Epidemiologic and Clinical Characteristics and Risk Factors for Severe Community-Acquired Clostridium Difficile Infection in Children.

Although children most frequently suffer from milder forms of community-acquired Clostridium difficile infection, severe cases and fatal outcomes have been recorded. In this study we identified older children (>12 years of age) and patients who had surgery up to 6 months before Clostridium difficile infection onset as a subgroup at somewhat higher risk for severe community-acquired Clostridium difficile infection.

Invasive meningococcal disease in South-Eastern European countries: Do we need to revise vaccination strategies?

Invasive meningococcal disease (IMD) is an acute life-threatening infection caused by the gram-negative bacterium, Neisseria meningitidis. Globally, there are approximately half a million cases of IMD each year, with incidence varying across geographical regions. Vaccination has proven to be successful against IMD, as part of controlling outbreaks, and when incorporated into national immunization programs. The South-Eastern Europe Meningococcal Advocacy Group (including representatives from Croatia, the Czech Republic, Greece, Hungary, Poland, Romania, Serbia, Slovenia and Ukraine) was formed in order to discuss the potential challenges of IMD faced in the region. The incidence of IMD across Europe has been relatively low over the past decade; of the countries that came together for the South-Eastern Meningococcal Advocacy Group, the notification rates were lower than the European average for some country. The age distribution of IMD cases was highest in infants and children, and most countries also had a further peak in adolescents and young adults. Across the nine included countries between 2010 and 2020, the largest contributors to IMD were serogroups B and C; however, each individual country had distinct patterns for serogroup distribution. Along with the variations in epidemiology of IMD between the included countries, vaccination policies also differ.

Distribution of Epstein-Barr Virus LMP1 Variants in Patients with Infectious Mononucleosis and Association with Selected Biochemical and Hematological Parameters.

The molecular diversity of Epstein-Barr virus (EBV) is exceptionally complex and based on the characterization of sequences coding for several viral genes. The aim of this study was to analyze the distribution of EBV types 1 and 2 and to characterize LMP1 variants in a cohort of 73 patients with infectious mononucleosis (IM), as well as to investigate a possible association between viral diversity and relevant clinical parameters. Population-based sequencing of EBNA-2 gene showed the presence of EBV type 1 in all IM patients. Analysis of LMP1 gene found a restricted repertoire of LMP1 variants with the predominance of wild-type B95-8, China1, Mediterranean and North Carolina variants with the presence of more than one LMP1 variant in 16.4% of patients. Co-infections with different LMP1 variants were associated with significantly higher levels of C-reactive protein and lower levels of maximal neutrophil counts and minimal platelet count. The results of this study have shown a narrow repertoire of LMP1 variants and an exclusive presence of EBV type 1 in a cohort of IM from Croatia, suggesting a characteristic local molecular pattern of this virus. The clinical importance of distinct immunobiological features of IM patients with LMP1 variant co-infections needs to be investigated further.

Interspecies transmission of porcine-originated G4P[6] rotavirus A between pigs and humans: a synchronized spatiotemporal approach.

As a leading viral cause of acute gastroenteritis in both humans and pigs, rotavirus A (RVA) poses a potential public health concern. Although zoonotic spillover of porcine RVA strains to humans is sporadic, it has been detected worldwide. The origin of chimeric human-animal strains of RVA is closely linked to the crucial role of mixed genotypes in driving reassortment and homologous recombination, which play a major role in shaping the genetic diversity of RVA. To better understand how genetically intertwined porcine and zoonotic human-derived G4P[6] RVA strains are, the present study employed a spatiotemporal approach to whole-genome characterization of RVA strains collected during three consecutive RVA seasons in Croatia (2018-2021). Notably, sampled children under 2 years of age and weanling piglets with diarrhea were included in the study. In addition to samples tested by real-time RT-PCR, genotyping of VP7 and VP4 gene segments was conducted. The unusual genotype combinations detected in the initial screening, including three human and three porcine G4P[6] strains, were subjected to next-generation sequencing, followed by phylogenetic analysis of all gene segments, and intragenic recombination analysis. Results showed a porcine or porcine-like origin for each of the eleven gene segments in all six RVA strains. The G4P[6] RVA strains detected in children most likely resulted from porcine-to-human interspecies transmission. Furthermore, the genetic diversity of Croatian porcine and porcine-like human G4P[6] strains was propelled by reassortment events between porcine and porcine-like human G4P[6] RVA strains, along with homologous intragenotype and intergenotype recombinations in VP4, NSP1, and NSP3 segments. Described concurrent spatiotemporal approach in investigating autochthonous human and animal RVA strains is essential in drawing relevant conclusions about their phylogeographical relationship. Therefore, continuous surveillance of RVA, following the One Health principles, may provide relevant data for assessing the impact on the protectiveness of currently available vaccines.

