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1.
J Infect Dis ; 229(1): 95-107, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-37477875

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Humanos , Lactente , Anticorpos Neutralizantes , Anticorpos Antivirais , Vetores Genéticos , Imunogenicidade da Vacina , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/genética
2.
Eur J Pediatr ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913227

RESUMO

Infective endocarditis (IE) is a rare disease in children and is associated with significant morbidity and mortality. In recent years, significant changes have occurred in pediatric care that could have influenced the microbiology and presentation of IE. The aim of this work was to study epidemiological, microbiological, and clinical features of IE treated at a Pediatric Cardiac Surgery Reference Center located in Madrid (Spain) in a 10-years' period. A descriptive observational retrospective study was performed, including pediatric patients < 16 years old with definite or possible IE admitted to a reference center between January 2012 and December 2021. Thirty-two IE episodes were identified. Twenty-eight (87.5%) had congenital heart disease (CHD), 8 (25.0%) were preterm infants, 1 (3.1%) was immunocompromised and 6 (18.8%) had other chronic conditions; in 11 (34.4%) episodes more than one underlying condition was associated. In 20 (62.5%) episodes there was an indwelling central venous catheter (CVC); children with other comorbidities (preterm, immunocompromised, other chronic conditions) were more likely to have a CVC at diagnosis compared with patients with isolated CHD (p < 0.001). Thirty-six microbiological isolates were obtained in the 32 episodes; 4 (12.5%) episodes had 2 isolated microorganisms. Microbiological isolates were 20 (55.6%) Gram-positive bacteria (GPB), 10 (27.8%) non-HACEK Gram-negative bacteria (GNB), 1 (2.8%) HACEK-group bacterium, 4 (11.1%) fungi and 1 (2.8%) Coxiella burnetii. In 10 (31.3%) episodes, patients were colonized by multidrug-resistant bacteria (MDRB) and the etiology of IE in 3 (30.0%) of those episodes was the colonizing MDRB. MDRB colonization was associated with MDRB IE (p = 0.007). The most common complication was septic embolism: 11 (34.4%) episodes (9 pulmonary and 2 cerebral). In-hospital mortality was 6.3% (n = 2), all of them due to underlying conditions and not to IE or its complications. Clinical features and complications of IE episodes caused by non-HACEK GNB and those caused by GPB were compared, finding no statistically significant differences.    Conclusion: Risk factors for developing IE, the proportion of embolic complications, and mortality rate were consistent with previously published findings. Proportion of IE cases attributed to non-HACEK GNB was higher than previously reported, suggesting an evolving epidemiology of IE. One-third of children colonized with MDRB subsequently developed IE caused by the same MDRB strains, so empirical coverage of MDRB organisms must be considered when IE is suspected in MDRB colonized patients. No significant differences in clinical features and complications were observed when comparing IE episodes caused by non-HACEK GNB and those caused by GPB, however larger cohort studies are needed. What is Known: • Infective endocarditis (IE) is a rare disease in children, associated with significant morbidity and mortality. • The main risk factor for developing IE in children is an underlying congenital heart disease. What is New: • With current changing epidemiology in pediatric IE, a higher proportion of IE caused by non-HACEK Gram-negative bacteria should be expected. • A significant percentage of children colonized by multidrug-resistant bacteria can develop an IE due to those bacteria.

3.
J Infect Dis ; 227(11): 1293-1302, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-36484484

RESUMO

BACKGROUND: Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing 3 proteins (fusion, nucleoprotein, and M2-1), administered to 12-23-month-old RSV-seropositive children followed up for 2 years after vaccination. METHODS: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (at a 1:1 ratio) (days 1 and 31). Doses escalated from 0.5 × 1010 (low dose [LD]) to 1.5 × 1010 (medium dose [MD]) to 5 × 1010 (high dose [HD]) viral particles after safety assessment. Study end points included anti-RSV-A neutralizing antibody (Nab) titers through year 1 and safety through year 2. RESULTS: Eighty-two participants were vaccinated, including 11, 14, and 18 in the RSV-LD, RSV-MD, and RSV-HD groups, respectively, and 39 in the placebo groups. Solicited adverse events were similar across groups, except for fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups after dose 1, without further increase after dose 2. RSV-A Nab titers remained higher than prevaccination levels at year 1. CONCLUSIONS: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed after dose 1, with no observed booster effect after dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. CLINICAL TRIALS REGISTRATION: NCT02927873.


