Bacterial etiology and antimicrobial resistance pattern of pediatric bloodstream infections: a 5-year experience in an Iranian referral hospital.

BACKGROUND: Bloodstream infections (BSI) are the major cause of morbidity and mortality in children in developing countries. The purpose of the current study was to establish the antimicrobial susceptibility pattern of bacterial isolates from bloodstream infections at Children's Medical Center Hospital (CMC), Tehran, Iran. METHODS: We retrospectively recorded all positive blood cultures and antimicrobial susceptibility of all bloodstream isolates among children admitted to CMC, during 5 years. Specimen culture, bacterial identification, and antimicrobial susceptibility testing were performed according to standard laboratory methods. RESULTS: From 3,179 pathogens isolated from the blood cultures 2,824 bacteria were cultured, with 1,312 cases being identified as Gram-positive bacteria (46%) and 1,512 cases as Gram-negative bacteria (54%). The most common Gram-negative bacteria isolated were as follows: Pseudomonas spp. (n = 266, 17.6%), Klebsiella pneumoniae (n = 242, 16%), Stenotrophomonas maltophilia (n = 204, 13.5%), Enterobacter spp. (n = 164, 10.8%), Escherichia coli (n = 159, 10.5%), Pseudomonas aeruginosa (n = 126, 8.3%), Serratia marcescens (n = 121, 8%), and Acinetobacter baumannii (n = 73, 4.8%). The most common Gram-positive bacteria isolated were coagulase-negative staphylococci (CONS) (n = 697, 53%), Streptococcus spp. (n = 237, 18%), Staphylococcus aureus (n = 202, 15%) and Enterococcus spp. (n = 167, 12.7%). 34% of bacterial strains were isolated from ICUs. The rates of methicillin resistance in S. aureus and CONS were 34% and 91%, respectively. E. coli isolates showed high resistance to cefotaxime (84%). All isolates of K. pneumoniae were susceptible to colistin and 56% were susceptible to imipenem. P. aeruginosa isolates showed high susceptibility to all antibiotics. CONCLUSIONS: Our findings emphasize the need of clinicians having access to up-to-date bacterial susceptibility data for routinely prescribed drugs. Continuous monitoring of changes in bacterial resistance will aid in the establishment of national priorities for local intervention initiatives in Iran. The increased risk of BSI caused by antibiotic-resistant organisms, emphasizes the significance of implementing appropriate antibiotic prescribing regulations and developing innovative vaccination techniques in Iran.

Changing Epidemiology and Antimicrobial Resistance of Bacterial Childhood Diarrhea: Insights from a 7-Year Study in an Iranian Referral Hospital.

Acute gastroenteritis (AGE) poses a significant public health challenge for children in developing countries. Considering the high prevalence of AGE in Iranian children, the aim of this study was to investigate and analyze the patterns and changes in bacterial identification as well as antibiotic resistance in AG over the course of 7 years. From January 2015 to December 2021, a total of 15,300 pediatric patients with AGE were admitted to the Children's Medical Center, an Iranian academic referral hospital, Tehran, Iran. Among these cases, 8.9% (1329 individuals) yielded positive stool cultures. The predominant bacterial etiology of AGE was identified as Shigella sonnei (n = 424, 31.9%), and Salmonella group D (n = 367, 27.6%), followed by Shigella flexneri: 16.3% (217 cases), Salmonella group C (n = 152, 11.4%), Salmonella group B (n = 91, 6.8%), Escherichia coli (n = 65, 4.9%), Shigella boydii (n = 10, 0.75%), and Shigella dysenteriae (n = 3, 0.2%). Notably, S. sonnei exhibited high resistance rates to trimethoprim-sulfamethoxazole (97.6%) and nalidixic acid (95.3%). S. flexneri and S. boydii isolates displayed significant resistance to ampicillin (96.8% and 88.9%, respectively). Salmonella group D demonstrated elevated resistance to ciprofloxacin (81.3%) and nalidixic acid (88.5%), with notable sensitivity to trimethoprim-sulfamethoxazole and cefotaxime (97.3% and 97.5%, respectively). E. coli displayed resistance rates of 80%, 74%, and 66% to trimethoprim-sulfamethoxazole, cefotaxime, and ciprofloxacin, respectively. The fluctuating prevalence of S. sonnei and Salmonella group D, two predominant bacterial isolates associated with AGE, underscores the dynamic nature of these pathogens. The notable increase in antibiotic resistance observed in S. sonnei raises concerns, underscoring the critical need for judicious and careful antibiotic use.

Systematic review and meta-analysis on the serological, immunological, and cardiac parameters of the multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 infection.

