Prevalence of TB/ HIV co-infection in Iran: a systematic review and meta-analysis.

INTRODUCTION: Co-infection of TB/ HIV is an emerging threat to a global public health. Although several studies have investigated the prevalence of TB/HIV co-infection in Iran, the results are inconsistent. The current systematic review and meta-analysis was planned to estimate the overall prevalence of TB/HIV co-infection in Iran. METHODS: Electronic databases, including MEDLINE (via PubMed), SCOPUS, SID and Mag Iran (two Persian scientific search engines) were searched up to 27 Apr 2017. The random effect model was used for estimating the prevalence of TB/ HIV co-infection. Heterogeneity was assessed by subgroup analysis. RESULTS: Forty-eight articles met our inclusion criteria, with a total of 21,388 individuals. The meta-analysis demonstrates that the prevalence of TB/ HIV co-infection in Iran was 14% [95% confidence interval CI:12-15%]. According to the meta-analysis of 5 subgroups, the prevalence of TB/ HIV co-infection in the subgroup with high intravenous drug users (IVDU) [27%, 95% CI: 20-35%], in border provinces of Iran [17%, 95% CI: 13-21%], in the subgroup with pulmonary tuberculosis (PTB) ≥ 20% [22%, 95% CI: 17-27%], in patients <40 years of age [25%, 95 CI: 19-31%] was significantly higher. There were no significant differences between the prevalence of co-infection among low and high-quality studies. Pulmonary TB was the predominant type of TB among co-infected patients [77%, 95% CI: 71 to 84%]. CONCLUSIONS: Our study demonstrates that the overall prevalence of TB/HIV co-infection in Iran was 14% [95% CI: 12-15%], which was a high rate. Some factors such as using intravenous drugs, living in border provinces of Iran, having PTB, and age <40 years had an impact on the prevalence of co-infection. Results revealed the need of HIV surveillance program among TB patients and screening of HIV-positive patients for diagnosis and treatment of TB. Further large-scale studies about the prevalence of this infection in all provinces of Iran are needed.

Antimicrobial-resistance pattern of Shigella species in children: a six-year study in an Iranian referral Hospital.

BACKGROUND: Shigella species are a frequent cause of shigellosis and shigellosis is considered as one of the most common causes of diarrhea in children. This disease is endemic in many developing countries such as Iran. This study was carried out to determine the prevalence and pattern of antimicrobial resistance of Shigella species among pediatric patients with acute diarrhea in Children Medical Center (CMC) Hospital, with a diagnosis of acute diarrhea to CMC Hospital from March 2011 through March 2016. Isolation and identification techniques, as well as the susceptibility tests are described in detail. RESULTS: Of the 46,795 stool specimens that were sent to the microbiology laboratory of the CMC Hospital for culture and susceptibility testing, 573 (1.2%) were positive for Shigella species. The most common species of Shigella were S. sonnei (n= 335, 58.4%) and S. flexneri (n=229, 40%), followed by S. boydii (n=8, 1.4%) and S. dysenteriae (n=1, 0.2%). S. flexneri was most sensitive to gentamicin (n=17/19, 89%) and amikacin (n=15/18, 83%), while high frequency of resistance to trimethoprim- sulfamethoxazole (n=204/224, 91%) and ampicillin (n=216/228, 95%) was seen. S. boydii was most sensitive to ampicillin (n=5 out of 7, 71%) and cefotaxime (n=6/7, 86%) and the high frequency of resistance was seen against trimethoprim-sulfamethoxazole (n=5/7, 71%). For S. sonnei, the highest sensitivity was reported against amikacin and gentamicin (87% and 80%, respectively), while the highest resistance to trimethoprim- sulfamethoxazole (n=325/331, 98%) and ciprofloxacin (n= 66 out of 76, 87%) was reported. Ciprofloxacin was examined on 115 out of 573 isolates and 84 isolates were resistant (73%). Multidrug-resistance (MDR), (i.e. resistance to three or more classes of antimicrobial agents) was classified into 11 distinct patterns. CONCLUSIONS: In this study, S. sonnei was the predominant Shigella species. High frequency of resistance to common antimicrobials such as trimethoprim-sulfamethoxazole and ampicillin limits the empirical therapy for the management of shigellosis in Iran. On the other hand, it should be noted that third-generation cephalosporins can be convenient replacing drugs.

Molecular characteristics and antibiotic resistance profiles of Escherichia coli strains isolated from urinary tract infections in children admitted to children's referral hospital of Qom, Iran.