Respiratory syncytial virus (RSV) is among the main causes of bronchiolitis and pneumonia regularly leading to hospitalization in children. A safe and effective vaccine to prevent RSV infection in this age group has not yet been found, despite great efforts over several decades. This study tested a new candidate RSV vaccine, expressing 3 important pieces of the virus, in toddlers who already had a previous RSV infection. The vaccine was generally well tolerated. Vaccination triggered antibodies against RSV that were able to block the virus in laboratory tests and that persisted for 1 year.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Humanos , Lactente , Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus Sincicial Respiratório Humano/genética
4.
Eur J Pediatr ; 182(1): 461-466, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36282324

RESUMO

Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11-2.45, p = 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12-8.25, p = 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43-13.5, p = 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05-9.82, p < 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG.    Conclusions: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment. What is Known: • Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low. What is New: • Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes. • In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.


Assuntos
Imunoglobulinas Intravenosas , Alta do Paciente , Humanos , Criança , Imunoglobulinas Intravenosas/efeitos adversos , Estudos Retrospectivos , Febre/tratamento farmacológico , Febre/etiologia , Esteroides/uso terapêutico
5.
Eur J Pediatr ; 182(10): 4647-4654, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37561198

RESUMO

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.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Recém-Nascido , Gravidez , Feminino , Humanos , Lactente , SARS-CoV-2 , COVID-19/diagnóstico , Estudos Prospectivos , Espanha/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle
6.
J Antimicrob Chemother ; 77(10): 2784-2792, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-35971971

RESUMO

BACKGROUND: Although integrase inhibitor (INI)-based regimens are now the first-line choice for all people living with HIV, experience among children and adolescents is still scarce. We describe the characteristics and outcomes of a paediatric/adolescent cohort on INI-based ART. METHODS: Retrospective analysis of HIV-infected patients below 18 years of age who started an INI-based regimen from 2007 to 2019, enrolled in the Spanish National Adult (CoRIS) and Paediatric (CoRISpe) cohorts. Resistance mutations were identified by the Stanford HIV Drug Resistance Database. RESULTS: Overall, 318 INI-based regimens were implemented in 288 patients [53.8% female; median age at start of 14.3 years (IQR 12.0-16.3)]. Most were born in Spain (69.1%), vertically infected (87.7%) and treatment-experienced (92.7%). The most frequently prescribed INI was dolutegravir (134; 42.1%), followed by raltegravir (110; 34.6%) and elvitegravir (73; 23.0%). The median exposure was 2.0 years (IQR 1.1-3.0). The main reasons to start an INI-based therapy were treatment simplification (54.4%) and virological failure (34.3%). In total, 103 (32.4%) patients interrupted their regimen: 14.5% for simplification and 8.5% due to virological failure. Most subjects who received dolutegravir (85.8%) and elvitegravir (83.6%) did not interrupt their regimen and maintained undetectable viral load. There were only five virological failures with dolutegravir and three with elvitegravir. There were no interruptions related to adverse events. Seven patients with virological failure presented major resistance mutations to INIs; none of them were on dolutegravir. CONCLUSIONS: INI-based regimens were effective and safe for HIV treatment in children and adolescents. Dolutegravir and elvitegravir presented an excellent profile, and most patients achieved and maintained viral suppression.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , HIV-1 , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Criança , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis , Humanos , Masculino , Oxazinas/farmacologia , Piridonas/farmacologia , Raltegravir Potássico/uso terapêutico , Estudos Retrospectivos
7.
HIV Med ; 23(11): 1195-1201, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36178091

RESUMO

OBJECTIVE: Late presenters (LP) for HIV care are associated with higher morbidity and mortality rates. Our aim was to describe the characteristics associated with LP among adolescents in Spain. Identification of particular features may help in the design of strategies for improvement. METHODS: Late-presenting adolescents diagnosed at 12-19 years of age and enrolled in the Spanish paediatric and adult HIV/AIDS cohorts (CoRIS-CoRISpe) from 2004 to 2019 were selected. LP were defined as those presenting with CD4 count <350 cells/mm3 or an AIDS-defining event in the 6 months following HIV diagnosis. Confirmed low CD4 count in the next 3 months and before antiretroviral treatment initiation defined confirmed LP (cLP). RESULTS: Of 410 adolescents newly diagnosed with HIV, 303 (73.9%) had available data for assessing late presentation. Of these, 34.7% were LP and 23.7% were cLP. The median CD4 count for cLP was 235 cells/mm3 (interquartile range 122-285). In a multivariable analysis, adolescents at the highest risk of late presentation were early adolescents (age 12-14 years; odds ratio [OR] 6.50; 95% confidence interval [CI] 2.61-18.2), middle adolescents (age 15-17 years; OR 1.85; 95% CI 0.92-3.59), and adolescents born abroad (OR 1.71; 95% CI 0.97-3.00), particularly those of African origin (OR 3.08; 95% CI 1.38-6.79). CONCLUSIONS: One-quarter of adolescents presented late for HIV care in Spain. Early adolescents, middle adolescents, and those born abroad presented a sevenfold, twofold, and twofold higher risk of being cLP, respectively. Enhancing the awareness of HIV risk and the access to care, especially for younger and foreign adolescents, could help reduce late presentation and tackle the adolescent HIV epidemic.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Adulto , Adolescente , Humanos , Criança , Espanha/epidemiologia , Diagnóstico Tardio , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Contagem de Linfócito CD4 , Antirretrovirais/uso terapêutico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fatores de Risco
8.
J Pediatr ; 241: 126-132.e3, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34571020

