Measles immunity status in Iranian infants and children and outbreak concerns: Time for reconsidering the vaccination schedule?

INTRODUCTION: Measles vaccination has greatly reduced the disease burden worldwide, but challenges remain due to variations in vaccine effectiveness across age groups. This study aimed to assess the serological profile of measles antibodies across different age groups, evaluate the impact of maternal immunity on antibody levels in infants under 12 months, and assess measles immunity in vaccinated individuals. MATERIAL AND METHODS: This cross-sectional study was conducted from June 2022 to January 2023 at the Children's Medical Center, a referral hospital in Iran. Serum samples were tested for measles-specific IgG and IgM antibodies using a commercial enzyme-linked immunosorbent assay (ELSA). An avidity assay was performed to assess measles virus-specific IgG antibodies on the samples that were positive and borderline for the measles IgG ELISA. RESULTS: The study included 969 participants across various age groups. Among them, 23% (221 out of 953) tested positive for measles IgM ELISA, and 52% (504 out of 969) for measles IgG ELISA. Regarding the avidity assay for measles virus-specific IgG, the majority (418 out of 573, 73%) showed high-avidity antibodies. Measles-specific IgG levels varied significantly across different age groups, with infants below 6 months old showing a mean IgG level of 477 mIU/mL, declining to 230 mIU/mL between 6 and 12 months, and increasing significantly to 683 mIU/mL in the 12 to 18 month age group, reaching a peak at 938 mIU/mL among children aged 18-72 months. CONCLUSION: The increasing IgM positivity among young Iranians suggests a rising risk of measles outbreaks, possibly due to vaccination gaps. Inadequate antibody levels in infants raise concerns about vaccination effectiveness. Considering declining maternal antibodies, vaccinating infants at 6-9 months could be beneficial. Boosters for adolescents and women may further mitigate outbreak risks.

Pediatric Cystic Echinococcosis in Tehran, Iran: A 9-Year Retrospective Epidemiological and Clinical Survey of Hospitalized Cases.

Cystic echinococcosis (CE), the second most significant foodborne parasitic disease worldwide, poses a significant global health burden. Understanding its clinical and laboratory features is crucial for effective management. This study aimed to investigate the epidemiological, laboratory, and clinical characteristics of pediatric CE in an Iranian referral hospital. A cross-sectional study reviewed hospital records of patients with CE admitted to Children's Medical Center, Tehran, Iran, from 2011 to 2020. Data on demographics, diagnostics, clinical presentation, laboratory findings, and treatment were collected and analyzed. A total of 114 patients, with a mean age of 7.33 ± 2.9 years, were diagnosed with CE. The male-to-female ratio was 1.78, and 73.7% were urban residents. Abdominal pain (69%) and coughing (65%) were the most common symptoms. In confirming the cyst involvement across anatomical sites, pathology emerged as the most reliable method, with effectiveness ranging from 95% to 100%. Abdominal ultrasonography and computed tomography scan were frequently utilized imaging modalities, displaying effectiveness percentages of 71-85%. Liver and lung involvement predominated (66%), with 39% of cases showing multiorgan involvement. Spleen involvement was less common (6%), and neurological involvement was rare (1-2%). The majority of patients (n = 63, 67.7%) displayed cysts larger than 50 mm. All patients received albendazole treatment, and 104 patients (91.2%) underwent surgical procedures, with three postsurgical deaths. In conclusion, hospital records over 9 years indicate an increasing prevalence of CE, emphasizing the need for heightened awareness and effective public health interventions to control this parasitic infection.

Molecular Epidemiology of Carbapenemase-Producing Pseudomonas aeruginosa: An Iranian Referral Hospital-Based Study.

