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Background: The aim of this study was to analyze data on pediatric cases of COVID-19 admitted to a tertiary referral hospital in northwest Greece., Methods: A retrospective analysis was conducted on the most common clinical manifestations and laboratory findings, stratified by age group and SARS-CoV-2 strain., Results: A total of 254 children were hospitalized, with a mean age of 4.5 years. Underlying conditions were present in 10.2% of cases; two children required pediatric intensive care unit (PICU) admission, and one child died. The most common hematological manifestations, in general, were neutropenia (30%) and lymphopenia (23%), whereas the findings varied when the children were stratified by age group. Eight children developed multisystem inflammatory syndrome (MIS-C), with the most common findings being anemia (75%), lymphopenia (50%), and thrombocytopenia (25%). Analysis of the SARS-CoV-2 strains revealed the proportions of the dominant strain over time. Fever was the predominant symptom across all strains, particularly in the Omicron group, which also had a high incidence of gastrointestinal symptoms. The longest hospital admission occurred in children with the Omicron strain, followed by the Wuhan, Alpha, and Delta strains., Conclusions: Fever was the most consistent symptom across all age groups and virus strains. The most common hematological manifestations were neutropenia (30%) and lymphopenia (23%). The Omicron strain was associated with the longest hospital stay. more...

Background : The etiology of type 1 diabetes (T1D) remains an area of active research, with genetic and environmental factors being investigated. This meta-analysis aimed to determine if rotavirus vaccination influences the onset of T1D in children. Methods : Following PRISMA 2020 guidelines, two researchers independently searched multiple databases, including PubMed and Google Scholar, for studies published in English from 2006 to September 2024. They used the search terms "rotavirus vaccination" and "type 1 diabetes", and assessed study quality using the ROBINS-E tool. The analysis pooled hazard ratios (HRs) from selected studies using a fixed-effects model, with statistical significance set at p < 0.05 and heterogeneity evaluated using the I 2 statistic. Results : A systematic search identified 90 records, of which 5 studies met the inclusion criteria. These studies, encompassing a total population of 4,427,291 children from developed countries, suggest a protective effect of rotavirus vaccination against T1D. The pooled HR was 0.87 (95% CI: 0.78-0.98), indicating a 13% lower risk of T1D in vaccinated children compared to unvaccinated ones ( p = 0.03). Moderate heterogeneity was noted (χ 2 = 10.02, df = 4, p = 0.04, I 2 = 60%). Conclusions : This analysis suggests that rotavirus vaccination may reduce the risk of T1D in children from high-income Western countries. While these findings are promising, they may not be generalizable to settings outside similar advanced healthcare systems. Further research is needed to confirm the protective effects of rotavirus vaccination against T1D across diverse populations. more...

Anaphylaxis, the most severe end of the spectrum of allergic reactions, has shown increasing incidence globally over recent years. This hypersensitivity reaction can occur at any age, including infancy. Recent data, although scarce, show that anaphylaxis is increasingly reported in infancy, with food identified as the leading cause of anaphylaxis cases in this age group. Infants constitute a unique subgroup with specific challenges regarding diagnosis of anaphylaxis due to a variety of factors, such as lack of age-specific diagnostic criteria, inability of infants to describe their symptoms, and the broad spectrum of clinical manifestations that may be mistaken as normal findings. Additionally, there are special issues in reference to the treatment of anaphylaxis during infancy, such as the limited availability of weight-appropriate epinephrine autoinjectors for infants weighing <15 kg. In this study, we review the current literature regarding specific characteristics of anaphylaxis in infants as well as unique challenges in terms of diagnosis, acute treatment, and long-term management of this medical emergency in this vulnerable age group., Competing Interests: The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. more...

Respiratory Syncytial Virus (RSV) is a common respiratory pathogen with high morbidity and mortality, especially in children under two years of age. Severe RSV infection poses a significant threat to healthcare systems, making vaccination an utmost need. In August 2023, the U.S. FDA approved an RSV maternal vaccine to prevent lower respiratory tract disease (LRTD) in infants throughout their first six months of life. This cross-sectional survey was designed to evaluate pregnant women's willingness to receive the vaccine during pregnancy. An anonymous survey was administered from April 2023 to December 2023 to pregnant women aged above 16 years old attending gynecology wards of randomly selected public and private hospitals in Crete. The primary outcome was the intention to receive the vaccine. Univariable and multivariable analyses were carried out to identify factors associated with the intention to get vaccinated. Questionnaires were distributed to a sample of 335 pregnant females who agreed to participate in this study. The intention to get vaccinated against RSV was positively associated with educational level, the presence of school-age children, RSV infection awareness, intention to get routine pregnancy vaccines according to the National Immunization Program (NIP), and previous vaccination against COVID-19. The majority of pregnant females were not familiar with the term RSV and the upcoming vaccine. An educational campaign regarding RSV infection and its vaccine is required to improve women's perceptions and to support healthcare workers in promoting it upon its availability in Greece. more...

