was 58.23 ± 16.9years. Only one patient was HIV positive, and all but one were Iranian. The most frequent symptom was coughing (92.3%), and 100% of the patients had nodular lesions. In addition, bronchiectasis and cavitation were present in 84.6% and 88.5% respectively. All the patients were resistant to every first-line drug. Two patients failed the treatment, and twenty-four were cured, after which no recurrence of the disease was observed.Conclusion: M. simiae may present with clinical and radiological manifestations consistent with tuberculosis, and be resistant to anti-TB agents. A more efficient treatment for NTMs such as M. simiae is needed, to shorten the period of treatment and proved fewer adverse effects than current therapies.