RESUMO

OBJECTIVES: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. STUDY DESIGN: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase. RESULTS: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever. CONCLUSIONS: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , COVID-19/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Soroconversão , Adolescente , COVID-19/epidemiologia , Teste Sorológico para COVID-19 , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Sistema de Registros , Estudos Soroepidemiológicos , Espanha/epidemiologia , Fatores de Tempo
9.
Eur J Pediatr ; 181(3): 1105-1115, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34738173

RESUMO

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


Assuntos
COVID-19 , Adolescente , COVID-19/complicações , COVID-19/epidemiologia , Humanos , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica
10.
Clin Infect Dis ; 72(9): e397-e401, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32710613

RESUMO

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Criança , Humanos , Espanha/epidemiologia , Síndrome , Síndrome de Resposta Inflamatória Sistêmica
11.
Eur J Pediatr ; 180(4): 1279-1286, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33205252

RESUMO

Nontuberculous mycobacterial lymphadenitis often presents a diagnostic challenge. This study aimed to evaluate the role of fine-needle aspiration cytology in the diagnosis of nontuberculous mycobacterial lymphadenitis in children. We conducted a retrospective review of fine-needle aspiration cytology performed in patients < 17 year-old with subacute lymphadenitis from 2003 to 2016 in a tertiary hospital in Spain. Confirmed nontuberculous mycobacterial lymphadenitis (isolation of nontuberculous mycobacterial in culture from fine-needle aspiration cytology or biopsy samples) and probable nontuberculous mycobacterial lymphadenitis ("granulomatous inflammation" in cytopathologic examinations from fine-needle aspiration cytology or biopsy and clinical-epidemiological history compatible with nontuberculous mycobacterial) were selected. Forty-one patients with nontuberculous mycobacterial lymphadenitis were included: 14 confirmed and 27 probable. Fine-needle aspiration cytology was done in all of them. For 34 patients with excised lymphadenopathy, cytopathology from fine-needle aspiration cytology was concordant with biopsy in 100% cases. Culture results were available from 78.0% (32/41) of patients with fine-needle aspiration cytology and from 85.3% (29/34) with excisional biopsy. Among 22 patients with microbiological results from fine-needle aspiration cytology and biopsy, fine-needle aspiration cytology allowed advanced results in concordance with biopsy or with positive isolation not found in biopsy in 90.1% (20/22) of patients. Sensitivity of nontuberculous mycobacterial cultures obtained by fine-needle aspiration cytology compared to biopsy was 45.5% vs. 36.4% (p = 0.07). Two patients with previous skin alterations presented fistulas after fine-needle aspiration cytology (4.9%); no other complications were described.Conclusion: Fine-needle aspiration cytology provides quick cytopathologic information and is an accurate and safe technique for the diagnosis of nontuberculous mycobacterial lymphadenitis, especially in cases with challenging work-up. What is Known: • Nontuberculous mycobacterial (NTM) infection is an important cause of subacute lymphadenitis in children. • Fine-needle aspiration cytology (FNAC) is an available technique for the diagnosis of lymphadenitis of unknown etiology. What is New: • FNAC is an accurate and safe technique for the diagnosis of NTM lymphadenitis in children. • FNAC can provide reliable samples for cytopathological studies and even a better sensitivity for microbiological culture than excisional biopsy in the study of suspected NTM lymphadenitis.


