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Early diagnosis of tuberculosis (TB) in children is hampered by non-specific symptoms, low bacillary loads, and difficulties in obtaining respiratory samples. We evaluated urinary metabolomics using high-resolution nuclear magnetic resonance (HR- 1 H-NMR) spectroscopy as a non-invasive tool to discriminate TB disease, TB infection (TBI), and healthy controls (HC). Urine samples from 101 children enrolled in the Spanish Paediatric TB Network (pTBred) were retrospectively analysed, including 62 TB cases (26 microbiologically confirmed [cTB]), 17 TBI, and 22 HC. Metabolic fingerprints were generated via 1 H-NMR spectroscopy. Group discrimination was assessed using partial least squares discriminant analysis (PLS-DA) with cross-validation. Metabolites were selected using VIP > 2 and p  < 0.05. Validated PLS-DA models (TB vs. HC, cTB vs. HC and cTB vs. TBI) achieved ≥ 70% accuracy (AUC-ROC 0.867–0.971), with sensitivities ranging from 69.1% to 90.0% and specificities from 77.3% to 86.7%. Discrimination was strongest for cTB vs. TBI (AUC-ROC 0.971; sensitivity 90.0%; specificity 86.7%). A set of discriminatory metabolites was identified across validated comparisons. Compared with HC, TB disease was characterized by increased levels of phenylalanine and two unidentified NMR signals, together with reductions in several energy and nitrogen-related metabolites; benzoate and histidine showed borderline differences. In contrast, TBI was associated with higher levels of isoleucine, N-acetylglutamine, glutamine, creatinine and 2-hydroxyvalerate. Urine HR- 1 H-NMR metabolomics suggests potential distinct metabolic signatures across TB states. While not yet suitable as a confirmatory test, these preliminary findings show potential as a triage tool to help prioritise children for microbiological testing and may eventually reduce the need for invasive sampling.

Purpose To describe the prevalence of imported infections in pediatric patients prior to immunosuppressive therapy after implementing a structured screening protocol, and to assess adherence and diagnostic yield. Methods Retrospective study of patients <18 years from non-Western countries screened between 2020 and 2024 at a tertiary hospital in Madrid, Spain. Screening followed a standardized protocol including serology, tuberculosis testing, stool analysis, and vaccination assessment. Results Sixty-three children were included (median age 9.5 years; 55.6% male), mainly from Latin America (65.1%), with hematologic malignancies (52.4%) or awaiting solid organ transplant (33.3%). Only 19% completed full screening. At least one infection was detected in 28.6%, mainly toxoplasmosis (7/57, 12.3%), strongyloidiasis (5/56, 8.9%), malaria (3/22, 13.6%), and schistosomiasis (3/25, 12%). Immunity to hepatitis B (65.5%), measles and varicella (<50%) was suboptimal. Conclusion Imported infections were frequent, supporting systematic screening before immunosuppression.

Dengue fever has significantly increased globally, extending into non-endemic regions. This study aims to describe the epidemiological and clinical characteristics of pediatric dengue cases diagnosed in Madrid, Spain, over ten years. We conducted a retrospective observational study across four tertiary hospitals, including all confirmed dengue cases in children under 16 between 2015 and 2024. Epidemiological data, clinical presentation, laboratory findings, and outcomes were collected, with severity assessed according to the 2009 WHO criteria. Forty-six cases were identified, with 72% diagnosed in the last three years and a peak incidence in 2024. Children visiting friends and relatives (VFR) constituted the majority of cases (56%). The most frequent clinical features were fever (100%) and gastrointestinal symptoms (78%), while laboratory findings included leukopenia (72%), thrombocytopenia (70%), and hypertransaminasemia (74%). Five cases (10%) met the criteria for severe dengue, one being fatal in a patient with pre-existing oncological disease. We identified no autochthonous cases. These results highlight the growing impact of imported pediatric dengue in non-endemic regions, the particular vulnerability of VFR travelers, and the need for clinical awareness, improved diagnostic availability and prevention strategies, especially in climate-influenced vector expansion.

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs . -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs . -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.

Antibiotics are frequently prescribed to children with pneumonia, although viruses are responsible for most cases. We aimed to evaluate the impact of multiplex polymerase chain reaction (mPCR) on antibiotic use. We conducted a prospective study of children under 14 years of age admitted for suspected viral pneumonia, from October 2019 to June 2022 (except March–November 2020). A mPCR respiratory panel (FilmArray® 2plus, bioMérieux, Marcy-l’Étoile, France) was performed within 72 h of admission. Patients with positive reverse transcription PCR for respiratory syncytial virus, influenza, or SARS-CoV-2 were excluded. We compared the patients with historical controls (2017–2018) who had suspected viral pneumonia but did not undergo an aetiological study. We included 64 patients and 50 controls, with a median age of 26 months. The respiratory panel detected viral pathogens in 55 patients (88%), including 17 (31%) with co-infections. Rhinovirus/enterovirus (n = 26) and human metapneumovirus (n = 22) were the most common pathogens, followed by adenovirus and parainfluenza (n = 10). There were no statistically significant differences in the total antibiotic consumption (83% of cases and 86% of controls) or antibiotics given for ≥72 h (58% vs. 66%). Antibiotics were prescribed in 41% of the cases and 72% of the controls at discharge (p = 0.001). Ampicillin was the most commonly prescribed antibiotic among the patients (44% vs. 18% for controls, p = 0.004), while azithromycin was the most commonly prescribed among the controls (19% vs. 48% for patients and controls, respectively; p = 0.001). Our findings underscore the need for additional interventions alongside molecular diagnosis to reduce antibiotic usage in paediatric community-acquired pneumonia.

