Acute viral bronchiolitis as a cause of pediatric acute respiratory distress syndrome.

The Pediatric Acute Lung Injury Consensus Conference (PALICC) published pediatric-specific guidelines for the definition, management, and research in pediatric acute respiratory distress syndrome (PARDS). Acute viral bronchiolitis (AVB) remains one of the leading causes of admission to PICU. Respiratory syncytial virus (RSV) is the most common cause of AVB. We aimed to evaluate the incidence of PARDS in AVB and identify the risk of RSV as a trigger pathogen for PARDS. This study is a retrospective single-center observational cohort study including children < 2 years of age admitted to the pediatric intensive care unit at St Mary's Hospital, London, and presented with AVB in 3 years (2016-2018). Clinical and demographic data was collected; PALICC criteria were applied to define PARDS. Data was expressed as median (IQR range); non-parametric tests were used. In this study, 144 infants with acute viral bronchiolitis were admitted to PICU in the study period. Thirty-nine infants fulfilled criteria of PARDS with RSV as the most common virus identified. Bacterial infection was identified as a risk factor for development of PARDS in infants with AVB.Conclusion: AVB is an important cause of PARDS in infants. RSV is associated with a higher risk of PARDS in AVB. Bacterial co-infection is a significant risk factor for development of PARDS in AVB. What is Known: • Bronchiolitis is a common cause of respiratory failure in children under 2 years. • ARDS is a common cause of PICU admission. What is New: • Evaluation of bronchiolitis as a cause of PARDS according to the PALLIC criteria. • Evaluation of different viruses' outcome in PARDS especially RSV as a commonest cause of AVB.

Peripheral lymphocytes analyses in children with chronic hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV)-specific immune response is believed to play a crucial role in viral clearance. There is, nevertheless, no reliable parameter to monitor this immune response or predict chronic HCV infection development. METHOD: An observational case-control study was performed to identify such parameters, peripheral blood mononuclear cells from 57 children with chronic HCV were systemically phenotyped, and the serum level of Interferon gamma and interleukin (IL) -17 was measured. The data were compared with 37 age-matched healthy volunteers (controls). RESULTS: Children with chronic HCV infection had a lower frequency of natural killer cells (NK) cells, CD56Dim NK cells and expansion of CD56Bright NK cells compared with controls (P = 0.001, P < 0.0001 and P < 0.0001 respectively). Increased CD56Dim NK cells were negatively correlated with the higher viral load, R2  = 0.29, P = 0.05, while, increased NK T cells were positively correlated with high viral load, R2  = 0.17, P = 0.011. T helper cells, naive T cells, CD127 negative T cells, and HLA-DR-positive T cells significantly increased in patients than in controls. The frequency of CD4+CD25high+ T regulatory (Treg) cells increased in HCV-infected patients, compared with those in control, and FOXP3 was upregulated within them. Treg cells' increase was positively correlated with high viral load, R2  = 0.45, P = 0.004. The level of IL-17 was higher in HCV patients than that in control, P < 0.0001. CONCLUSION: Although the contribution of those markers to the chronic HCV establishment in children remains elusive, the results may provide important clues for reliable indicators of HCV infection.

The efficacy of hepatitis B vaccination program in upper Egypt: Flow cytometry and the evaluation of long term immunogenicity.

Anti-HBs levels wanes with time. Many studies discussed the B cell response to HBV vaccine. However, the data about memory T cell response are limited. To evaluate the efficacy of hepatitis B vaccine via evaluating anti-HBs levels and HBsAg specific memory T-lymphocytes through descriptive study. The study was conducted in a tertiary care setting. This study included 440 vaccinated persons during infancy. Group I: 6 to less than 10 years old; Group II: 10 to less than 14 years old; Group III: 14 to less than 17 years old; Group IV: 17 years old. The serum samples were screened for HBV markers. Cytokines secretion by HBsAg-specific memory CD45RO(+) CD4(+) T cells was measured after in vitro culture using flow cytometry. The mean titer of anti-HBs was higher in group I in comparison to others (P-value = 0.000 for each). IFN-γ and IL-4 secreted by memory CD4(+) T cells were positive in all with anti-HBs >100 mIU/ml, while positive in 87% and 75% of participants with anti-HBs <10 mIU/ml and positive in 73% and 32% of participants with absent anti-HBs. The percentage of cells secreting IFN-γ and those secreting IL-4 were higher among participants with serum anti-HBs >100 mIU/ml than those having <10 mIU/ml or absent (P < 0.001 for each). Anti-HBs positivity decreased with time since childhood vaccination. Breakthrough infections are rare in vaccinated persons. Hepatitis-B vaccine is efficient in controlling HBV infection. Flow cytometry is a useful tool to assess the long term persistence of T cell memory after childhood vaccination. J. Med. Virol. 88:1567-1575, 2016. © 2016 Wiley Periodicals, Inc.

Impact of Geographical Location on the Gut Microbiota Profile in Egyptian Children with Type 1 Diabetes Mellitus: A Pilot Study.