Incidence and Clinical Phenotype of Multisystem Inflammatory Syndrome in Children After Two SARS-CoV-2 Pandemic Waves: A Croatian Prospective Nationwide Study.

This prospective nationwide study in Croatia (March 1, 2020-December 31, 2021) embraced 121 children with multisystem inflammatory syndrome. Incidence rates, disease course and outcomes were similar to those reported from other European countries. The severe acute respiratory syndrome coronavirus 2 virus Alpha strain appeared associated with a higher propensity to result in multisystem inflammatory syndrome in children than the Delta strain but did not appear related to disease severity.

Parents' attitudes toward childhood COVID-19 immunization in Croatia: a multicenter cross-sectional study.

AIM: To assess parents' attitudes toward childhood COVID-19 immunization in Croatia. METHODS: In this multicenter cross-sectional study, we collected data from four tertiary care facilities in Zagreb, Split, and Osijek between December 2021 and February 2022. During the visit to the Pediatric Emergency Departments, parents were asked to fill out a highly-structured questionnaire about their attitudes toward COVID-19 immunization in children. RESULTS: The sample consisted of 872 respondents. A total of 46.3% of respondents were hesitant about vaccinating their child against COVID-19, 35.2% definitely did not intend to vaccinate their child, and 18.5% definitely intended to vaccinate their child. Parents who were themselves vaccinated against COVID-19 were more likely than unvaccinated parents (29.2% and 3.2%, P<0.001) to vaccinate their children. Parents agreeing with the epidemiological guidelines were more inclined to vaccinate their children, as were parents of older children and parents of children vaccinated according to the national program schedule. Child comorbidities and respondents' history of COVID-19 were not associated with childhood vaccination intention. Ordinal logistic regression revealed that the most important predictors for a positive parents' attitude toward vaccinating their child were parents' vaccination status and regular vaccination of their child according to the national immunization program schedule. CONCLUSION: Our results demonstrate Croatian parents' mostly hesitant and negative attitudes toward childhood COVID-19 immunization. Future vaccination campaigns should target unvaccinated parents, parents with younger children, and parents of children with chronic diseases.

Knowledge and attitudes of pregnant women on maternal immunization against COVID-19 in Croatia.

OBJECTIVES: The aim of this study was to assess pregnant women's knowledge and attitudes regarding maternal COVID-19 immunization during pregnancy. METHODS: A cross-sectional study was performed in two teaching hospitals between May and October 2021 in Zagreb, Croatia. During antenatal clinic visit pregnant women were approached and asked to fill out a predesigned questionnaire about their knowledge and attitudes towards COVID-19 vaccination. Collected data was later analyzed. RESULTS: A total of 430 women participated in the study. Only 16% of women expressed their willingness to be vaccinated against COVID-19 if offered, despite that 71% of them believe that COVID-19 might be a serious illness in pregnant women. The most important obstacle in having better acceptance of the vaccines is in the assumption that the vaccines are not safe for pregnant women (73%) or the fetus (75%), or that the vaccines are not effective (41%). The relationship exists between acceptance of vaccination in general and willingness to get other vaccines in pregnancy and readiness to be vaccinated against COVID-19 in pregnancy. Only one out of 55 women who were not adherent to the current vaccination recommendations in Croatia would accept the COVID-19 vaccine during pregnancy if offered. 21 (5%) women stated that vaccination against influenza and pertussis during pregnancy is necessary and 13 (62%) of them would get vaccinated against COVID-19 if offered. CONCLUSIONS: This study showed that the crucial reasons for refusing vaccination against COVID-19 among pregnant women in Croatia are the concerns about the vaccines' effectiveness and safety. All healthcare providers should put more effort into education of pregnant women on risks of COVID-19, as well as on the benefits and safety of the vaccines.

Campylobacter jejuni subdural hygroma infection in a 2-year old boy: case report and a brief literature review.

BACKGROUND: Campylobacter jejuni is a common cause of acute gastroenteritis, but central nervous system infections are rare manifestations of Campylobacter infection. Therefore, C. jejuni trauma-related subdural hygroma infection in children is poorly described in the literature. CASE PRESENTATION: We described a 2-year old boy with lobar holoprosencephaly presenting with subdural hygroma following head trauma. C. jejuni infection was confirmed from a subdural hygroma sample by culture as well as by DNA sequencing of a broad range 16S rDNA PCR product. Cerebrospinal fluid from the ventriculoperitoneal shunt remained sterile. Combined neurosurgical and antimicrobial treatment led to complete recovery. Review of the literature showed that the most common manifestation of Campylobacter central nervous system infection is meningitis, mostly in neonates, and subdural hygroma infection was described for only one case. CONCLUSIONS: Subdural hygroma infection caused by C. jejuni is a rare clinical condition in children. Molecular methods represent an important tool for the detection of rare or unexpected pathogens. No standard recommendations for antimicrobial treatment of C. jejuni subdural space infection in children are available, but meropenem treatment combined with surgery seems to be an effective approach.