Background/objectives: Some individuals with obesity may exhibit fewer metabolic disturbances and face a lower long-term risk of complications; however, the existence of this so-called "metabolically healthy obesity" (MHO) compared to "metabolically unhealthy obesity" (MUO) remains controversial. We hypothesized that children with MHO might have a more favorable profile than children with MUO. Markers of glucose metabolism and insulin sensitivity were compared between children and adolescents diagnosed with MHO and MUO., Methods: This study recruited prospectively 104 children and adolescents (aged 6-16 years, 47 boys) with obesity. All participants underwent an oral glucose tolerance test (OGTT), and a comparative analysis was performed on HOMA-IR, QUICKI, insulin sensitivity index (ISI), insulinogenic index (IGI), disposition index (DI), and oral disposition index (oDI). Glucose metabolism indices were compared in these subgroups according to pubertal status., Results: Forty-seven children (45.2%) were diagnosed with MHO. The whole-body ISI differed significantly between the MHO and MUO groups (4.02 vs. 2.7, p < 0.01). The IGI was statistically lower in the MHO group compared to MUO (1.26 vs. 1.54, p < 0.01), while neither the DI nor the oDI differed significantly. A higher ISI (4.5 vs. 3.9, p < 0.01) was observed in prepubertal MHO individuals compared to MHO adolescents., Conclusions: Children classified as MHO according to the more recent criteria exhibit a more favorable metabolic profile than those with MUO. However, a completely healthy profile was not demonstrated in the MHO group, as many crucial metabolic profile parameters were comparable to those observed in the MUO group. The findings of this study indicate that all children with obesity, irrespective of whether they are categorized as having MUO or MHO, necessitate close monitoring. more...

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Myocarditis represents an inflammation affecting the heart muscles, a condition relatively uncommon among children. Its diagnosis poses challenges due to the diverse range of its non-specific symptoms. Non-typhoidal Salmonella (NTS) species are known as rare but noteworthy contributors to myocarditis, especially among immunocompetent young patients. We present two cases of NTS myocarditis in previously healthy children, in an attempt to shed light on the epidemiology, diagnostic methods, and prognosis, aiming to offer a greater understanding of this rare condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ladomenou et al.) more...

The Omicron variant is associated with increased transmissibility, but evidence about the impact of Omicron in seropositivity of children is limited. This study aims to evaluate SARS-CoV-2 seroprevalence in children during the different variants' subperiods. A prospective multicenter seroprevalence study was conducted in 7 University public hospitals in Greece from November 2021 to August 2022 (3 subperiods: November 2021-February 2022, March 2022-May 2022, June 2022-August 2022). Children from different age groups, admitted to the hospital or examined in outpatient clinics for reasons other than COVID-19 were enrolled. Neutralizing antibodies (Nabs), anti-Spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 IgG in serum were evaluated. A total of 2127 children (males:57,2%; median age:4,8years) were enrolled. Anti-N IgG seropositivity increased from 17,8% in the first sub-period to 40,7% in the second sub-period and then decreased in the third sub-period (36,7%). Anti-S IgG seropositivity appeared to have an increasing trend over the study period, starting from 34,8% and reaching 80,7%. Children aged 1-4 years old have significantly higher anti-N IgG titers compared to children aged 0-1 years old (p < 0,001). Infants have significantly lower anti-S IgG titers compared to all other age groups (p < 0,001). Immunocompromised children and infants have the lowest seropositivity for NAbs.Conclusions During the Omicron period, seropositivity significantly increased, as a result of higher transmissibility. Neonates and infants have lower antibody titers compared to other age groups, while young children aged 1-4 years old present higher antibody titers, suggesting that this age group may mount a higher antibody response. Continuous surveillance seroprevalence studies are needed in children, in order to identify the true extent of SARS-CoV-2 and guide the planning of adequate public health measures., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Background: Atopic dermatitis (AD) at a young age often precedes the development of food allergies. Although AD affects millions of infants worldwide, prenatal and postnatal risk factors, and their association with the development of food allergies later on, are not fully elucidated. This study seeks to investigate AD epidemiology in infancy and its risk factors, examining early-life factors (both prenatal and postnatal) that could contribute to the later development of food allergies., Methods: Between January 2019 and December 2019, 501 infants were included in this prospective cohort study. Longitudinal data collection was performed through maternal interviews, the first one conducted within three days after the delivery and the second within 24 to 36 months after the delivery, encompassing variables such as demographics, family history of atopy, maternal smoking, antibiotic use during pregnancy, the mode of delivery, breastfeeding history, food practices, and greenness exposure within 3 days from delivery, while they were still in the hospital., Results: Maternal smoking during pregnancy ( p = 0.001) and an older sibling atopy history ( p = 0.03) was significantly linked to AD incidence. Cesarean section delivery ( p = 0.04) was associated with a higher risk of food allergies in infants with AD. Having a garden at home correlated with a higher likelihood of AD ( p = 0.01), and food elimination without medical guidance ( p = 0.02) due to AD correlated with an elevated risk of food allergies., Conclusions: Encouraging timely allergenic food introduction while promoting dietary diversity, rich in plant-based foods, maternal smoking cessation, and professional dietary guidance may help minimize AD and food allergy risk. Future studies should address the role of greenness in the development of AD and food allergies. more...

