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.

Comparison of nasopharyngeal samples for SARS-CoV-2 detection in a paediatric cohort.

AIM: The diagnosis of coronavirus disease 2019 (COVID-19) depends on accurate and rapid testing. Choosing an appropriate sample may impact diagnosis. Naso-oropharyngeal swabs (NOS) are most frequently used, despite several limitations. Since studies suggest nasopharyngeal aspirate (NPA) as a superior alternative in children, we hypothesised collecting both nasopharyngeal swab and aspirate would improve our diagnostic accuracy. METHODS: Observational, longitudinal, prospective study from 7 March to 7 May in a tertiary paediatric hospital in Lisbon. The objective was to compare the rate of detection of SARS-CoV-2 between NOS and NPA samples collected simultaneously. RESULTS: A total of 438 samples collected from 85 patients with confirmed COVID-19. There were 47.7% overall positive specimens - 32% (70/219) positive NOS and 63.5% (139/219) positive NPA. The tests were 67.6% concordant (k = 0.45). 50.3% had positive NPA with negative NOS, while 1.3% had positive NOS with negative NPA. NPA proved to be more sensitive (98.6% with 95% confidence interval 91.2-99.9% vs. 49.6% with 95% confidence interval 41.1-58.2%, P < 0.001). Additionally, the difference between NPA and NOS positive samples was statistically significant across all population groups (age, health condition, clinical presentation, contact with COVID-19 patients or need for hospitalisation), meaning NPA is more sensitive overall. CONCLUSIONS: Nasopharyngeal aspirates had greater sensitivity than naso-oropharyngeal swabs in detecting SARS-CoV-2. Our results suggest paediatric patients would benefit from collecting nasopharyngeal aspirates in hospital settings, whenever feasible, to improve diagnosis of COVID-19.

Pediatric Complicated Pneumonia Caused by Streptococcus pneumoniae Serotype 3 in 13-Valent Pneumococcal Conjugate Vaccinees, Portugal, 2010-2015.

Despite use of 7-valent pneumococcal conjugate vaccine, incidence of pleural effusion and empyema (pediatric complicated pneumococcal pneumonia [PCPP]) is reportedly increasing globally. We cultured and performed PCR on 152 pleural fluid samples recovered from pediatric patients in Portugal during 2010-2015 to identify and serotype Streptococcus pneumoniae. We identified only 17 cases by culture, but molecular methods identified S. pneumoniae in 68% (92/135) of culture-negative samples. The most frequent serotypes were 3, 1, and 19A, together accounting for 62% (68/109) of cases. Nineteen cases attributable to 13-valent pneumococcal conjugate vaccine (PCV13) serotypes (mostly serotype 3) were detected among 22 children age-appropriately vaccinated with PCV13. The dominance of the additional serotypes included in PCV13 among PCPP cases in Portugal continues, even with PCV13 available on the private market (without reimbursement) since 2010 and with average annual coverage of 61% among age-eligible children. Our data suggest reduced effectiveness of PCV13 against serotype 3 PCPP.

Multiresistant Kawasaki Disease in a Young Infant with Giant Aneurysms Growing Fast.

BACKGROUND: Kawasaki disease (KD) is a type of vasculitis in which giant coronary artery aneurysms (CAAs) can occur. There are no specific guidelines for managing giant CAAs that develop quickly and are at risk of rupture. Regarding cardiovascular drugs, only beta-blockers are formally recommended in the acute phase of KD. CASE PRESENTATION: A 6-month-old male patient with multiresistant Kawasaki disease and giant CAAs that continued to enlarge after controlling systemic inflammation was examined. The patient required three doses of intravenous immunoglobulin, methylprednisolone pulses, and anakinra and infliximab to normalize systemic inflammation. Due to the rapid increment of aneurysms' dimensions and the risk of rupture, we introduced anticoagulant therapy and propranolol plus captopril, and titration doses were introduced according to a tolerated decrease in heart rate and arterial pressure. CAAs increment stabilized and slowly reduced their dimensions. CONCLUSIONS: The authors describe an atypical case of multiresistant KD with giant rapidly increasing CAAs even after controlling systemic inflammation. The introduction of a beta-blocker and an angiotensin-converting enzyme (ACE) inhibitor was demonstrated to be useful for stabilizing giant CAAs growth and reducing the potential risk of rupture.

