Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI).

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17-20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families.

Results of the REIV-TOXO national survey on prenatal screening for toxoplasmosis in Spain.

INTRODUCTION: Currently, the status of serological screening for toxoplasmosis in pregnant women in Spain is unknown, and there is no official recommendation. The objective of this study is to show the current practice of gestational screening for toxoplasmosis in hospitals belonging to the Spanish Network for Research on Congenital Toxoplasmosis (REIV-TOXO). METHODS: An electronic survey was sent between April 2021 and September 2021 to investigators from 118 hospitals of REIV-TOXO, representing all Spanish regions. Nine items related to gestational screening for toxoplasmosis were collected. This information was compared with cases of congenital toxoplasmosis (CT) identified in REIV-TOXO to determine if these were diagnosed in the presence of gestational screening. RESULTS: During the study period, serological screening was performed in 53.3% (63/118) hospitals, with variations between regions and even among hospitals within the same region. Testing performed in each trimester was the most common practice (57.7%), followed by a single determination (24.4%). 89.4% of CT cases between January 2015 and September 2021 were diagnosed due to gestational screening. CONCLUSION: The decision to perform gestational screening for toxoplasmosis in Spain is highly heterogeneous, with significant local and regional differences. Despite this, screening still allows the diagnosis of most CT cases. It is urgent to have current epidemiological data to inform decision-making in public health.

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

BACKGROUND: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. METHODS: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. RESULTS: Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. CONCLUSIONS: Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.

PACTA-Ped: programa de optimización de antimicrobianos en un hospital de tercer nivel en España / PACTA-Ped: Antimicrobial stewardship programme in a tertiary care hospital in Spain

Introducción: La lucha contra la resistencia a los antimicrobianos es actualmente prioritaria; son necesarios esfuerzos para mejorar la prescripción y reducir la propagación de infecciones en el entorno pediátrico. Métodos: Estudio longitudinal prospectivo sobre el uso de antimicrobianos realizado desde el inicio del programa de optimización del uso de antimicrobianos (PROA) en enero de 2016 hasta diciembre de 2017 (período 2; P2) en el hospital infantil. Los resultados obtenidos se han comparado retrospectivamente con el periodo anterior al inicio del PROA (2014-2015, periodo 1; P1). La población estudiada fueron niños ingresados que recibieron antimicrobianos de amplio espectro, antifúngicos o tratamiento antibiótico intravenoso durante más de 5 días.Resultados: Durante el P2 se incluyeron un total de 160 pacientes. Los antibióticos más comunes para los que se realizó una recomendación fueron: meropenem (41,6%) y cefotaxima (23,4%). En el 45% de los episodios se recomendó «no cambiar» el antimicrobiano prescrito. La tasa de aceptación de las recomendaciones por parte de los facultativos responsables fue del 89%. Se objetivó una disminución promedio del 27,8 y del 22,9% en los días de tratamiento (DOT)/1.000 días de ingreso y el número de tratamientos iniciados/1.000 ingresos, respectivamente. El uso de carbapenémicos, cefalosporinas y glucopéptidos disminuyó del P1 al P2. El coste medio anual del tratamiento antimicrobiano pasó de 150.356€/año durante en el P1 a 98.478€/año en el P2. Conclusiones: Nuestro PROA conllevó una disminución significativa en el uso de antibióticos y antifúngicos de amplio espectro. Los costes asociados con la prescripción de antimicrobianos disminuyeron desde el inicio del PROA y resultó una acción coste-efectiva durante el período de estudio.(AU)

Introduction: Fighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. Methods: We conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children's hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014–2015, period 1 [P1]). The sample consisted of paediatric in patients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. Results: A total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended “no change” to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from €150 356/year during P1 to €98 478/year in P2. Conclusion: Our ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.(AU)

PACTA-Ped: Antimicrobial stewardship programme in a tertiary care hospital in Spain.

INTRODUCTION: Fighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. METHODS: We conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children's hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014-2015, period 1 [P1]). The sample consisted of paediatric inpatients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. RESULTS: A total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended "no change" to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from є150 356/year during P1 to є98 478/year in P2. CONCLUSION: Our ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.

Safety, efficacy, and immunogenicity of a replication-defective human cytomegalovirus vaccine, V160, in cytomegalovirus-seronegative women: a double-blind, randomised, placebo-controlled, phase 2b trial.