BACKGROUND: Urinary tract infections (UTIs) are a highly prevalent infection among children and Escherichia coli is one of the most important pathogens causing pediatric UTIs. Production of extended spectrum b-lactamase (ESBL) enzymes is an important factor in the emergence of antibiotic resistance among these bacteria. This study aimed to determine the resistance patterns, the frequency of ESBL-encoding genes and the genetic diversity of E. coli strains isolated from children with UTIs who were admitted to children's referral hospital of Hazrat Masoumeh, Qom, Iran. METHODS: A total of 102 consecutive non-duplicative strains of E.coli that were isolated from children with UTIs were included into the study. Antibiotic susceptibility of the isolates was determined by disk diffusion method according to the CLSI guidelines. The ability of the isolates to produce ESBLs was phenotypically determined by both combined disk test and double disk synergy test. The ESBL encoding genes (bla CTX-M, bla SHV, and bla TEM) in phenotypically confirmed ESBL-positive isolates was detected by PCR method. The genetic relatedness of the isolates was designated by enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). RESULTS: Eighty-three percent (n=85) of the children were female. Most of the infected boys (88%, n=15) were less than 1 year of age and most of the infected girls (48%, n=41) aged 1 to 6 years old. The highest sensitivity was observed to nitrofurantoin (8%, n=8), followed by amikacin (12%, n=12) and piperacillin-tazobactam (17%, n=17). In contrast, the highest resistance rate was seen to ampicillin (94%, n=96) and cefazolin (93%, n=95). Eighty-eight percent (90 out of 102) of the strains were multidrug-resistant (MDR). Fifty-eight percent (n=59) of the strains were ESBL-positive and results of the combined disk test was in concordance with PCR. The blaCTX-M was the most frequent ESBL encoding gene (88%, n=52), followed by blaTEM (54%, n=32), and blaSHV (15%, n=9). Based on the ERIC-PCR technique, isolates were clustered in 13 different types. There was no relationship between different ERIC types and origin of the isolates (i.e. hospitalized or outpatients), ESBL-producing ability, and antibiotic resistance patterns. CONCLUSIONS: High prevalence of ESBL-positive isolates of E. coli (58%) was found in our study and all of them were MDR. In addition, there were statistically significant differences in the resistance rates of ESBL-producers, and non-producers to some antibiotics, which result in limiting their therapeutic options. Continuous surveillance of the emergence of ESBL-producing isolates and their antibiotic resistance profiles as well as using appropriate typing methods is needed for reducing their spread, selecting appropriate treatment regimens and finding hospital outbreaks.

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.

Construction and evaluation of a whole-cell pneumococcal vaccine candidate.

AIMS: Pneumococcal infections are a major public health problem, especially in developing countries, and the current pneumococcal vaccines do not cover all pathogenic strains. New, more economical serotype-independent vaccines based on species-common protein antigens are being pursued. The pneumococcal whole-cell vaccine which is based on noncapsular antigens common to all strains induces serotype-independent immunity. In the present study, we developed a new candidate for a whole-cell pneumococcal vaccine in which two important virulence factors, the capsule and pneumolysin, were deleted. METHODS AND RESULTS: Protection was elicited by immunization against colonization in mice with a killed mutant strain and the antibody response in the mice serum was evaluated. This candidate vaccine was effective in preventing nasopharyngeal colonization. The mice immunized with this candidate vaccine had significantly higher serum antibody titres than mice that received the adjuvant alone. CONCLUSIONS: Based on obtained results in this study, the engineered whole-cell pneumococci can be considered as a vaccine candidate in future studies. SIGNIFICANCE AND IMPACT OF THE STUDY: This candidate vaccine can overcome the limitations of available polysaccharide vaccines.

High frequency of metronidazole and clarithromycin-resistant Helicobacter pylori in formalin-fixed, paraffin-embedded gastric biopsies.

