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RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

[Introduction] Childhood 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., [Methods] Prospective, 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., [Results] 86 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, [Conclusions] In 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., This study did not receive any project-specific funding. DA-A was supported by the Spanish Ministry of Health – Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union (FEDER) (Contrato Río Hortega CM18/00100). AN-J was supported by 'Subvencions per a la Intensificació de Facultatius Especialistes' (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016-2020) (SLT008/18/00193). DBG was supported by the Spanish Ministry of Science and Innovation – Instituto de Salud Carlos III and Fondos FEDER by 'Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 (INT20/00086)'. BS-G was supported by the Spanish Ministry of Health – Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union (FEDER) (Contrato Juan Rodés JR16/00036).

Background Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time. Methods Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome. Results Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (pp=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674). Conclusions In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.

[Background]: Currently, data on treatment, outcome, and prognostic factors in children with tuberculous meningitis (TBM) in Europe are limited. To date, most existing data on TBM originate from adult studies, or studies conducted in low-resource settings., [Methods]: We designed a multicenter, retrospective study involving 27 pediatric healthcare institutions in 9 European countries via an established pediatric TB research network, before and after the 2014 revision of World Health Organization (WHO) dosing recommendations., [Results]: Of 118 children, 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2, and 11 (9.3%) grade 3. Fifty-eight (49.1%) children received a standard 4-drug treatment regimen; other commonly used drugs included streptomycin, prothionamide, and amikacin. Almost half of the patients (48.3%; 56/116) were admitted to intensive care unit, with a median stay of 10 (interquartile range [IQR] 4.5–21.0) days. Of 104 children with complete outcome data, 9.6% (10/104) died, and only 47.1% (49/104) recovered fully. Main long-term sequelae included spasticity of 1 or more limbs and developmental delay both in 19.2% (20/104), and seizure disorder in 17.3% (18/104). Multivariate regression analyses identified microbiological confirmation of TBM, the need for neurosurgical intervention, and mechanical ventilation as risk factors for unfavorable outcome., [Conclusions]: There was considerable heterogeneity in the use of TB drugs in this cohort. Despite few children presenting with advanced disease and the study being conducted in a high-resource setting, morbidity and mortality were high. Several risk factors for poor outcome were identified, which may aid prognostic predictions in children with TBM in the future., TPtbnet is supported by the Deutsche Gesellschaft für Internationale Zusammenarbeit. M. Te. was supported by a Clinical Lectureship provided by the UK National Institute for Health Research (NIHR), and by a grant from the Technology Strategy Board/Innovate UK. R. B. R. is funded by an NIHR Academic Clinical Lectureship at the London School of Hygiene & Tropical Medicine (grant number CL-2018-20-001). A. N.-J. was supported by Subvencions per a la Intensificació de Facultatius Especialistes (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016–2020; ref. SLT008/18/00193). O. N. is supported by Consejeria de Salud y Familias, Servicio Andaluz de Salud 2020 (grant number A1-0049-2020).

SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.

Background: Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. Methods: Patients

Introduction: Invasive meningococcal disease (IMD) has a high morbidity and mortality in children and adults. The aim of this study was to describe the clinical and epidemiological characteristics of patients with IMD, to compare them among children and adults, and to determine prognostic factors and changes in epidemiology during a 14-year period. Methods: A retrospective study was conducted on patients admitted to a third level hospital with IMD between 2004 and 2017. An analysis was made of the clinical, epidemiological and microbiological data. Results: A total of 84 patients were diagnosed with IMD, of which 50 (59.5%) were children. Median age was 2 years (IQR 0.7–7.5) for children and 41.2 years (IQR 26.4–69.3) for adults. Diagnosis was bacteraemia in 47 patients (56%), meningitis in 24 (28.6%), and both in 13 (15.5%). Serogroup B (MenB) was the most common cause of IMD (40.5%), followed by serogroup C (MenC) in 15.5%, which was more common among adults (26.5% vs 8%, P = .022). Incidence rate decreased between 2004–2010 and 2011–2017, from 3.14 to 1.33 cases/100 000 emergencies attended in the study hospital (P

Clinical features of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 are non-specific. In this retrospective cohort study of 39 patients evaluated for MIS-C, 11 had non-SARS-CoV-2 infections, 3 of whom were also diagnosed with MIS-C. Clinical features were similar in patients with MIS-C and patients with non-SARS-CoV-2 infections. Clinicians should consider non-SARS-CoV-2 infections in patients undergoing MIS-C evaluation.