BACKGROUND: A vaccine that prevents cytomegalovirus (CMV) infection in women could reduce the incidence of congenital CMV infection, a major cause of neurodevelopmental disability. We aimed to assess the safety and efficacy of a replication-defective investigational CMV vaccine, V160, in CMV-seronegative women. METHODS: This phase 2b, randomised, double-blind, placebo-controlled study was conducted at 90 sites in seven countries (USA, Finland, Canada, Israel, Spain, Russia, and Australia). Eligible participants were generally healthy, CMV-seronegative, non-pregnant, 16-35-year-old women of childbearing potential with exposure to children aged 5 years or younger. Participants were randomly assigned using central randomisation via an interactive response technology system 1:1:1 to one of three groups: V160 three-dose regimen (V160 at day 1, month 2, and month 6), V160 two-dose regimen (V160 on day 1, placebo at month 2, and V160 at month 6), or placebo (saline solution at day 1, month 2, and month 6). The primary outcomes were the efficacy of three doses of V160 in reducing the incidence of primary CMV infection during the follow-up period starting 30 days after the last dose of vaccine using a fixed event rate design, and the safety and tolerability of the two-dose and three-dose V160 regimens. We planned to test the efficacy of a two-dose regimen of V160 in reducing the incidence of primary CMV infection only if the primary efficacy hypothesis was met. Analyses for the primary efficacy endpoint were performed on the per-protocol efficacy population; safety analyses included all randomly assigned participants who received study vaccine. The primary efficacy hypothesis was tested at prespecified interim and final analyses. The study was ongoing and efficacy data continued to accrue at the time of final testing of the primary efficacy hypothesis. Vaccine efficacy was re-estimated after final testing of the primary efficacy hypothesis based on all available efficacy data at end of study. This trial is registered at ClinicalTrials.gov (NCT03486834) and EudraCT (2017-004233-86) and is complete. FINDINGS: Between April 30, 2018, and Aug 30, 2019, 7458 participants were screened, of whom 2220 were randomly assigned to the V160 three-dose group (n=733), V160 two-dose group (n=733), or placebo group (n=734). A total of 523 participants in the V160 three-dose group and 519 in the placebo group were included in the final hypothesis testing. Of these, there were 11 cases of CMV infection in the V160 three-dose group and 20 cases in the placebo group. The vaccine efficacy for the V160 three-dose group was 44·6% (95% CI -15·2 to 74·8) at the final testing of the primary efficacy hypothesis, a result corresponding to failure to demonstrate the primary efficacy hypothesis. On the basis of this result, the study was terminated for futility. The re-estimate of vaccine efficacy for the V160 three-dose group based on all available efficacy data at end of study (556 participants in the V160 three-dose group and 543 in the placebo group) was 42·4% (95% CI -13·5 to 71·1). A total of 728 participants in the V160 three-dose group, 729 in the V160 two-dose group, and 732 in the placebo group were included in the safety analyses. The most common solicited injection-site adverse event was injection-site pain (680 [93%] in the V160 three-dose group, 659 [90%] in the V160 two-dose group, and 232 [32%] in the placebo group). The most common solicited systemic adverse event was fatigue (457 [63%] in the V160 three-dose group, 461 [63%] in the V160 two-dose group, and 357 [49%] in the placebo group). No vaccine-related serious adverse events or deaths were reported. INTERPRETATION: V160 was generally well tolerated and immunogenic; however, three doses of the vaccine did not reduce the incidence of primary CMV infection in CMV-seronegative women compared with placebo. This study provides insights into the design of future CMV vaccine efficacy trials, particularly for the identification of CMV infection using molecular assays. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

Clinical outcomes and antibody transfer in a cohort of infants with in utero or perinatal exposure to SARS-CoV-2 (Coronascope Study).

