Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: A systematic review and meta-analysis

Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis, all published articles which investigated the effects of these polymorphisms on the risk of TB in the Iranian population were retrieved. PubMed and Scopus were searched with no date or language restrictions. In this meta-analysis, the Comprehensive Meta-Analysis (CMA) version 2.0 and random effects model were applied. The association of polymorphisms with TB risk was assessed by measuring the odds ratio (ORs) at 95 CI. Heterogeneity was investigated based on Cochran Q-test and I2-index statistics. The significance level was set at 0.05. Also, Egger's regression intercept was determined to measure publication bias. A total of six articles on Iranian populations were included. TaqI (5/6 included studies) showed a significant association with the increased risk of TB based on ORs (allele comparison: 1.57 (1.0, 2.3), p-value: 0.02; additive model of tt/TT: 1.57 (0.9, 2.5), p-value: 0.05; recessive model (tt/Tt + TT): 1.99 (1.2, 3.2), p-value: 0.00; dominant model (tt + Tt/TT): 1.98 (1.1, 3.5), p-value: 0.01). BsmI showed a significant positive effect on TB risk only in its dominant genotype (bb + bB/BB) (1.44 (1.0, 1.9); p-value: 0.02). FokI and ApaI did not show any significant effects on TB development in Iranian populations. Findings showed the significant effect of TaqI polymorphism in all genetic models and the dominant model of BsmI on the increased risk of TB. However, the effects of TaqI and BsmI should be further investigated in a larger sample size. © 201

Incidence, mortality, and burden of severe acute respiratory infection in Iran in 2015

Background: Severe Acute Respiratory Infection (SARI) is responsible for mortality and hospital admissions in millions of people across the world. The present study, for the first time, aimed at estimating the incidence, mortality, and burden of SARI in Iran in 2015. Methods: Disability Adjusted Life Years (DALYs) was used as an index to estimate the burden of SARI. The SARI-related DALYs was calculated using a method developed by the WHO for assessing the Global Burden of Diseases. DALYs are calculated as the sum of the Years Lost due to Disability (YLDs) and the Years of Life Lost (YLLs) due to premature mortality. The data on the incidence and mortality were obtained from the SARI surveillance system of Iran's Ministry of Health and Medical Education. The average duration until remission or death and the disease disability weight were set at four weeks and 0.373, respectively. Results: In 2015, the incidence of SARI was 21309 and 20885 among males and females, respectively. Moreover, 773 males and 737 females died from this disease (Case fatality rate was about 0.035). Total SARI-related DALYs in males and females was 17264 and 16720, respectively. Furthermore, YLLs was responsible for more than 96 of SARI-related DALYs in 2015. Conclusion: There was no significant difference between males and females in terms of the incidence, mortality, and burden of SARI in 2015. Epidemiological data are required to adopt appropriate policies and responses to prevent and control SARI. The incidence, mortality, fatality, and burden of SARI are significant in Iran. It is necessary to develop appropriate strategies, such as vaccination against major pathogens of the disease at least in high-risk groups, strengthening the disease surveillance system, and attracting the attention of policy makers and health authorities of the country. © 2019, Iranian Journal of Public Health. All rights reserved

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0) patients. Two patients (7.7) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7) developed one type of autoimmunity, and 16 patients (59.3) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6). In 13 patients (61.9), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7), gastrointestinal (48.1), rheumatologic (25.9), and dermatologic (22.2) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity. © 2020 Georg Thieme Verlag. All rights reserved

Outpatient parenteral antimicrobial therapy in children with febrile urinary tract infection: a prospective randomized clinical trial

"nBackground: Acute pyelonephritis may lead to permanent renal scarring. The standard recommendation for treatment of febrile children with urinary tract infection (UTI) is hospitalization for intravenous antibiotics. The purpose of this study was to compare the efficacy of outpatient intravenous ceftriaxone and cefixime versus inpatient of the same regimen for children with febrile UTI.   "nMethods: In a randomized clinical trial, we compared the efficacy of administration two days intravenous ceftriaxone followed by an oral cefixime for eight days (as outpatient group) versus four days intravenous ceftriaxone followed by an oral cefixime for six days (as inpatient group), in 203 children (99 cases in outpatient group and 104 cases in inpatient group) 3 months to 15 years of age with febrile UTI, in terms of short-term clinical outcomes (sterilization of the urine and defeverescence) and long-term morbidity (incidence of reinfection and renal scarring documented by DMSA scintigraphy. "nResults: Repeat urine cultures were sterile within 48 hours in all children, mean time to defeverescence was 27.58 (SD=±12.62) and 31.44 (SD=±17.06) hours for children in outpatient and inpatient groups, respectively (P=0.067). Reinfection occurred in 9.1% of outpatient and 13.4% of inpatient group (P=0.326). Renal scarring developed in 11% of children of outpatient and 7.6% of children of inpatient group (P=0.884). There was no significant difference between the two groups in respect of renal scarring. "nConclusions: Outpatient ceftriaxone for two days followed by cefixime to complete a 10 days course can be recommended as a safe and effective treatment for children with febrile UTI

Main Polymorphisms in Aspirin-Exacerbated Respiratory Disease

Aspirin exacerbated respiratory disease (AERD) is a condition caused by increased bronchoconstriction in people with asthma after taking aspirin or another NSAID. Molecular analysis of the human genome has opened up new perspectives on human polymorphisms and disease. This study was conducted to identify the genetic factors that influence this disease due to its unknown genetic factors. We evaluated research studies, letters, comments, editorials, eBooks, and reviews. PubMed/MEDLINE, Web of Sciences, Cochrane Library, and Scopus were searched for information. We used the keywords polymorphisms, aspirin-exacerbated respiratory disease, asthma, allergy as search terms. This study included 38 studies. AERD complications were associated with polymorphisms in ALOX15, EP2, ADRB2, SLC6A12, CCR3, CRTH2, CysLTs, DPCR1, DPP10, FPR2, HSP70, IL8, IL1B, IL5RA, IL-13, IL17RA, ILVBL, TBXA2R, TLR3, HLA-DRB and HLA-DQ, HLA-DR7, HLA-DP. AERD was associated with heterogeneity in gene polymorphisms, making it difficult to pinpoint specific gene changes. Therefore, diagnosing and treating AERD may be facilitated by examining common variants involving the disease

Evaluation of Antibody Response to Polysaccharide Vaccine and Switched Memory B Cells in Pediatric Patients with Inflammatory Bowel Disease

Background/Aims: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. Methods: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. Results: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 μg/mL vs 219.8±59.0 μg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. Conclusions: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods. (Gut Liver 2014;8:24-28)