Browsing by Author "Meiere, Anija"
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Item Comparison of Characteristics and Outcomes of Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome in Children(2023-03) Klavina, Lizete; Smane, Liene; Kivite-Urtane, Anda; Vasilevska, Lauma; Davidsone, Zane; Smitins, Emils; Gardovska, Dace; Lubaua, Inguna; Roge, Ieva; Pucuka, Zanda; Meiere, Anija; Pavare, Jana; Rīga Stradiņš University; Department of Paediatrics; Institute of Public Health; Department of Public Health and EpidemiologyBackground and Objectives: Since the first cases of multisystem inflammatory syndrome in children (MIS-C) in April 2020, the diagnostic challenge has been to recognize this syndrome and to differentiate it from other clinically similar pathologies such as Kawasaki disease (KD) and toxic shock syndrome (TSS). Our objective is to compare clinical signs, laboratory data and instrumental investigations between patients with MIS-C, KD and TSS. Materials and Methods: This retrospective observational study was conducted at the Children’s Clinical University Hospital, Latvia (CCUH). We collected data from all pediatric patients <18 years of age, who met the Centers for Disease Control and Prevention case definition for MIS-C, and who presented to CCUH between December 2020 and December 2021. We also retrospectively reviewed data from inpatient medical records of patients <18 years of age diagnosed as having KD and TSS at CCUH between December 2015 and December 2021. Results: In total, 81 patients were included in this study: 39 (48.1%) with KD, 29 (35.8%) with MIS-C and 13 (16.1%) with TSS. In comparison with TSS and KD, patients with MIS-C more often presented with gastrointestinal symptoms (abdominal pain (p < 0.001), diarrhea (p = 0.003)), shortness of breath (p < 0.02) and headache (p < 0.003). All MIS-C patients had cardiovascular involvement and 93.1% of MIS-C patients fulfilled KD criteria, showing higher prevalence than in other research. Patients with KD had higher prevalence of cervical lymphadenopathy (p < 0.006) and arthralgias (p < 0.001). In comparison with KD and TSS, MIS-C patients had higher levels of ferritin (p < 0.001), fibrinogen (p = 0.04) and cardiac biomarkers, but lower levels of platelets and lymphocytes (p < 0.001). KD patients tended to have lower peak C-reactive protein (CRP) (p < 0.001), but higher levels of platelets. Acute kidney injury was more often observed in TSS patients (p = 0.01). Pathological changes in electrocardiography (ECG) and echocardiography were significantly more often observed in MIS-C patients (p < 0.001). Conclusions: This research shows that MIS-C, KD and TSS have several clinical similarities and additional investigations are required for reaching final diagnosis. All the patients with suspected MIS-C diagnosis should be examined for possible cardiovascular involvement including cardiac biomarkers, ECG and echocardiography.Item Emergency medical services utilisation among febrile children attending emergency departments across Europe : an observational multicentre study(2023-09) Tan, Chantal D.; Vermont, Clementien L.; Zachariasse, Joany M.; Zavadska, Dace; On behalf of PERFORM consortium (Personalised Risk assessment in febrile children to optimize Real-life Management across the European Union); Balode, Anda; Bārzdiņa, Arta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Sidorova, Aleksandra; Urbāne, Urzula Nora; Rīga Stradiņš UniversityChildren constitute 6–10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37–61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1–42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1–59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1–0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4–1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05). Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6–10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37–61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1–59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe.Item Febrile illness in high-risk children : a prospective, international observational study(2023-02) van der Velden, Fabian J.S.; de Vries, Gabriella; Martin, Alexander; Zavadska, Dace; PERFORM consortium; Balode, Anda; Bārzdiņa, Arta; Deksne, Dārta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Rudzāte, Aleksandra; Urbāne, Urzula Nora; Department of Paediatrics; Rīga Stradiņš UniversityTo assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the ‘Biomarker Validation in HR patients’ database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population.What is Known:• Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom.• Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low.What is New:• Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective.• The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers.Item Genomic investigations of unexplained acute hepatitis in children(2023-03-30) Morfopoulou, Sofia; Buddle, Sarah; Torres Montaguth, Oscar Enrique; Breuer, Judith; DIAMONDS Consortium; PERFORM consortium; Zavadska, Dace; Laivacuma, Sniedze; Rudzāte, Aleksandra; Barzdina, Arta; Madelane, Monta; Grāvele, Dagne; Balode, Anda; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavare, Jana; Pucuka, Zanda; Urbane, Urzula Nora; Selecka, Katrina; Deksne, Dārta; Rīga Stradiņš UniversitySince its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.Item Guideline adherence in febrile children below 3 months visiting European Emergency Departments : an observational multicenter study(2022-12) Tan, Chantal D.; van der Walle, Eline E.P.L.; Vermont, Clementien L.; Zavadska, Dace; PERFORM consortium (Personalised Risk assessment in febrile children to optimize Real-life Management across the European Union); Balode, Anda; Bārzdiņa, Arta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Urbāne, Urzula Nora; Deksne, Dārta; Selecka, Katrina; Sidorova, Aleksandra; Department of Paediatrics; Rīga Stradiņš UniversityFebrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment. There is practice variation in management due to differences in guidelines and their usage and adherence. We aimed to assess whether management in febrile children below 3 months attending European Emergency Departments (EDs) was according to the guidelines for fever. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0–18 years) attending twelve EDs in eight European countries. In febrile children below 3 months (excluding bronchiolitis), we analyzed actual management compared to the guidelines for fever. Ten EDs applied the (adapted) NICE guideline, and two EDs applied local guidelines. Management included diagnostic tests, antibiotic treatment, and admission. We included 913 children with a median age of 1.7 months (IQR 1.0–2.3). Management per ED varied as follows: use of diagnostic tests 14–83%, antibiotic treatment 23–54%, admission 34–86%. Adherence to the guideline was 43% (374/868) for blood cultures, 29% (144/491) for lumbar punctures, 55% (270/492) for antibiotic prescriptions, and 67% (573/859) for admission. Full adherence to these four management components occurred in 15% (132/868, range 0–38%), partial adherence occurred in 56% (484/868, range 35–77%). Conclusion: There is large practice variation in management. The guideline adherence was limited, but highest for admission which implies a cautious approach. Future studies should focus on guideline revision including new biomarkers in order to optimize management in young febrile children.What is Known:• Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment.• There is practice variation in management of young febrile children due to differences in guidelines and their usage and adherence.What is New:• Full guideline adherence is limited, whereas partial guideline adherence is moderate in febrile children below 3 months across Europe.• Guideline revision including new biomarkers is needed to improve management in young febrile children.Item Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens(2023-08-18) Willems, Esther; Gloerich, Jolein; Suppers, Anouk; PERFORM consortium; Zavadska, Dace; Balode, Anda; Bārzdiņa, Arta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Urbāne, Urzula Nora; Pavāre, Jana; Pučuka, Zanda; Rīga Stradiņš UniversityMechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.Item INCIDENCE OF VACCINE PREVENTABLE DISEASES IN PEDIATRIC POPULATION OF LATVIA(2016) Klagisa, Renata; Meiere, Anija; Rīga Stradiņš UniversityChildhood and adolescent immunizations are one of the most effective means of preventing such serious diseases as diphtheria, pertussis, rubella etc. These infectious diseases are termed as vaccine preventable diseases because vaccination continues to be the most effective strategy to reduce morbidity and mortality from these diseases. Despite this, immunization is an emotional issue for many parents. As vaccine preventable diseases become less common and parents have little familiarity with the devastating effects of vaccine preventable illnesses, the benefits of immunization may seem less important than the potential adverse effects.Item LONG COVID-19 SYMPTOM PROFILE IN CHILDREN AND ADOLESCENTS