Special Issue "Advances in Pediatric Infection and Immunity"

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Global and Public Health".

Deadline for manuscript submissions: 15 September 2021.

Special Issue Editor

Dr. Anna Nilsson
E-Mail Website
Guest Editor
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, 171 76 Stockholm, Sweden
Interests: Pediatric infection; Immunity

Special Issue Information

Dear Colleagues,

Discriminating between bacterial and viral infections in children is still a diagnostic dilemma for the clinician. However, the usage of new methodologies has opened up the possibility of exploring genome-wide expression and transcriptional signatures, uncovering activated pathways consisting of many genes associated with either bacterial or viral infection. As there is diversity in the mechanisms of pathogen recognition by specific receptors, and host responses are altered by different microbes, pathogen specific (virus, bacteria, etc.) transcriptional signatures could be translated into useful clinical biomarkers, and thus used for identification.

For this Special Issue, we invite submissions describing new potential biomarkers that could improve the diagnostics of bacterial versus viral infections in children. We welcome reviews and original articles considering novel approaches as well as identifying gaps in knowledge.

Dr. Anna Nilsson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Bacterial Infection
  • Viral Infection
  • Biomarkers
  • Pathogen-Recognition
  • Host Response

Published Papers (6 papers)

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Research

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Article
Diagnostic Performance of SARS-CoV-2 Rapid Antigen Test in a Large, German Cohort
Children 2021, 8(8), 682; https://doi.org/10.3390/children8080682 - 08 Aug 2021
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Abstract
We assessed the performance of a rapid antigen test (RAT) in everyday clinical practice. Between 1 November 2020 until 1 April 2021 all in-patients at the Helios University Hospital Wuppertal, Germany, as well as the accompanying relatives at the Children’s Hospital received a [...] Read more.
We assessed the performance of a rapid antigen test (RAT) in everyday clinical practice. Between 1 November 2020 until 1 April 2021 all in-patients at the Helios University Hospital Wuppertal, Germany, as well as the accompanying relatives at the Children’s Hospital received a SARS-CoV-2 RAT and a SARS-CoV-2 RT-PCR prior to admission. Out of 3686 patients, 22 (0.6%) subjects were tested positive by RT-PCR and RAT, and 3591 (97.4%) were negative by both methods, showing discordant results: RT-PCR+/RAT− in 58 (1.6%) and RT-PCR−/RAT+ in 15 patients (0.4%). Overall sensitivity and specificity of RAT was 27.5% (95%CI 18.1–38.6%) and 99.6% (95%CI 99.3–99.8%), respectively. The sensitivity was slightly higher in adults (30.4%, 95%CI 18.8–90.9%) than in pediatric subjects (20.8%, 95%CI 7.1–42.2%). False negative RAT had a statistically higher Ct-value (p < 0.001) compared to true positive values, and overall sensitivity increased to 80% [59.3–93.2%] with Ct value < 30. While the sensitivity of the RAT was poor compared with the RT-PCR, the specificity was excellent. However, the sensitivity increased with lower Ct value, and with the right anamnesis the RAT can be a quick and easy approach to distinguish people who are infectious with SARS-CoV-2 from noninfectious people, enabling appropriate triage in clinical practice while waiting for the RT-PCR result. Full article
(This article belongs to the Special Issue Advances in Pediatric Infection and Immunity)
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Article
Genetic Sequence Variants in TLR4, MBL or IL-1 Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL
Children 2020, 7(12), 296; https://doi.org/10.3390/children7120296 - 16 Dec 2020
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Abstract
Sequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for TLR4, MBL, and IL-1Ra were investigated in relation to clinical utility of identifying [...] Read more.
Sequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for TLR4, MBL, and IL-1Ra were investigated in relation to clinical utility of identifying severe episodes of febrile neutropenia (FN) in a cohort of children undergoing treatment for acute lymphoblastic leukemia. The study included 122 children, where data on FN and microbiological findings were retrospectively collected from medical records. Sequence variants in genes coding for MBL, TLR4, and IL-1Ra were identified by pyrosequencing, TaqMan SNP genotyping assay, and gel electrophoresis. A total of 380 episodes of FN were identified and in 139 episodes, there was a microbiological defined infection. Age and treatment intensity were all associated with the risk of developing FN. No sequence variant was associated to increased numbers of FN episodes. Two sequence variants in the TLR4 gene increased the risk of viral infection, whilst sequence variants in the IL-1Ra gene were associated to a decreased risk of bacterial blood-stream infection (BSI). The investigated sequence variants did not associate with increased risk for FN or to severe infections, as to why the clinical utility as a risk-stratification tool is low. Most episodes of FN were classified as fever with unknown origin, emphasizing the need for improved microbial detection methods. Full article
(This article belongs to the Special Issue Advances in Pediatric Infection and Immunity)
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Article
Safety and Dose-Dependent Effects of Echinacea for the Treatment of Acute Cold Episodes in Children: A Multicenter, Randomized, Open-Label Clinical Trial
Children 2020, 7(12), 292; https://doi.org/10.3390/children7120292 - 15 Dec 2020
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Abstract
Background: Due to the frequency and severity of cold symptoms in children, and the risk of associated complications, effective treatments are urgently needed. Here we evaluated the safety profile and treatment benefits of Echinacea in children with acute cold and flu symptoms. Methods: [...] Read more.
Background: Due to the frequency and severity of cold symptoms in children, and the risk of associated complications, effective treatments are urgently needed. Here we evaluated the safety profile and treatment benefits of Echinacea in children with acute cold and flu symptoms. Methods: A total of 79 children (4–12 years) were randomized to a treatment regimen of three or five times daily Echinaforce Junior tablets (total of 1200 or 2000 mg Echinacea extract, EFJ) for the prospective treatment of upcoming cold and flu episodes at first signs. Parents recorded respiratory symptoms daily during episodes in their child and physicians and parents subjectively rated tolerability. Results: EFJ was used to treat 130 cold episodes in 68 children and was very well tolerated by more than 96% positive physician’s ratings. EFJ-treated cold episodes lasted 7.5 days on average, with nine out of 10 episodes being fully resolved after 10 days. Five EFJ tablets daily reduced the average episode duration by up to 1.7 days (p < 0.02) in comparison to three EFJ tablets daily regimen. Effective symptom resolution finally contributed to a low antibiotic prescription rate in this study of 4.6%. Conclusions: EFJ tablets present a valuable option for the treatment of acute cold episodes in children showing a wide safety margin and increased therapeutic benefits at five tablets daily. Full article
(This article belongs to the Special Issue Advances in Pediatric Infection and Immunity)
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Article
The Impact of Moderate-Dose Acetylsalicylic Acid in the Reduction of Inflammatory Cytokine and Prevention of Complication in Acute Phase of Kawasaki Disease: The Benefit of Moderate-Dose Acetylsalicylic Acid
Children 2020, 7(10), 185; https://doi.org/10.3390/children7100185 - 16 Oct 2020
Cited by 2 | Viewed by 667
Abstract
Background: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA. We aimed to evaluate the impact of different doses of ASA on inflammation control while minimizing adverse effects in the acute [...] Read more.
Background: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA. We aimed to evaluate the impact of different doses of ASA on inflammation control while minimizing adverse effects in the acute phase treatment of KD. Methods: The enrolled 323 patients with KD were divided into three groups according to ASA dose: moderate-dose (30–50 mg/kg/day), high-dose (80–100 mg/kg/day), and non-ASA. Results: High-dose ASA group showed a significantly shorter duration of fever from the start of treatment to remission than other groups. Baseline level and delta score of interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-α, and transforming growth factor β were not statistically different among the groups. The number of patients who received additional treatments in the non-ASA group was more than other groups. Coronary artery dilatation was not significantly different among the groups. One patient with high-dose ASA was diagnosed with Reye syndrome. Conclusion: Different doses of ASA did not show any differences in changes of inflammatory bio-makers and cytokines. However, high-dose ASA showed occurrence of Reye syndrome, and non-ASA showed intravenous immunoglobulin refractoriness. We suggest that moderate-dose ASA may be beneficial for the treatment of patients in the acute phase of KD. Full article
(This article belongs to the Special Issue Advances in Pediatric Infection and Immunity)
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Review