Salmonellosis in Children at a Portuguese Hospital: A Retrospective Study.

INTRODUCTION: Salmonellosis represents a considerable health, social and economic burden in both high- and low-income countries. Recently, in Portugal, most cases of Salmonella infections have been reported in children under 15 years of age. The main aim of this study was to characterize, from an epidemiological, microbiological, and clinical perspective, cases of Salmonella isolation among children. MATERIAL AND METHODS: The authors performed a descriptive study using retrospective analysis of cases of salmonellosis, in pediatric age, at a Portuguese Level II Hospital, between January 2015 and July 2020. RESULTS: The population included a total of 63 children, of which 81% were Portuguese. Ethnicity was identified in 13 children, most of whom were African. The median age at diagnosis was four years old (3.5 - 9 years old). Despite the small number of cases per year in our study (11), one-third were severe enough to require hospitalization. Overall, 13% of patients were treated with antibiotics. In 63% of the isolates, serotype was identified: Salmonella Enteriditis (38%), Salmonella Typhimurium (22%), and Salmonella Typhi (3%). Antibiotic resistance rates were 19% for ampicillin and 6.4% for amoxicillinclavulanic acid and cotrimoxazole. No resistance to third-generation cephalosporins was found. CONCLUSION: Given the obtained results, we intend to improve knowledge on salmonellosis in Portugal and, consequently improve prevention strategies, treatment and its notification. Although the incidence of salmonellosis has been decreasing in recent years it is the second most frequent gastrointestinal infection in the European Union, contributing to significant rates of hospitalizations and use of antibiotics in Portugal.

Multisystem Inflammatory Syndrome in Children Associated with COVID-19 in a Tertiary Level Hospital in Portugal.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe manifestation of coronavirus disease 2019 (COVID-19). The aim of this study was to describe the characteristics of children with MIS-C admitted to a pediatric tertiary hospital in Portugal. MATERIAL AND METHODS: Observational descriptive study of MIS-C patients admitted between April 2020 and April 2021. Demographic and clinical characteristics, diagnostic tests, and treatment data were collected. The diagnosis of MIS-C was based on the World Health Organization and Centers for Disease Control and Prevention criteria. RESULTS: We reported 45 children with MIS-C. The median age was seven years (IQR 4 - 10 years) and 60.0% were previously healthy. SARS-CoV-2 infection was confirmed in 77.8% by RT-PCR or antibody testing for SARS-CoV-2, and in 73.3%, an epidemiological link was confirmed. All the patients had a fever and organ system involvement: hematologic (100%), cardiovascular (97.8%), gastrointestinal (97.8%), mucocutaneous (86.7%), respiratory (26.7%), neurologic (15.6%), and renal (13.3%) system. Neurological (p = 0.035) and respiratory (p = 0.035) involvement were observed in patients with a more severe presentation. There was a significant difference of medians when comparing disease severity groups, namely in the values of hemoglobin (p = 0.015), lymphocytes (p = 0.030), D-dimer (p = 0.019), albumin (p < 0.001), NT-proBNP (p = 0.005), ferritin (p = 0.048), CRP (p = 0.006), procalcitonin (p = 0.005) and IL-6 (p = 0.002). From the total number of children, 93.3% received intravenous immunoglobulin, 91.1% methylprednisolone, and one patient (2.2%) received anakinra. Thirteen patients (28.8%) required intensive care and there were no deaths. Of the 21 patients evaluated, 90.4% had reduction of exercise capacity and of the 15 patients who underwent cardiac magnetic resonance, 53.3% had sequelae of cardiac injury. CONCLUSION: We observed a large spectrum of disease presentation in a group of patients where most were previously healthy. A small percentage of patients (28.9%) had a severe presentation of the disease. MIS-C is a challenge in current clinical practice and its diagnosis requires a high level of clinical suspicion as the timely initiation of therapy is essential to prevent complications. However, there is no scientific consensus on the treatment and follow-up of these patients.