Assuntos
Linfadenite , Infecções por Mycobacterium não Tuberculosas , Adolescente , Biópsia por Agulha Fina , Criança , Humanos , Linfadenite/diagnóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Estudos Retrospectivos , Espanha
12.
Eur J Pediatr ; 180(7): 2099-2106, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33606120

RESUMO

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


Assuntos
COVID-19 , SARS-CoV-2 , Criança , Estudos Transversais , Febre/epidemiologia , Febre/etiologia , Humanos , Lactente , RNA Viral
13.
Clin Infect Dis ; 71(10): e594-e603, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-32201897

RESUMO

BACKGROUND: This phase 1b study evaluated the pharmacokinetics, safety, and antiviral effects of the respiratory syncytial virus (RSV)-specific fusion inhibitor JNJ-53718678 (JNJ-8678) in hospitalized RSV-infected patients aged > 1 to ≤24 months. METHODS: Patients categorized by age (cohort 1: ≥6 to ≤24 months; cohort 2: ≥3 to < 6 months; cohort 3: > 1 to < 3 months) were randomized to oral JNJ-8678 or placebo once daily for 7 days. Dose increases followed data review committee recommendations (cohort 1: 2/6/8/9 mg/kg; cohort 2: 1.5/4.5/6 mg/kg; cohort 3: 1/3/5 mg/kg). Cohort 1 included a 9 mg/kg dose, as target exposures were not reached at lower doses. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modeling. Safety was assessed by adverse events (AEs), laboratory tests, and electrocardiograms. To assess antiviral effects, RSV RNA viral load from nasal swabs was quantified over time using reverse-transcription quantitative polymerase chain reaction. RESULTS: Patients received JNJ-8678 (n = 37) or placebo (n = 7). Pharmacokinetic parameters were similar at the highest doses for cohorts 1-3 (area under the plasma concentration-time curve from time of administration up to 24 hours postdosing at day 7: 35 840, 34 980, and 39 627 ng × hour/mL, respectively). Two grade 3 AEs were reported (both bronchiolitis; 1 JNJ-8678, 1 placebo), reported as serious AEs; all other AEs were grade 1 or 2. Two additional serious AEs were reported (rhinitis [JNJ-8678]; pneumonia [placebo]). No deaths, grade 4 AEs, or AEs leading to discontinuation were reported. Median RSV viral load change from baseline in JNJ-8678 vs placebo by day 3 was -1.98 vs -0.32 log10 copies/mL. CONCLUSIONS: In RSV-infected infants, JNJ-8678 was well tolerated. Target exposures were reached and antiviral activity was observed. CLINICAL TRIALS REGISTRATION: NCT02593851.


Assuntos
Imidazolidinas , Infecções por Vírus Respiratório Sincicial , Idoso , Antivirais/uso terapêutico , Método Duplo-Cego , Humanos , Imidazolidinas/uso terapêutico , Indóis/uso terapêutico , Lactente , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico
15.
Pediatr Infect Dis J ; 43(1): 40-48, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37922511

RESUMO

BACKGROUND: Virologic characterization of newly HIV-diagnosed adolescents could help to improve their specific needs. The objective was to describe the transmitted drug resistance mutations (TDR) and its transmission by clusters in this population in Spain. METHODS: TDR to retrotranscriptase and protease inhibitors included in the WHO TDR list 2009 implemented in the Calibrated Population Resistance tool v8.0 (Stanford) were studied in HIV pol sequences from all HIV-diagnosed adolescents (12-19-year-old) enrolled during 2004-2019 period in the Spanish pediatric and adult (CoRISpe-CoRIS) cohorts. The found TDR were compared with the provided by the Stanford algorithm v9.0 2021. HIV-1 variants and transmission clusters were also studied. RESULTS: Among 410 HIV-1 adolescents diagnosed, 141 (34.4%) had available ART-naive sequences. They were mostly male (81.6%), Spanish (55.3%) and with behavioral risk (92.2%), mainly male-to-male sexual contact (63.1%). TDR prevalence was significantly higher by Stanford versus WHO list (18.4% vs. 7.1%; P = 0.004). The most prevalent TDR by the WHO list was K103N (3.6%) and by Stanford E138A (6.6%), both at retrotranscriptase. E138A, related to rilpivirine/etravirine resistance, was absent in the WHO list. One in 4 adolescents carried HIV-1 non-B variants. We described 5 transmission clusters, and 2 carried TDR mutations. CONCLUSIONS: Our data suggest a high TDR prevalence in adolescents with a new HIV diagnosis in Spain, similar to adults, 2 active TDR transmission clusters, and the need for the WHO TDR list update. These findings could have implications for the options of the recently available rilpivirine-related long-acting treatment and in first-line regimen election.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Adulto , Humanos , Masculino , Adolescente , Criança , Adulto Jovem , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha/epidemiologia , Farmacorresistência Viral/genética , Mutação , HIV-1/genética , Rilpivirina/uso terapêutico , Prevalência , Genótipo , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico
16.
Contemp Clin Trials ; 142: 107540, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38636725

