Browsing by Author "Launes, Cristian"
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Publication Concentrations of nitrogen compounds are related to severe rhinovirus infection in infants. A time-series analysis from the reference area of a pediatric university hospital in Barcelona(Wiley, 2022-09) Armero, Georgina; Penela-Sánchez, Daniel; Belmonte, Jordina; Gomez-Barroso, Diana; Larrauri, Amparo; Henares, Desiree; Vallejo, Violeta; Jordan, Iolanda; Muñoz-Almagro, Carmen; Brotons, Pedro; Launes, Cristian; Instituto de Salud Carlos IIIBackground: There is scarce information focused on the effect of weather conditions and air pollution on specific acute viral respiratory infections, such as rhinovirus (RV), with a wide clinical spectrum of severity. Objective: The aim of this study was to analyze the association between episodes of severe respiratory tract infection by RV and air pollutant concentrations (NOx and SO2 ) in the reference area of a pediatric university hospital. Methods: An analysis of temporal series of daily values of NOx and SO2 , weather variables, circulating pollen and mold spores, and daily number of admissions in the pediatric intensive care unit (PICU) with severe respiratory RV infection (RVi) in children between 6 months and 18 years was performed. Lagged variables for 0-5 days were considered. The study spanned from 2010 to 2018. Patients with comorbidities were excluded. Results: One hundred and fifty patients were admitted to the PICU. Median age was 19 months old (interquartile range [IQR]: 11-47). No relationship between RV-PICU admissions and temperature, relative humidity, cumulative rainfall, or wind speed was found. Several logistic regression models with one pollutant and two pollutants were constructed but the best model was that which included average daily NOx concentrations. Average daily NOx concentrations were related with the presence of PICU admissions 3 days later (odds ratio per IQR-unit increase: 1.64, 95% confidence interval: 1.20-2.25)). Conclusions: This study has shown a positive correlation between NOx concentrations at Lag 3 and children's PICU admissions with severe RV respiratory infection. Air pollutant data should be taken into consideration when we try to understand the severity of RVis.Publication Genomic and serologic characterization of enterovirus A71 brainstem encephalitis(Lippincott Williams & Wilkins (LWW), 2020-05) Leon, Kristoffer E; Schubert, Ryan D; Casas-Alba, Didac; Hawes, Isobel A; Ramachandran, Prashanth S; Ramesh, Akshaya; Pak, John E; Wu, Wesley; Cheung, Carly K; Crawford, Emily D; Khan, Lillian M; Launes, Cristian; Sample, Hannah A; Zorn, Kelsey C; Cabrerizo, Maria; Valero-Rello, Ana; Langelier, Charles; Muñoz-Almagro, Carmen; DeRisi, Joseph L; Wilson, Michael R; Instituto de Salud Carlos III; European Regional Development FundOBJECTIVE: In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization. METHODS: RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. RESULTS: mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject. CONCLUSION: mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.Publication Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis(Springer, 2024-03-04) Launes, Cristian; Camacho, Juan; Pons-Espinal, Marina; López-Labrador, F Xavier; Esteva, Cristina; Cabrerizo, Maria; Fernandez-Garcia, Maria Dolores; Fogeda, Marta; Masa-Calles, Josefa; Lopez-Perea, Noemi; Echevarria, Juan Emilio; Muñoz-Almagro, Carmen; Tarrago Asensio, David; Conferencia de Rectores de las Universidades Españolas; Consejo Superior de Investigaciones Científicas (España); Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)Purpose: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). Methods: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. Results: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. Conclusion: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.Publication Impact of the bacterial nasopharyngeal microbiota on the severity of genus enterovirus lower respiratory tract infection in children: A case-control study(Wiley, 2023-06) Penela-Sánchez, Daniel; Rocafort, Muntsa; Henares, Desiree; Jordan, Iolanda; Brotons, Pedro; Cabrerizo, Maria; Launes, Cristian; Muñoz-Almagro, Carmen; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Introduction: Rhinoviruses (RV) and enteroviruses (EV) are among the main causative etiologies of lower respiratory tract infection (LRTI) in children. The clinical spectrum of RV/EV infection is wide, which could be explained by diverse environmental, pathogen-, and host-related factors. Little is known about the nasopharyngeal microbiota as a risk factor or disease modifier for RV/EV infection in pediatric patients. This study describes distinct nasopharyngeal microbiota profiles according to RV/EV LRTI status in children. Methods: Cross-sectional case-control study, conducted at Hospital Sant de Déu (Barcelona, Spain) from 2017 to 2020. Three groups of children <5 years were included: healthy controls without viral detection (Group A), mild or asymptomatic controls with RV/EV infection (Group B), and cases with severe RV/EV infection admitted to the pediatric intensive care unit (PICU) (Group C). Nasopharyngeal samples were collected from participants for viral DNA/RNA detection by multiplex-polymerase chain reaction and bacterial microbiota characterization by 16S rRNA gene sequencing. Results: A total of 104 subjects were recruited (A = 17, B = 34, C = 53). Children's