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Background: Rotavirus (RV) is a leading cause of pediatric diarrhea and mortality worldwide. The virus causes acute gastroenteritis characterized by moderate to severe vomiting, diarrhea, dehydration, and fever. Microbial dysbiosis caused by RV infection may significantly influence disease prognosis and the development of other chronic diseases. The gut microbiome plays a vital role in enteric immune response for rotavirus vaccine (RVV) that requires further elucidations. The current study evaluates the gut microbiome of RV positive children and compares gastroenteritis manifestation in children admitted to the Pediatric Emergency Centre, Hamad Medical Cooperation, Doha, Qatar. Stool samples were collected from thirty-nine RV positive and eight healthy control children. 16S rRNA sequence was performed using the Illumina MiSeq platform., Results: The data demonstrated a significant increase in microbiome diversity denoted by higher relative abundances of phylum Proteobacteria (p = 0.031), Fusobacteria (p = 0.044) and genus Streptococcus (p ≤ 0.001) in the infected group relative to the control. Similarly, district clustering pattern (PERMANOVA p = 0.01) and higher species richness (Shannon entropy p = 0.018) were observed in the children who received two RVV doses compared with the non-vaccinated or single-dose groups. These microbiome changes were represented by over-abundance of phylum Bacteroidetes (p = 0.003) and Verrucomicrobia (p ≤ 0.001), and lower expression of family Enterobacteriaceae in two RVV doses group. However, microbiome composition was not associated with diarrhea, vomiting, and other parameters of gastroenteritis., Conclusions: The observations assert significant microbial signatures of RVV, which is dose-dependent, and suggest manipulating these microbes as a novel approach for improving RVV efficacy. Further studies are warranted to investigate the immune status of these patients and mechanistic investigation to enhance RVV seroconversion.

Background: The treatment of Enterobacteriaceae family including diarrheagenic E. coli (DEC) has been increasingly complicated due to the emergence of resistant strains. Here we report on the phenotypic resistance profiles and ESBL genotype and virulence profiles of Enteroaggregative E. coli (EAEC) and Enteropathogenic E. coli (EPEC) isolated from children hospitalized with acute gastroenteritis in Qatar (AGE)., Results: E. coli were isolated and characterized from 76 diarrheagenic stool positive samples, collected from hospitalized children less than 10 years old. Isolates were tested for antibiotic susceptibility against eighteen clinically relevant antibiotics using E-test method. Conventional PCR was performed to detect genes encoding ESBL and virulence factors. Chi-square test was performed to compare the individual antibiotic resistance between EPEC and EAEC. A significant percentage (73.7%) of isolates were resistant to at least one antibiotic. Overall, high resistance (70%) was reported to the first-line antibiotics such as ampicillin, tetracycline (46.4%), and sulfamethoxazole-trimethoprim (42.9%). Further, 39.5% of the isolates were multidrug resistant (MDR), with 22.4% being ESBL producers. On the other hand, all isolates were susceptible to carbapenem, fosfomycin, amikacin and colistin. The incidences of resistance to the 18 antibiotics between EPEC and EAEC were not significantly different by Pearson chi -square test (P > 0.05). Genetic analysis revealed that 88.23% of ESBL production was bla CTX-M-G1 (bla CTX-M-15 , bla CTX-M-3 ) - encoded. Several different combinations of virulence markers were observed, however, there was no specific trend among the isolates apart from absence of the bundle-forming pilus (bfpA) gene, which encodes the type IV fimbriae in EPEC adherence factor (EAF) plasmid (pEAF), among all EPEC (atypical). 15% of the EAEC strains were positive for a combination of astA, aap & capU, while 10% were positive for three different combinations. The aap, aatA, capU and aggR virulence genes showed the highest frequency of 65, 60, 55 and 55% respectively. Others genes, east, astA, and aai, showed frequencies of 35, 30 and 20% respectively., Conclusions: Atypical EPEC and EAEC were the primary etiological agents of diarrhea in children among DEC pathotypes. Our results indicated high rate of antimicrobial resistance pattern of DEC strains, which necessities the development of regulatory programs and reporting systems of antimicrobial resistance in DEC and other AGE-associated bacteria to insure effective control of diarrheal diseases. Results from this study demand a further research on identifying the phenotypic and genotypic profiles of more DEC pathotypes in various clinical samples.