Introdução: A síndrome inflamatória multissistémica em crianças (MIS-C) é uma manifestação rara, mas grave da doença por coronavírus 2019 (COVID-19). Este estudo teve como objetivo descrever as características de crianças com MIS-C internadas num hospital pediátrico terciário em Portugal. Material e Métodos: Estudo observacional e descritivo de doentes com MIS-C internados de abril de 2020 a abril de 2021. Analisaram-se dados demográficos, clínicos, exames de diagnóstico e terapêutica. O diagnóstico baseou-se nos critérios da Organização Mundial de Saúde e Centers for Disease Control and Prevention. Resultados: Foram identificadas 45 crianças, com mediana de idades de sete anos (AIQ 4 - 10 anos) sendo 60,0% previamente saudáveis. A infeção por SARS-CoV-2 foi confirmada por RT-PCR ou serologia em 77,8% dos doentes e 73,3% tinham link epidemiológico. Todos os casos cursaram com febre e envolvimento multiorgânico: hematológico (100%), cardiovascular (97,8%), gastrointestinal (97,8%), mucocutâneo (86,7%), respiratório (26,7%), neurológico (15,6%) e renal (13,3%). O envolvimento neurológico (p = 0,035) e respiratório (p = 0,035) ocorreu nos doentes mais graves. Houve uma diferença significativa das medianas quando comparados grupos de gravidade da doença, nomeadamente nos valores de hemoglobina (p = 0,015), linfócitos (p = 0,030), D-dímeros (p = 0,019), albumina (p < 0,001), NT-proBNP (p = 0,005), ferritina (p = 0,048), pCr (p = 0,006), procalcitonina (p = 0,005) e IL-6 (p = 0,002). Destas crianças, 93,3% realizaram imunoglobulina intravenosa, 91% metilprednisolona e um (2,2%) realizou anakinra. Treze doentes (28,8%) necessitaram de cuidados intensivos e não se registaram óbitos. Dos 21 doentes avaliados seis meses após a alta, 90,4% apresentaram diminuição da tolerância ao esforço e 8/15 (53,3%) lesão cardíaca persistente. Conclusão: Observámos um amplo espectro de apresentação da doença num grupo de doentes previamente saudável, na sua maioria. Uma pequena percentagem de pacientes (28,9%) teve uma apresentação grave da doença. O diagnóstico da MIS-C é um desafio na prática clínica atual e requer um elevado nível de suspeição pois o início atempado de terapêutica é fundamental para prevenir complicações. No entanto, não existe ainda consenso científico sobre a melhor terapêutica e seguimento destes doentes.

Ketogenic Diet and Drug-Induced Hepatotoxicity During Tuberculosis Treatment.

When therapy with hepatotoxic drugs is being considered, all other possible contributing agents of liver damage should be held to account. While not generally considered a risk factor, we present 2 cases in which ketogenic diet (KD) may have played a role in liver injury due to antituberculosis drugs. Ketogenic diet has been linked to liver injury, and while its pathophysiology remains obscure, carnitine depletion could play a role, as it is a mechanism of liver damage common to KD and antituberculosis drug regimens.

COVID-19 in a tertiary paediatric centre in Portugal: a single-centre retrospective study.

OBJECTIVE: To describe the demographic, clinical, laboratory and imaging features of the first 300 SARS-CoV-2-infected children presenting to a tertiary paediatric centre in Portugal. DESIGN: Single-centre, retrospective, descriptive study of paediatric patients who had a confirmed SARS-CoV-2 infection from 7 March to 20 September 2020. SETTING: Tertiary paediatric referral centre (Hospital Dona Estefânia, Lisbon, Portugal). PATIENTS: 18 years or younger. MAIN OUTCOME MEASURES: Incidence, mortality, age of infection, clinical characteristics, treatment prescribed and outcome. RESULTS: Three hundred patients with confirmed COVID-19 presented to the centre. One hundred and seventeen (39%) patients were admitted to the hospital: 69 with COVID-19 and 48 for other reasons. The most common symptoms in children admitted with COVID-19 were fever (49) and cough (38). Six patients required intensive care. Two children died and seven reported short-term sequelae. CONCLUSIONS: COVID-19 is usually a mild disease in children, but a small proportion of patients develop severe and critical disease. Fatal outcomes were rare and only occurred in children with severe previous medical conditions.

The Protective Role of Self-Compassion in the Relationship between Perfectionism and Burnout in Portuguese Medicine and Dentistry Students.