In recent years, there has been a significant increase in infections caused by carbapenemase-producing strains, with carbapenem-resistant Pseudomonas aeruginosa (CRPA) emerging as a priority pathogen according to the World Health Organization. This study aimed to evaluate the molecular epidemiology of CRPA isolated from patients referred to Children's Medical Center in Tehran, Iran. P. aeruginosa isolates collected from different children's wards were screened for common carbapenem-resistant genes by polymerase chain reaction (PCR). Genetic relatedness between isolates was assessed by pulsed-field gel electrophoresis (PFGE). The study included 133 participants, with 50% being male, and revealed a median age of 2 years (interquartile range: 6 months to 6 years). Carbapenem resistance was detected in 15% of cases (n = 20), with CRPA isolates predominantly found in the emergency ward (60%). The median age of patients with CRPA was significantly higher than those with carbapenem-susceptible P. aeruginosa (6 years vs. 1 year). PCR analysis revealed metallo-ß-lactamase production in 45% of CRPA isolates (n = 9), with blaNDM being the most prevalent gene. PFGE analysis of the CRPA isolates identified three clusters (Cluster I, II, and III). Cluster I, comprising 65% of all isolates (n = 13), was predominantly found in the emergency ward. Notably, blaNDM-producing strains were prevalent in the emergency ward. Our study highlights the significant prevalence of CRPA in the emergency ward of our hospital and underscores the importance of targeted surveillance and infection control measures to curb its spread within health care settings.

Post-discharge follow-up of pediatric COVID-19 patients: insights into serological dynamics.

Introduction: Limited data are available regarding SARS-CoV-2 serological response dynamics in pediatric patients with COVID-19, contributing to gaps in our understanding of the immune response in this population. This study aimed to investigate SARS-CoV-2 IgG seropositivity in patients diagnosed with COVID-19 during hospitalization and 2-4 weeks after discharge. Methods: A cohort of patients, consisting of 31 individuals with confirmed acute COVID-19 infection and 27 diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), was enrolled in the study. Follow-up clinic appointments were scheduled for 2-4 weeks post-discharge. During admission and follow-up, blood samples were collected from each patient for laboratory analysis. Anti-nucleoprotein SARS-CoV-2 IgG levels were determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: In this study, a cohort of 58 patients was examined. At admission, 52% (n = 14) of MIS-C patients and 10% (n = 3) of acute COVID-19 patients had positive SARS-CoV-2 IgG test. Only 48 cases were referred to the hospital, and follow-up data was available for 20 cases with MIS-C and 28 cases with acute COVID-19. All patients (n = 15) who initially tested positive for SARS-CoV-2 IgG at admission remained positive serology during follow-up (100%). Among the 33 patients who initially tested negative, 12 (37.5%) showed a positive serology result during follow-up, while 21 (62.5%) remained negative. Within this subgroup, 11 cases (44%) were diagnosed with acute COVID-19, and one patient (12.5%) presented with MIS-C. Fourteen cases with acute COVID-19 infection (56%) and seven cases with MIS-C (87.5%) consistently showed negative serology results throughout the study. During follow-up, the median lymphocyte count demonstrated a significant difference, with 0.96 × 109 cells per L (IQR: 0.75-3.0 × 109 cells per L) in the SARS-CoV-2 IgG-negative group and 2.9 × 109 cells per L (IQR = 1.33-7.22 × 109 cells per L) in the SARS-CoV-2 IgG-positive group (p-value = 0.03). Patients who demonstrated seropositivity during the follow-up were associated with a notably severe disease (p-value = 0.028). Conclusion: Our study highlights the dynamic nature of SARS-CoV-2 IgG antibody responses in pediatric patients with COVID-19 infection. We observed a notable increase in seropositivity rates during follow-up. Furthermore, patients who were seropositive at follow-up demonstrated a severe disease course and lower lymphocyte counts compared to those with persistently negative serology. Our findings underscore the importance of longitudinal serological monitoring in understanding disease progression and immune response dynamics in pediatric COVID-19 cases.

Predictive factors for COVID-19 severity and mortality in hospitalized children.