Vaccination in pediatric acquired inflammatory immune-mediated neuromuscular disorders.

AIM: To analyse literature data on vaccine related induction, worsening of the disease and disease reccurrences as well as vaccine safety and efficacy among pediatric patients with acquired inflammatory immune-mediated neuromuscular disorders (NMD). METHODS: Medline, Pub Med and Scopus database search from 1975 to 2020 focused on pediatric age was conducted including peer reviews, meta analyses and epidemiological studies on vaccination and Guillain-Barré syndrome (GBS), Bell's palsy, optic neuritis (ON), myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP) and immune-mediated inflammatory myopathy (IM). RESULTS AND CONCLUSION: s: There are no strong evidence supporting relationship between vaccination with different pediatric vaccines and development of first episodes or reccurrences of GBS, Bell's palsy, optic neuritis (ON), juvenile MG, CIDP, and IM. The vaccination and revaccination with inactivated vaccines is considered safe in children with medical history of GBS, Bell's palsy, ON, MG and IM. Caution when immunization against influenza, quadrivalent conjugated meningococcal vaccine (MCV4) and pneumococcal disease and avoiding tetanus toxoid immunization in CIDP patients is suggested. Patients with immune mediated acquired NMD should be vaccinated with live vaccines before the initiation of immunosupressive treatment. Immunosuppressed patients with low protective antibody titers should be considered for revaccination.

Immunization funding across 28 European countries.

INTRODUCTION: Disease prevention and improving vaccination coverage in Europe are key elements contributing to resilient health systems and ensuring better health outcomes for all. The aim of this study was to describe the immunization funding landscape across all European Union 28 countries (EU28). AREAS COVERED: Data collected in a targeted literature review supported descriptive analysis on the different indicators that were looked at: vaccines included in the EU28 national immunization programs (NIP), national immunization funding, immunization funding per capita (2015-2019) and percentage of health-care budget allocated to immunization. EXPERT OPINION: Immunization funding represents a small proportion of total healthcare spend in Europe (median 0.3%). In the context of the current COVID-19 pandemic, demographic changes, and the potential introduction of new vaccines; the need for adequate financing of immunization programs will be important, to establish resilient immunization systems and provide sustainable protection of the population against vaccine-preventable diseases.

PLAIN LANGUAGE SUMMARYWhat is the context?Herpes zoster, or shingles, is a viral disease characterized by a painful, localized skin rash. It affects approximately 32% of US citizens at least once in their lifetime.The risk of contracting shingles increases with age.Most American adults over 50 years have not received the shingles vaccine, and vaccination rates are especially low for African-Americans.What is new?This is the first study to evaluate what drives shingles vaccination decisions among US adults ≥ 50 years of age. We also assessed the differences between African-American and non-African-American adults, and inside the African-American group.In this choice experiment, 1,454 people ≥ 50 years completed a survey of 8 choice questions, as well as questions on their previous experiences with vaccines, socioeconomic, and demographic characteristics. Seven factors were evaluated.We found that American adults preferred to get vaccinated, and the most influential factors were costs and vaccine effectiveness while location of vaccination was the least important. There were differences in preferences between African-American and non-African-American adults, mainly driven by costs and vaccine effectiveness. 3 different groups of African-American adults with systematically different preferences could be identified; two were likely to vaccinate, with one being more cost sensitive at lower price thresholds, and the third was unlikely to vaccinate.What is the impact?Decisions on shingles vaccination appear to be mostly driven by costs, which could be a barrier to those who do not have appropriate insurance, especially among some African-Americans.However, healthcare professionals should continue to educate patients on other vaccine characteristics, as they also influence vaccination decisions.

First Data on Human Lyme Borreliosis in Kosovo: Prospective Evaluation of the Disease from a Tick Bite Perspective.