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Review
Early Microbial–Immune Interactions and Innate Immune Training of the Respiratory System during Health and Disease
Children 2021, 8(5), 413; https://doi.org/10.3390/children8050413 - 19 May 2021
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Abstract
Over the past two decades, several studies have positioned early-life microbial exposure as a key factor for protection or susceptibility to respiratory diseases. Birth cohorts have identified a strong link between neonatal bacterial colonization of the nasal airway and gut with the risk [...] Read more.
Over the past two decades, several studies have positioned early-life microbial exposure as a key factor for protection or susceptibility to respiratory diseases. Birth cohorts have identified a strong link between neonatal bacterial colonization of the nasal airway and gut with the risk for respiratory infections and childhood asthma. Translational studies have provided companion mechanistic insights on how viral and bacterial exposures in early life affect immune development at the respiratory mucosal barrier. In this review, we summarize and discuss our current understanding of how early microbial–immune interactions occur during infancy, with a particular focus on the emergent paradigm of “innate immune training”. Future human-based studies including newborns and infants are needed to inform the timing and key pathways implicated in the development, maturation, and innate training of the airway immune response, and how early microbiota and virus exposures modulate these processes in the respiratory system during health and disease. Full article
(This article belongs to the Special Issue Advances in Pediatric Infection and Immunity)
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Other

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Brief Report
Human Species D Adenoviruses Isolated from Diarrheal Feces Show Low Infection Rates in Primary Nasal Epithelial Cells
Children 2021, 8(7), 563; https://doi.org/10.3390/children8070563 - 30 Jun 2021
Viewed by 350
Abstract
The importance of adenovirus (Ad) research is significantly increasing with respect to virotherapy for vaccine development, tumor, and gene therapy. Due to the different species and subtypes of this virus, the characterization of the biological significance of especially rare Ad is necessary. Previously, [...] Read more.
The importance of adenovirus (Ad) research is significantly increasing with respect to virotherapy for vaccine development, tumor, and gene therapy. Due to the different species and subtypes of this virus, the characterization of the biological significance of especially rare Ad is necessary. Previously, rare Ad types 70, 73, and 74 were originally isolated from fecal samples of immunocompromised patients and they represent recombinants of other Ad types. Here we investigated transduction experiments of these reporter gene tagged Ad types in primary cells exemplified by subject-derived primary nasal epithelial cells (NAEPCs). To analyze the transduction rates, we performed flow cytometry, quantitative polymerase chain reaction (PCR), and cytokine analyses 25 h post-infection. We found that, in contrast to Ad type 5 (as a positive control), the transduction rates of NAEPCs with Ad types 70, 73, and 74 were interestingly low. The major Ad receptor (coxsackievirus-adenovirus receptor and CD46) expression levels showed no significant change after infection with Ad types 70, 73 and 74. Moreover, Interleukin 6 (IL-6) was not released after in vitro Ad transduction. Due to the high risk of developing life-threatening complications in immunocompromised patients by these human species D Ads, even more attention needs to be investigated into the development of diagnostic and therapeutic concepts to prevent and treat those opportunistic infections in susceptible patients. Full article
(This article belongs to the Special Issue Advances in Pediatric Infection and Immunity)
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