BACKGROUND: Understanding the factors influencing disease progression and severity in pediatric COVID-19 cases is essential for effective management and intervention strategies. This study aimed to evaluate the discriminative ability of clinical and laboratory parameters to identify predictors of COVID-19 severity and mortality in hospitalized children. METHODS: In this multicenter retrospective cohort study, we included 468 pediatric patients with COVID-19. We developed a predictive model using their demographic, clinical, and laboratory data. The performance of the model was assessed using various metrics including sensitivity, specificity, positive predictive value rates, and receiver operating characteristics (ROC). RESULTS: Our findings demonstrated strong discriminatory power, with an area under the curve (AUC) of 0.818 for severity and 0.873 for mortality prediction. Key risk factors for severe COVID-19 in children include low albumin levels, elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and underlying medical conditions. Furthermore, ROC curve analysis highlights the predictive value of CRP, LDH, and albumin, with AUC values of 0.789, 0.752, and 0.758, respectively. CONCLUSION: Our study indicates that laboratory values are valuable in predicting COVID-19 severity in children. Various factors, including CRP, LDH, and albumin levels, demonstrated statistically significant differences between patient groups, suggesting their potential as predictive markers for disease severity. Implementing predictive analyses based on these markers could aid clinicians in making informed decisions regarding patient management.

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.

High prevalence of carbapenem resistance and clonal expansion of blaNDM gene in Klebsiella pneumoniae isolates in an Iranian referral pediatric hospital.

BACKGROUND: The increasing global concern regarding antibiotic resistance necessitates in-depth studies to comprehend the phenotypic and genotypic characteristics of resistant bacterial strains. This study aimed to investigate the prevalence, antibiotic resistance profiles, and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in an Iranian referral pediatrics hospital. METHODS: In this study, we examined CRKP isolates collected from hospitalized pediatric patients across various wards. The isolates underwent antimicrobial susceptibility testing, the polymerase chain reaction (PCR) analysis for carbapenemase genes (blaNDM, blaVIM and blaIMP), and genetic relatedness assessment using pulsed-field gel electrophoresis (PFGE). RESULTS: Among 166 K. pneumoniae isolates, 54 (32.5%) exhibited resistance to carbapenems. Notably, all these resistant isolates were resistant to imipenem, with 35 (65%) displaying resistance to both imipenem and meropenem. Of the 54 CRKP isolates, 24 (44%) were metallo-ß-lactamases (MBL)-producing. The prevalence of the blaNDM gene among CKCP and MBL-producing isolates was 20% (n = 11) and 44% (n = 24), respectively. The blaVIM and blaIMP genes were not detected in any of the isolates. Twenty-six CRKP isolates (48%) were recovered from ICUs. PFGE analysis of CRKP isolates revealed 20 clusters, with cluster S being the most prevalent, comprising 24% of the total (n = 13). CONCLUSION: Our study reveals a concerning prevalence of carbapenem resistance in K. pneumoniae isolates. Specifically, the detection of the blaNDM gene in 20% of CRKP isolates, with a significant proportion (82%) observed in isolated CRKP from the ICUs and emergency departments, underscores the potential clonal expansion of these resistant strains within these critical hospital wards.

Diagnostic accuracy of the IFN-γ release assay using RD1 immunodominant T-cell antigens for diagnosis of extrapulmonary tuberculosis.

The diagnosis of extrapulmonary tuberculosis (EPTB) poses a significant challenge, with controversies surrounding the accuracy of IFN-γ release assays (IGRAs). This study aimed to assess the diagnostic accuracy of RD1 immunodominant T-cell antigens, including ESAT-6, CFP-10, PE35, and PPE68 proteins, for immunodiagnosis of EPTB. Twenty-nine patients with EPTB were enrolled, and recombinant PE35, PPE68, ESAT-6, and CFP-10 proteins were evaluated in a 3-day Whole Blood Assay. IFN-γ levels were measured using a Human IFN-γ ELISA kit, and the QuantiFERON-TB Gold Plus (QFT-Plus) test was performed. Predominantly, the patients were of Afghan (62%, n = 18) and Iranian (38%, n = 11) nationalities. Eighteen individuals tested positive for QFT-Plus, accounting for 62% of the cases. The positivity rate for IGRA, using each distinct recombinant protein (ESAT-6, PPE68, PE35, and CFP-10), was 72% (n = 21) for every protein tested. Specifically, among Afghan patients, the positivity rates for QFT-Plus and IGRA using ESAT-6, PPE68, PE35, and CFP-10 were 66.7%, 83.3%, 83.3%, 77.8%, and 88.9%, respectively. In contrast, among Iranian patients, the positivity rates for the same antigens were 54.5%, 54.5%, 54.5%, 63.6%, and 45.5%, respectively. In conclusion, our study highlights the potential of IGRA testing utilizing various proteins as a valuable diagnostic tool for EPTB. Further research is needed to elucidate the underlying factors contributing to these disparities and to optimize diagnostic strategies for EPTB in diverse populations.