BACKGROUND: Clarithromycin and metronidazole resistance of Helicobacter pylori is increasing worldwide and has resulted in a loss in the effectiveness of therapeutic regimens. We aimed to evaluate common mutations of resistance genes to clarithromycin (A2143G, A2142G and A2142C) and metronidazole (rdxA and frxA) in H. pylori strains in formalin-fixed, paraffin-embedded gastric biopsies. METHODS: A total of 110 tissue blocks from children suspected of H. pylori infection were included. After DNA extraction, UreC PCR was performed. Specific primers and restriction enzymes by PCR-RFLP were used for analysis of A2143G and A2142G mutations. To detect A2142C and assess frequent mutations of metronidazole resistance, specific primers and PCR method were used. RESULTS: One hundred cases of H. pylori (91%) were by PCR. Of 34 (34%) clarithromycin-resistant isolates 17 (50%), 10 (29%) and 7 (21%) had A2143G, A2142G, A2142C, respectively. Resistance rate to metronidazole was 60% (N = 60). In sequencing rdxA and frxA in the mutated strains, missense mutations were most frequent (60 and 57%, respectively), and there were differences in frameshift and non-sense mutations (p < 0.001). CONCLUSION: Resistance rate to clarithromycin was high and the highest percentage of mutation was of A2143G. PCR-RFLP was used directly with formalin-fixed gastric biopsies, thus, avoiding the requirement for time-consuming culture-based methods. The isolates that developed resistance were mainly associated with mutations of both rdxA and frxA genes.

Improving T-cell assays for diagnosis of latent TB infection: Confirmation of the potential role of testing Interleukin-2 release in Iranian patients

BACKGROUND: Since gamma interferon release assays (IGRAs) cannot differentiate between active tuberculosis and latent tuberculosis infection (LTBI), development of rapid and specific diagnosis tools are essential for discriminating between active tuberculosis (TB) from LTBI. Both IGRAs are based on Mycobacterium tuberculosis-specific antigens, namely, early secretory antigenic target 6 (ESAT-6) and 10kDa culture filtrate (CFP-10). The aim of this study was to evaluate the potential value of IL-2 secretion by whole blood cells after stimulation with rESAT-6 and rCFP-10 for discriminating between active and latent tuberculosis. METHODS: Interleukin-2 and IFN-γ were measured after blood stimulation of 90 cases (30 with active TB, 30 with LTBI and 30 healthy controls) with recombinant ESAT-6 and CFP-10. Receiver operating characteristic (ROC) curve analysis was conducted to determine the best IL-2 and IFN-γ result thresholds in discriminating between cases with active or latent TB, and the corresponding sensitivity and specificity were recorded. RESULTS: The IFN-γ release assay demonstrated a good sensitivity and specificity (sensitivity 83-84% and specificity 92%) for diagnosis of tuberculosis. The discrimination performance of IL-2 assay (assessed by the area under ROC curve) between LTBI and patients with active TB were 0.75 and 0.8 following stimulation with rESAT-6 and rCFP-10, respectively. Maximum discrimination was reached at a cut-off of 11.6pg/mL for IL-2 after stimulation with recombinant rESAT-6 with 72% sensitivity and 79% specificity and 10.7pg/mL for IL-2 following stimulation with rCFP-10 with 75% sensitivity and 79% specificity, respectively. CONCLUSION: This study demonstrates that rESAT-6 and rCFP-10 can provide a sensitive and specific diagnosis of TB. In addition, it was shown that IL-2 may be serving as a marker for discriminating LTBI and active TB

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Improving T-cell assays for diagnosis of latent TB infection: Confirmation of the potential role of testing Interleukin-2 release in Iranian patients.

BACKGROUND: Since gamma interferon release assays (IGRAs) cannot differentiate between active tuberculosis and latent tuberculosis infection (LTBI), development of rapid and specific diagnosis tools are essential for discriminating between active tuberculosis (TB) from LTBI. Both IGRAs are based on Mycobacterium tuberculosis-specific antigens, namely, early secretory antigenic target 6 (ESAT-6) and 10kDa culture filtrate (CFP-10). The aim of this study was to evaluate the potential value of IL-2 secretion by whole blood cells after stimulation with rESAT-6 and rCFP-10 for discriminating between active and latent tuberculosis. METHODS: Interleukin-2 and IFN-γ were measured after blood stimulation of 90 cases (30 with active TB, 30 with LTBI and 30 healthy controls) with recombinant ESAT-6 and CFP-10. Receiver operating characteristic (ROC) curve analysis was conducted to determine the best IL-2 and IFN-γ result thresholds in discriminating between cases with active or latent TB, and the corresponding sensitivity and specificity were recorded. RESULTS: The IFN-γ release assay demonstrated a good sensitivity and specificity (sensitivity 83-84% and specificity 92%) for diagnosis of tuberculosis. The discrimination performance of IL-2 assay (assessed by the area under ROC curve) between LTBI and patients with active TB were 0.75 and 0.8 following stimulation with rESAT-6 and rCFP-10, respectively. Maximum discrimination was reached at a cut-off of 11.6pg/mL for IL-2 after stimulation with recombinant rESAT-6 with 72% sensitivity and 79% specificity and 10.7pg/mL for IL-2 following stimulation with rCFP-10 with 75% sensitivity and 79% specificity, respectively. CONCLUSION: This study demonstrates that rESAT-6 and rCFP-10 can provide a sensitive and specific diagnosis of TB. In addition, it was shown that IL-2 may be serving as a marker for discriminating LTBI and active TB.