We aimed to describe the outcomes, focusing on the hearing and neurological development, of infants born to mothers with COVID-19 during pregnancy and to evaluate the persistence of maternal antibodies in the first months of life. An observational, prospective study at a tertiary hospital in Madrid (Spain) on infants born to mothers with COVID-19 during pregnancy between March and September 2020 was conducted. A follow-up visit at 1-3 months of age with a physical and neurological examination, cranial ultrasound (cUS), SARS-CoV-2 RT-PCR on nasopharyngeal swab, and SARS-CoV-2 serology were performed. Hearing was evaluated at birth through the automated auditory brainstem response and at six months of age through the auditory steady-state response. A neurodevelopmental examination using the Bayley-III scale was performed at 12 months of age. Of 95 infants studied, neurological examination was normal in all of them at the follow-up visit, as was the cUS in 81/85 (95%) infants, with only mild abnormalities in four of them. Serology was positive in 47/95 (50%) infants, which was not associated with symptoms or severity of maternal infection. No hearing loss was detected, and neurodevelopment was normal in 96% of the infants (median Z score: 0). CONCLUSION: In this cohort, the majority of infants born to mothers with COVID-19 during pregnancy were healthy infants with a normal cUS, no hearing loss, and normal neurodevelopment in the first year of life. Only half of the infants had a positive serological result during the follow-up. WHAT IS KNOWN: • Hearing loss and neurodevelopmental delay in infants born to mothers with COVID-19 during pregnancy has been suggested, although data is inconsistent. Maternal antibody transfer seems to be high, with a rapid decrease during the first weeks of life. WHAT IS NEW: • Most infants born to mothers with COVID-19 during pregnancy had normal hearing screening, cranial ultrasound, and neurodevelopmental status at 12 months of life. Antibodies against SARS-CoV-2 were only detected in 50% of the infants at two months of life.

Discrepancies in Management of Congenital Cytomegalovirus in Preterm Infants: An International Survey.

We performed an international survey regarding management of infants with congenital cytomegalovirus (cCMV) born at less than 32 weeks gestation or with birth weight under 1500 g. Replies from 51 level 3 neonatal intensive care units across 13 countries demonstrated striking discrepancies in screening practices, testing for cCMV, further investigations of confirmed cases, indications for initiation, and duration of treatment.

Epidemiology and clinical features of Streptococcus pyogenes bloodstream infections in children in Madrid, Spain.

Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13 years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16 years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1: 2005-June 2011 vs P2: July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI: -2.7, + 15.4]; p = 0.163). Median age was 24.1 months (IQR: 14.0-53.7), peaking during the first four years of life (89/109 cases; 81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7 vs. 13 days; p = 0.003) and received intravenous antibiotics less frequently (72.5% vs. 94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10 vs. 21 days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI: 2.16-29.41]). Two children (1.8%) died.   Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).

The role of the T-cell mediated immune response to Cytomegalovirus infection in intrauterine transmission.

INTRODUCTION: Prognostic markers for fetal transmission of Cytomegalovirus (CMV) infection during pregnancy are poorly understood. Maternal CMV-specific T-cell responses may help prevent fetal transmission and thus, we set out to assess whether this may be the case in pregnant women who develop a primary CMV infection. METHODS: A multicenter prospective study was carried out at 8 hospitals in Spain, from January 2017 to April 2020. Blood samples were collected from pregnant women at the time the primary CMV infection was diagnosed to assess the T-cell response. Quantitative analysis of interferon producing specific CMV-CD8+/CD4+ cells was performed by intracellular cytokine flow cytometry. RESULTS: In this study, 135 pregnant women with a suspected CMV infection were evaluated, 60 of whom had a primary CMV infection and samples available. Of these, 24 mothers transmitted the infection to the fetus and 36 did not. No association was found between the presence of specific CD4 or CD8 responses against CMV at the time maternal infection was diagnosed and the risk of fetal transmission. There was no transmission among women with an undetectable CMV viral load in blood at diagnosis. CONCLUSIONS: In this cohort of pregnant women with a primary CMV infection, no association was found between the presence of a CMV T-cell response at the time of maternal infection and the risk of intrauterine transmission. A detectable CMV viral load in the maternal blood at diagnosis of the primary maternal infection may represent a relevant biomarker associated with fetal transmission.