Purpose: Lyme borreliosis (LB) occurs throughout Europe. No clinical and seroprevalence studies for LB in Kosovo have been publicly available thus far. Therefore, this study aimed to investigate LB from a tick bite perspective in the Pristina region, Kosovo. Methods: This single-center prospective observational study enrolled consecutive adult participants (≥18 years of age) with tick bite (embedded tick in the skin), who were examined at the Clinic of Infectious Diseases, Pristina, between January 2015 and August 2018. At the first visit related to the index tick bite, ticks (the complete ticks or parts of the ticks) were removed from the skin, blood samples were taken for serological tests, and antibiotic treatment was started when deemed necessary. The complete, undamaged ticks removed were proceeded for entomological identification. Participants were followed up at 2 months (serological tests were repeated) and 6 months after the index event for the development of clinical manifestations of LB and/or seroconversion against Borrelia burgdorferi. Results: A total of 380 subjects were included in the study. Most cases were seen in May and June in all study years. All 117 preserved ticks were identified as Ixodes ricinus. Immunoglobulin G seroprevalence among subjects during the first visit in the study was 28/380 (7.4%). Erythema migrans (EM) was clinically diagnosed in 74/380 patients (19.5%, 95% confidence interval 15.6-23.8). Only 15 clinically diagnosed EM (in seronegative patients) were serologically confirmed with seroconversion (2 months later), 3.9% of all subjects included in the study. There were three cases with clinical manifestation between the second and third visit: EM recidivans, multiple erythema, or several nonspecific systemic symptoms. Doxycycline and amoxicillin were mainly used for the treatment of borrelial skin lesions. Conclusion: This assessment can help indicate the need for disease awareness and reinforce the importance of primary prevention measures, early diagnosis, and appropriate treatment.

Pediatric tertiary emergency care departments in Zagreb, Rijeka, and Split before and during the coronavirus disease 2019 pandemic: a Croatian national multicenter study.

AIM: To assess the number of visits to pediatric emergency departments in Croatia and reasons for visiting before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We reviewed the medical records of pediatric patients visiting emergency departments of four tertiary medical centers between February 25 and April 25, 2018 and 2019, and between February 25 and April 24, 2020. Antimicrobial prescription was analyzed as well. RESULTS: There were altogether 46 544 visits - 18218 in 2018, 19699 in 2019, and 8634 in 2020. The overall number of visits in 2020 significantly decreased compared with 2018 and 2019 (52% and 56% reduction, respectively), mostly due to a decreased number of visits due to certain infectious diseases: acute gastroenteritis (89.2%), sepsis/bacteremia (81.2%), urinary tract infections (55.3%), and lower respiratory tract infections (58%). Most visits were self-referrals regardless of the analyzed period, and the majority of patients did not require hospitalization. There were no significant differences in the number of visits requiring urgent medical care, such as those due to seizures and urgent surgery. The most frequently prescribed antibiotic in all periods was amoxicillin, followed by amoxicillin/clavulanate and oral cephalosporins. CONCLUSION: A significant reduction in the number of pediatric emergency department visits and hospital admissions is indirectly related to the COVID-19 pandemic. Most of the reduction was due to a decreased number of infectious disease cases. However, the number of visits requiring urgent medical intervention did not change.

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.

Epidemiological and clinical features of Croatian children and adolescents with a PCR-confirmed coronavirus disease 2019: differences between the first and second epidemic wave.

AIM: To describe epidemiological and clinical features of Croatian children and adolescents with a polymerase chain reaction (PCR)-confirmed coronavirus disease 2019. METHODS: Data on patients aged ≤19 years with a positive SARS-CoV-2 PCR test recorded in the period March 12-May 12 (first wave) and June 19-July 19, 2020 (second wave) were retrospectively analyzed. The periods were separated by several weeks with no incident cases. RESULTS: We analyzed data on 289 children and adolescents (6.5% of all cases; incidence rate [IR]=3.54, 95% confidence interval [CI] 3.14-3.97/million person-days), 124 in the first wave (IR=2.27) and 165 in the second wave (IR=6.37): IRR second/first=2.71 (2.13-3.44). During the first wave, the incidence was highest in infants (IR=3.48), while during the second wave it progressively increased to IR = 7.37 in 15-19-year olds. Family members were the key epidemiological contacts (72.6% cases), particularly during the first wave (95.8% vs 56.3%). Overall, 41.3% patients were asymptomatic, 25.3% in the first and 52.6% in the second wave. Age 15-19 years (vs younger) was associated with a higher (RR = 1.26, 1.02-1.54) and infection in the second wave with a lower probability (RR=0.66, 0.53-0.81) of being symptomatic. The most common symptoms were fever, cough, and rhinorrhea. In children aged ≥7 years, headache, anosmia/ageusia, and sore throat were also recorded. Only one child suffered a severe disease. All but 18 (7.8%) children were treated only symptomatically, and all fully recovered. CONCLUSION: A large proportion of SARS-CoV-2 PCR-positive children/adolescents were asymptomatic. The associated disease was predominantly mild, comparably so in the first and second pandemic wave.