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.

Impaired in-vitro responses to IL-12 and IFN-γ in Iranian patients with Mendelian susceptibility to mycobacterial disease

INTRODUCTION: Diagnosis of specific molecular defects of Mendelian susceptibility to mycobacterial diseases (MSMD) patients is important with respect to their clinical outcomes and their response to therapy. The aim of this study was to perform functional tests on blood samples of a group of patients who were suspected of having MSMD. METHODS: This study was performed on 11 cases who had mycobacterial infections and suspected MSMD. Whole blood cell culture was performed in presence of different stimulators. The supernatants were assayed for IFN-γ, IL-12p40 by ELISA method. RESULTS: All patients presented with complications of BCG vaccine in the form of localised lymphadenitis or disseminated BCG infection and chronic mycobacterial osteomyelitis. Infections with Salmonellaspecies occurred in two patients. In-vitro studies showed that 10 cases had impaired response to IL-12. However, the baseline levels of IL-12p40 were normal, while one of our patients may have a potential IFN-γ signalling defect or an IL-12p40 defect. CONCLUSIONS: Early detection of MSMD and commencing of appropriate combination therapy could prevent severe or even fatal complications of uncontrolled mycobacterial infections

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Emergence of community-acquired methicillin-resistant Staphylococcus aureus in an Iranian referral paediatric hospital.

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals has been changed in recent years due to the arrival of community-associated MRSA (CA-MRSA) strains into healthcare settings. The aim of this study is to investigate the distribution of staphylococcal cassette chromosome mec (SCCmec) type V as well as SCCmec IV subtypes, which have been associated with community-acquired infection among healthcare-associated MRSA (HA-MRSA) isolates. Antimicrobial susceptibility, SCCmec type, spa type and the presence of Panton-Valentine leukocidin (PVL) genes were determined for all HA-MRSA isolates in an Iranian referral hospital. In this study of 48 HA-MRSA isolates, 13 (27%), three (6.2%), five (10.4%) and one (2%) belonged to SCCmec subtypes IVa, IVb, IVc and IVd, respectively. Only two isolates (4.2%) belonged to SCCmec types V Notably, one isolate was found to harbour concurrent SCCmec subtypes IVb and IVd. MRSA containing SCCmec subtype IVb, IVc and IVd as well as type V isolates were all susceptible to chloramphenicol, clindamycin and rifampicin, while the sensitivity to these antibiotics was lower among MRSA containing SCCmec subtype IVa. The most frequently observed spa ttype was t037, accounting for 88% (22/25). Three other spa type was t002, t1816 and t4478. Large reservoirs of MRSA containing type IV subtypes and type V now exist in patients in this Iranian hospital. Therefore, effective infection control management in order to control the spread of CA-MRSA is highly recommended.

Clinical, laboratory and imaging findings of the patients with disseminated bacilli Calmette–Guerin disease

OBJECTIVES: In the present study, we reviewed 44 cases of disseminated BCG infection during a 10-year period in an Iranian referral children medical centre hospital. MATERIAL AND METHODS: In this study, all of the patients with clinical and laboratory findings that were compatible with a diagnosis of disseminated BCG were included. RESULTS: Through 10 years evaluation, 44 patients were found with disseminated BCG disease. Hepatomegaly and splenomegaly were seen in 68% and 66% of patients, respectively. Osteomyelitis was observed in 9% of our cases. Decrease in blood cells including anaemia, leucopoenia, neutropenia and thrombocytopenia were associated with more severe disease and even deaths. Moreover, 80% and 70% of patients who died had high level of C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Among the dead patients, 80% had abnormal sonography. Thirty nine percent of patients had immunodeficiency, while more than half of the patients who died had no identified immunodeficiency. CONCLUSION: These findings confirm the need to do sonography as well as bone imaging immediately in all patients with BCGitis. Assessment of the inflammatory factors in order to predict the prognosis of the disease is recommended. Furthermore, complete blood count would provide important information and should perform in all patients with BCGitis

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Investigation of ERG11 gene expression among fluconazole-resistant Candida albicans: first report from an Iranian referral paediatric hospital.