Infección congénita por CMV en recién nacidos hijos de madre con infección por VIH / Congenital cytomegalovirus infection in newborns born to HIV-infected mothers

Introducción: La infección congénita por CMV (CMVc) es más frecuente en hijos expuestos al. VIH durante la gestación, con tasas reportadas en la era pre-TAR del 2 al 7%. El control de la carga viral de VIH y la recuperación inmunológica asociada al tratamiento antirretroviral (TAR) podrían ser factores que influyan en su transmisión. El objetivo de este trabajo fue describir la epidemiología de la infección CMVc en recién nacidos expuestos al VIH en el Hospital Universitario 12 de Octubre, entre los años 2000-2017. Material y métodos: Estudio observacional y retrospectivo. Se recogieron variables epidemiológicas y clínicas a través de la historia clínica de los sujetos incluidos. Se realizó análisis estadístico con el programa informático SPSS 24.0. Resultados: Se incluyeron 288 pares de madres/hijos. Observamos una tasa de CMVc del 2,1% (IC 95% 0,7-4,9). Conclusiones: La tasa de CMVc fue menor a la comunicada en la era pre-TAR, aunque aún parece superior a la observada en niños no expuestos al VIH.(AU)

Introduction: Congenital citomegalovirus (CMVc) infection is more common in children exposed to HIV during pregnancy, with reported rates in pre-ART era from 2 to 7%. The use of combined antiretroviral treatment (ARTc) could be a determining factor in reducing this risk of CMV transmission. The aim of this study was to describe the epidemiology of CMVc infection in newborns of HIV-infected mothers at Hospital Universitario 12 de Octubre, Madrid, Spain, from 2000 to 2017. Material and methods: An observational and retrospective study was carried out. Epidemiological and clinical variables were collected. Statistical analysis was performed with the SPSS 24.0 computer program. Results: 288 mother–infant pairs were included in the study. We observed a CMVc rate of 2.1% (95% CI 0.9–4.9). Conclusions: The rate of CMVc in HIV-exposed children observed was lower than that reported in pre-ARTc era but seems higher than those described in general population.(AU)

Accuracy of Xpert Ultra for the diagnosis of paediatric tuberculosis in a low TB burden country: a prospective multicentre study.

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<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. 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.

Congenital cytomegalovirus infection in newborns born to HIV-infected mothers.

INTRODUCTION: Congenital citomegalovirus (CMVc) infection is more common in children exposed to HIV during pregnancy, with reported rates in pre-ART era from 2 to 7%. The use of combined antiretroviral treatment (ARTc) could be a determining factor in reducing this risk of CMV transmission. The aim of this study was to describe the epidemiology of CMVc infection in newborns of HIV-infected mothers at Hospital Universitario 12 de Octubre, Madrid, Spain, from 2000 to 2017. MATERIAL AND METHODS: An observational and retrospective study was carried out. Epidemiological and clinical variables were collected. Statistical analysis was performed with the SPSS 24.0 computer program. RESULTS: 288 mother-infant pairs were included in the study. We observed a CMVc rate of 2.1% (95% CI 0.9-4.9). CONCLUSIONS: The rate of CMVc in HIV-exposed children observed was lower than that reported in pre-ARTc era but seems higher than those described in general population.

Tuberculosis screening after detection of a case in a paediatric haemato-oncology unit in a low prevalence country.

BACKGROUND: There are no guidelines to screen haemato-oncologic children when a tuberculosis (TB) outbreak is suspected. METHODS: After exposition to an adult with active TB, children exposed from a haemato-oncology unit were screened according to immunosuppression status and time of exposure. Until an evaluation after 8-12 weeks from last exposure, isoniazid was indicated to those with negative initial work-up. RESULTS: After 210 interventions, we detected a case of pulmonary TB, and another with latent TB infection. Pulmonary findings and treatment approach were challenging in some patients. CONCLUSIONS: The TB screening of oncologic children required a multidisciplinary approach, and clinicians managed challenging situations.

Tuberculosis screening after detection of a case in a paediatric haemato-oncology unit in a low prevalence country / Cribado de tuberculosis tras la detección de un caso en una unidad de hematooncología pediátrica en un país con baja prevalencia

Background: There are no guidelines to screen haemato-oncologic children when a tuberculosis (TB) outbreak is suspected. Methods: After exposition to an adult with active TB, children exposed from a haemato-oncology unit were screened according to immunosuppression status and time of exposure. Until an evaluation after 8–12 weeks from last exposure, isoniazid was indicated to those with negative initial work-up. Results: After 210 interventions, we detected a case of pulmonary TB, and another with latent TB infection. Pulmonary findings and treatment approach were challenging in some patients. Conclusions: The TB screening of oncologic children required a multidisciplinary approach, and clinicians managed challenging situations.(AU)