nasopharyngeal microbiota composition varied according to their RV/EV infection status. Richness and diversity were decreased among children with severe infection. Nasopharyngeal microbiota profiles enriched in genus Dolosigranulum were related to respiratory health, while genus Haemophilus was specifically predominant in children with severe RV/EV LRTI. Children with mild or asymptomatic RV/EV infection showed an intermediate profile. Conclusions: These results suggest a close relationship between the nasopharyngeal microbiota and different clinical presentations of RV/EV infection.Publication Lower Respiratory Tract Infection and Genus Enterovirus in Children Requiring Intensive Care: Clinical Manifestations and Impact of Viral Co-Infections(Multidisciplinary Digital Publishing Institute (MDPI), 2021-10-14) Penela-Sánchez, Daniel; Gonzalez-de-Audicana, Jon; Armero, Georgina; Henares, Desiree; Esteva, Cristina; de-Sevilla, Mariona-Fernández; Ricart, Silvia; Jordan, Iolanda; Brotons, Pedro; Cabrerizo, Maria; Muñoz-Almagro, Carmen; Launes, Cristian; Instituto de Salud Carlos III; Sociedad Española de Enfermedades Infecciosas y Microbiología ClínicaInfection by rhinovirus (RV) and enterovirus (EV) in children ranges from asymptomatic infection to severe lower respiratory tract infection (LRTI). This cohort study evaluates the clinical impact of RV/EV species, alone or in codetection with other viruses, in young children with severe LRTI. Seventy-one patients aged less than 5 years and admitted to the Paediatric Intensive Care Unit (PICU) of a reference children's hospital with RV or EV (RV/EV) LRTI were prospectively included from 1/2018 to 3/2020. A commercial PCR assay for multiple respiratory pathogens was performed in respiratory specimens. In 22/71, RV/EV + respiratory syncytial virus (RSV) was found, and 18/71 had RV/EV + multiple viral detections. Patients with single RV/EV detection required invasive mechanical ventilation (IMV) as frequently as those with RSV codetection, whereas none of those with multiple viral codetections required IMV. Species were determined in 60 samples, 58 being RV. No EV-A, EV-C, or EV-D68 were detected. RV-B and EV-B were only found in patients with other respiratory virus codetections. There were not any associations between RV/EV species and severity outcomes. To conclude, RV/EV detection alone was observed in young children with severe disease, while multiple viral codetections may result in reduced clinical severity. Differences in pathogenicity between RV and EV species could not be drawn.Publication Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016(European Centre for Disease Prevention and Control (ECDC), 2019-02) Gonzalez-Sanz, Ruben; Casas-Alba, Didac; Launes, Cristian; Muñoz-Almagro, Carmen; Ruiz-García, Montserrat; Alonso, Mercedes; González-Abad, María José; Megías, Gregoria; Rabella, Nuria; Del Cuerpo, Margarita; Gozalo-Margüello, Mónica; González-Praetorius, Alejandro; Martínez-Sapiña, Ana; Goyanes-Galán, María José; Romero, María Pilar; Calvo, Cristina; Antón, Andrés; Imaz, Manuel; Aranzamendi, Maitane; Hernández-Rodríguez, Águeda; Moreno-Docón, Antonio; Rey-Cao, Sonia; Navascués, Ana; Otero, Almudena; Cabrerizo, MariaIntroductionEnterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions.AimOur objective was to investigate the epidemiology and clinical characteristics of the outbreak.MethodsWe carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3'-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries.ResultsMost EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported.ConclusionAn emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases.Publication Surveillance for Enteroviruses Associated with Hand, Foot, and Mouth Disease, and Other Mucocutaneous Symptoms in Spain, 2006-2020.(Multidisciplinary Digital Publishing Institute (MDPI), 2021-04-28) Martínez-López, Nieves; Muñoz-Almagro, Carmen; Launes, Cristian; Navascués, Ana; Imaz-Pérez, Manuel; Reina, Jordi; Romero, María Pilar; Calvo, Cristina; Ruiz-García, Montserrat; Megias, Gregoria; Valencia-Ramos, Juan; Otero, Almudena; Cabrerizo, MariaHand, foot, and mouth disease (HFMD) is a mild illness caused by enteroviruses (EV), although in some Asian countries, large outbreaks have been reported in the last 25 years, with a considerable incidence of neurological complications. This study describes epidemiological and clinical characteristics of EV infections involved in HFMD and other mucocutaneous symptoms from 2006 to 2020 in Spain. EV-positive samples from 368 patients were included. EV species A were identified in 85.1% of those typed EV. Coxsackievirus (CV) A6 was the prevalent serotype (60.9%), followed by EV-A71 (9.9%) and CVA16 (7.7%). Infections affected children (1-6 years old) mainly, and show seasonality with peaks in spring-summer and autumn. Clinical data indicated few cases of atypical HFMD as well as those with neurological complications (associated with the 2016 EV-A71 outbreak). Phylogenetic analysis of CVA6 VP1 sequences showed different sub-clusters circulating from 2010 to present. In conclusion, HFMD or exanthemas case reporting has increased in Spain in recent years, probably associated with an increase in circulation of CVA6, although they did not seem to show greater severity. However, EV surveillance in mucocutaneous manifestations should be improved to identify the emergence of new types or variants causing outbreaks and more severe pathologies.