RESUMO

BACKGROUND: There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing. METHODS: D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom. D3 has enrolled 386 children aged 2- < 15 years, virologically suppressed for ≥6 months, with no prior treatment failure. Participants were randomised 1:1 to receive DTG/3TC or DTG plus two nucleoside reverse transcriptase inhibitors(NRTIs), stratified by region, age (2- < 6, 6- < 12, 12- < 15 years) and DTG use at enrolment (participants permitted to start DTG at enrolment). The primary outcome is confirmed HIV-1 RNA viral rebound ≥50 copies/mL by 96-weeks. The trial employs the Smooth Away From Expected(SAFE) non-inferiority frontier, which specifies the non-inferiority margin and significance level based on the observed event risk in the control arm. The nested PK substudy evaluates WHO weight-band-aligned dosing in the DTG/3TC arm. DISCUSSION: D3 is the first comparative trial evaluating DTG/3TC in children and adolescents. Implications of integrating a PK substudy and supplying data for prompt regulatory submission, were carefully considered to ensure the integrity of the ongoing trial. The trial uses an innovative non-inferiority frontier for the primary analysis to allow for a lower-than-expected confirmed viral rebound risk in the control arm, while ensuring interpretability of results and maintaining the planned sample size in an already funded trial. TRIAL REGISTRATION: International Standard Randomised Clinical Trial Number Register: ISRCTN17157458. European Clinical Trials Database: 2020-001426-57. CLINICALTRIALS: gov: NCT04337450.


Assuntos
Infecções por HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piperazinas , Piridonas , Humanos , Adolescente , Infecções por HIV/tratamento farmacológico , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Piridonas/farmacocinética , Criança , Oxazinas/administração & dosagem , Oxazinas/uso terapêutico , Pré-Escolar , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piperazinas/administração & dosagem , Masculino , Feminino , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacocinética , Carga Viral , Estudos de Equivalência como Asunto , RNA Viral , Quimioterapia Combinada , Combinação de Medicamentos , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/farmacocinética
17.
An Pediatr (Engl Ed) ; 99(5): 312-320, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37891136

RESUMO

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.


Assuntos
Anti-Infecciosos , Gestão de Antimicrobianos , Humanos , Criança , Estudos Retrospectivos , Centros de Atenção Terciária , Antifúngicos , Espanha , Estudos Prospectivos , Estudos Longitudinais , Antibacterianos/uso terapêutico
18.
Microorganisms ; 12(1)2023 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-38257857

RESUMO

BACKGROUND: Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix®) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response. METHODS: A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination. RESULTS: There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration. CONCLUSIONS: CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination.

19.
Pediatrics ; 152(4)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37767606

RESUMO

BACKGROUND: Children with sickle cell disease (SCD) are at a high risk of invasive bacterial infections (IBI). Universal penicillin prophylaxis and vaccination, especially against Streptococcus pneumoniae, have deeply changed its epidemiology. Analysis of IBI in children with SCD in a post-13-valent pneumococcal vaccine era is limited. METHODS: Twenty-eight pediatric hospitals from 5 European countries retrospectively collected IBI episodes in SCD children aged 1 month to 18 years between 2014 and 2019. IBI was defined as a positive bacterial culture or polymerase chain reaction from a normally sterile fluid: blood, cerebrospinal, joint, or pleural fluid and deep surgical specimen. RESULTS: We recorded 169 IBI episodes. Salmonella spp. was the main isolated bacteria (n = 44, 26%), followed by Streptococcus pneumonia (Sp; n = 31, 18%) and Staphylococcus aureus (n = 20, 12%). Salmonella prevailed in osteoarticular infections and in primary bacteremia (45% and 23% of episodes, respectively) and Sp in meningitis and acute chest syndrome (88% and 50%, respectively). All Sp IBI occurred in children ≤10 years old, including 35% in children 5 to 10 years old. Twenty-seven (17%) children had complications of infection and 3 died: 2 because of Sp, and 1 because of Salmonella. The main risk factors for a severe IBI were a previous IBI and pneumococcal infection (17 Sp/51 cases). CONCLUSIONS: In a post-13-valent pneumococcal vaccine era, Salmonella was the leading cause of bacteremia in IBI in children with SCD in Europe. Sp came second, was isolated in children ≤10 years old, and was more likely to cause severe and fatal cases.

20.
J Pediatric Infect Dis Soc ; 12(6): 322-331, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37255317

RESUMO

BACKGROUND: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. METHODS: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). RESULTS: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. CONCLUSIONS: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.


Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , COVID-19/diagnóstico , COVID-19/genética , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/genética , Hospitais , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/genética , Teste para COVID-19
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