Diverse clinical and laboratory features of multisystem inflammatory syndrome (MIS-C) have been reported in the literature. Despite the worldwide distribution, systemic studies regarding the laboratory results do not exist. Therefore, we aimed to perform this systematic review and meta-analysis to evaluate the serological, immunological, and cardiac parameters of the MIS-C associated with SARS-CoV-2 infection. We searched the PubMed, Scopus, and Web of Science databases using specific keywords for any papers published in English since the disease onset and the first report until July 19, 2020. The inclusion criteria were children <21 years diagnosed with MIS-C without any limitation on defining criteria. Forty-eight studies were included in the final analysis, with a total population size of 3543 children with MIS-C. The median age of the included patients was 8.3 (6.7-9) years. The pooled prevalence of male patients was 59% (95% CI: 56%-61%) and 62% (95% CI: 55%-69%) were admitted in ICU. The pooled prevalence of positive SARS-CoV-2 RT-PCR, SARS-CoV-2 IgM, and SARS-CoV-2 IgG antibody tests was 33% (95% CI: 27%-40%), 39% (95% CI: 22%-58%) and 81% (95% CI: 76%-86%), respectively. The positivity rate of the inflammatory markers was as follows: CRP (96%, 95% CI: 90%-100%), d-dimer (87%, 95% CI: 81%-93%), ESR (81%, 95% CI: 74%-87%), procalcitonin (88%, 95% CI: 76%-97%), ferritin (79%, 95% CI: 69%-87%), and fibrinogen (77%, 95% CI: 70%-84%). The pooled prevalence of elevated brain natriuretic peptide (BNP) level, pro-BNP, and troponin were found in 60% (95% CI: 44%-75%), 87% (95% CI: 75%-96%), and 55% (95% CI: 45%-64%), respectively. The majority of patients had positive SARS-CoV-2 IgG test. Nearly one-third of the cases showed negative RT-PCR results. Cardiac and inflammatory markers were elevated in the majority of cases. These findings suggest that hyperinflammation and cardiac dysfunction are common complications of MIS-C.

Clinical and laboratory features of SARS-CoV-2 variants across multiple rounds of pandemic waves in hospitalized children in an Iranian referral hospital.

BACKGROUND: Since the onset of the COVID-19 pandemic, SARS-CoV-2 has evolved into independent new forms, variants of concern (VOCs). While epidemiological data showed increased transmissibility of VOCs, their impact on clinical outcomes is less clear. This study aimed to investigate the differences between the clinical and laboratory features of children infected with VOCs. METHODS: This study included all cases with SARS-CoV-2-positive nasopharyngeal swabs obtained from patients referred to Children's Medical Center (CMC), an Iranian referral hospital, between July 2021 and March 2022. The inclusion criteria for this study included all patients, regardless of age, who had a positive test anywhere in the hospital setting. Exclusion criteria for the study included those whose data was obtained from non-hospital outpatient settings, or referred from another hospital. The SARS-CoV-2 genome area encoding the S1 domain was amplified and sequenced. The type of variant in each sample was identified based on the mutations in the S1 gene. Demographic characteristics, clinical data, and laboratory findings were collected from the patient's medical records. RESULTS: This study included 87 pediatric cases with confirmed COVID-19, with a median age of 3.5 years (IQR: 1-8.12). Data from sequencing reveals the type of variants as 5 (5.7%) alpha, 53 (60.9%) Delta, and 29 (33.3%) Omicron. The incidence of seizure was higher in patients with Alpha and Omicron infection compared to the Delta group. A higher incidence of diarrhea was reported in Alpha-infected patients, and a higher risk of disease severity, distress, and myalgia was associated with Delta infection. CONCLUSION: Laboratory parameters did not mostly differ among the patients infected with Alpha, Delta, and Omicron. However, these variants may manifest different clinical features. Further studies with larger sample sizes are required to fully understand the clinical manifestations of each variant.

Antimicrobial susceptibility and genotyping of microorganisms isolated from sputum culture of children with cystic fibrosis in an Iranian referral children's hospital.

BACKGROUND: Chronic bacterial infections of the airways are present in most patients with cystic fibrosis (CF). Although most pathogens are acquired from the environment, there is great evidence of patient-to-patient transmission. Therefore, evaluating the genetic variation of strains isolated from CF patients is recommended for the purpose of examining hospital infection. AIM: The aim of this study was to determine the antibiotic susceptibility pattern and genotyping of Staphylococcus aureus and Pseudomonas aeruginosa strains isolated from sputum samples of children with CF referred to a single pediatric CF center in Tehran, Iran. METHODS: In this cross-sectional study, the antimicrobial susceptibility profiles of strains isolated from patients with CF during 1 year were determined. Pseudomonas aeruginosa and S. aureus isolates were genotyped using the random amplified polymorphic DNA polymerase chain reaction method and were analyzed using GelCompar II software. RESULTS: Of 534 patients with CF, 384 had negative sputum cultures (72%), and 94 strains of P. aeruginosa (18%) and 53 strains of S. aureus (10%) were isolated. The mean age of the patients was 8.22 ± 5.7 years (range, 2 months to 18 years). The P. aeruginosa strains showed high sensitivity to ceftazidime (96%), piperacillin/tazobactam (96%), and imipenem (94%). All strains of S. aureus were susceptible to vancomycin, and 13% of the strains were methicillin-resistant S. aureus. High resistance to penicillin (92%) and erythromycin (88.5%) were reported. The results of P. aeruginosa genotyping revealed that there were six major clusters in this hospital. Also, based on the analysis of genotyping results, S. aureus strains were obtained from five clusters, most of which were located in cluster B1 (34 isolates, 64%). CONCLUSION: The results of this study show the possibility of strains being transferred from one part of the hospital to another (especially from the respiratory ward to other areas). Hence, high attention should be paid to the basic methods of preventing infection.