In this cross-sectional study of 284 children and adolescents with clinically or radiologically suspected tuberculosis in a low-endemic country, the QuantiFERON-TB Gold Plus assay specificity, sensitivity, positive predictive value and negative predictive value were 91.5%, 87.3%, 86.4%, and 91.2%, respectively. The specificity was higher than that observed in tuberculin skin tests performed simultaneously, but similar to previous-generation interferon-gamma release assays.

INTRODUCTION: The 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. METHODS: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one ( Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

Children are at higher risk of tuberculosis (TB) dissemination and extrapulmonary disease, contributing greatly to TB-associated morbidity and long-term sequelae. However, there are very few studies that assess the impact and clinical spectrum of pediatric extrapulmonary TB (EPTB) in low-prevalence regions.Children18 years of age diagnosed with TB in Madrid region (2005-2013) were reviewed. We compared the epidemiology, clinical characteristics and the performance of diagnostic tests in childhood extrapulmonary and pulmonary disease. We performed a multivariate logistic regression to identify factors associated with EPTB.During the study period, 93 of 526 pediatric TB cases had EPTB (17.7%). The most common site was lymphatic TB (34.5%). The source case was not identified in most extrapulmonary cases, contrary to pulmonary TB (28% vs. 63.3%; P0.001). The tuberculin-skin-test induration was smaller in EPTB cases (5 mm 22% vs. 5%; P0.001), but the sensitivity of interferon-gamma-release-assays was similar (76.9% vs. 79.4%). Children with EPTB presented higher rate of bacteriologic confirmation (66% vs. 49.4%; P0.01), and higher incidence of multidrug resistant TB (8.2% vs. 1.6%; P = 0.03). Complications were present in 40.2% extrapulmonary cases. EPTB was associated with the child's foreign origin [odds ratio (OR) 2.3 (1.1-5.3)], immune disorders [OR 5.8 (1.9-17.1)] and drug resistance [OR 2.4 (1.1-5.4)].In our low-prevalence region, childhood EPTB was linked to immigrant status, immune disorders and drug resistance, and presented high rate of complications. Our study underscores the relevance of improved diagnostic tools and systematic TB screening in high risk populations.

Resumen: Introducción: En España no existen presentaciones pediátricas de fármacos antituberculosos, salvo para rifampicina. Algunos pediatras prescriben fórmulas magistrales (FM), mientras que otros administran comprimidos triturados. No existe consenso al respecto, ni estudios de farmacocinética que avalen estos procedimientos. Ante esta situación, la Red Española de Estudio de la Tuberculosis Pediátrica (pTBred) desarrolla el Proyecto Magistral, con el objetivo de analizar, en su primera fase, la conveniencia de desarrollar formas farmacéuticas específicas para niños, así como estudiar otros aspectos relacionados con la administración de antituberculosos en niños. Material y métodos: Estudio transversal, multicéntrico y de ámbito nacional, mediante encuesta on-line enviada por correo electrónico a los instituciones pertenecientes a pTBred entre febrero y marzo del 2015 Resultados: Se recibieron 54 respuestas de 67 instituciones consultadas. La mayoría de los centros trituran los comprimidos. Un porcentaje elevado, aunque menor, administra FM, cuya disponibilidad es variable entre las instituciones. El 83% responde que sería ideal disponer de combinaciones fijas de antituberculosos, adaptadas a las dosis pediátricas y administradas mediante FM o en un comprimido. Entre las instituciones encuestadas existen diferencias en el tratamiento de la infección tuberculosa latente, el uso de la terapia directamente observada y la monitorización de efectos adversos. Conclusiones: Nuestra encuesta revela gran heterogeneidad en la prescripción de antituberculosos en niños debido a la falta de formulaciones específicas para esta edad, que podría tener implicaciones en la adherencia al tratamiento y evolución. pTBred propone elaborar un pionero y útil documento de consenso sobre la administración de medicación antituberculosa en niños. Abstract: Introduction: There are no paediatric formulations of anti-tuberculous drugs in Spain, with the only exception being rifampicin. Some paediatricians often prescribe composite formulations (CF), while others prefer to give crushed tablets. Nevertheless, there is no consensus in this regard, or any pharmacokinetic studies validating these procedures. In this situation, the Spanish Network for the Study of Paediatric Tuberculosis (pTBred) has launched the Magistral Project, which has as its first phase aims to analyse the desirability of developing child-friendly pharmaceutical formulations and other aspects regarding the anti-tuberculous drug prescription in children. Material and methods: A cross-sectional, multicentre, nationwide study was conducted, based on an online questionnaire sent to members of pTBred between February and March 2015. Results: Fifty-four responses from 67 consulted institutions were received. Most of the respondents reported prescribing crushed tablets. A significant number of those surveyed, although being fewer, prescribe CF, for which availability varies widely among institutions. Eighty-three percent replied that it would be essential to have fixed dose combinations of anti-tuberculous drugs, specifically adapted to paediatric doses and administered by CF or tablets. Among the surveyed institutions, differences were found in the management of latent tuberculosis infection, in the use of directly observed therapy, and in the monitoring of adverse events. Conclusions: Our survey reveals great diversity in anti-tuberculous drug prescription in children, due to the lack of suitable infant formulations, which could have an impact on treatment adherence and outcomes. pTBred intends to develop a pioneering and useful consensus document on the management of anti-tuberculous medication in children.