The objective of this article is to assess the adherence of pregnant women to the national recommendations for influenza and pertussis vaccination and the reasons behind their non-adherence. This was a retrospective observational study conducted in a well-defined puerperant population of adequate healthcare standards from December 2018 to December 2019. The study was carried out with 1006 puerperants and 66 health care practitioners. Data were collected, including demographic-obstetric features of pregnant women, whether they received antenatal vaccination, the reasons for having been vaccinated or not as well as health professional's opinion regarding antenatal immunization. The uptake of influenza and pertussis vaccine during pregnancy was suboptimal with lack of recommendation of the vaccine by the healthcare providers being the main barrier. Factors positively associated with antenatal vaccination against influenza were higher level of maternal education and advanced maternal age while antenatal vaccination against pertussis was positively associated with higher level of maternal education. This large-scale retrospective study reveals the inadequacy of antenatal vaccination rates against pertussis and influenza in Crete, Greece. Results suggest that obstetricians' confidence in vaccination is of outmost importance for implementing immunization in pregnancy and any doubts on vaccine effectiveness and safety should be resolved. Routine antenatal vaccination counseling and pregnancy immunization campaigns are essential to improve vaccine uptake during pregnancy. more...

Background and Aim: Hypogonadism in adolescent females presents as delayed puberty or primary amenorrhea. Constitutional delay of growth and puberty, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism represent the principal differential diagnosis of delayed puberty. Girls with hypogonadism require hormone replacement therapy to initiate and sustain puberty. We aimed to provide a brief review concerning treatment for female adolescents with hypogonadism and further to focus on current data regarding long-term effects of therapy., Methods: The published studies and articles of the international literature were used regarding the approach to adolescent girls with hypogonadism., Results: The aim of therapy is the development of secondary sexual characteristics and achievement of target height, body composition and bone mass, to promote psychosexual health and, finally, to maximize the potential for fertility. Hypogonadal females need long-term HRT, so it is of great importance to fully define risks and benefits of therapy., Conclusions: The optimal pubertal induction in women contains both estrogens and progesterone regimens.  Different therapeutic options have been described over the years in the literature, but larger randomized trials are required in order to define the ideal approach. The latest acquisitions in the field seem to propose that transdermal 17β-estradiol and micronized progesterone present the most physiological formulations available for this purpose. Further studies and follow up are needed concerning the long-term effects of HRT in adolescents. more...

Objectives: This study aimed to assess the clinical characteristics, treatment and outcomes of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 in five different geographical regions of Iran., Methods: In this multicenter observational study, patients <21 years were included between March 2020 and October 2021. By Disease Control and Prevention (CDC) checklist, demographic characteristics, comorbidities, clinical signs and symptoms, laboratory and radiology findings, and treatment were collected. Statistical analysis was using Chi-square and t-test in STATA14., Results: In total 225 patients with median age of 55 (26-96) months were included that 59.56% boys. 57.33% were admitted to the PICU with a median of 7 days (4-10). 95.56% of patients were discharged with recovery and the rest died. All of the patients in our study were included based on the MIS-C criteria. However, some patients had Kawasaki symptoms, so we compared the clinical and epidemiological characteristics of the two groups. Conjunctival injection, cervical lymphadenopathy>1.5 cm diameter, and strawberry tongue in Kawasaki-like MIS-C patients were higher than of MIS-C patients, and this difference was significant(p<0.001). The most common comorbidity was obesity (24.86%). Most patients tested for COVID-19 and about 60% of the patients had a positive test by serology or reverse transcription-polymerase chain reaction (RT-PCR). Gastrointestinal (88.89%) and hematologic signs (84.44%) were most common. Most drugs used in patients were IVIG and steroids. 88.07% and 61.29% of the patients had at least one problem in echocardiography and lung CT, respectively., Conclusions: The best outcome was seen in patients who were treated with both IVIG and steroids on the first days of admission. Myocarditis was common in two groups of patients. According to most patients had echocardiography abnormal, screening of heart function is recommended for patients., Competing Interests: The authors have declared that no competing interests exist. more...

Pantoea agglomerans  is primarily an environmental and agricultural organism that rarely causes disease in healthy individuals. We present a case of  P. agglomerans  bacteremia in an immunocompetent four-year old boy without comorbidities who presented with fever and increased inflammatory markers. As the exact source of bacteremia could not be established, our case was considered to be an event of primary blood stream infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Haralampidou et al.) more...

As the COVID-19 pandemic evolves, the medical community continues to report a variety of clinical manifestations of SARS-CoV-2 in the pediatric population. Although younger age groups experience less severe disease, attention is given to the immunologic manifestations of the disease. Pericarditis is a rare cardiac complication of COVID-19 infection. We discuss the first case of delayed presentation of pericarditis following recovery from COVID-19 infection in the pediatric population. A 15-year-old male adolescent presented to the emergency department (ED) with a two-day history of left-sided, sub-sternal chest pain that worsened during inspiration and a low-grade fever. Twenty days prior to this presentation, the patient experienced fever and was tested positive for SARS-CoV-2. His family history was remarkable for Hashimoto thyroiditis and rheumatoid arthritis, with his mother having experienced 18 episodes of pericarditis during the exacerbations of her disease. RT-PCR for SARS-CoV-2 was negative on this occasion and the serology assay identified positive IgG antibodies against the virus. The ECG was suggestive for pericarditis and the diagnosis was confirmed by the presence of pericardial effusion on ECHO. The rest of the aetiological investigations for pericarditis were negative. In view of the strong family history of autoimmunity, questions were raised in the medical team of our hospital regarding the etiology of his pericarditis and on whether it represented a postinflammatory immune-mediated presentation of SARS-CoV-2 or a new-onset autoimmune disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Lamprinos et al.) more...