Purpose: To investigate the compositional and functional characteristics of T1DM-associated gut microbiota in two Egyptian cities and to study the geographical locality effects. Patients and Methods: This case-control study included 32 children with controlled T1DM and 16 controls, selected from two different regions of Egypt. The gut microbiota of both diabetic and control children was analyzed through 16S rRNA gene sequencing; this was done using the Illumina MiSeq platform. Results: Consistent findings among the diabetic children included significantly lower alpha diversity than the control children, as well as a lower mean Firmicutes/Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and the genera Prevotella and Ruminococcus. In the diabetic children, there were also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and the genera Lactobacilli, Bacteroides, and Faecalibacterium. When comparing the two diabetic groups, the Ismailia group (IsDM) was found to have a significantly higher F/B ratio and diversity indices, with resultant differences at the functional level. Conclusion: There are a number of consistent changes in the microbiota profile characterizing the diabetic groups irrespective of the geographical location including significantly lower alpha diversity, mean Firmicutes/ Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and genera Prevotella and Ruminococcus. There are also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and genera Lactobacilli, Bacteroides, and Faecalibacterium pointing to the greater driving power of the disease.

Ledipasvir/Sofosbuvir in Adolescents With Chronic Hepatitis C Genotype 4 With and Without Hematological Disorders: Virological Efficacy and Impact on Liver Stiffness.

BACKGROUND: Egypt has the highest prevalence of hepatitis C virus (HCV) infection. Anti-HCV antibodies were detectable in 3% of children in Upper Egypt. Our aim was to evaluate the efficacy of ledipasvir/sofosbuvir for chronic HCV genotype 4 in adolescents with/without hematological disorders and to determine the effect of sustained virological response (SVR) on liver stiffness. METHODS: Sixty-five adolescents were recruited. There were 3 patient groups: group 1, 44 treatment-naive without hematological disorders; group 2, 6 previously treated; and group 3, 15 treatment-naive with hematological disorders. All patients received sofosbuvir 400 mg/ledipasvir 90 mg per day for 12 weeks. Serum HCV RNA levels were measured before treatment, at week 12, and at 12 weeks after the end of treatment (SVR12). Liver stiffness and the aspartate aminotransferase-platelet ratio index (APRI) score were estimated at baseline and at SVR12. RESULTS: SVR12 was 100%. At SVR12, there was a significant improvement in liver stiffness in all groups. The APRI score showed significant improvements in groups 1 and 3 (P < .001 and P = .004, respectively). The treatment was well tolerated, with minimal and self-limited side effects. CONCLUSIONS: Treatment of chronic HCV in adolescents using ledipasvir/sofosbuvir was effective, with a cure rate (at SVR12) of 100%. Significant improvement in liver stiffness was found in all groups.

Antimicrobial Resistance and Comparative Genome Analysis of Klebsiella pneumoniae Strains Isolated in Egypt.

Klebsiella pneumoniae is an important human pathogen in both developing and industrialised countries that can causes a variety of human infections, such as pneumonia, urinary tract infections and bacteremia. Like many Gram-negative bacteria, it is becoming resistant to many frontline antibiotics, such as carbapenem and cephalosporin antibiotics. In Egypt, K. pneumoniae is increasingly recognised as an emerging pathogen, with high levels of antibiotic resistance. However, few Egyptian K. pneumoniae strains have been sequenced and characterised. Hence, here, we present the genome sequence of a multidrug resistant K. pneumoniae strain, KPE16, which was isolated from a child in Assiut, Egypt. We report that it carries multiple antimicrobial resistance genes, including a blaNDM-1 carbapenemase and extended spectrum ß-lactamase genes (i.e., blaSHV-40, blaTEM-1B, blaOXA-9 and blaCTX-M-15). By comparing this strain with other Egyptian isolates, we identified common plasmids, resistance genes and virulence determinants. Our analysis suggests that some of the resistance plasmids that we have identified are circulating in K. pneumoniae strains in Egypt, and are likely a source of antibiotic resistance throughout the world.

Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli from Egyptian children with diarrhoea: Similarities and differences.

Enteroaggregative Escherichia coli (EAEC) is a common diarrhoeagenic human pathogen, isolated from patients in both developing and industrialized countries, that is becoming increasingly resistant to many frontline antibiotics. In this study, we screened 50 E. coli strains from children presenting with diarrhea at the outpatients clinic of Assiut University Children's Hospital, Egypt. We show that all of these isolates were resistant to multiple classes of antibiotics and identified two as being typical EAEC strains. Using whole genome sequencing, we determined that both isolates carried, amongst others, blaCTX-M and blaTEM antibiotic resistance genes, as well as many classical EAEC virulence determinants, including the transcriptional regulator, AggR. We demonstrate that the expression of these virulence determinants is dependent on AggR, including aar, which encodes for a repressor of AggR, Aar. Since biofilm formation is the hallmark of EAEC infection, we examined the effect of Aar overexpression on both biofilm formation and AggR-dependent gene expression. We show that whilst Aar has a minimal effect on AggR-dependent transcription it is able to completely disrupt biofilm formation, suggesting that Aar affects these two processes differently. Taken together, our results suggest a model for the induction of virulence gene expression in EAEC that may explain the ubiquity of EAEC in both sick and healthy individuals.