ptbnet TB Meningitis Study Group., [Introduction] Tuberculous meningitis (TBM) is often diagnostically challenging. Only limited data exist on the performance of interferon-γ release assays (IGRA) and molecular assays in children with TBM in routine clinical practice, particularly in the European setting., [Methods] Multicentre, retrospective study involving 27 healthcare institutions providing care for children with tuberculosis (TB) in nine European countries., [Results] Of 118 children included, 54 (45.8%) had definite, 38 (32.2%) probable and 26 (22.0%) possible TBM; 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Of 108 patients who underwent cranial imaging 90 (83.3%) had at least one abnormal finding consistent with TBM. At the 5-mm cut-off the tuberculin skin test had a sensitivity of 61.9% (95% CI 51.2–71.6%) and at the 10-mm cut-off 50.0% (95% CI 40.0–60.0%). The test sensitivities of QuantiFERON-TB and T-SPOT.TB assays were 71.7% (95% CI 58.4–82.1%) and 82.5% (95% CI 58.2–94.6%), respectively (p=0.53). Indeterminate results were common, occurring in 17.0% of QuantiFERON-TB assays performed. Cerebrospinal fluid (CSF) cultures were positive in 50.0% (95% CI 40.1–59.9%) of cases, and CSF PCR in 34.8% (95% CI 22.9–43.7%). In the subgroup of children who underwent tuberculin skin test, IGRA, CSF culture and CSF PCR simultaneously, 84.4% had at least one positive test result (95% CI 67.8%–93.6%)., [Conclusions] Existing immunological and microbiological TB tests have suboptimal sensitivity in children with TBM, with each test producing false-negative results in a substantial proportion of patients. Combining immune-based tests with CSF culture and CSF PCR results in considerably higher positive diagnostic yields, and should therefore be standard clinical practice in high-resource settings., This project was carried out without dedicated funding. ptbnet is supported by the Deutsche Gesellschaft für Internationale Zusammenarbeit. M. Tebruegge was supported by a Clinical Lectureship provided by the UK National Institute for Health Research (NIHR), and by a grant from the Technology Strategy Board/Innovate UK. B. Santiago-Garcia is funded by Spanish Ministry of Health – Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union (FEDER) (Contrato Juan Rodés, grant JR16/00036). R. Basu Roy is funded by an NIHR Academic Clinical Lectureship at the London School of Hygiene and Tropical Medicine. A. Noguera-Julian was supported by “Subvencions per a la Intensificació de Facultatius Especialistes” (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016–2020) (SLT008/18/00193). Funding information for this article has been deposited with the Crossref Funder Registry.