Monitoring Over a Decade in the Serotype Prevalence of Streptococcus pneumoniae in Iran: A Systematic Review and Meta-analysis.

BACKGROUND: There is no comprehensive information about the circulating serotypes of Streptococcus pneumoniae in Iran in recent years. This study aimed to summarize information about the changes over a decade in the serotype prevalence of S. pneumoniae in Iran. METHODS: We performed a comprehensive search in PubMed/Medline, Web of Science, Science Direct, and the Iranian Database, such as Magiran and SID, from January 2011 to February 2023. The systematic process, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), was carried out by two researchers who were both independent and calibrated. Statistical analyses were carried out using Comprehensive Meta-Analysis software. Identifying and measuring heterogeneity were done using I2 and the chi-square test. Finally, Begg's rank correlation test was used in combination with a funnel plot to evaluate any possible publication bias. RESULTS: The search returned 16 relevant results, with a total of 1575 isolates. Of those studies, eight studies reported the distribution of S. pneumoniae serotypes among patients, three studies among healthy individuals, and five studies among both groups. As the meta-analysis revealed, the most common serotypes were 23F (n = 299, 14.1% [95% CI: 9.7-19.9]; I2 = 84.3%; P<0.001 for heterogeneity), 19F (n = 221, 13.4% [95% CI: 9.9-17.9; I2 = 76.7%; P<0.001 for heterogeneity]), and 19A (n = 102, 8.7% [95% CI: 6.5-11.7; I2 = 54.3%; P<0.001 for heterogeneity]). Moreover, Begg's test (P = 0.160, 0.173, and 0.176 for 23F, 19F, and 19A, respectively) showed no evidence of publication bias. CONCLUSION: Based on our pooled results, the majority of the serotypes of pneumococci in the Iranian population were 23F, 19F, and 19A, respectively, over the last decade. The findings can be valuable in selecting effective pneumococcal vaccine candidates and targeted antibiotics in Iranian patients.

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.

Association of body mass index with COVID-19 outcome in a pediatric tertiary referral hospital in Iran.

BACKGROUND: One of the challenging risk factors for severe COVID-19 infection is obesity and high body mass index (BMI). In this study we assessed the association between BMI and outcomes of hospitalized pediatric patients with COVID-19 in Iran. METHOD: This retrospective cross-sectional study was performed in the biggest referral pediatric hospital in Tehran from March 7 to August 17, 2020. All hospitalized children ≺18 years of age with laboratory-confirmed COVID-19 were included in the study. We evaluated the association of BMI with COVID-19 outcomes (death, severity of clinical course, oxygen therapy, intensive care unit [ICU] admission, ventilator requirement). The secondary objectives were investigating the association of gender, underlying comorbidity, and patient age with COVID-19 outcomes. The limits for obesity, overweight, and underweight were set at BMI >95 percentile, 85≤ BMI ≤ 95, and BMI<5 percentile, respectively. RESULTS: In total, 189 confirmed pediatric cases of COVID-19 (0.1-17 years) with a mean age of 6.4 ± 4.7 years were included. Overall, 18.5% of the patients were obese and 33% were underweight. We found that BMI had no significant relation with COVID outcomes in pediatric cases but after subgrouping the participants, underlying comorbidities and lower BMI in previously ill children were independently associated with a poor clinical outcome of COVID-19. In addition, the previously ill children with higher BMI percentiles were at a relatively lower risk of ICU admission (95% CI: 0.971-0.998, OR: 0.98, p = 0.025) and better clinical course of COVID-19 (95% CI: 0.970-0.996, OR: 0.98, p = 0.009). The BMI percentile had a statistically significant direct relationship with age (Spearman correlation coefficient= 0.26, p<0.001). When we separated the children with underlying comorbidity, the BMI percentile was significantly lower (p<0.001) in comparison to the previously healthy children. CONCLUSION: Based on our results, obesity is not related to COVID-19 outcomes in pediatric patients, but after controlling for confounding effects, underweight in children with underlying comorbidities was more likely to be associated with a poor prognosis of COVID-19.