Recent studies have documented the high prevalence of burnout among medicine and dentistry students, with potentially catastrophic consequences for both students and patients. Both environmental and personality factors play a part in burnout; perfectionism, a common trait in medicine students' personalities, has been linked to psychological distress and increasing students' vulnerability to burnout. Self-compassion, i.e., treating oneself kindly through hardship, has recently emerged as a buffer between perfectionism and psychological distress. While using a novel three-factor conceptualization of perfectionism (BIG3), this study aims to analyze if self-compassion has a protective role in the relationship between perfectionism and burnout, in a sample of medicine and dentistry students, through mediation analysis. We found that self-compassion significantly mediated the relationship between all three forms of perfectionism and burnout: as a partial mediator in self-critical and rigid perfectionism, as well as a full mediator in narcissistic perfectionism. Our findings underline self-compassion's relevance in burnout prevention and management, supporting its use as an intervention target in burnout reduction programs and strategies.

[Pediatric Tuberculosis: 12 Years of Experience in a Tertiary Referral Center in Portugal]. / Tuberculose em Idade Pediátrica: Experiência de 12 Anos num Centro Terciário de Referência em Portugal.

INTRODUCTION: The diagnosis of tuberculosis in children is a challenge namely because extrapulmonary tuberculosis and severe disease are more frequent in this age group. The aim of this study was to evaluate and reflect about severe tuberculosis in pediatric age, in a metropolitan area of Lisbon. MATERIAL AND METHODS: Descriptive study about patients under 18 years of age admitted with tuberculosis disease in a tertiary pediatric hospital, from 2008 to 2019 (12 years). RESULTS: We report 145 patients, average of 12 cases/year, with an increase in the last three years. Median age of 12.9 years, 42.8% born in Portuguese-speaking African countries and 20% had a chronic disease. The diagnosis was pulmonary tuberculosis in 52.4% (n = 76) and extrapulmonary tuberculosis in 47.6%: lymphatic (n = 26), skeletal (n = 15), miliary (n = 8), meningeal (n = 7), peritoneal/ intestinal (n = 6), pleural (n = 4), renal (n = 1), cutaneous (n = 1), thoracic wall (n = 1) and salivary glands (n = 1). The tuberculin test was positive in 78/99 (78.8%) and Interferon Gamma Release Assay in 61/90 (67.8%). In 20.7% (n = 30) acid-fast bacilli were identified in gastric aspirate/sputum and the agent was identified in 59.3% (n = 86). Tuberculosis was resistant in 11% (n = 16). Patients with extrapulmonary tuberculosis were younger (p = 0.006) and had more prolonged therapy (p < 0.001). Therapy-related complications occurred in 11% (n = 16). One patient died (with terminal cancer). CONCLUSION: This study highlights the need for screening of tuberculosis in children from endemic countries, patients with immunosuppression and chronic disease.

Introdução: Em Pediatria, o diagnóstico de tuberculose constitui um desafio, pois a doença pode frequentemente manifestar-se através de formas graves e extrapulmonares. O objetivo deste estudo foi avaliar e refletir sobre a tuberculose grave com necessidade de internamento, em idade pediátrica, numa área metropolitana de Lisboa.Material e Métodos: Estudo descritivo de doentes com idade inferior a 18 anos, internados com o diagnóstico de tuberculose num hospital pediátrico terciário, de 2008 a 2019 (12 anos).Resultados: Identificados 145 doentes, numa média de 12 casos por ano, e um aumento do número de casos nos últimos três anos. A mediana de idades dos doentes era de 12,9 anos, 42,8% nascidos em países africanos de língua oficial portuguesa e 20% tinham doença crónica. Diagnosticou-se tuberculose pulmonar em 52,4% (n = 76) e tuberculose extrapulmonar em 47,6%: ganglionar (n = 26), óssea (n = 15), miliar (n = 8), meníngea (n = 7), peritoneal/intestinal (n = 6), pleural (n = 4), renal (n = 1), cutânea (n = 1), da parede torácica (n = 1) e glândulas salivares (n = 1). A prova tuberculínica foi positiva em 78/99 (78,8%) e o Interferon Gamma Release Assay em 61/90 (67,8%). Em 20,7% (n = 30) identificaram-se bacilos ácido-álcool resistentes no exame direto do suco gástrico/expetoração e o agente foi identificado em 59,3% (n = 86). A tuberculose resistente ocorreu em 11% (n = 16). Os doentes com tuberculose extrapulmonar eram mais jovens (p = 0,006) e fizeram tratamentos mais prolongados (p < 0,001). Ocorreram complicações da terapêutica em 11% (n = 16). Registou-se um óbito numa doente com neoplasia avançada.Conclusão: Este estudo alerta para a necessidade do rastreio da infeção em crianças de países endémicos, imunossuprimidos e com doença crónica.