Background: In recent decades, the increase in population movements has turned the focus to imported diseases. The COVID-19 pandemic has negatively impacted the access to health care systems, especially in highly vulnerable populations. We address the effects of the pandemic on the health screening of migrant unaccompanied minors (UM) in Spain. Method: Retrospective cross-sectional study including UM screened for imported diseases with a unified protocol at a pediatric reference unit for tropical and infectious diseases in Madrid, Spain. We compared the pre-pandemic (2018–2019) and post-pandemic periods (2020–2021). Results: A total of 192 minors were screened during the study period, with a drop in UM’s referral to our center in the post-pandemic years (140 in 2018–2019 vs. 52 in 2020–2021). Out of 192, 161 (83.9%) were diagnosed with at least one medical condition. The mean age was 16.8 years (SD 0.8) and 96.9% were males. Most cases were referred for a health exam; only 38% of children were symptomatic. Eosinophilia was present in 20.8%. The most common diagnosis were latent tuberculosis infection (LTBI) (72.9%), schistosomiasis (15.1%), toxocariasis (4.9%) and strongyloidiasis (4.9%). The prevalence of LTBI did not vary significantly (69.3% vs. 82.7%, p = 0.087). A total of 38% of the patients diagnosed with LTBI never started treatment or were lost to follow-up, as were two out of three patients with active pulmonary tuberculosis. Conclusions: In this series, the number of UM referred for health screening has dropped dramatically after the COVID pandemic, and two years after the beginning of the pandemic, access to care is still limited. Lost to follow-up rates are extremely high despite institutionalization. Specific resources, including multidisciplinary teams and accessible units are needed to improve diagnoses and linkage to care in this vulnerable population.

IntroductionThe QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting.MethodsCross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020.ResultsOf 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations.ConclusionsOur non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially.

We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. We enrolled 1200 children. A total of 666 (55.5%) were hospitalised, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalised children, the proportions were 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were age in months (OR: 1.007; 95% CI 1.004 to 1.01), MIS-C (OR: 14.4, 95% CI 8.9 to 23.8), chronic cardiac disease (OR: 4.8, 95% CI 1.8 to 13), asthma or recurrent wheezing (OR: 2.5, 95% CI 1.2 to 5.2) and after excluding MIS-C patients, moderate/severe liver disease (OR: 8.6, 95% CI 1.6 to 47.6). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare . Conclusion : Hospitalised children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease. What is Known: • All studies suggest that children are less susceptible to serious SARS-CoV-2 infection when compared to adults. Most studies describe symptoms at presentation. However, it remains unclear how these symptoms group together into clinically identifiable syndromes and the severity associated with them. What is New: • We have gathered the primary diagnoses into five major syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, fever without a source and mild syndrome. Classification of the children in one of the syndromes is unique and helps to assess the risk of critical illness and to define the spectrum of the disease instead of just describing symptoms and signs.

IntroductionChildhood pulmonary tuberculosis (TB) remains a diagnostic challenge. This study aimed to evaluate the performance of Xpert Ultra for the diagnosis of pulmonary TB in children in a low TB prevalence setting.MethodsProspective, multicentre, diagnostic accuracy study. Children with clinical or radiological suspicion of pulmonary TB were recruited at 11 paediatric units in Spain. Up to three gastric or sputum specimens were taken on 3 consecutive days, and analysed by Xpert MTB/RIF, Xpert Ultra and culture in parallel.Results86 children were included (median age 4.9 years, IQR 2.0–10.0; 51.2% male). The final diagnosis was pulmonary TB in 75 patients (87.2%); 33 (44.0%) were microbiologically confirmed. A total of 219 specimens, comprising gastric aspirates (n=194; 88.6%) and sputum specimens (n=25; 11.4%), were analysed. Using culture as reference standard and comparing individual specimens, the sensitivity was 37.8% (14/37) for Xpert MTB/RIF and 81.1% (30/37) for Xpert Ultra (p<0.001); specificity was 98.4% (179/182) and 93.4% (170/182), respectively (p=0.02). In the per-patient analysis, considering positive results on any specimen, the sensitivity was 42.9% (9/21) for Xpert MTB/RIF and 81.0% for Xpert Ultra (17/21, p=0.01); specificity was 96.9% (63/65) and 87.7% (57/65, p=0.07), respectively.ConclusionsIn children with pulmonary TB in a low burden setting, Xpert Ultra has significantly higher sensitivity than the previous generation of Xpert assay and only marginally lower specificity. Therefore, in children undergoing evaluation for suspected pulmonary TB, Xpert Ultra should be used in preference to Xpert MTB/RIF whenever possible.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good.What is Known:• Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI).• The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce.What is New:• SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission.• Bacterial coinfection rarely coexists in those infants.• Inflammatory markers were not increased in children without bacterial coinfection.• Outcome is good in most patients.