Enteroadsorbent Polymethylsiloxane Polyhydrate vs. Probiotic Lactobacillus reuteri DSM 17938 in the Treatment of Rotaviral Gastroenteritis in Infants and Toddlers, a Randomized Controlled Trial.

Purpose: The aim of this study was to compare two adjunct therapies in the treatment of childhood rotavirus gastroenteritis (RVGE). We compared the recommended treatment, probiotic Lactobacillus reuteri DSM 17938 (BioGaia®), vs. a novel treatment, enterosorbent polymethylsiloxane polyhydrate (Enterosgel®). Methods: This was an open-label, randomized, clinical controlled trial at the University Hospital for Infectious Diseases (UHID) in Zagreb, Croatia. A total of 149 children aged 6-36 months with acute rotaviral gastroenteritis over a period of <48 h, with no significant chronic comorbidity, were randomized to receive the standard therapy with L. reuteri DSM 17938 (hereafter L. reuteri) or polymethylsiloxane polyhydrate (hereafter PMSPH) therapy, during 5 days. The primary end point was time to recovery in days in both groups. The recovery was defined as absence of fever and vomiting and either the first firm stool, absence of stool for more than 24 h, or return of usual bowel habit. Results: A total of 75 children were randomized into the L. reuteri group and 74 were randomized into the PMSPH group; after excluding missing data, the data from 65 children in each group were analyzed. There was no significant difference in the treatment efficacy between the two regimens with an estimated median time of recovery of 6 days in both groups (p = 0.754). No significant side effects were observed in either group. Conclusion: Novel enterosorbent PMSPH had a similar efficacy to probiotic L. reuteri in the treatment of rotaviral gastroenteritis in preschool children. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04116307 [October 3, 2019] (retrospectively registered). https://clinicaltrials.gov/show/NCT04116307.

Challenges in early diagnosis of Kawasaki disease in the pediatric emergency department: differentiation from adenoviral and invasive pneumococcal disease.

Early recognition and distinction of Kawasaki disease (KD) from other febrile infectious diseases is one of the biggest challenges in pediatric emergency departments (PED). The aim of this study was to assess the utility of clinical findings and routinely used laboratory parameters for early discrimination between KD, invasive pneumococcal disease (IPD) and adenovirosis (AdV). A retrospective, cross-sectional study of children aged 3-36 months consecutively admitted to the PED and diagnosed with either KD (n = 110), AdV (n = 440) or IPD (n = 122) was conducted. At first presentation to the PED, 56.3% of KD patients had none or only one clinical criterion, 31% of patients with AdV and 11% with IPD had > 2 criteria. The levels of platelets (Plt), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were higher and white blood cells (WBC) significantly lower in KD than in IPD and AdV group. The WBC < 20 ×109/l showed a sensitivity of 80.9% and specificity of 79.7% in comparison to AdV. The ROC curve showed a significant, but low sensitivity for AST, ALT and Plt. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) did not show any significant diagnostic accuracy. Significant association between incomplete KD and rash, WBC < 20 ×109 and Plt > 400 ×109/L compared to AdV and conjuctivitis, rash and Plt > 400 × 109/L, was found. Due to the time delay and nonspecific early presentation, differentiating KD from IPD and AdV is challenging. Tools used for identification of patients at risk for severe bacterial infections in PED lack sensitivity for identification of KD cases. New biomarkers are warranted for distinction of KD from IPD or AdV.

Molecular characterization of a collection of Neisseria meningitidis isolates from Croatia, June 2009 to January 2014.

In the last decade, the incidence of invasive meningococcal disease (IMD) in Croatia remained stable at approximately 1 case per 100 000 inhabitants, affecting mainly children aged ≤5 years. We report the molecular characterization of meningococci causing IMD occurring from June 2009 to January 2014 in Croatia. Genomic DNA from 50 clinical isolates was analysed for serogroup, multilocus sequence typing and allele type of the two outer membrane protein genes, porA and the iron-regulated fetA. Furthermore, 22 of them were characterized by using whole-genome sequencing to define the meningococcal vaccine four-component meningococcal serogroup B (4CMenB) antigen genes factor H-binding protein (fHbp), Neisseria heparin-binding antigen (nhba) and Neisseria adhesin A (nadA) and the antimicrobial target resistance genes for penicillin (penicillin binding protein 2, penA), ciprofloxacin (DNA gyrase subunit A, gyrA) and rifampicin (ß-subunit of RNA polymerase, rpoB). The Etest was used to phenotypically determine the antimicrobial susceptibility of isolated meningococci. The main serogroup/clonal complex combinations were MenB cc41/44, MenC/cc11, MenW/cc174 and MenY/cc23. PorA P1.7-2, FetA F5-5 and F1-5 were the most represented through the serogroups. Meningococci with decreased susceptibility to penicillin (38.9 %) and one strain resistant to ciprofloxacin were identified. Forty-two percent of MenB showed the presence of at least one of the 4CMenB vaccine antigens (fHbp, NHBA, NadA and PorA). Our findings highlight the genetic variability of meningococci causing IMD in Croatia, especially for the serogroup B. Molecular-based characterization of meningococci is crucial to enhance IMD surveillance and to better plan national immunization programmes.

Risk factors for coronary artery abnormalities in children with Kawasaki disease: a 10-year experience.