Tuberculosis (TB) is the most important infectious disease all over the world, with a high morbidity and mortality. Paediatric tuberculosis has been a neglected epidemic, due to the difficulties in assessing its global impact, reduced incidence and lower infectivity compared to adults. In 2015, the WHO reported 1 million cases of paediatric TB and 169,000 deaths. In Europe, the emergence of MDR TB is a major concern, representing 16% of the new diagnosis in Eastern Europe. In 2014, it was estimated that about 219,000 children were infected by MDR-TB-strains in Europe, and 2120 developed the disease. Spain is the Western European country with more paediatric cases, with an incidence 4.3/100,000 inhabitants in 2014. Paediatric tuberculosis mortality in Spain is rare, but extra-pulmonary disease is associated with significant complications. The prevalence of paediatric drug resistant TB in Spain is over 4%, higher than the estimated incidence in adult population, representing mayor difficulties for therapeutic intervention. These data reveal that paediatric TB is still a Public Health priority in our country.The difficulties in diagnosis and the lack of optimal paediatric drug formulations are the major challenges for controlling the childhood's tuberculosis epidemic. A group of national paeditric TB experts has reviewed the international guidelines and the most recent evidences, and has established new recommendations for the management of paediatric TB contacts, latent infection and active TB disease, especially focused in drug resistant cases. This document replaces the former national guidelines from the Spanish Society for Pediatric Infectious Diseases, although the prior recommendations on the diagnosis remain valid. Resumen: La tuberculosis (TB) es la enfermedad infecciosa más importante del mundo, asociando enorme morbimortalidad. La TB pediátrica ha sido una epidemia oculta por su escasa capacidad infectiva y menor incidencia comparada con adultos. El informe-OMS 2015 estimó un millón de niños enfermos de TB en el mundo y 169.000 fallecidos. En Europa, el problema acuciante es la tuberculosis multirresistente, con tasas del 16% en nuevos diagnósticos, especialmente en países del este. En 2014, 219.000 niños se infectaron por cepas-MDR en Europa, 2.120 desarrollaron enfermedad. España es el país de Europa con mayor número de casos pediátricos, con una incidencia en 2014: 4,3/100.000 habitantes. La mortalidad por TB pediátrica en nuestro país es excepcional, pero las formas extrapulmonares ocasionan importantes complicaciones. La TB resistente en niños en España presenta una prevalencia >4%, superando incluso la notificada en adultos. Estos datos reflejan que la TB en niños en nuestro medio continúa siendo un problema de salud pública prioritario.Las dificultades diagnósticas del niño y la falta de formulaciones pediátricas óptimas son el mayor desafío para control de TB infantil. El Grupo de expertos de TB pediátrica realiza un análisis de las nuevas tendencias internacionales y guías terapéuticas de tuberculosis en niños, según nuevas evidencias disponibles; y considera una prioridad actualizar las guías pediátricas nacionales de exposición a TB, infección tuberculosa latente y enfermedad, y particularmente los casos de resistencia a fármacos. Este documento, por tanto, sustituye a todos los previos en cuanto a las pautas terapéuticas, aunque siguen estando vigentes las indicaciones diagnósticas.