Background: Acute severe childhood asthma is an infrequent, but potentially life-threatening emergency condition. There is a wide range of different approaches to this condition, with very little supporting evidence, leading to significant variation in practice. To improve knowledge in this area, there must first be consensus on how to conduct clinical trials, so that valid comparisons can be made between future studies. We have formed an international working group comprising paediatricians and emergency physicians from North America, Europe, Asia, the Middle East, Africa, South America, Central America, Australasia and the United Kingdom., Methods/design: A 5-stage approach will be used: (1) a comprehensive list of outcomes relevant to stakeholders will be compiled through systematic reviews and qualitative interviews with patients, families, and clinicians; (2) Delphi methodology will be applied to reduce the comprehensive list to a core outcome set; (3) we will review current clinical practice guidelines, existing clinical trials, and literature on bedside assessment of asthma severity. We will then identify practice differences in tne clinical assessment of asthma severity, and determine whether further prospective work is needed to achieve agreement on inclusion criteria for clinical trials in acute paediatric asthma in the emergency department (ED) setting; (4) a retrospective chart review in Australia and New Zealand will identify the incidence of serious clinical complications such as intubation, ICU admission, and death in children hospitalized with acute severe asthma. Understanding the incidence of such outcomes will allow us to understand how common (and therefore how feasible) particular outcomes are in asthma in the ED setting; and finally (5) a meeting of the Pediatric Emergency Research Networks (PERN) asthma working group will be held, with invitation of other clinicians interested in acute asthma research, and patients/families. The group will be asked to achieve consensus on a core set of outcomes and to make recommendations for the conduct of clinical trials in acute severe asthma. If this is not possible, the group will agree on a series of prioritized steps to achieve this aim., Discussion: The development of an international consensus on core outcomes is an important first step towards the development of consensus guidelines and standardised protocols for randomized controlled trials (RCTs) in this population. This will enable us to better interpret and compare future studies, reduce risks of study heterogeneity and outcome reporting bias, and improve the evidence base for the management of this important condition.

Background: The β-lactam antibiotics have traditionally been the main treatment of Enterobacteriaceae infections, nonetheless, the emergence of species producing β- Lactamases has rendered this class of antibiotics largely ineffective. There are no published data on etiology of urinary tract infections (UTI) and antimicrobial resistance profile of uropathogens among children in Qatar. The aim of this study is to determine the phenotypic and genotypic profiles of antimicrobial resistant Enterobacteriaceae among children with UTI in Qatar., Methods: Bacteria were isolated from 727 urine positive cultures, collected from children with UTI between February and June 2017 at the Pediatric Emergency Center, Doha, Qatar. Isolated bacteria were tested for antibiotic susceptibility against sixteen clinically relevant antibiotics using phoenix and Double Disc Synergy Test (DDST) for confirmation of extended-spectrum beta-lactamase (ESBL) production. Existence of genes encoding ESBL production were identified using polymerase chain reaction (PCR). Statistical analysis was done using non-parametric Kappa statistics, Pearson chi-square test and Jacquard's coefficient., Results: 201 (31.7%) of samples were confirmed as Extended Spectrum β -Lactamases (ESBL) Producing Enterobacteriaceae. The most dominant pathogen was E. coli 166 (83%) followed by K. pneumoniae 22 (11%). Resistance was mostly encoded by bla CTX-M (59%) genes, primarily bla CTX-MG1 (89.2%) followed by bla CTX-MG9 (7.7%). 37% of isolated bacteria were harboring multiple bla genes (2 genes or more). E. coli isolates were categorized into 11 clusters, while K. pneoumoniae were grouped into five clonal clusters according to the presence and absence of seven genes namely bla TEM, bla SHV, bla CTX-MG1, bla CTX-MG2, bla CTX-MG8 bla CTX-MG9 , bla CTX-MG25., Conclusions: Our data indicates an escalated problem of ESBL in pediatrics with UTI, which mandates implementation of regulatory programs to reduce the spread of ESBL producing Enterobacteriaceae in the community. The use of cephalosporins, aminoglycosides (gentamicin) and trimethoprim/sulfamethoxazole is compromised in Qatar among pediatric population with UTI, leaving carbapenems and amikacin as the therapeutic option for severe infections caused by ESBL producers., Competing Interests: Ethical approval for this study was obtained from the Medical Research Centre (MRC), Hamad Medical Corporation (HMC), Doha, Qatar, protocol no. 16434/16.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.