Protocol-based cardiotoxicity monitoring in hydroxychloroquine medicated COVID-19 pediatric patients.

INTRODUCTION/OBJECTIVES: By May 2020, SARS-CoV-2 had caused more than 400 000 deaths worldwide. Initially, hydroxychloroquine was a treatment option for COVID-19. More recent studies have questioned its safety and efficacy and, until stronger evidence is available, it was suspended from therapy protocols. We describe our experience treating COVID-19 Portuguese pediatric patients with hydroxychloroquine, having applied a protocol for monitoring cardiac toxicity. METHODS: An observational retrospective study of COVID-19 pediatric patients, admitted from March to April 2020 and treated with hydroxychloroquine. Cardiotoxicity was assessed using ECG recordings and corrected QT-time (QTc). Patients were classified into risk-groups depending on QTc value: normal, slightly elevated or severely elevated (>500 ms). RESULTS: Total of 14 patients, with a median age of 10 years [four months; 17 years], treated with hydroxychloroquine for a median of five days. Hydroxychloroquine was used in monotherapy in six patients (mainly mild disease with comorbidities), and in association with lopinavir/ritonavir (3) and azithromycin (5) in moderate to severe disease. Other QT-prolonging therapies were used in five patients: oseltamivir (3), omeprazole (1), morphine (1) and ketamine (1). At 48 hours of treatment, two patients temporarily suspended hydroxychloroquine due to QTc prolongation (>500 ms). All patients completed the whole treatment. No other side effects or deaths occurred. CONCLUSION: Clinical trials are evolving to define hydroxychloroquine effectivity and safety. Our considerable pediatric population supports the need for cardiotoxicity monitoring during therapy but suggest its use seems to be safe in COVID-19 pediatric patients, even in association with other QT-prolonging therapies.

INTRODUÇÃO/OBJETIVO: A hidroxicloroquina foi inicialmente uma das opções terapêuticas na Covid-19. Descreve-se o tratamento com hidroxicloroquina em doentes Covid-19 pediátricos, tendo aplicado um protocolo de monitoração cardíaca pelo seu potencial arritmogénico. MÉTODOS: Estudo observacional retrospetivo de doentes pediátricos com Covid-19, internados de março a abril 2020, medicados com hidroxicloroquina. A monitoração cardíaca foi realizada por eletrocardiogramas regulares e cálculo do intervalo QT corrigido durante o tratamento. Os doentes foram classificados consoante o valor de QTc: normal, moderadamente aumentado ou muito aumentado (>500 msg). RESULTADOS: Total de 14 doentes, com mediana de 10 anos [4 meses; 17 anos], medicados com HCQ durante uma mediana de 5 dias em doentes com pneumonia ou comorbilidades. A monoterapia foi realizada em 6 doentes, 4 com fatores de risco, e em associação com lopinavir/ritonavir (3) e azitromicina (5) na doença grave e moderada. Foram ainda usados fármacos capazes de prolongar o intervalo QT: oseltamivir (3), omeprazol (1), cetamina e morfina (1) em 5 doentes. Após 48 horas de terapêutica, dois doentes apresentaram intervalo QTc muito aumentado, condicionando suspensão temporária do fármaco. Todos os doentes concluíram o tratamento sem outros efeitos adversos. CONCLUSÃO: A HCQ permanece em ensaios clínicos para avaliação da sua efetividade e segurança. A nossa amostra considerável em doentes pediátricos apoia a necessidade de monitoração de toxicidade cardíaca, mas sugere na população estudada, mesmo na associação com outros fármacos que prolongam o intervalo QT, a segurança de sua utilização.

Bone and joint tuberculosis in paediatrics: a 13-year retrospective study.