Antecedentes: No existen pautas para el cribado de niños hematooncológicos cuando se sospecha de un brote de tuberculosis (TB). Métodos: Después de la exposición a un adulto con TB activa, se evaluó a los niños expuestos de una unidad de hematooncología según el estado de inmunosupresión y el tiempo de exposición. Hasta una evaluación después de ocho a12 semanas desde la última exposición, se indicó isoniazida para aquellos con un proceso inicial negativo. Resultados: Tras 210 intervenciones se detectó un caso de tuberculosis pulmonar y otro con infección por TB latente. Los hallazgos pulmonares y el método de tratamiento fueron un desafío en algunos pacientes. Conclusiones: El cribado de TB en niños oncológicos requirió un método multidisciplinario y los médicos manejaron situaciones complejas.(AU)

Hand Hygiene Compliance Rates in 9 Pediatric Intensive Care Units Across Europe: Results from the Reducing Antimicrobial use and Nosocomial Infections in Kids Network.

A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric wards is lacking in Europe. We managed to setup such a mechanism in 9 pediatric intensive care units in 7 European countries, using World Health Organization's definitions and common methodology which allows for benchmarking among units and countries. Median hand hygiene compliance was found high 82.3% (interquartile range 71.6-94.5%), but gaps in practices were identified.

Oral saliva swab reverse transcription PCR for Covid-19 in the paediatric population.

OBJECTIVES: To evaluate the performance of oral saliva swab (OSS) reverse transcription PCR (RT-PCR) compared with RT-PCR and antigen rapid diagnostic test (Ag-RDT) on nasopharyngeal swabs (NPS) for SARS-CoV-2 in children. DESIGN: Cross-sectional multicentre diagnostic study. SETTING: Study nested in a prospective, observational cohort (EPICO-AEP) performed between February and March 2021 including 10 hospitals in Spain. PATIENTS: Children from 0 to 18 years with symptoms compatible with Covid-19 of ≤5 days of duration were included. Two NPS samples (Ag-RDT and RT-PCR) and one OSS sample for RT-PCR were collected. MAIN OUTCOME: Performance of Ag-RDT and RT-PCR on NPS and RT-PCR on OSS sample for SARS-CoV-2. RESULTS: 1174 children were included, aged 3.8 years (IQR 1.7-9.0); 73/1174 (6.2%) patients tested positive by at least one of the techniques. Sensitivity and specificity of OSS RT-PCR were 72.1% (95% CI 59.7 to 81.9) and 99.6% (95% CI 99 to 99.9), respectively, versus 61.8% (95% CI 49.1 to 73) and 99.9% (95% CI 99.4 to 100) for the Ag-RDT. Kappa index was 0.79 (95% CI 0.72 to 0.88) for OSS RT-PCR and 0.74 (95% CI 0.65 to 0.84) for Ag-RDT versus NPS RT-PCR. CONCLUSIONS: RT-PCR on the OSS sample is an accurate option for SARS-CoV-2 testing in children. A less intrusive technique for younger patients, who usually are tested frequently, might increase the number of patients tested.

Differences in saliva ACE2 activity among infected and non-infected adult and pediatric population exposed to SARS-CoV-2.

BACKGROUND: Variations in the ACE2 activity in saliva could explain the striking differences of susceptibility to infection and risk of severe disease. METHODS: We analyze the activity of ACE2 in saliva in different population groups across a wide age range and disease status during April to June 2020, before SARS-CoV-2 vaccine implementation, and we establish differences between infected people and participants considered resistant (highly exposed healthcare workers and children who cohabited with parents with COVID-19 without isolation and remain IgG negative). RESULTS: We included 74 adults, of which 47 (64%) were susceptible and 27 (36%) were resistant, and 79 children, of which 41 (52%) were susceptible and 38 (48%) were resistant. Resistant adults have significantly lower ACE2 activity in saliva than susceptible adults and non-significant higher values than susceptible and resistant children. ACE2 activity is similar in the susceptible and resistant pediatric population (p = 0.527). In contrast, we observe an increase in activity as the disease's severity increases among the adult population (mild disease vs. severe disease, 39 vs. 105 FU, p = 0.039; severe disease vs. resistant, 105 vs. 31 FU, p < 0.001). CONCLUSIONS: using an enzymatic test, we show that ACE2 activity in saliva correlates with the susceptibility to SARS-Cov-2 infection and disease severity. Children and adults with low-susceptibility to SARS-Cov-2 infection showed the lowest ACE2 activity. These findings could inform future strategies to identify at-risk individuals.