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 Resistance Patterns of Gram-negative Bacteria in an Iranian Referral Pediatric Hospital: A Present Danger of New Delhi Metallo-ß- lactamase.

BACKGROUND: Antimicrobial resistance among gram-negative bacteria has been growing, particularly in developing countries, like Iran. The emergence and spread of carbapenem-resistance mechanisms is a major public health concern because no definite treatments have yet been established for this problem. This study aimed to evaluate antibiotic susceptibility of gram-negative bacteria, metallo-ß-lactamases (MBLs) and carbapenemase-producing genes, including bla NDM, bla VIM, and bla IMP in patients referred to Children's Medical Center, Tehran, Iran. MATERIAL AND METHODS: In this cross-sectional study, a total of 944 gram-negative isolates were tested in the study, and antimicrobial susceptibility testing was performed. Moreover, MBL production of carbapenem-resistant isolates, as well as the presence of bla NDM, bla VIM, and bla IMP, was investigated. RESULTS: The most common gram-negative isolated bacteria were Escherichia coli (489 samples, 52%), followed by Klebsiella pneumoniae (167 samples, 18%), Pseudomonas aeruginosa (101 samples, 11%), Enterobacter spp. (64 samples, 7%), Pseudomonas spp. (35 samples, 4%), Acinetobacter baumannii (18 samples, 2%), and Burkholderia cepacia (17 samples, 2%). Imipenemresistant was found in 75%, 61%, and 60% of Stenotrophomonas maltophilia, Enterobacter spp., and A. baumannii isolates, respectively. Moreover, the highest resistance to meropenem was observed in S. maltophilia, A. baumannii, P. aeruginosa, and B. cepacia (100%, 96%, 83%, and 61.5%, respectively). Double disk synergy test (DDST) results showed that 112 out of 255 carbapenem- resistant isolates (44%) were MBL-producing ones. The presence of the bla NDM gene was identified in 32 (29%) of MBL-producing isolates, 13 of which were K. pneumoniae, 7 P. aeruginosa, and 7 E. coli, 3 Enterobacter spp., and 2 Klebsiella spp., respectively. The presence of the bla IMP and bla VIM genes was detected in 2 (2%) and 1 (1%) of MBL-producing isolates. These genes were detected in only MBL-producing P. aeruginosa isolates. CONCLUSION: Our findings suggest the emergence of NDM-producing strains in our hospital, and bla NDM was the most frequently detected carbapenemase gene in MBL-producing P. aeruginosa, K. pneumoniae, and Klebsiella spp. Since such bacteria can easily spread among patients in the hospital, a strong infection control and prevention plan is highly recommended.

Enhancement of hypericin nanoparticle-mediated sonoinduced disruption of biofilm and persister cells of Streptococcus mutans by dermcidin-derived peptide DCD-1L.