Contribution of antimicrobial photo-sonodynamic therapy in wound healing: an in vivo effect of curcumin-nisin-based poly (L-lactic acid) nanoparticle on Acinetobacter baumannii biofilms.

BACKGROUND: The biofilm-forming ability of Acinetobacter baumannii in the burn wound is clinically problematic due to the development of antibiotic-resistant characteristics, leading to new approaches for treatment being needed. In this study, antimicrobial photo-sonodynamic therapy (aPSDT) was used to assess the anti-biofilm efficacy and wound healing activity in mice with established A. baumannii infections. METHODS: Following synthesis and confirmation of Curcumin-Nisin-based poly (L-lactic acid) nanoparticle (CurNisNp), its cytotoxic and release times were evaluated. After determination of the sub-significant reduction (SSR) doses of CurNisNp, irradiation time of light, and ultrasound intensity against A. baumannii, anti-biofilm activity and the intracellular reactive oxygen species (ROS) generation were evaluated. The antibacterial and anti-virulence effects, as well as, histopathological examination of the burn wound sites of treated mice by CurNisNp-mediated aPSDTSSR were assessed and compared with silver sulfadiazine (SSD) as the standard treatment group. RESULTS: The results showed that non-cytotoxic CurNisNp has a homogeneous surface and a sphere-shaped vesicle with continuous release until the 14th day. The dose-dependent reduction in cell viability of A. baumannii was achieved by increasing the concentrations of CurNisNp, irradiation time of light, and ultrasound intensity. There was a time-dependent reduction in biofilm growth, changes in gene expression, and promotion in wound healing by the acceleration of skin re-epithelialization in mice. Not only there was no significant difference between aPSDTSSR and SSD groups in antibacterial and anti-virulence activities, but also wound healing and re-epithelialization occurred more efficiently in aPSDTSSR than in the SSD group. CONCLUSIONS: In conclusion, CurNisNp-mediated aPSDT might be a promising complementary approach to treat burn wound infections.

Evaluation of human coronavirus OC43 and SARS-COV-2 in children with respiratory tract infection during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is an overwhelming crisis across the world. Human Coronavirus OC43 (HCoV-OC43) is a Betacoronavirus responsible mostly for mild respiratory symptoms. Since the presentations of HCoV-OC43 and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) are believed to resemble a lot, the aim of this study was to evaluate the frequency and characteristics of HCoV-OC43 in the current pandemic and the rate of coinfection for the two viruses. One hundred and seventeen patients referred to Children's Medical Center, Tehran, Iran with respiratory symptoms were included. Real-time reverse transcription-polymerase chain reaction (RT-PCR) methods were performed for the detection of HCoV-OC43 and SARS-COV-2. Totally, 23 (20%) had a positive RT-PCR for HCoV-OC43 and 25 (21%) were positive for SARS-COV-2. Two patients (2%) had a positive PCR for both HCoV-OC43 and SARS-COV-2. The two groups showed significant differences in having contact with family members with suspected or confirmed COVID-19 (p = 0.017), fever (p = 0.02), edema (p = 0.036), vomiting (p < 0.001), abdominal complaints (p = 0.005), and myalgia (p = 0.02). The median level of lymphocyte count in patients with HCoV-OC43 was significantly lower than patients with SARS-COV-2 infection (p = 0.039). The same frequency of SARS-COV-2 and HCoV-OC43 was found in children with respiratory symptoms during the COVID-19 pandemic. The rate of coinfection of SARS-COV-2 with HCoV-OC43 in our study was 0.08. Further research into the cocirculation of endemic coronaviruses, such as HCoV-OC43 and SARS-CoV2, in different regions, is highly recommended. Attempts to determine the geographic distribution and recruit more flexible test panel designs are also highly recommended.

Evaluation of response to different COVID-19 vaccines in vaccinated healthcare workers in a single center in Iran.