The multiplicity of mechanisms of resistance to azole antifungal agents has been described. As fluconazole-resistant clinical Candida albicans isolates that constitutively over-express ERG11 have been identified in previous studies, the aim of this study is to investigate this molecular mechanism involved in fluconazole resistance of C. albicans clinical isolates. Fluconazole susceptibility testing was carried out on clinical isolates of Candida spp. obtained from hospitalised children in an Iranian referral children's hospital. A polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique was used to differentiate Candida spp. The resistant C. albicans isolates were subjected to RT-qPCR using primers that identify ERG11 gene expression. Of the 142 Candida spp. isolates studied, C. albicans was the most predominant isolate, occurring in 68.3% (97/142) of the patients. According to the CLSI method, the majority of the C. albicans isolates (91.7%, 89/97), categorised as susceptible (minimum inhibitory concentration [MIC] ≤8 µg/mL), five isolates were considered resistant (MIC ≤64 µg/mL) and three had dose-dependent susceptibility (MIC = 8.16-32 µg/mL). The ERG11 gene in the five fluconazole-resistant C. albicans isolates was upregulated 4.15-5.84-fold relative to the ATCC 10231 control strain. In this study, the expression of ERG11 was upregulated in all the fluconazole-resistant C. albicans isolates. There are limited data on the antifungal susceptibility of Candida spp. as well as the molecular mechanism of azole resistance in Iran, especially for isolates causing infections in children. Therefore, the surveillance of antifungal resistance patterns and investigation of other mechanisms of azole resistance in all Candida spp. isolates is recommended.

Impaired in-vitro responses to IL-12 and IFN-γ in Iranian patients with Mendelian susceptibility to mycobacterial disease.

INTRODUCTION: Diagnosis of specific molecular defects of Mendelian susceptibility to mycobacterial diseases (MSMD) patients is important with respect to their clinical outcomes and their response to therapy. The aim of this study was to perform functional tests on blood samples of a group of patients who were suspected of having MSMD. METHODS: This study was performed on 11 cases who had mycobacterial infections and suspected MSMD. Whole blood cell culture was performed in presence of different stimulators. The supernatants were assayed for IFN-γ, IL-12p40 by ELISA method. RESULTS: All patients presented with complications of BCG vaccine in the form of localised lymphadenitis or disseminated BCG infection and chronic mycobacterial osteomyelitis. Infections with Salmonella species occurred in two patients. In-vitro studies showed that 10 cases had impaired response to IL-12. However, the baseline levels of IL-12p40 were normal, while one of our patients may have a potential IFN-γ signalling defect or an IL-12p40 defect. CONCLUSIONS: Early detection of MSMD and commencing of appropriate combination therapy could prevent severe or even fatal complications of uncontrolled mycobacterial infections.

Clinical, laboratory and imaging findings of the patients with disseminated bacilli Calmette-Guerin disease.

OBJECTIVES: In the present study, we reviewed 44 cases of disseminated BCG infection during a 10-year period in an Iranian referral children medical centre hospital. MATERIAL AND METHODS: In this study, all of the patients with clinical and laboratory findings that were compatible with a diagnosis of disseminated BCG were included. RESULTS: Through 10 years evaluation, 44 patients were found with disseminated BCG disease. Hepatomegaly and splenomegaly were seen in 68% and 66% of patients, respectively. Osteomyelitis was observed in 9% of our cases. Decrease in blood cells including anaemia, leucopoenia, neutropenia and thrombocytopenia were associated with more severe disease and even deaths. Moreover, 80% and 70% of patients who died had high level of C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Among the dead patients, 80% had abnormal sonography. Thirty nine percent of patients had immunodeficiency, while more than half of the patients who died had no identified immunodeficiency. CONCLUSION: These findings confirm the need to do sonography as well as bone imaging immediately in all patients with BCGitis. Assessment of the inflammatory factors in order to predict the prognosis of the disease is recommended. Furthermore, complete blood count would provide important information and should perform in all patients with BCGitis.

Human herpesvirus 6 infection in febrile children: frequency in an Iranian referral hospital.