Acute diarrhea is one of the most frequent causes of doctor visits and hospital admissions for children. Our objective was to evaluate the association between probiotics administration and reduction of acute infectious diarrhea duration in children dwelling in developed countries. Bibliographic databases, gray literature, and reference lists were searched up to September 29, 2019. Double-blind, randomized controlled trials that examined probiotics efficacy in children with acute infectious diarrhea residing in developed countries were included. Data were synthesized by generic inverse variance method using fixed- and random-effects model. Twenty trials met the eligibility criteria (n = 3469 patients) and were included in the qualitative synthesis, and 19 studies in meta-analysis. Twelve trials (n = 840) were assessed as high/unclear risk of bias and eight (n = 2629) as low risk of bias. Comparisons revealed a moderate effectiveness of probiotics in low risk of bias studies (MD = - 13.45 h; 95% CI - 24.26, - 2.62; p = 0.02, Bayesian meta-analysis pooled effect MD = - 0.38, 95% CrI - 2.3, 1.58) and a notable effect in studies with high/unclear risk for bias (MD = - 19.70 h; 95% CI - 28.09, - 11.31; p = 0.0004). In trials of optimal methodological quality (n = 1989), probiotics effect was absent (MD = - 3.32 h; 95% CI - 8.78, 2.13, p = 0.23).Conclusion: Outcomes suggest that probiotics do not demonstrate sufficient clinical impact in reducing diarrhea duration in children in the developed countries.Systematic Review Registration: This review is registered at PROSPERO (ID: CRD42020152966). What is Known: • Probiotics, due to the conflicting study results, are administered without adequate evidence as an adjuvant therapeutic agent for eliminating duration of acute infectious diarrhea in pediatric patients. What is New: • In developed countries, probiotics are demonstrated as ineffective in reducing the duration of acute infectious diarrhea in children., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Aim: We reported a case of Miller Fisher syndrome following a breakthrough varicella zoster virus infection in an otherwise healthy 6-year-old male. The objective of this review was to summarize the infectious etiologic agents known to trigger Miller Fisher syndrome., Methods: Review of the literature on infections associated with Miller Fisher syndrome., Results: We identified 762 studies after duplicates were removed. Titles, abstracts, and full texts were screened. Finally, 37 studies were included in qualitative synthesis after citations and reference list were checked. The age range of cases reported was 0-78 years, and male sex was predominant in studies where these parameters were reported. The most common causative agent was Campylobacter jejuni followed by Haemophilus influenzae., Conclusions: Our review highlights the importance of recognizing the infections triggering Miller Fisher syndrome. We also present a unique case of Miller Fisher syndrome associated with breakthrough varicella zoster virus infection. Preventive policies may consider population immunization for certain causative agents. more...

Aim: Co-infections with viral and bacterial enteropathogens often augment severity of diarrhoea, however, there is limited evidence on the clinical importance of bacterial enteric co-infections. We investigated the rate, type and impact of bacterial enteropathogens and their associations in children with gastroenteritis., Methods: Retrospective cohort study that included children 0-18 years old with acute bacterial diarrhoea during a 27-year period (1993-2019), in Crete, Greece. Differences in clinical characteristics and pathogen associations were investigated between single and multiple infections., Results: Two or more bacteria were isolated in stool culture in 53 out of 1932 children (2.74%). Patients with co-infections were younger (p 0.0001) and had higher hospitalisation rates (p 0.03). Escherichia coli (E. coli) was the most prevalent pathogen associated with co-infections, in particular the E. coli enteropathogenic strains O127 and O111 (p 0.001), and Salmonella spp the least (p 0.001). Co-occurrence analysis revealed two positively associated pathogen pairs, E. coli with Campylobacter spp and E. coli (p 0.001) with Salmonella spp (p 0.04)., Conclusion: Bacterial enteropathogen co-infection was most common with E. coli strains and related to higher hospitalisation rates and younger age., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.) more...

Aim: We reported a case of Miller Fisher syndrome following a breakthrough varicella zoster virus infection in an otherwise healthy 6-year-old male. The objective of this review was to summarize the infectious etiologic agents known to trigger Miller Fisher syndrome., Methods: Review of the literature on infections associated with Miller Fisher syndrome., Results: We identified 762 studies after duplicates were removed. Titles, abstracts, and full texts were screened. Finally, 37 studies were included in qualitative synthesis after citations and reference list were checked. The age range of cases reported was 0-78 years, and male sex was predominant in studies where these parameters were reported. The most common causative agent was Campylobacter jejuni followed by Haemophilus influenzae., Conclusions: Our review highlights the importance of recognizing the infections triggering Miller Fisher syndrome. We also present a unique case of Miller Fisher syndrome associated with breakthrough varicella zoster virus infection. Preventive policies may consider population immunization for certain causative agents. more...