Due to the recent coronavirus disease 2019 (COVID-19) pandemic and emergent administration of various vaccines worldwide, comprehensive studies on the different aspects of vaccines are in demand. This study evaluated antibody response after the second dose of the COVID-19 vaccine in the Children's Medical Center personnel. The blood samples of 174 healthcare workers were gathered at least 10 days after vaccination. The administered vaccines included Oxford/AstraZeneca, COVAXIN, Sinopharm, and Sputnik V. This study assessed all antibodies employing ELISA methods, including anti-SARS-CoV-2 neutralizing antibody by DiaZist and Pishtazteb kits, anti-SARS-CoV-2-nucleocapsid by Pishtazteb kit, and anti-SARS-CoV-2-Spike by Razi kit. The cutoff for the tests' results was calculated according to the instructions of each kit. Totally, 174 individuals with an average age of 40 ± 9 years participated in this study, the proportion of men was 31%, and the frequency of past COVID-19 infection was 66 (38%). Sixteen (9%) personnel received Oxford/AstraZeneca, 28 (16%) COVAXIN, 29 (17%) Sinopharm, and 101 (58%) Sputnik V. anti-SARS-CoV-2-nucleocapsid and anti-SARS-CoV-2-Spike were positive in 37 (21%), and 163 (94%) participants and their mean level were more in adenoviral-vectored vaccines (p value < 0.0001). Neutralizing antibody was positive in 74% using Pishtazteb kit while 87% using DiaZist kit. All antibodies' levels were significantly higher in those with a past COVID-19 infection (p value < 0.0001). In conclusion, Oxford/AstraZeneca and Sputnik V had a similar outcome of inducing high levels of anti-SARS-Cov-2-spike and neutralizing antibodies, which were more than Sinopharm and COVAXIN. The titers of Anti-SARS-CoV-2-nucleocapsid antibody were low in all of these four vaccines.

Children with SARS-CoV-2 infection during the novel coronaviral disease (COVID-19) outbreak in Iran: an alarming concern for severity and mortality of the disease.

BACKGROUND: The rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections led to public health crises globally and the number of pediatric patients with Coronavirus Disease 2019 (COVID-19) is still rising. The aim of this study was to describe the epidemiological, clinical, laboratory, and imaging features of hospitalized patients with COVID-19 at an Iranian referral pediatrics hospital and to compare these parameters between hospitalized patients with and without severe disease, multisystem inflammatory syndrome in children (MIS-C) and children with acute COVID-19, as well as deceased and discharged cases. METHODS: This study included hospitalized children and adolescents (≤ 18 years) with suspected COVID-19 who had positive results for SARS-CoV-2. RESULTS: Among the 262 patients with suspected COVID-19, 142 confirmed COVID-19 cases were included in the study. A total of 11 children were diagnosed as MIS-C. The majority of the cases with MIS-C were male, (n = 9, 82%) which is significantly higher than children (n = 61, 47%) with acute COVID-19 (P = 0.03). Fifty patients (35%) were shown to have a more severe form of COVID-19. Ninety percent of the cases (n = 45) with severe COVID-19 had comorbidities that was significantly higher than cases with non-severe or mild disease (n = 41, 45%; P < 0.0001). A mortality rate of 10% was reported (n = 14). Ninety-three percent of the deceased cases (n = 13) had comorbidities that were significantly higher than discharged patients (n = 73, 57%; P = 0.009). CONCLUSION: The increasing number of children with severe COVID-19 is cause for great concern. Underlying diseases, mainly cardiovascular diseases, cancer, and malignancies, are associated with greater risk of development of severe COVID-19 and even death in children. On the other hand, pediatric patients with MIS-C usually develop a milder form of the disease. However, evaluation specific immunological responses in children to explore the delayed inflammatory syndrome are highly recommended.

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: update and new insights from the second report of an Iranian referral hospital.

INTRODUCTION: Here, we are sharing our second report about children affected by Multisystem Inflammatory Syndrome in Children (MIS-C). The aim of the present study was to update our knowledge about children with MIS-C. Furthermore, we tried to compare clinical manifestations, laboratory features and final outcome of patients based on disease severity, in order to better understanding of the nature of this novel syndrome. METHODS: This retrospective study was conducted at Children's Medical Center Hospital, the hub of excellence in paediatrics in Iran, located in Tehran, Iran. We reviewed medical records of children admitted to the hospital with the diagnosis of MIS-C from July 2020 to October 2021. RESULTS: One hundred and twenty-two patients enrolled the study. Ninety-seven (79.5%) patients had mild to moderate MIS-C (MIS-C without overlap with KD (n = 80); MIS-C overlapping with KD (n = 17)) and 25 (20.5%) patients showed severe MIS-C. The mean age of all patients was 6.4 ± 4.0 years. Nausea and vomiting (53.3%), skin rash (49.6%), abdominal pain (46.7%) and conjunctivitis (41.8%) were also frequently seen Headache, chest pain, tachypnea and respiratory distress were significantly more common in patients with severe MIS-C (P < 0.0001, P = 0.021, P < 0.0001 and P < 0.0001, respectively). Positive anti-N severe acute respiratory syndrome coronavirus 2 IgM and IgG were detected in 14 (33.3%) and 23 (46.9%) tested patients, respectively. Albumin, and vitamin D levels in children with severe MISC were significantly lower than children with mild to moderate MIS-C (P < 0.0001, P = 0.05). Unfortunately, 2 (1.6%) of 122 patients died and both had severe MIS-C. CONCLUSION: Patients with MIS-C in our region suffer from wide range of signs and symptoms. Among laboratory parameters, hypoalbuminemia and low vitamin D levels may predict a more severe course of the disease. Coronary artery dilation is frequently seen among all patients, regardless of disease severity.