Intestinal barrier integrity and function in infants with cholestasis.

BACKGROUND/AIMS: The safety of the human body is maintained by effective monitoring of the mucosal surface integrity and protection against potentially harmful compounds. This function of the gut called intestinal barrier function can be affected by cholestasis and the absence of bile in the intestinal lumen. We aimed to determine whether the gut barrier integrity is impaired in infants with cholestasis by evaluation of the intestinal fatty acid binding proteins (I-FABP) and ileal bile acid binding protein (I-BABP) as markers of intestinal epithelial cell damage and plasma D-lactate level as a marker of gut wall permeability. METHODS: This case-control study included 53 infants with cholestasis and 29 controls. Serum levels of I-FABP, I-BABP, and D-lactate were measured in all subjects. RESULTS: Both groups of patients with neonatal hepatitis and biliary atresia showed significantly higher levels of I-FABP and I-BABP than the controls. There were no differences in the serum D-lactate level between the cases and controls. There was no difference between the two groups of patients (I and II) regarding any of the parameters studied. No significant correlations between serum levels of I-FABP, I-BABP, or D-lactate and total or direct bilirubin levels were found in the cholestatic infants. CONCLUSIONS: The intestinal epithelial barrier integrity is breached nearly in all parts of the intestine in infants with cholestasis. Further research is recommended to determine the impact of this finding on the management of these infants. The relationship between physical intestinal barrier damage and its functional failure remains subject for further research.

Nosocomial Clostridium difficile-associated diarrhoea in Assiut University Children's Hospital, Egypt.

BACKGROUND: There are no large epidemiological studies of Clostridium difficile-associated disease (CDAD) in hospitalised children. AIM: To describe the frequency, demography, clinical features and outcome of nosocomial CDAD in children admitted to Assiut University Children's Hospital, Egypt. PATIENTS AND METHODS: In this descriptive cross-sectional study, 72 children developed nosocomial diarrhoea between April 2010 and March 2011. A medical history, clinical assessment and culture for Clostridium difficile and direct toxin detection from stool samples by enzyme immuno-assay were undertaken in all patients. RESULTS: CDAD was diagnosed in 17 (23·6%) patients. Those aged ≤12 months were the most commonly affected (eight, 47%). The main cause of admission was respiratory disorders (eight, 47% of cases), followed by surgical problems (three, 17·7%). Ten patients (58·8%) had severe symptoms. There were no statistically significant differences between any of the demographic or laboratory data for children with CDAD and children with other causes of nosocomial diarrhoea. None of the patients developed complications. Seven children with CDAD (41·2%) had recurrence. CONCLUSION: CDAD is an important cause of nosocomial diarrhoea in children in Assiut University Children's Hospital. Established guidelines should be followed in all hospitals to minimise exposure to the pathogen. Physicians can do much to reduce the risk of a severe outcome in children by early identification and rapid management. Further research should be undertaken to identify the risk factors for recurrence.

Clinico-laboratory study on children with auto-immune hepatitis in Upper Egypt.

BACKGROUND AND STUDY AIMS: Auto-immune hepatitis (AIH) in children is a rare chronic progressive liver disorder. It is characterised serologically by high aminotransferase levels, elevated immunoglobulin G (IgG) and the presence of autoantibodies. AIH is divided into two types according to the autoantibody profile. This study aims to assess frequency, clinical manifestations, biochemical features and outcome of AIH in children attending Assuit University Hospitals in Upper Egypt with acute icteric hepatitis and seronegative viral markers (anti-hepatitis A virus (HAV) IgM, HbsAg, anti-hepatitis C virus (anti-HCV) Ab). PATIENTS AND METHODS: The study includes 34 children with AIH, diagnosed on the basis of the International Scoring Criteria of Auto-immune Hepatitis, recruited from Assuit University Hospitals, during the period from January 2005 to December 2009. All patients received prednisolone 2mgkg(-1)day(-1). Follow-up was done for 1year. RESULTS: Among 34 children diagnosed as AIH, 24 were females (70.5%) and 10 were males (29.5%). Jaundice represented the most consistent finding in all patients. According to the autoantibody profile, 25 children were classified as type 1 and nine children were classified as type 2. Corticosteroid therapy was started. Complete remission was observed in 67.6% of patients and partial remission in 17.6%. There was no significant statistical difference in clinical and biochemical features of AIH in patients regarding the response to treatment. Mild side effects of steroid therapy were encountered in 48.2% of patients. After complete withdrawal of corticosteroids, six patients (20.7%) developed relapse. CONCLUSION: AIH type 1 was the main form of AIH in children referred to Assiut University Hospitals. Girls were more affected than boys. AIH type 1 exhibited a more active, ongoing immunologic process. Steroid alone can be used successfully in most cases. Children with AIH type 2 had a higher frequency of relapse after corticosteroid withdrawal. Further studies on a larger number of cases and long-term follow-up are recommended.