Invasive meningococcal disease (IMD) remains a major cause of mortality and morbidity in children worldwide. A systemic review in PubMed and Cochrane Controlled Trials Register was performed for articles on risk factors for IMD in children and adolescents published during a 20-year period (19/09/1998 to 19/09/2018). Inclusion and exclusion criteria were established and applied. The data were meta-analyzed using random-effect model and the results were presented on forest plots separately for each risk factor. We identified 12,559 studies (duplicates removed). Titles, abstracts, and full texts were screened and finally, six studies (five case-control and one cohort study) were included in qualitative synthesis, five in meta-analysis. The median age of meningococcal disease (MD) cases was 72.2 months (0-19 years). Household crowding, smoking exposure, close relationships, and recent respiratory tract infections conferred a more than twofold risk for IMD in exposed individuals compared to controls [overcrowded living OR 2.52 (95% CI 1.75-3.63), exposure to smoke OR 2.10 (95% CI 1.00-4.39), kissing OR 2.00 (95% CI: 1.13-3.51), and recent respiratory tract infection OR 3.13 (95% CI 2.02-4.86)]. Attendance of religious events was associated with a decreased risk [0.47 (95% CI, 0.28-0.79)].Conclusion: Our review highlights the importance of individual characteristics as risk factors for IMD in childhood and adolescence. Preventive policies may consider individual as well as social-environmental factors to target individuals at risk.What is Known:• Close relationships, household crowding, and recent respiratory tract infections are major risk factors for IMD.• Passive smoking is a major risk factor for IMD.What is New:• Intimate kissing, household crowding, and passive smoking were found to double the risk of IMD.• Recent respiratory tract infections almost tripled the risk for IMD. more...

Aim: We explored the impact of vaccination on bacterial meningitis in a well-defined population of children on the island of Crete, Greece, over a 27-y period., Methods: This was a retrospective observational study of all mandatory notifications of bacterial meningitis in patients aged 1 mo-14 y from 1991 to 2017., Results: There were 245 patients with proven (n = 227) or suspected (n = 18) bacterial meningitis, and eight deaths were recorded, giving a case fatality rate of 3.3%. The mean annual incidence rate (IR) per 100 000 children was 4.9 for Neisseria meningitidis, 2.2 for Streptococcus pneumoniae and 0.4 for Haemophilus influenzae type b (Hib). Cases of meningitis C dropped significantly after the conjugate meningitis C vaccine was licensed for routine vaccination in Greece in 2000 (IR of 1.5 vs 0.3, P < 0.028) while the Streptococcus pneumoniae cases showed a threefold decrease after the PCV13 vaccine was licensed in Greece in 2009 (IR 2.7 vs 1.0, P < 0.03). Vaccination had already eliminated Hib in Greece in the 1990s., Conclusion: Bacterial meningitis cases decreased in children following the introduction of the meningitis C and PCV13 vaccines in Greece. Hib had already disappeared and significant reductions in meningitis C and Streptococcus pneumoniae were observed., (© 2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.) more...

Aim: Early diagnosis of tuberculosis infection can significantly contribute to the control of the disease. The aim of the present study was to describe the tuberculin skin test (TST) trends over a 24-year period (1990-2013) and explore the value of universal tuberculosis screening in a low-burden area., Methods: All first graders that underwent TST during the 24-year study period (1990-2013) on the island of Crete, Greece, were retrospectively included in the study., Results: A total of 82 402 children (92.3% of Greek nationality; 51.0% male) underwent TST, of whom 335 (0.41%, 95% CI 0.37-0.46) were found to have positive TST while 0.27% of the study population had a TST between 5 and 9 mm. The tuberculin index declined significantly between 1990-1994 and 2010-2013 (0.67 vs 0.26; RR 2.73, 95% CI 1.82-4.09; p < 0.0001). Positive TST result was significantly higher in the immigrant than the native group (0.66% vs 0.24%; RR 3.76 95%, CI 2.89-4.84; p < 0.0001). In the last study years, 386 children (488 native; 153 immigrant) should be tested for one to be found TST positive., Conclusion: Our findings question the massive tuberculin testing in low-burden areas and point to selective screening of high-risk groups., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.) more...

DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity, and allergy. The aim of this study was to assess the effect of different factors in the development of infections, autoimmunity, and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low immunoglobulin M levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3 + , CD3 + CD4 + , and naïve CD4 + CD45RA + CD27 + T lymphocytes compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T cells, as suggested by an accelerated decline of the naïve T lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4 + T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency., (© 2019 by The American Society of Hematology.) more...

Background: Urinary tract infection (UTI) is the most common serious bacterial infection in childhood. The aim of the present study was therefore to identify the organisms responsible for community-acquired febrile UTI in children, to investigate their susceptibility to commonly used antibiotics, and to identify possible risk factors for antibiotic resistance., Methods: A total of 284 children (male, 38%; female, 62%), who were hospitalized due to a community-acquired UTI over a 5 year period in a general district hospital of southern Greece, were enrolled in the study., Results: Escherichia coli was the leading uropathogen followed by Klebsiella spp. (9.15%) and Proteus spp. (5.28%). E. coli isolates were most commonly resistant to ampicillin (41.8%), followed by piperacillin (40.3%), amoxicillin-clavulanic acid (28.6%) and trimethoprim-sulfamethoxazole (17.8%), while 27 strains (12.6%) were multi-drug resistant (MDR). Of the E. coli strains, 4.21% were producing extended-spectrum beta-lactamases. Parenteral second- and third-generation cephalosporins, the most commonly used antibiotic agents (81.3%) in the present cohort, remained highly active against E. coli and other urinary isolates, given that >95% of E. coli strains were susceptible to cefuroxime and cefotaxime. Vesicoureteral reflux was a significant risk factor for MDR (P = 0.04)., Conclusion: Contrary to current local practice, amoxicillin/clavulanic acid may not be the best option for the empirical treatment of community-acquired UTI in southern Greece., (© 2018 Japan Pediatric Society.) more...

