Evaluation of interleukin-12 receptor Beta1 and interferon gamma receptor 1 deficiency in patients with disseminated BCG infection

Introduction: Disseminated BCG infections among other complications of Bacillus Calmette-Guérin (BCG) vaccine are rare and have occurred in children with immunodeficiency disorders such as mendelian susceptibility to mycobacterial disease (MSMD) which could be due to defects in some elements of IL-12/IFN-γ axis. MSMD-causing mutations have been identified in 10 genes during the last two decades. Among them, mutations in the IL12Rβ1 and IFN gamma R1 genes constitute about 80% of recorded cases of MSMD syndrome. The aim of this study was to investigate IL-12RBeta1 and IFN- gammaR1 deficiencies in patients with disseminated BCG infection. Methods: This study was performed on 31 children with disseminated BCG infections who referred to children's medical center. Whole blood cell culture was performed in presence of BCG, IL-12 and IFN- gamma stimulators. The supernatants were assayed for IFN-gamma and IL-12p70 by ELISA method. In order to evaluate IL12Rbeta1 and IFN- gammaR1 receptors expression, flow cytometry staining was performed on the patients’ T-cells stimulated with PHA. Results: Flow cytometry staining of 31 Iranian patients with disseminated BCG infections with the average age of 43 months showed lack of the expression of IL-12RBeta1 and IFN- gamma R1 genes in PHA-T-cells of the nine and one patients, respectively in whom the incomplete production of IFN- gamma and IL-12 was reported by ELISA. Among these 10 patients, eight cases had related parents (80%). Conclusion: It is recommended that to avoid BCG complications, screening be performed for MSMD before BCG inoculation in individuals with positive family history of primary immunodeficiency diseases and inhabitants of areas with high frequency of consanguinity

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Evaluation of interleukin-12 receptor ß1 and interferon gamma receptor 1 deficiency in patients with disseminated BCG infection.

INTRODUCTION: Disseminated BCG infections among other complications of Bacillus Calmette-Guérin (BCG) vaccine are rare and have occurred in children with immunodeficiency disorders such as mendelian susceptibility to mycobacterial disease (MSMD) which could be due to defects in some elements of IL-12/IFN-γ axis. MSMD-causing mutations have been identified in 10 genes during the last two decades. Among them, mutations in the IL12Rß1 and IFNγR1 genes constitute about 80% of recorded cases of MSMD syndrome. The aim of this study was to investigate IL-12Rß1 and IFN-γR1 deficiencies in patients with disseminated BCG infection. METHODS: This study was performed on 31 children with disseminated BCG infections who referred to children's medical center. Whole blood cell culture was performed in presence of BCG, IL-12 and IFN-γ stimulators. The supernatants were assayed for IFN-γ and IL-12p70 by ELISA method. In order to evaluate IL12Rß1 and IFN-γR1 receptors expression, flow cytometry staining was performed on the patients' T-cells stimulated with PHA. RESULTS: Flow cytometry staining of 31 Iranian patients with disseminated BCG infections with the average age of 43 months showed lack of the expression of IL-12Rß1 and IFN-γR1 genes in PHA-T-cells of the nine and one patients, respectively in whom the incomplete production of IFN-γ and IL-12 was reported by ELISA. Among these 10 patients, eight cases had related parents (80%). CONCLUSION: It is recommended that to avoid BCG complications, screening be performed for MSMD before BCG inoculation in individuals with positive family history of primary immunodeficiency diseases and inhabitants of areas with high frequency of consanguinity.

High frequency of vancomycin resistant Enterococcus faecalis in children: an alarming concern.

INTRODUCTION: Enterococcus spp. is considered as important etiological agents of nosocomial infections. However, a little is known about the epidemiology of vancomycin resistant Enterococcus faecalis (VREF). The aim of this study was to investigate the frequency of VREF and detecting of two prevalent resistance genes (vanA, vanB) at Children Medical Center Hospital, an Iranian referral pediatric Hospital. MATERIALS AND METHODS: During January 2013 to December 2013, 180 E. faecalis were isolated from clinical samples of hospitalized children. Antimicrobial testing was performed by Kirby-Bauer disk diffusion to gentamicin, amikacin, ceftriaxone, cefotaxime, ceftazidim, cefixime, piperacillin/tazobactam, cefepime, trimethoprim/sulfamethoxazole, erythromycin, clindamycin, linezolide and E-test method vancomycin and teicoplanin according to Clinical Laboratories Standards Institute (CLSI). Two prevalent resistance genes (vanA, vanB) were investigated in VREF isolates. RESULTS: Seventy-five (42%) of patients were male and 105 (58%) were female. Mean age of patients was 34.74 months. Cephalosporin resistance was found in majority of E. faecalis isolates (98.7 to ceftazidim, 95% to cefixime, 93.3% to ceftriaxone, and 89.4% to cefotaxime). Most of the isolated were susceptible to cefepime (91.7%). In addition, high level of erythromycin and clindamycin resistance was reported (93.4% and 91.2%). There were no linezolid-resistant E. faecalis among all isolates. Teicoplanin resistance was observed in 13.8% of E. faecalis (n = 25). Minimum Inhibitory concentration (MIC) ≥ 32 µg/ml for vancomycin was found in 29 isolates (16%) and vanA gene was detected in 21 (72%) VREF strains, while vanB gene was not detected in any of these isolates. The mortality rate of all cases was 3.4%. CONCLUSIONS: This study revealed high rate of vancomycin resistance in E. faecalis strains. Therefore, periodic surveillance of antibacterial susceptibilities is highly recommended to detect emerging resistance.