Three-year evaluation of the nosocomial infections in pediatrics: bacterial and fungal profile and antimicrobial resistance pattern.

BACKGROUND: Nosocomial infections (NIs) could lead to considerably higher mortality rates, length of the hospital stays and costs, and represent a serious public health concern worldwide. Besides, the unreasonable use of antibiotics could lead to get resistant to different antibiotics and create limited therapeutic options, increased risks of treatment failure and poor patient management. The current study aimed to evaluate the prevalence and antimicrobial susceptibility of NIs in an Iranian referral pediatrics hospital during 3 years. METHODS: During the 3-year period, all electronic medical records of nosocomial infection episodes in hospitalized patients were retrospectively reviewed. The bacterial and fungal profile and antimicrobial susceptibility profiles of isolates recovered from different samples of patients with NIs were determined. RESULTS: In this study, a total of 718 patients with NIs was found, among which 61.3% were male (N = 440). The median age of the patients was 2.5 years (IQR: 1 month to 3 years). Klebsiella pneumonia and Candida spp. isolates were the most prevalent microorganisms (N = 125, 17.4%, N = 121, 16.9%, respectively), followed by Pseudomonas aeruginosa (N = 72, 10%) and Coagulase-negative Staphylococci (CoNS) (N = 69, 9.6%). Pseudomonas aeroginusa strains showed high sensitivity to the studied antibiotics. Acinetobacter baumannii strains displayed more than 90% resistance to the almost all antibiotics. All of the tested isolates of S. maltophilia were susceptible to Trimethoprim-sulfamethoxazole (100%) and showed high susceptibility rate to ciprofloxacin (96.4%). Vancomycin resistance was not reported in S. aureus isolates, while 64% of Enterococcus spp. was resistant to vancomycin. The rates of methicillin resistance for S. aureus and CoNS isolates were 45.5% and 85.7%, respectively. CONCLUSIONS: High frequency of antimicrobial resistance to the commonly tested antibiotics is a concerning alarm. Therefore, effective infection control programs and rational antibiotic use policies should be established promptly.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

Prevalence of active tuberculosis infection in transplant recipients: A systematic review and meta-analysis.

INTRODUCTION: Tuberculosis (TB) is considered as a serious complication of organ transplant; therefore, the detection and appropriate treatment of active TB infection is highly recommended for the reduction of mortality in the future. The aim of this review was to conduct a systematic review and meta-analysis assessing the prevalence of active TB infection in transplant recipients (TRs). MATERIAL AND METHODS: Electronic databases, including MEDLINE (via PubMed), SCOPUS and Web of Science were searched up to December 24, 2017. The prevalence of active TB was estimated using the random effects meta-analysis. Heterogeneity was evaluated by subgroup analysis. Data were analyzed by STATA version 14. RESULTS: The pooled prevalence of post-transplant active TB was estimated 3% [95% CI: 2-3]. The pooled prevalence of active TB in different transplant forms was as follows: renal,3% [95% CI: 2-4]; stem cell transplant (SCT), 1% [95% CI: 0-3]; lung, 4% [95% CI: 2-6]; heart, 3% [95% CI: 2-4]; liver, 1% [95% CI: 1], and hematopoietic stem cell transplant (HSCT), 2% [95% CI: 1-3]. The prevalence of different clinical presentations of TB was as follows: pulmonary TB (59%; 95% CI: 54-65), extra pulmonary TB (27%; 95% CI: 21-33), disseminated TB (15%; 95% CI: 12-19) and miliary TB (8%; 95% CI: 4-13). The pooled prevalence of different diagnostic tests was as follows: chest X-ray, 57% [95% CI, 46-67]; culture, 56% [95% CI, 45-68]; smear, 49% [95% CI, 40-58]; PCR, 43% [95% CI, 40-58]; histology, 26% [95% CI, 20-32], and tuberculin skin test, 19% [95% CI, 10-28]. CONCLUSION: A high suspicion level for TB, the early diagnosis and the prompt initiation of therapy could increase the survival rates among SOT patients. Overall, renal and lung TRs appear to have a higher predisposition for acquiring TB than other type of recipients. Monitoring of the high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection among TRs especially in endemic areas.