The immune system poses one of the greatest challenges for the scientific community. The general pediatrician should be able to screen and identify an immunodeficient patient based on certain clinical indications. Further investigation is crucial for the distinction between primary or secondary immunodeficiency as well as for between cellular and humoral immunity defects. Full blood count is the best initial laboratory test when suspecting a primary immunodeficiency, focusing on the absolute lymphocyte count, while lymphocyte subset count offers the advantage of detecting the cell type that causes the immune defect. The aim of the present review was to guide the general pediatrician in the investigation and diagnosis of an immunodeficient patient. Even though an immunodeficiency may seem a very difficult disease to diagnose, a balanced and rational way of thinking, along with the help of modern technological advances, can easily guide us in the right direction., (© 2018 Japan Pediatric Society.) more...

Asthma is a heterogeneous chronic respiratory disease characterized by an increased burden of infections. Respiratory tract infections associated with an increased risk for asthma especially when occurring in the first months of life, also represent the most common cause of asthma exacerbations. The association between asthma and the increased frequency of infections and microbiota dysbiosis might be explained by a common mechanism, such as an underlying immune system defect. Apart from the well-established association between primary immunodeficiencies and asthma, several alterations in the immune response following infection have also been observed in asthmatic patients. An impairment in lung epithelial barrier integrity exists and is associated with both an increased susceptibility to infections and the development of asthma. Asthmatic patients are also found to have a deficient interferon (IFN) response upon infection. Additionally, defects in Toll-like receptor (TLR) signaling are observed in asthma and are correlated with both recurrent infections and asthma development. In this review, we summarize the common pathophysiological background of asthma and infections, highlighting the importance of an underlying immune system defect that predispose individuals to recurrent infections and asthma. more...

Patients with juvenile idiopathic arthritis (JIA) can experience a severe disease course, with progressive destructive polyarthritis refractory to conventional therapy with disease-modifying antirheumatic drugs including biologics, as well as life-threatening complications including macrophage activation syndrome (MAS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative immunomodulatory strategy for patients with such refractory disease. We treated 16 patients in 5 transplant centers between 2007 and 2016: 11 children with systemic JIA and 5 with rheumatoid factor-negative polyarticular JIA; all were either refractory to standard therapy, had developed secondary hemophagocytic lymphohistiocytosis/MAS poorly responsive to treatment, or had failed autologous HSCT. All children received reduced toxicity fludarabine-based conditioning regimens and serotherapy with alemtuzumab. Fourteen of 16 patients are alive with a median follow-up of 29 months (range, 2.8-96 months). All patients had hematological recovery. Three patients had grade II-IV acute graft-versus-host disease. The incidence of viral infections after HSCT was high, likely due to the use of alemtuzumab in already heavily immunosuppressed patients. All patients had significant improvement of arthritis, resolution of MAS, and improved quality of life early following allo-HSCT; most importantly, 11 children achieved complete drug-free remission at the last follow-up. Allo-HSCT using alemtuzumab and reduced toxicity conditioning is a promising therapeutic option for patients with JIA refractory to conventional therapy and/or complicated by MAS. Long-term follow-up is required to ascertain whether disease control following HSCT continues indefinitely., (© 2018 by The American Society of Hematology.) more...

Primary immune deficiencies (PID) in children are a rare but serious group of genetic disorders of the immune system which apart from the host's defenses, can also affect every system of the human body, including the gastrointestinal tract. In their severe form they can lead to increased susceptibility to serious infections during infancy and even death. In the less severe form, they can present later in childhood or adolescence with subtle signs and symptoms. As PID can often mimic gastrointestinal diseases, children presenting with atypical gastrointestinal disease and/or failure to respond to conventional therapy should be evaluated for an underlying primary immune disorder and initiated appropriate treatment. The current review of the literature will summarize the gastrointestinal manifestations of primary immune deficiencies in children. more...

Among the neurological manifestations of systemic lupus erythematosus (SLE), chorea is rare, presenting in less than 7% of the pediatric SLE patients. It can appear early in the onset of SLE, be the first or even the sole clinical feature of the illness and has strongly been associated with the presence of antiphospholipid antibodies. We report on the case of a 13-year old boy, admitted with acute onset chorea and finally diagnosed with SLE. Subsequently, we present a short review of the literature on the epidemiology, suggested pathogenesis, clinical presentation and treatment of this rare presentation of SLE. more...