Resumen: La tuberculosis (TB) es la enfermedad infecciosa más importante del mundo, asociando enorme morbimortalidad. La TB pediátrica ha sido una epidemia oculta por su escasa capacidad infectiva y menor incidencia comparada con adultos. El informe-OMS 2015 estimó un millón de niños enfermos de TB en el mundo y 169.000 fallecidos. En Europa, el problema acuciante es la tuberculosis multirresistente, con tasas del 16% en nuevos diagnósticos, especialmente en países del este. En 2014, 219.000 niños se infectaron por cepas-MDR en Europa, 2.120 desarrollaron enfermedad. España es el país de Europa con mayor número de casos pediátricos, con una incidencia en 2014: 4,3/100.000 habitantes. La mortalidad por TB pediátrica en nuestro país es excepcional, pero las formas extrapulmonares ocasionan importantes complicaciones. La TB resistente en niños en España presenta una prevalencia > 4%, superando incluso la notificada en adultos. Estos datos reflejan que la TB en niños en nuestro medio continúa siendo un problema de salud pública prioritario.Las dificultades diagnósticas del niño y la falta de formulaciones pediátricas óptimas son el mayor desafío para control de TB infantil. El Grupo de expertos de TB pediátrica realiza un análisis de las nuevas tendencias internacionales y guías terapéuticas de tuberculosis en niños, según nuevas evidencias disponibles; y considera una prioridad actualizar las guías pediátricas nacionales de exposición a TB, infección tuberculosa latente y enfermedad, y particularmente los casos de resistencia a fármacos. Este documento, por tanto, sustituye a todos los previos en cuanto a las pautas terapéuticas, aunque siguen estando vigentes las indicaciones diagnósticas. Abstract: Tuberculosis (TB) is the most important infectious disease all over the world, with a high morbidity and mortality. Pediatric tuberculosis has been a neglected epidemic, due to the difficulties in assessing its global impact, reduced incidence and lower infectivity compared to adults. In 2015, the WHO reported 1 million cases of paediatric TB and 169,000 deaths. In Europe, the emergence of MDR TB is a major concern, representing 16% of the new diagnosis in Eastern Europe. In 2014, it was estimated that about 219,000 children were infected by MDR-TB-strains in Europe, and 2,120 developed the disease. Spain is the Western European country with more paediatric cases, with an incidence 4.3/100,000 inhabitants in 2014. Paediatric tuberculosis mortality in Spain is rare, but extra-pulmonary disease is associated with significant complications. The prevalence of paediatric drug resistant TB in Spain is over 4%, higher than the estimated incidence in adult population, representing mayor difficulties for therapeutic intervention. These data reveal that paediatric TB is still a Public Health priority in our country.The difficulties in diagnosis and the lack of optimal paediatric drug formulations are the major challenges for controlling the childhood's tuberculosis epidemic. A group of national paeditric TB experts has reviewed the international guidelines and the most recent evidences, and has established new recommendations for the management of paediatric TB contacts, latent infection and active TB disease, especially focused in drug resistant cases. This document replaces the former national guidelines from the Spanish Society for Pediatric Infectios Diseases, although the prior recommendations on the diagnosis remain valid.

Background The rates of isoniazid (INH) and multidrug-resistant (MDR) tuberculosis (TB) among European children vary between 10.4% and 3.5%. Spain is a low endemic country with reported rates of 4.9% of INH resistance and 1.3% of MDR in adults. However, data regarding patterns of TB resistance in children are scarce. Our aim is to determine the incidence and risk factors for pediatric-resistant TB in our setting to help developing age-targeted guidelines. Methods A multicenter, retrospective study including 22 hospitals from Madrid region (EREMITA study group) was performed from January 2005 to June 2010. Medical records from children diagnosed with TB were reviewed for demographic characteristics, clinical presentation and outcomes. Risk factors for INH and MDR TB were identified. Results Of 396 children diagnosed with TB, 72.4% were born to foreign parents. Microbiologic confirmation by culture (n = 200) or PCR (n = 8) was documented in 208 children (52.5%). Drug susceptibility results were available in 188 children: 9.6% (n = 18) were resistant to INH and 3.1% (n = 6) were MDR. INH resistance was more common in immigrants compared with native families (11.9% vs. 0%; P = 0.013), as was also MDR (4.5% vs. 0%; P = 0.34). Extrapulmonary TB and previous antituberculous treatment were significantly associated with INH and MDR, while immunosuppression was associated only with MDR. Conclusions The rates of INH and MDR TB were different according to the parents' origin, with higher rates among children born to foreign parents. Local surveillance of drug-resistant TB is critical to develop appropriate guidelines for treatment.

Background: Mycobacterium lentiflavum is considered a rare pathogen causing nontuberculous mycobacterial (NTM) lymphadenitis. Methods: A multicenter, retrospective study was performed in immunocompetent children

