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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.

Background The impact of low body mass index (BMI) at initiation of rifampicin-resistant tuberculosis (RR-TB) treatment on outcomes is uncertain. We evaluated the association between BMI at RR-TB treatment initiation and end-of-treatment outcomes. Methods We performed an individual participant data meta-analysis of adults aged ≥18 years with RR-TB whose BMI was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (BMI Results Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (interquartile range) age was 37 years (29 to 47), and 455 (9%) had HIV. Compared with nonunderweight patients, the aOR among underweight patients was 1.7 (95% CI, 1.4–1.9) for any unfavorable outcome, 3.1 (2.4–3.9) for death, and 1.6 (1.2–2.0) for failure/recurrence. Significant effect modification was found for World Health Organization region of treatment. Among HIV-negative patients, 24-month mortality was 14.8% (95% CI, 12.7%–17.3%) for underweight and 5.6% (4.5%–7.0%) for not underweight patients. Among patients with HIV, corresponding values were 33.0% (25.6%–42.6%) and 20.9% (14.1%–27.6%). Conclusions Low BMI at treatment initiation for RR-TB is associated with increased odds of unfavorable treatment outcome, particularly mortality.

BackgroundCoronavirus disease 2019 (COVID-19) is a pandemic disease. Experiments with influenza and severe acute respiratory syndrome (SARS) have shown supplemental vitamin D can reduce the risk of infection and death.AimThis study was performed to evaluate the relationship between vitamin D levels and the severity and outcome of admitted patients with COVID-19.Material and MethodsThis cross-sectional study was performed on COVID-19 cases diagnosed by examining RT-PCR assay for SARS-CoV-2 or a set of symptoms and typical findings in lung CT scan. Based on clinical and radiologic characteristics, the patients were categorized as mild, moderate, severe, and critical. Calcium, phosphorus, albumin, creatinine, and serum 25 hydroxy vitamin D were measured and their correlation with the severity and outcome were analyzed.ResultsFrom May 1 to June 31, 2020, 508 patients ((442 patients in general wards and 66 patients in intensive care unit (ICU)) were included in this study. The participants were 56±17 years old (mean ±SD) (range from 14 to 95 years) and 52% were male. According to the past medical history, 190 (37.4%) of them had comorbidity. Concerning severity, 13.2%, 42.3%, 35.4%, and 9.1% had the mild, moderate, severe, and critical disease, respectively. The in-hospital mortality rate was 10.8%. In the multivariate regression analysis, age had a positive correlation and use of vitamin D supplement, serum level of 25 OH vitamin D, calcium, and albumin had a negative correlation with disease severity and admission to ICU. Poor outcome was inversely related to serum levels of vitamin D, calcium, albumin, and renal function. Vitamin D deficiency increased the rate of ICU admission by 2.7 times (95%CI=1.288-5.91, P=0.009).ConclusionIn patients who are hospitalized due to COVID-19, low 25-hydroxyvitamin D, hypocalcemia, and hypoalbuminemia are associated with severe disease, ICU admission, and an increase in mortality.

The success of treatment strategies to control the disease relapse requires determining factors affecting the incident short-time and long-time of disease relapse. Therefore, this study was aimed to identify the factors affecting of short-and long-time of occurrence of disease relapse in patients with tuberculosis (TB) using a parametric mixture cure model.In this historical cohort study; the data was collected from 4564 patients with TB who referred to the Tuberculosis and Lung Diseases Research Center of Dr. Masih Daneshvari Hospital from 2005 to 2015. In order to evaluate the factors affecting of short-and long-time of occurrence of disease relapse, a parametric mixture cure model was used.In this study, the estimation of the annual incidence of TB relapse showed that the probability of recurrence in the first year is 1% and in the third and tenth years after treatment is 3% and 5%, respectively. In addition, the results of this study showed that the variables of residence, exposure to cigarette smoke, adverse effects of drug use, incarceration, and pulmonary and extra- pulmonary tuberculosis were the factors affecting the short-time recurrence of TB. The variables of drug use, pulmonary and extra- pulmonary tuberculosis, and also incarceration affected the long-term recurrence of this disease.Cure models by separating factors affecting the short-time occurrence from the long-time occurrence of disease relapse can provide more accurate information to researchers to control and reduce TB relapse.

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.

OBJECTIVE To screen for Tuberculosis (TB) in human immunodeficiency virus (HIV) people in an effort to improve early TB diagnosis and reduce TB transmission. METHODS 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. RESULTS Of the 154 HIV patients included, 58 (38%) had tuberculosis with a mean CD4 cell count of 68 cells/mm3 . Active TB was found in 56 (47%) patients with a history of intravenous drug use. Cough (OR = 3.1, 95% CI 1.2-7.79), positive TST (OR = 8.15, 95% CI 3.28-20.25) and an abnormal chest X-ray (OR = 5.1, 95% CI 1.84-14.2) were the predicting factors for detecting active TB among HIV patients. The sensitivity and specificity of a combination of any symptoms with chest X-ray, smear, TST or all of these were 96.5% and 86.5%, respectively. CD4 cell count

Item does not contain fulltext BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Funding: World Health Organization and Canadian Institutes of Health Research. Background: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ. Methods: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1–3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology. Findings: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8–9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1–7·3), but no significant effect on mortality (aOR 0·7, 0·4–1·1) or acquired rifampicin resistance (aOR 0·1, 0·0–1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2–0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates. Interpretation: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis. Funding World Health Organization and Canadian Institutes of Health Research. Postprint

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.

Active tuberculosis (TB) is one of the major opportunistic infections that may occur in solid organ transplant recipients. Diagnosis and treatment of latent and active TB are challenging in this population due to lack of randomized clinical trials. In this review, we discuss the clinical manifestations of TB, diagnosis of latent TB and treatment of both latent and active TB.

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.

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

Hepatic toxicity is the most serious adverse effect of anti-tuberculosis drugs. This study was performed to evaluate the efficacy of silymarin as a hepatoprotective herbal agent. In a randomized double blind clinical trial, 70 new cases of pulmonary tuberculosis were divided into two groups. The intervention group was assigned to receive silymarin and the control group received placebo. Tuberculosis was treated by classic regimen consisting isoniazid, rifampin, pyrazinamide and ethambutol. No statistically significant difference was found between the two groups concerning the frequency of drug induced liver injury or mild elevation of liver enzymes. Silymarin was safe without any major side effect. Our results showed no significant hepatoprotective effect of silymarin among patients on tuberculosis treatment.

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.

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.

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.