Rituximab (RTX) is a monoclonal antibody against CD20, commonly used in the treatment of hematological malignancies and autoimmune diseases. The use of RTX is related to the development of hypogammaglobulinemia and infections. Aim of this review is to summarize the evidence supporting the association of specific risk factors with the development of hypogammaglobulinemia and infections post-RTX. Immunological complications are more common in patients with malignant diseases as compared to non-malignant diseases. Moreover, the use of more than one dose of RTX, maintenance regimens, low pre-treatment basal immunoglobulin levels and the association with Mycophenolate and purine analogues represent risk factors for the development of hypogammaglobulinemia. The number of RTX courses, the evidence of low IgG levels for more than 6 months, the use of G-CSF, the occurrence of chronic lung disease, cardiac insufficiency, extra-articular involvement in patients with rheumatoid arthritis, low levels of IgG and older age have been correlated with a higher risk of infections. Even though the heterogeneity of the studies in terms of study population age and underlying disease, RTX schedules as well as differences in pre-treatment or concomitant therapy doesn't allow drawing definitive conclusions, the study of the literature highlight the association of specific risk factors with the occurrence of hypogammaglobulinemia and/or infections. A long term randomized controlled clinical trial could be useful to define a personalized evidence-based risk management plan for patients treated with RTX. more...

Children are often referred to immunologists for the evaluation of reduced serum immunoglobulins. Knowledge of the immunoglobulin levels in healthy children of different ages is necessary when estimating immunological deficiency states of various kinds. After the measurement of the serum levels of the three major isotypes, examination of the capacity of the child to form antibodies to several antigens is a reasonable next step in the evaluation. We can rely on vaccine responses to make the distinction between significant primary immunodeficiency diseases and transiently low immunoglobulin levels. On the other hand, normal values of IgM, IgG and IgA are not always enough to exclude a more serious condition. Regardless of immunoglobulin concentrations, if a child's history indicates that further evaluation is warranted, a complete humoral immunity study should be carried out, including IgG subclasses, specific antibody responses and identification of B lymphocyte populations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/) more...

Aim: Information on the epidemiology of childhood urinary tract infections (UTIs) is scarce and mostly based on retrospective data. This study investigated incidence rates, morbidity and risk factors for UTIs in a prospective cohort of children., Methods: We explored UTIs in a representative cohort of 1049 neonates from birth to 6 years of age, using maternal interviews that were verified by hospital records. The majority (88.2%) completed the first-year, and more than half (56.2%) completed the 6-year follow-up., Results: By 6 years of age, more than 10% of our sample had been affected by UTIs. The cumulative incidence for the first year of life was 3.77%, without significant differences between genders, and for one to 6 years, it was 6.81% and 5.7 times higher in girls than boys. Clinical information was available for 63 children: 25 were hospitalised, 16 suffered recurrences, 10 received prophylaxis, eight had urinary tract malformations, three required surgery, and two had impaired renal function., Conclusion: UTIs affected approximately 4% and 10% of children by the ages of one and 6 years, respectively, and their incidence was related to gender and age. Morbidity was considerable, recurrences were common, and despite advances in management, long-term consequences may still be encountered., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.) more...

In this study, we investigated the long-term trends in the epidemiology and susceptibility of bacterial enteropathogens among children in a well-defined area of adequate health standards. The study included all children younger than 14 years of age treated for enteritis at Heraklion University General Hospital on the island of Crete during the 18-year period from January 1993 to December 2010. Stool specimens were tested for Salmonella, Shigella, Campylobacter, enteropathogenic Escherichia coli (EPEC), Yersinia, and Aeromonas species. Of the 33,032 stool samples from patients of any age, 2,912 (8.82%) were positive for bacterial enteropathogens. The 1,597 isolates from children were identified as S. enterica (42.3%), Campylobacter spp. (33.6%), EPEC (17.4%), Y. enterocolitica (5.82%), A. hydrophila (0.44%), and Shigella spp. (0.38%). A decline in prevalence was observed for all bacterial enteropathogens. Taken as a total, enteropathogens were susceptible to gentamicin, ceftriaxone, ciprofloxacin, co-trimoxazole, and amoxicillin in 98.8%, 88.0%, 83.0%, 67.1%, and 59.6%, respectively. During the study period, the susceptibility rates decreased for co-trimoxazole (p<0.0001) and ciprofloxacin (p<0.001), and increased for amoxicillin (p<0.0001). Our findings suggest declining long-term trends in the prevalence of bacterial enteropathogens and changes in susceptibility rates to first-line antibacterial agents. These changing trends in the long-term morbidity and susceptibility call for ongoing surveillance and tailored management. more...