Resumen: La Red Española de Estudio de la Tuberculosis Pediátrica ha evidenciado una falta de consenso nacional en la administración de antituberculosos en niños, propiciada por la escasez de presentaciones pediátricas específicas. Es prioritario homogeneizar el tratamiento de la tuberculosis en niños en nuestro país. Un grupo de expertos españoles en tuberculosis infantil y en el área de medicamentos pediátricos proponen una actuación conjunta, con la finalidad de mejorar esta situación en nuestro medio. Para ello se constituye un Grupo de Trabajo, liderado por pTBred, en el que participan otras 5 sociedades e instituciones científicas. Se proponen las siguientes fórmulas magistrales en forma de suspensión o solución oral para el tratamiento de la tuberculosis en niños: isoniacida 50 mg/ml, pirazinamida 100 mg/ml y etambutol 50 mg/ml. Se especifican materias primas, periodo de validez y condiciones de conservación y administración. Se establecen recomendaciones para el uso de fármacos combinados a dosis fijas. Si no se consigue la dosis apropiada mediante fármacos combinados a dosis fijas, y no se dispone de fórmula magistral, se recomienda la administración mediante comprimidos triturados. El adecuado cumplimiento terapéutico y la administración de dosis óptimas de los fármacos antituberculosos constituyen pilares fundamentales en el control y erradicación de la enfermedad. La oportunidad de disponer de este documento multidisciplinar en España favorecerá el correcto tratamiento de la tuberculosis pediátrica, y será una guía útil para todos los pediatras y farmacéuticos que lo precisen. Abstract: The Spanish Network for the Study of Paediatric Tuberculosis has shown a lack of national consensus on the treatment of tuberculosis in children, partly due to the unavailability of paediatric presentations of antituberculosis drugs. The harmonisation of tuberculosis treatment in children is a priority in Spain. A joint action is proposed by a group of Spanish experts in childhood tuberculosis and in the area of Paediatric Pharmacology. To this end, a pTBred-led workgroup of members from five scientific bodies has been created. Drug pharmaceutical compounding in oral suspensions or oral solutions are recommended as follows: isoniazid 50 mg/mL, pyrazinamide 100 mg/mL, and ethambutol 50 mg/mL. Raw materials, period of validity, and storage conditions are specified. Recommendations for the use of fixed-dose combination drugs are also established. If oral solutions/suspensions or fixed-dose combination drugs are not appropriate, the use of crushed tablets is recommended. Adherence to treatment and optimal dosing of antituberculosis drugs are critical in the control and eradication of TB. This multidisciplinary document provides an opportunity to promote the appropriate treatment of paediatric tuberculosis in Spain, and should become a useful tool for paediatricians and pharmacists.

Introduction: There are no paediatric formulations of anti-tuberculous drugs in Spain, with the only exception being rifampicin. Some paediatricians often prescribe composite formulations (CF), while others prefer to give crushed tablets. Nevertheless, there is no consensus in this regard, or any pharmacokinetic studies validating these procedures. In this situation, the Spanish Network for the Study of Paediatric Tuberculosis (pTBred) has launched the Magistral Project, which aims at its first phase to analyse the desirability of developing child-friendly pharmaceutical formulations and other aspects regarding the anti-tuberculous drug prescription in children. Material and methods: A cross-sectional, multicentre, nationwide study was conducted, based on an online questionnaire sent to members of pTBred between February and March 2015. Results: Fifty-four responses from 67 consulted institutions were received. Most of the respondents reported prescribing crushed tablets. A significant number of those surveyed, although being fewer, prescribe CF, for which availability varies widely among institutions. Eighty-three percent replied that it would be essential to have fixed dose combinations of anti-tuberculous drugs, specifically adapted to paediatric doses and administered by CF or tablets. Among the surveyed institutions, differences were found in the management of latent tuberculosis infection, in the use of directly observed therapy, and in the monitoring of adverse events. Conclusions: Our survey reveals great diversity in anti-tuberculous drug prescription in children, due to the lack of suitable infant formulations, which could have an impact on treatment adherence and outcomes. pTBred intends to develop a pioneering and useful consensus document on the management of anti-tuberculous medication in children. Resumen: Introducción: En España no existen presentaciones pediátricas de fármacos antituberculosos, salvo para rifampicina. Algunos pediatras prescriben fórmulas magistrales (FM), mientras que otros administran comprimidos triturados. No existe consenso al respecto, ni estudios de farmacocinética que avalen estos procedimientos. Ante esta situación, la Red Española de Estudio de la Tuberculosis Pediátrica (pTBred) desarrolla el Proyecto Magistral, con el objetivo de analizar, en su primera fase, la conveniencia de desarrollar formas farmacéuticas específicas para niños, así como estudiar otros aspectos relacionados con la administración de antituberculosos en niños. Material y métodos: Estudio transversal, multicéntrico y de ámbito nacional, mediante encuesta on-line enviada por correo electrónico a los instituciones pertenecientes a pTBred entre febrero y marzo del 2015. Resultados: Se recibieron 54 respuestas de 67 instituciones consultadas. La mayoría de los centros trituran los comprimidos. Un porcentaje elevado, aunque menor, administra FM, cuya disponibilidad es variable entre las instituciones. El 83% responde que sería ideal disponer de combinaciones fijas de antituberculosos, adaptadas a las dosis pediátricas y administradas mediante FM o en un comprimido. Entre las instituciones encuestadas existen diferencias en el tratamiento de la infección tuberculosa latente, el uso de la terapia directamente observada y la monitorización de efectos adversos. Conclusiones: Nuestra encuesta revela gran heterogeneidad en la prescripción de antituberculosos en niños debido a la falta de formulaciones específicas para esta edad, que podría tener implicaciones en la adherencia al tratamiento y evolución. pTBred propone elaborar un pionero y útil documento de consenso sobre la administración de medicación antituberculosa en niños.