Kawasaki disease (KD) is an acute systemic vasculitis of childhood. Due to development of coronary artery aneurysms (CAA) it is considered the most common cause of acquired heart disease in children. The clinical and laboratory features of patients with complete and incomplete KD were compared in order to identify the possible predictors of CAA development. A cross-sectional study of children with KD treated at the University Hospital for Infectious Diseases, Zagreb, between January 2003 and December 2012 was conducted. A total of 111 KD patients were included; 70.3% patients had complete KD. Patients with complete KD had more frequently rash, changes on extremities and mucous membranes, as well as higher serum bilirubin, aminotransferases, gamma-glutamyl transferase and lactate dehydrogenase levels. Patients with incomplete KD had longer duration of fever before the diagnosis (8 vs. 7 days) and delayed IVIG treatment (day 8 vs. 7). CAA was detected in seven children (6.3%). Disease duration before hospitalization >6 days (OR 7.16, 95% CI 1.51-100.35), age <6 months (OR 25.86, 95% CI 1.68-398.35) and platelet count >771 after the 7th day of disease (OR 13.33, 95% CI 2.19-80.87) were independently associated with CAA development. The diagnosis and treatment in incomplete KD can be delayed due to the absence of major criteria. Age, duration of symptoms prior hospitalization and platelet count were identified as independent predictors of CAA development.

Adenovirus respiratory infections in hospitalized children: clinical findings in relation to species and serotypes.

BACKGROUND: There are >50 adenovirus (ADV) serotypes that are divided into 7 species (A-G). The aim of this study was to characterize ADV serotypes and species in hospitalized infants and children in the City of Zagreb and Zagreb County and to describe clinical features and laboratory findings of ADV infections according to the causative ADV serotype. METHODS: During the 3-year period from January 2006 to November 2008, 135 children (<10 years of age) with ADV respiratory infection, based on virus isolation, were treated at 2 hospitals in Zagreb. Demographics, clinical presentations and laboratory findings were evaluated. RESULTS: Of the 135 ADV isolates, 77 (57.0%) were type 2, followed by 26 (19.3%) of type 1, 15 (11.1%) isolates of type 3, 2 (1.5%) of type 6 and only 1 (0.7%) was type 7. Male-to-female ratio was 3.2:1 (103 boys and 32 girls). The mean age was 22.9 months. The most common symptoms were fever (98%), rhinorrhea (89%) and cough (71%). The mean peak body temperature was 39.8°C. Tonsillitis was present in 79 (59%) and acute otitis media in 37 (28%) patients. Leukocytosis (>15.0×109/L) was noted in 103 (77%) patients. Serum C-reactive protein was >40 mg/L in 74 patients (56%). The erythrocyte sedimentation rate was ≥30 mm/h in 91 (71%) of the 127 patients tested. CONCLUSIONS: In this study, the most common isolated serotype was ADV type 2. Most affected children were younger than 3 years. ADV infections in young children can present with prolonged fever, leukocytosis and significantly elevated C-reactive protein and erythrocyte sedimentation rate, mimicking bacterial infections.

Analysis of biennial outbreak pattern of respiratory syncytial virus according to subtype (A and B) in the Zagreb region.

BACKGROUND: The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years. METHODS: The study group consisted of 696 inpatients, aged 0-5 years, who were hospitalized with acute respiratory tract infections caused by RSV, in Zagreb, in the period 1 January 2006-31 December 2008. The virus was identified in nasopharyngeal secretions using direct immunofluorescence. The virus subtype was determined on real-time polymerase chain reaction. RESULTS: Of 696 RSV infections identified in children, subtype A virus caused 374 infections, and subtype B, 318. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by four epidemic waves of RSV infections: the first, smaller, in the spring of 2006; the second, larger, in December 2006/January 2007; the third in spring 2008, followed by a fourth outbreak beginning in November of 2008. The biennial virus cycles were persistent although the predominant RSV subtype in the first two epidemic waves was subtype B, and in the second two it was subtype A. CONCLUSION: Over a 3 year period of observation, the biennial RSV cycle in Croatia cannot be explained by a difference in the predominant circulating subtype of RSV. Other unknown factors account for the biennial cycle of RSV epidemics in Croatia.

Ischemic stroke associated with adenoviral infection in a 4-year-old boy.

We present a case of childhood arterial ischemic stroke associated with proven adenoviral upper respiratory tract infection in a previously healthy 4-year-old boy. Adenoviral meningitis and encephalitis have been reported repeatedly, thus confirming the neuroinvasive capability of these viruses. However, an association between adenoviral infection and arterial ischemic stroke has not been described thus far. HIV and varicella zoster virus are the only microorganisms that have been consistently associated with arterial ischemic stroke in the absence of acute central nervous system infection. In HIV-infected individuals ischemic stroke can be caused by vasculitis and hypercoagulability. Granulomatous arteritis of the vessel wall causes post-varicella cerebral infarction and ischemic stroke after herpes zoster ophthalmicus. We suggest that in our patient a post-varicella cerebral infarction-like mechanism of adenoviral spread to the affected artery wall occurred through the ophthalmic branch of the trigeminal nerve. Adenoviruses are neuroinvasive and inflamed conjunctiva might have permitted introduction of the virus into ophthalmic nerve tissue. In consequence, the stenotic lesion of the artery might have been induced by the presence of adenovirus and the subsequent inflammatory reaction. We recommend a prompt quest for adenoviral infection in all previously healthy children with fever and clinical presentation compatible with ischemic stroke, because timely diagnosis and treatment could improve the outcome and hasten neurological recovery.