Objective: To prospectively investigate the effects of breastfeeding on the frequency and severity of infections in a well-defined infant population with adequate vaccination coverage and healthcare standards., Study Design: In a representative sample of 926 infants, successfully followed up for 12 months, feeding mode and all infectious episodes, including acute otitis media (AOM), acute respiratory infection (ARI), gastroenteritis, urinary tract infection, conjunctivitis and thrush, were recorded at 1, 3, 6, 9 and 12 months of life., Results: Infants exclusively breastfed for 6 months, as per WHO recommendations, presented with fewer infectious episodes than their partially breastfed or non-breastfed peers and this protective effect persisted after adjustment for potential confounders for ARI (OR 0.58, 95% CI 0.36 to 0.92), AOM (OR 0.37, 95% CI 0.13 to 1.05) and thrush (OR 0.14, 95% CI 0.02 to 1.02). Prolonged exclusive breastfeeding was associated with fewer infectious episodes (r(s)=-0.07, p=0.019) and fewer admissions to hospital for infection (r(s)=-0.06, p=0.037) in the first year of life. Partial breastfeeding was not related to protective effect. Several confounding factors, including parental age and education, ethnicity, presence of other siblings, environmental tobacco smoke exposure and season of birth were demonstrated to have an effect on frequency of infections during infancy., Conclusions: Findings from this large-scale prospective study in a well-defined infant population with adequate healthcare standards suggest that exclusive breastfeeding contributes to protection against common infections during infancy regarding and lessens the frequency and severity of infectious episodes. Partial breastfeeding did not seem to provide this protective effect. more...

Summary Background: Factors predisposing to acute otitis media (AOM) are not thoroughly understood., Objectives: In this study we prospectively investigated incidence rates and risk factors of AOM in a systematic sample of infants in a well-defined population., Design and Subjects: Following interview soon after delivery in a representative sample of 1049 mother-infant pairs, information was collected 1, 3, 6, 9 and 12 months after birth. Episodes of AOM were recorded as by parental reports of diagnosis made by a physician. AOM frequency was further analyzed against 21 social, maternal, paternal, prenatal, perinatal and infantile factors., Results: Successful 12-month follow-up was achieved for 926/1049 infants (88.3%), of whom 265 (28.6%) were reported with episodes of AOM; 153 with a single, 55 with two, and 57 with three to six episodes (16.5%, 5.94%, and 6.16% respectively). Factors founded by multivariate analysis to predispose to AOM included presence of siblings (P<0.001), out-of-home daycare (P<0.001), ill health in pregnancy (P<0.01), and suboptimal breastfeeding (P<0.01). Multiple (3 or more) episodes were related to presence of siblings (P<0.0001), out-of-home daycare (P<0.001), ill health in pregnancy (P<0.001), and low parental education (P<0.001). 28 infants were hospitalized (10.6% of infants with AOM, 3.02% of the total cohort). Hospitalization was related to young maternal age (P<0.05)., Conclusions: Our findings confirm the high morbidity of AOM during infancy and point to several infant- and family-related predisposing factors, some of which are liable to intervention., (Copyright (c) 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.) more...

Aim: This prospective observational study investigated the effect of environmental tobacco smoke (ETS) on frequency and severity of common infantile infections., Methods: In a representative sample of 926 infants, parental smoking was recorded at months 1 and 9 postpartum, and all infantile infectious episodes were recorded at 1, 3, 6, 9 and 12 months postpartum., Results: Both parents were regular smokers all through the first year in 107 (11.6%), at least one smoked regularly or occasionally in 492 (53.1%), and parents did not smoke at all in 327 (35.3%) families. Among mothers, 168 (18.1%) smoked perinatally. Infantile ETS exposure was associated with increased frequency of total infectious episodes (p = 0.025) and hospitalizations for infection (p = 0.007). In ETS exposed infants, birth in autumn and presence of siblings contributed to increased frequency of most infections and of hospital admissions for infection. By contrast, exclusive breastfeeding protected against the effect of ETS on total infantile infections (OR 0.982, 95% CI 0.965-0.999; p = 0.036), hospital admissions for infection (OR 0.980, 95% CI 0.961-0.999; p = 0.036) and thrush (OR 0.973, 95% CI 0.951-0.996; p = 0.022)., Conclusion: Our findings point to harmful effect of ETS on infantile health and further suggest that this effect may be enhanced or diminished by other factors. ETS should be regarded as a preventable risk factor for infections in infancy. more...

Aim: To identify maternal and infantile factors affecting intention to breastfeed, early weaning and duration of breastfeeding., Design/subjects: In a prospective cohort study, 1049 mothers were interviewed after delivery and at 1, 3, 6, 9 and 12 months post-partum., Results: Of 1049 mothers, 942 (89.7%) intended to breastfeed. Negative attitude was associated with lack of breastfeeding previous offspring, multiparity, admission to neonatal ward, tobacco use, prematurity and male gender (OR: 10.1, 2.67, 3.02, 2.63, 2.40 and 1.54, respectively). Six hundred and twenty-three mothers (60.7%) were breastfeeding at month 1. Early weaning was associated with lack of breastfeeding previous offspring, tobacco use, prematurity, admission to neonatal ward, caesarean section (OR: 12.3, 3.39, 2.33, 2.22, 1.34), low education (p < 0.0001) and young age (p = 0.034). Factors negatively affecting total duration of breastfeeding included lack of breastfeeding previous offspring (3.91 vs. 16.2 weeks, p < 0.001), tobacco use (6.78 vs. 15.9 weeks, p < 0.001), low education (p < 0.001), early re-employment (12.5 vs. 15.1 weeks, p < 0.01) and prematurity (p < 0.005)., Conclusion: Maternal negative attitude, tobacco use and early re-employment are factors negatively affecting breastfeeding that can be liable to intervention. All health professionals involved in perinatal medicine share a part of responsibility in sustaining breastfeeding, particularly in high-risk groups of mothers. more...