BACKGROUND: Streptococcus mutans is considered a major significant contributor to dental caries and its effective removal is difficult due to the formation of biofilm. Therefore, the development of adjuvant therapeutic strategies with anti-biofilm properties is a promising approach. In the present study, we examined the effect of dermcidin-derived peptide DCD-1 L on the antibacterial activity of hypericin nanoparticle (HypNP)-mediated antimicrobial sonodynamic therapy (aSDT) against persister cells growing- and biofilm cultures of S. mutans. MATERIALS AND METHODS: Following synthesis and confirmation of HypNP, the fractional inhibitory concentration (FIC) index of HypNP and DCD-1 L was determined by checkerboard assay. Cellular uptake of HypNP-DCD-1 L and generation of endogenous reactive oxygen species (ROS) were assessed and followed by the determination of antimicrobial sonoactivity of HypNP-DCD-1 L against persister cells growing- and biofilm cultures of S. mutans. The water-insoluble extracellular polysaccharide (EPS) and expression of the gtfD, comDE, and smuT genes were then evaluated in persister cells growing- and biofilm cultures of S. mutans. RESULTS: There was a synergistic activity in the combination of HypNP and DCD-1 L against S. mutans with an FIC index value of 0.37. The HypNP-DCD-1L-mediated aSDT also displayed the highest cellular uptake and endogenous ROS generation by bacterial cells. When biofilm and persister cells of S. mutans were treated with HypNP-DCD-1 L and subsequently exposed to ultrasound waves, 5.1 log and 3.8 log reductions, respectively, in bacterial numbers were observed (P<0.05). According to the data, EPS in both persister cells growing- and biofilm cultures of S. mutans were significantly decreased after exposure to the HypNP-DCD-1L-mediated aSDT (P<0.05). In addition, the quantitative real-time PCR data illustrated the high level of similarities in very low-expression profiles of the gtfD before and after all treated groups for persister cells. While, following HypNP-DCD-1L-mediated aSDT treatment, the expression levels of gtfD, comDE, and smuT were significantly lower in treated persister cells growing- and biofilm cultures of S. mutans in comparison with control groups (P<0.05). CONCLUSIONS: Combined, the results of this study indicate that ultrasound waves-activated HypNP-DCD-1 L can sonoinactivate S. mutans biofilms and persister cells, as well as reduce effectively pathogenicity potency of S. mutans. Hence, HypNP-DCD-1L-mediated aSDT may be proposed as a promising adjunctive therapeutic approach for dental caries.

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.

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.

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.

Pediatric tuberculosis in Iran: a review of 10-years study in an Iranian referral hospital.

INTRODUCTION: Reductions in global tuberculosis incidence are considered as one of the End TB Strategy goal. The diagnosis of tuberculosis (TB) in children is challenging due to insufficient specimen material and the scarcity of bacilli in specimens. The purpose of this study was to evaluate the prevalence, characteristics, clinical profiles, laboratory findings and treatment outcomes of children infected with TB in an Iranian referral hospital during a 10-years period. METHODS: This study was a retrospective analysis of the medical records of 90 children (£15 years) with a diagnosis of tuberculosis who were admitted to Children's Medical Center Hospital, Tehran, Iran, between March 2006 and March 2016. The patients' information such as demographic, clinical manifestations, laboratory, radiological and histological tests results, and treatment outcomes were extracted from medical records and were analyzed. RESULTS: The total prevalence of TB was about 56.6 per 100,000 admitted patients. Most of the patients were between 5 to 12 years. Sixty-one percent were male. Twenty-two percent had the history of TB in their family. Underlying diseases were identified in 30 cases (33%). Thirty-four cases (38%) had pulmonary TB (PTB), 35 cases (39%) had extrapulmonary TB (EPTB), while disseminated TB (DTB) was found in 21 cases (23%). Distribution of DTB in males was higher than in females (36% vs. 6%). In patients < 1 year, DTB was the most frequent type (48 %); however, in patients > 1 year both PTB and EPTB had similar distributions (42%) and were more frequent than DTB (16%).  Conclusions: The total prevalence rate of TB in our study was 56.6 per 100,000 admitted patients. Since the mortality rate was higher in infants, children with DTB and children with underlying diseases, early detection and treatment of these patients will help to reduce the mortality rate of TB disease.