TESTED FOR SARS-COV-2(2024-02-01) Meiere, Anija; Smane, Liene; Ķīvīte-Urtāne, Anda; Kļaviņa, Lizete; Račko, Iveta; Roģe, Ieva; Pučuka, Zanda; Pavāre, Jana; Department of Paediatrics; Department of Public Health and EpidemiologyEven though more than two years have passed since the global pandemic started, COVID-19 continues to impact children all over the world. The most common course of SARS-CoV-2 infection in children is short term with no or mild symptoms. However, there are two long-term consequences: long COVID and multisystem inflammatory syndrome (MIS-C). A post-COVID19 programme for children has been created in Latvia; however, we know that the availability of this service is limited. We developed an online survey so that we could screen for those paediatric patients with long COVID who needed to see a specialist as soon as possible. The cross-sectional study from 1 November 2021 to 27 March 2022 included 220 patients. In our study, the most frequent symptoms in the age group < 1.5 years were irritability (50%), mood swings (50%), persistent cough (33.3%) and loss of appetite (33.3%). In the group aged 1.5–5 years, a persistent cough (54.4%), mood swings (43.9%) and irritability (42.1%) were the most common symptoms, while in the group aged 6–10 years, fatigue (56.6%), abdominal pain (55.3%), headache (50%), and mood swings (50%) were seen most often. Meanwhile in the 11–18 age group, impaired physical activity (66.7%), fatigue (62.3%) and drowsiness (62.3%) were the most frequently seen symptoms.Item A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM) : a multi-cohort machine learning study(2023-11) Jackson, Heather R; Zandstra, Judith; Menikou, Stephanie; Zavadska, Dace; PERFORM consortium; Balode, Anda; Bārzdiņa, Arta; Deksne, Dārta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Sidorova, Aleksandra; Urbāne, Urzula Nora; Rīga Stradiņš UniversityBACKGROUND: Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. METHODS: In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. FINDINGS: 376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma samples for the MS-A dataset, and 150 plasma samples for the MS-B dataset. Differential abundance analysis, and the first round of feature selection using FS-PLS identified 35 protein biomarker candidates, of which 13 had commercial ELISA or Luminex tests available. 16 proteins with ELISA or Luminex tests available were identified by literature review. Further evaluation via Luminex and ELISA and the second round of feature selection using FS-PLS revealed a six-protein signature: three of the included proteins are elevated in bacterial infections (SELE, NGAL, and IFN-γ), and three are elevated in viral infections (IL18, NCAM1, and LG3BP). Performance testing of the signature using Luminex assays revealed area under the receiver operating characteristic curve values between 89·4% and 93·6%. INTERPRETATION: This study has led to the identification of a protein signature that could be ultimately developed into a blood-based point-of-care diagnostic test for rapidly diagnosing bacterial and viral infections in febrile children. Such a test has the potential to greatly improve care of children who are febrile, ensuring that the correct individuals receive antibiotics. FUNDING: European Union's Horizon 2020 research and innovation programme, the European Union's Seventh Framework Programme (EUCLIDS), Imperial Biomedical Research Centre of the National Institute for Health Research, the Wellcome Trust and Medical Research Foundation, Instituto de Salud Carlos III, Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Grupos de Refeencia Competitiva, Swiss State Secretariat for Education, Research and Innovation.Item Qualitative Study on Family Health-Related Quality of Life Due to Pediatric COVID-19 Infection In Latvia(2024-02-01) Pučuka, Zanda; Meiere, Anija; Ķīvīte-Urtāne, Anda; Smane, Liene; Stars, Inese; Roģe, Ieva; Račko, Iveta; Kļaviņa, Lizete; Pavāre, Jana; Department of Paediatrics; Institute of Public Health; Department of Public Health and EpidemiologyThe coronavirus disease (COVID-19) pandemic and ensuing public health policies have immensely affected the lives of billions of people worldwide and been challenging for families. There have been studies exploring mental health of different age groups during a pandemic, but few have focused on family health-related quality of life (HRQoL). This qualitative study investigates the emotional well-being of families while caring for an acutely sick child with COVD-19, using semi-structured in-depth interviews. The results demonstrate that it is one of the most affected components of the family HRQoL.Item Raising AWaRe-ness of antimicrobial stewardship challenges in pediatric emergency care : results from the PERFORM study assessing consistency and appropriateness of antibiotic prescribing across Europe(2024-03-15) Kolberg, Laura; Khanijau, Aakash; van der Velden, Fabian J S; Herberg, Jethro; Zavadska, Dace; PERFORM consortium; Balode, Anda; Bārzdiņa, Arta; Deksne, Dārta; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Rudzāte, Aleksandra; Urbāne, Urzula Nora; Rīga Stradiņš UniversityBackground. Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. Methods. Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final “bacterial” or “viral” phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. Results. Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/β-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the “Watch” category. Conclusions. Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics.Item Relationship between molecular pathogen detection and clinical disease in febrile children across Europe : a multicentre, prospective observational study(2023-09) Shah, Priyen; Voice, Marie; Calvo-Bado, Leonides; Rudzate, Aleksandra; Zavadska, Dace; PERFORM consortium; Bārzdiņa, Arta; Deksne, Dārta; Balode, Anda; Gardovska, Dace; Grāvele, Dagne; Grope, Ilze; Meiere, Anija; Nokalna, Ieva; Pavāre, Jana; Pučuka, Zanda; Selecka, Katrina; Urbāne, Urzula Nora; Rīga Stradiņš UniversityBACKGROUND: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. METHODS: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. FINDINGS: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. INTERPRETATION: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. FUNDING: EU Horizon 2020 grant 668303.Item Short- and mid-term outcomes of multisystem inflammatory syndrome in children : a longitudinal prospective single-center cohort study(2023) Roge, Ieva; Kivite-Urtane, Anda; Smane, Liene; Meiere, Anija; Klavina, Lizete; Barzdina, Elza; Pavare, Jana; Department of Paediatrics; Department of Public Health and EpidemiologyBackground: Multisystem inflammatory syndrome in children (MIS-c) emerged during the coronavirus disease 2019 pandemic and is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the extensively studied clinical manifestation of acute condition, the short- and long-term effects of MIS-c on children's health are unknown. Methods: This was a prospective longitudinal cohort study. Children aged <18 years who met the Centers for Disease Prevention and Control (CDC) diagnostic criteria and who were admitted to the Children's Clinical University Hospital of Latvia (CCUH) between July 1, 2020, and April 15, 2022, were enrolled in the study. An outpatient follow-up program was initiated in July 2020. All children were evaluated at 2 weeks, 2 months (1–3 months), and 6 months (5–7 months) after discharge. The face-to-face interviews comprised four domains as follows: symptom assessment, physical examination, laboratory testing, and cardiological investigation [including electrocardiogram (ECG) and echocardiography (echo)]. Results: Overall, 21 patients with MIS-c were enrolled. The median age of the study group was 6 years. At the 2-week follow-up, almost half of the patients (N = 10, 47.6%) reported exercise intolerance with provoked tiredness. Laboratory tests showed a considerable increase in blood cell count, with a near doubling of leukocyte and neutrophil counts and a tripling of thrombocyte levels. However, a decline in the levels of inflammatory and organ-specific markers was observed. Cardiological investigation showed significant improvement with gradual resolution of the acute-phase pathological findings. Within 2 months, improvement in exercise capacity was observed with 5-fold and 2-fold reductions in physical intolerance (N = 2, 9.5%) and physical activity-induced fatigue (N = 5, 23.8%), respectively. Normalization of all blood cell lines was observed, and cardiological investigation showed no persistent changes. At the 6-month visit, further improvement in the children's exercise capacity was observed, and both laboratory and cardiological investigation showed no pathological changes. Conclusions: Most persistent symptoms were reported within the first 2 weeks after the acute phase, with decreased physical activity tolerance and activity-induced fatigue as the main features. A positive trend was observed at each follow-up visit as the spectrum of the children's complaints decreased. Furthermore, rapid normalization of laboratory markers and cardiac abnormalities was observed.