Introduction: Vesicoureteral reflux (VUR) is a common pediatric urologic disorder. After the first urinary tract infection (UTI), imaging studies are recommended, starting with a renal ultrasound (RUS). Voiding cystourethrography (VCUG) and dimercaptosuccinic acid (DMSA) scan are the other main radiologic studies used to detect VUR. We evaluated the use of RUS as a screening method for VUR in children below 2 years of age, in order to avoid unnecessary VCUG. Materials and Methods: Medical records and imaging studies of infants (

The Spanish Network for the Study of Paediatric Tuberculosis has shown a lack of national consensus on the treatment of tuberculosis in children, partly due to the unavailability of paediatric presentations of antituberculosis drugs. The harmonisation of tuberculosis treatment in children is a priority in Spain. A joint action is proposed by a group of Spanish experts in childhood tuberculosis and in the area of Paediatric Pharmacology. To this end, a pTBred-led workgroup of members from five scientific bodies has been created. Drug pharmaceutical compounding in oral suspensions or oral solutions are recommended as follows: isoniazid 50 mg/mL, pyrazinamide 100 mg/mL, and ethambutol 50 mg/mL. Raw materials, period of validity, and storage conditions are specified. Recommendations for the use of fixed-dose combination drugs are also established. If oral solutions/suspensions or fixed-dose combination drugs are not appropriate, the use of crushed tablets is recommended. Adherence to treatment and optimal dosing of antituberculosis drugs are critical in the control and eradication of TB. This multidisciplinary document provides an opportunity to promote the appropriate treatment of paediatric tuberculosis in Spain, and should become a useful tool for paediatricians and pharmacists. Resumen: La Red Española de Estudio de la Tuberculosis Pediátrica ha evidenciado una falta de consenso nacional en la administración de antituberculosos en niños, propiciada por la escasez de presentaciones pediátricas específicas. Es prioritario homogeneizar el tratamiento de la tuberculosis en niños en nuestro país. Un grupo de expertos españoles en tuberculosis infantil y en el área de medicamentos pediátricos proponen una actuación conjunta, con la finalidad de mejorar esta situación en nuestro medio. Para ello se constituye un Grupo de Trabajo, liderado por pTBred, en el que participan otras 5 sociedades e instituciones científicas. Se proponen las siguientes fórmulas magistrales en forma de suspensión o solución oral para el tratamiento de la tuberculosis en niños: isoniacida 50 mg/ml, pirazinamida 100 mg/ml y etambutol 50 mg/ml. Se especifican materias primas, periodo de validez y condiciones de conservación y administración. Se establecen recomendaciones para el uso de fármacos combinados a dosis fijas. Si no se consigue la dosis apropiada mediante fármacos combinados a dosis fijas, y no se dispone de fórmula magistral, se recomienda la administración mediante comprimidos triturados. El adecuado cumplimiento terapéutico y la administración de dosis óptimas de los fármacos antituberculosos constituyen pilares fundamentales en el control y erradicación de la enfermedad. La oportunidad de disponer de este documento multidisciplinar en España favorecerá el correcto tratamiento de la tuberculosis pediátrica, y será una guía útil para todos los pediatras y farmacéuticos que lo precisen.