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran.

During the coronavirus disease 2019 (COVID-19) pandemic, a new phenomenon manifesting as a multisystem inflammatory syndrome in children (MIS-C) which has a similar clinical presentation to Kawasaki disease, toxic shock syndrome and severe sepsis has emerged. Although the number of MIS-C reports is increasing, rare reports in Asia is still available. To our knowledge, this study is the largest series of published MIS-C cases in Iran. We performed a retrospective study of all patients with case definition for MIS-C admitted to the three paediatric hospitals in Iran. All of these hospitals are located within the most active COVID-19 pandemic areas (Tehran, Qom and Mazandaran) in Iran. Demographic characteristics, clinical data, laboratory findings, imaging and echocardiographic findings, treatment and outcomes were collected. Between 7 March and 23 June 2020, 45 children were included in the study. The median age of children was 7 years (range between 10 months and 17 years). Common presenting symptoms include fever (91%), abdominal pain (58%), nausea/vomiting (51%), mucocutaneous rash (53%), conjunctivitis (51%) and hands and feet oedema (40%) with median duration of symptoms prior to presentation of 5 (interquartile range (IQR) 3, 7) days. Fifty-three percent of children showed lymphopaenia. Overall, the majority of cases at admission had markedly elevated inflammatory markers erythrocyte sedimentation rate (ESR) (95.5%) and C-reactive protein (CRP) (97%). Ferritin was abnormal in 11 out of 14 tested patients (73%), and it was highly elevated (>500 ng/ml) in 47% of cases. Median fibrinogen level was 210 (IQR 165, 291) mg/dl, D-dimer was 3909 (IQR 848, 4528) ng/ml and troponin was 0.6 (IQR 0.1, 26) ng/ml, respectively. Twenty out of 31 patients (64.5%) had hypoalbuminaemia. In addition, hyponatraemia was found in 64% of cases. Twenty-five patients (56%) presented with cardiac involvement and acute renal failure was observed in 13 cases (29%). Pleural, ascitic, ileitis and pericardial effusions were found in 18%, 11%, 4% and 2% of cases, respectively. In conclusion, this is a first large case series of hospitalised children who met criteria for MIS-C in Iran. There was a wide spectrum of presenting signs and symptoms; evidence of inflammation with abnormal values of CRP, ESR, D-dimer, ferritin and albumin; and multi-organ involvement.

High prevalence of latent tuberculosis in hematopoietic stem cell transplant recipients: A First Report.

TB is an increasing health problem, and patients undergoing HSCT are more prone to develop tuberculosis. The aim of our study was to evaluate prevalence of latent tuberculosis in HSCT recipients. In this study, 84 patients (2 months to 18 years) who were candidates for HSCT at the referral hospital of Tehran Children's Medical Center were enrolled. The TST and the QFT-GIT test were performed in all 84 patients, simultaneously. LTBI was considered when one of the tests was positive. Overall, the prevalence of LTBI in HSCT recipients in our study was 12% (10 cases). TST induration ≥5 mm was seen in only three patients (3.5%). Eight patients (9.5%) had a positive result for IGRA test, and 11 of them (13%) had indeterminate QFT-GIT result. The agreement between the TST results (induration size ≥5 mm) and the QFT-GIT results was poor (kappa = 0.14). In conclusion, there was a high rate of discordance between TST and IGRA results with many more positive QFT-GIT tests. However, more studies are needed in this population to determine whether this discordance reflects true infection.

Epidemiologic and clinical findings of children with acquired immunodeficiency syndrome in four provinces of Iran.

INTRODUCTION: The human immunodeficiency virus (HIV) is still a remarkable challenge throughout the world, especially in developing countries. Despite the fact that HIV in children is becoming one of the most challenging diseases, it seems that pediatric AIDS in Iran is an unknown disease and there is a lack of studies about it. The aim of this study was to describe the characteristics of HIV-positive children who referred to the hospitals of Tehran, Kermanshah, Kurdistan, and Qom provinces of Iran. MATERIALS AND METHODS: This study was a retrospective investigation of medical records among 61 children with a diagnosis of HIV who were admitted to the children's hospitals in the four provinces of Iran during a 3-year period (2013-2016). RESULTS: The frequency of HIV in the center of Iran (Tehran and Qom provinces) was higher (N = 37, 61%). Most of the infected patients were between 5 and 15 years old, 52% were male, and 93% had a history of HIV in their family. Median age at diagnosis of HIV was 2 years. Most of the hospitalized patients were discharged and only two patients (3%) died due to HIV infection. The vast majority of patients (93%) were infected through maternal transmission and a low percentage (29%) were diagnosed before 1 year of age. All of them were in the third stage of the disease. All patients had a positive HIV PCR test. HIV EIA was positive in the majority of cases (98%). A history of addiction in the family was demonstrated in 22 cases (36%). Weight loss (N = 51, 84%), prolonged fever (N = 50, 81%), and respiratory infection (N = 26, 47%) were the most common symptoms. CONCLUSION: This study demonstrated a high frequency of pediatric HIV among children aged 5-15 years in four provinces of Iran. Novel strategies to prevent and eliminate mother-to-child transmission of HIV, diagnostic facilities, and treatment of infected mothers during pregnancy in our country are highly recommended.