Polymerase chain reaction (PCR) tests for virus in blood and saliva are frequently positive in persons with past infection, re-infection with new strains or latency with or without repeated reactivation of human herpesvirus 6 (HHV6). The aim of this study is to determine the frequency of HHV6 infections in children aged two years or under with an initial diagnosis of fever during an evaluation in the paediatric emergency department of the Children's Medical Center, an Iranian referral hospital, using PCR methodology. In all children, the clinical characteristics noted at the initial evaluation as well as demographic and laboratory findings were obtained. Among 150 patients (91 male, 59 female) admitted to the paediatric emergency department, HHV6 was found in 49 (33%; 14 female [29%] and 35 male [71%]). Rash was seen in 14/49 (29%) of HHV6-positive cases, while 35 cases without rash had a positive PCR test (71%). Seizures were found in 78/150 (52%) patients. There was no significant association between seizures and positive HHV6 results (43% in patients without seizure; 57% in cases that developed seizure). Although standard PCR on samples including blood cannot discriminate between latent and active HHV6 infection, nearly a third of patients (mainly children less than one year old) had HHV6 infection.

Diagnosis of latent tuberculosis infection among immunodeficient individuals: review of concordance between interferon-gamma release assays and the tuberculin skin test.

Mycobacterium tuberculosis remains as a major threat to global health. Nearly a third of the world's population is estimated to have latent M. tuberculosis infection, and this is considered to be a major reservoir of potential active disease. Immunocompromised individuals, such as those with chronic renal failure requiring haemodialysis, solid organ transplant recipients, and individuals infected with the human immunodeficiency virus (HIV) have an increased likelihood of progression from latent infection to active disease, due to impaired cell-mediated immunity. Owing to the absence of a systematic review evaluating concordance between interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among immunodeficient individuals, this literature review aims to evaluate the reported agreement between IGRAs and TST in the diagnosis of LTBI. It will also assess the utility of IGRAs among individuals with weak immune systems as well as determine the degree of concordance among three diagnostic tests (TST, QuantiFERON, and TSPOT-TB) for LTBI.

Diagnostic accuracy of IL-2 for the diagnosis of latent tuberculosis: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarkers for the diagnosis of latent tuberculosis. Related studies were identified through searches of PubMed, Embase, Web of Science, and complementary manual searches up to December 30, 2013. We used standard methods recommended for meta-analyses of diagnostic test evaluations. The analysis was based on a summary receiver operating characteristic (SROC) curve. Meta-regression analysis was used to assess the effects of some confounding factors on the results of the meta-analysis. The potential presence of publication bias was tested using the Deeks' funnel plots. The pooled estimates of IL-2 for latent tuberculosis infection (LTBI) diagnosis were as follows: sensitivity, 0.81 [95 % confidence interval (CI), 0.60 to 0.92]; specificity, 0.95 (95 % CI, 0.90 to 0.97); positive likelihood ratio (PLR), 15.2 (95 % CI, 8.1to 28.4); negative likelihood ratio (NLR), 0.20 (95 % CI, 0.09 to 0.47). We found that the SROC curve is positioned near the upper left corner of the curve and the area under the curve (AUC) was 0.96 (95 % CI, 0.94 to 0.98). In conclusion, according to the meta-analysis, IL-2 is a valid marker for the diagnosis of LTBI. When there is no definite gold standard for the diagnosis of LTBI, IL-2 release assay in addition to interferon-gamma release assays (IGRAs) can improve the ability of IGRAs to identify individuals with LTBI.

Candiduria in children: a first report from an Iranian referral pediatric hospital.

Candida spp. especially Candida albicans is considered as one of the most common cause of fungal infections. The aim of our study was to determine epidemiology of candiduria in children who were referred to an Iranian referral hospital. During May 2011 to February 2013, among 4813 urine culture positive, 209 candida spp. isolates (4.3%) was found. Forty-one percent of cadiduria infection was seen in patients between 1 month and 1 year, 24% in neonatant and 24% in patients 1 to 5 years. Cadiduria was mainly found in patients who had received more than 2 or 3 antibiotic during their hospitalization (37% and 24%, respectively). In our study, the highest frequency of cadiduria was seen in patients who had received more than 2 antibiotics and more than 3 antibiotics during their hospitalization; therefore, the strategic goals to optimize antimicrobial use including optimizing choice and duration of empiric therapy as well as monitoring and providing feedback regarding antibiotic resistance are recommended.