Epidemiology of echinococcosis in Iran: a systematic review and meta-analysis.

BACKGROUND: Echinococcosis is a zoonotic disease caused by the larval stages of taeniid cestodes of the genus Echinococcus. The two major types of infection in humans are cystic echinococcosis (CE) or hydatidosis and alveolar echinococcosis (AE). It is endemic in some parts of the world, such as the Middle East, with Iran being a part of it. This systematic review and meta-analysis were conducted to determine the prevalence of CE and AE echinococcosis and their epidemiological and clinical aspects in Iran. METHODS: Electronic databases, including MEDLINE (via PubMed), SCOPUS, Web of Science, SID and Mag Iran (two Persian scientific search engines) were searched from 1 January 1990 to 8 August 2017. The prevalence of CE and AE echinococcosis was estimated using the random effects meta-analysis. Heterogeneity was evaluated by subgroup analysis. Data were analyzed by STATA version 12. RESULTS: Of the 2051 records identified in the mentioned electronic databases, Seventy-eight articles met our eligibility criteria, with a total of 214124individuals. The meta-analysis was performed on only 37 out of 78 included studies. The pooled prevalence of CE and AE in Iran was 5% [95% confidence interval )CI(: 3-6%] and 2% [95% CI: 0-5%], respectively. Subgroup meta-analysis revealed that the prevalence of CE was significantly higher in North [9%, 95% CI: 4-18%] and West of Iran [6%, 95% CI: 3-11%], patients younger than 40 years of age [7%, 95% CI: 4-12%], villagers and nomads [6%, 95% CI: 2-12%], and studies that used the combination of serological, clinical, and imaging diagnostic methods [7%, 95% CI: 5-9%]. There were no significant differences between the prevalence of CE among low and high-quality studies. Housewives were the most affected group by hydatidosis (n=24/77, 31%), followed by illiterate people (n=11/77, 14%) and farmers (n= 9/77, 12%). Liver [55%, 95% CI: 46-65%] and lung [28%, 95% CI, 22-35%] were the most common sites of cyst formation. CONCLUSIONS: Given to the importance of echinococcosis on human health and domestic animals industry, it is necessary to implement monitoring and control measures in this regard.

Diagnostic accuracy of interferon (IFN)-γ inducible protein 10 (IP-10) as a biomarker for the discrimination of active and latent tuberculosis.

To assess the potency of Interferon (IFN)-γ inducible protein 10 (IP-10) stimulated by recombinant PE35 and PPE68 as a biomarker in differentiating between active and latent tuberculosis. Patients with active pulmonary TB (PTB) (n = 30), latent TB infection (LTBI) (n = 29), and BCG-vaccinated healthy controls (HCs) (n = 30) were enrolled and blood samples were taken from them. The diagnostic performance of IP-10 was evaluated by the Receiver operator characteristic (ROC) curve and the area under the curve (AUC) and their 95% confidence intervals (CI) were calculated. The median IP-10 concentrations following stimulation with recombinant PE35 and PPE68 were significantly higher in TB-infected group (both PTB and LTBI) compared with HCs (P < 0.05). It was also significantly higher in PTB patients compared with individuals with LTBI (P < 0.05). The discriminatory performance of IP-10 following stimulation with recombinant PE35 and PPE68 (assessed by AUC) between TB patients and HCs were similar (AUC: 0.79 [95% CI 0.68-0.89] and 0.79 [95% CI 0.69-0.89], respectively). AUCs of IP-10 following stimulation with recombinant PE35 and PPE68 for distinguishing between PTB and LTBI groups were 0.63 (95% CI 0.47-0.79) and 0.61 (0.45-0.77), respectively. Under the selected cut-off values, the sensitivity and specificity of IP-10 for distinguishing of TB-infected and HCs after stimulation with recombinant PE35 was 74.5% and 73%, respectively and after stimulation with recombinant PPE68 were 76.5% and 63%, respectively. Moreover, the sensitivity and specificity of IP-10 for differentiating of PTB and LTBI following stimulation with recombinant PE35 and PPE68 were 770 pg/ml (sensitivity: 63%; specificity: 62%) and 502 pg/ml (sensitivity: 80%; specificity: 52%), respectively. IP-10 stimulated by recombinant PE35 and PPE68 is a promising biomarker for TB diagnosis. However, it doesn't have desirable sensitivity and specificity in distinguishing between PTB and LTBI.

Epidemiologic, clinical, and laboratory characteristics of childhood brucellosis : A study in an Iranian children's referral hospital.

BACKGROUND: Brucellosis is endemic in Iran. Children constitute 20-25% of cases. We determined clinical, laboratory, and epidemiologic characteristics of pediatric brucellosis patients hospitalized at the Children's Medical Center from May 2011 to December 2016. METHODS: Medical records were reviewed retrospectively. For each patient, a questionnaire was provided containing demographic characteristics (sex, age, nationality, date of admission, city of residence, history of ingestion of unpasteurized dairy products, family history of brucellosis, history of contact with suspicious animals) and clinical information (signs and symptoms, laboratory findings, history of disease relapse, treatment). RESULTS: Included were 43 patients diagnosed with brucellosis (26 males, 60.5%; age 1-13 years, mean ± SD: 7.02 ± 3.5). A history of ingestion of raw or unpasteurized dairy products was present in 88% (N = 38) and 11 patients (26%) had had contact with a suspicious animal. Highest frequencies of brucellosis were recorded in 2013 (N = 10, 23%) and 2015 (N = 11, 26%). Most cases were admitted in the summer (N = 14, 33%) and spring (N = 12, 28%). Fever (N = 39, 91%), arthralgia (N = 33, 77%), and malaise (N = 33, 77%) were the main complaints. Anemia (65%), lymphocytosis (51%), and elevated erythrocyte sedimentation rate (86%) and C­reactive protein (67%) were the most prominent blood anomalies. Blood culture was positive in 30% (N = 11/37), bone marrow culture in 31% (N = 4/11). A positive Wright, Coombs Wright, and 2 ME test was observed in 67% (N = 29), 92% (N = 34/37), and 85% (N = 34/40) of cases, respectively. Median length of antibiotic therapy was 12 weeks (2-24 weeks). The most frequent drug regimen was combined trimethoprim-sulfamethoxazole and rifampicin (N = 24, 56%). Relapse occurred in 9 patients (21%), there were no deaths. CONCLUSIONS: Physicians should be aware of the manifestations, diagnosis, and treatment protocols of childhood brucellosis. Control programs and preventive measures, e.g., regular examination of domestic animals, mass vaccination of livestock, slaughter of infected animals, control of animal trade and migration, pasteurization of milk and milk products, training and increased public awareness of the dangers of consumption of unpasteurized dairy products, are highly recommended.

Prevalence of latent tuberculosis infection in transplant candidates: A systematic review and meta-analysis.

INTRODUCTION: Tuberculosis (TB) is considered as a serious complication for organ transplant recipients; therefore, the detection and appropriate treatment of latent infection are recommended for preventing active TB infections in the future. The objective of this review is to conduct a systematic review and meta-analysis of studies assessing the prevalence of latent TB infection (LTBI) in transplant candidates. METHODS: Electronic databases, including MEDLINE (via PubMed), SCOPUS were searched until 30 June 2017. The prevalence of LTBI was estimated using the random effects meta-analysis. Heterogeneity was evaluated by subgroup analysis. Data were analyzed by STATA version 14. RESULTS: The pooled prevalence of LTBI based on tuberculin skin test (TST) in different transplant types was as follows: liver 24% (14%-33%, 95% CI), lung 22% (18%-26%), renal 21% (16%-27%, 95% CI) and hematopoietic stem cell transplantation (HCT) 14% (9%-19%). The prevalence of LTBI based on Interferon Gamma Release Assay (IGRA) tests in renal transplant candidates was 31% (95% CI; 25-37%), which was much higher than the prevalence of LTBI in liver transplant candidates (25%, 95% CI; 17-33%) and HCT transplant candidates (13%, 95% CI; 10-16%) and there was statistically significant differences between them. The pooled prevalence of indeterminate results based on IGRAs test in different transplant types was as follows: renal 6% (4%-8%, 95% CI) and liver 12% (2%-21%, 95% CI). Subgroup analysis revealed that there were statistically significant differences between the overall prevalence of indeterminate results by using IGRA tests in liver transplant candidates (12%, 95% CI; 2-21%) and renal transplant candidates (6%, 95% CI; 4-8%). The pooled prevalence of post-transplant TB was 2% (1%-2%, 95% CI) and its occurrence was more common in renal recipients (4% (2%-7%, 95% CI)) than in the liver transplant patients (1% (0%-2%, 95% CI)). The prevalence of LTBI in the subgroup (i.e. the patients' mean age was <50 years) was significantly higher than the prevalence of LTBI by using TST/IGRAs in the other subgroup (i.e. the patients' mean age was ≥50 years). CONCLUSION: Our study suggests fair overall agreement between IGRAs and TST in patients requiring liver and HCT transplantation, while a superiority of IGRAs over TST in patients requiring renal transplantation was seen.