Introduction. Bone and joint tuberculosis (BJTB) is rare in developed countries, particularly in the paediatric population.Hypothesis/Gap Statement. The clinical features and sequelae of paediatric BJTB in Europe are not well characterized and should be assessed to achieve a better approach.Aim. To assess the management and outcomes of paediatric BJTB.Methodology. Longitudinal observational study of all paediatric patients (0-17 years old) diagnosed with BJTB between 2008 to 2020 in a tertiary-care hospital.Results. We identified 18 patients with BJTB, with a median age of 10 years (IQR 6-14.8), 66.7 % male. Most (72 %) were diagnosed after 2015 and were foreign-born (88.9 %), mainly from Portuguese-speaking African countries, and none had HIV. The most common symptoms were pain (77.8 %), fever (50 %) and bone deformity (44.4 %). Spinal TB (STB) affected 13 (72.2 %) and extra-spinal TB (ESTB) 9 (50 %) patients, and 4 (27.7 %) had both conditions. Diagnostic positive procedures included positive nucleic acid amplification technique (NAAT) (44.4 %), Mycobacterium tuberculosis isolation (44.4 %) and compatible histology (33.3 %). All completed antituberculous drugs for a median of 12 months (IQR 12-13) and nine (50 %) had surgery. Overall, acute complications occurred in 16 (88.9 %) patients - 11/13 (84.6 %) with STB and 5/5 (100 %) with ESTB - and included abscesses, spinal compression, spine deformity and pathological fractures. Sequelae were still present at the 12-month follow-up in seven cases (46.7 %), and were more common in foreign-born patients sent to Portugal to receive medical treatment (66.7 vs 20 %).Conclusions. Paediatric BJTB is difficult to diagnose and has high morbidity, requiring long-term follow-up. Over the last decade, foreign-born TB seems to be increasing, with still longer treatment courses and more acute complications and sequelae.

Saliva molecular testing bypassing RNA extraction is suitable for monitoring and diagnosing SARS-CoV-2 infection in children.

BACKGROUND: Adults are being vaccinated against SARS-CoV-2 worldwide, but the longitudinal protection of these vaccines is uncertain, given the ongoing appearance of SARS-CoV-2 variants. Children remain largely unvaccinated and are susceptible to infection, with studies reporting that they actively transmit the virus even when asymptomatic, thus affecting the community. METHODS: We investigated if saliva is an effective sample for detecting SARS-CoV-2 RNA and antibodies in children, and associated viral RNA levels to infectivity. For that, we used a saliva-based SARS-CoV-2 RT-qPCR test, preceded or not by RNA extraction, in 85 children aged 10 years and under, admitted to the hospital regardless of COVID-19 symptomatology. Amongst these, 29 (63.0%) presented at least one COVID-19 symptom, 46 (54.1%) were positive for SARS-CoV-2 infection, 28 (32.9%) were under the age of 1, and the mean (SD) age was 3.8 (3.4) years. Saliva samples were collected up to 48 h after a nasopharyngeal swab-RT-qPCR test. RESULTS: In children aged 10 years and under, the sensitivity, specificity, and accuracy of saliva-RT-qPCR tests compared to NP swab-RT-qPCR were, respectively, 84.8% (71.8%-92.4%), 100% (91.0%-100%), and 91.8% (84.0%-96.6%) with RNA extraction, and 81.8% (68.0%-90.5%), 100% (91.0%-100%), and 90.4% (82.1%-95.0%) without RNA extraction. Rescue of infectious particles from saliva was limited to CT values below 26. In addition, we found significant IgM positive responses to SARS-CoV-2 in children positive for SARS-CoV-2 by NP swab and negative by saliva compared to other groups, indicating late infection onset (>7-10 days). CONCLUSIONS: Saliva is a suitable sample type for diagnosing children aged 10 years and under, including infants aged <1 year, even bypassing RNA extraction methods. Importantly, the detected viral RNA levels were significantly above the infectivity threshold in several samples. Further investigation is required to correlate SARS-CoV-2 RNA levels to viral transmission.

Linezolid in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis in paediatric patients: experience of a paediatric infectious diseases unit.

Linezolid has been used in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis in adults with encouraging results, however experience in children is scarce. We describe our experience with the use of linezolid as part of a multidrug regimen in the treatment of 4 patients who had persistent positive cultures, despite prolonged combined therapy.

Clinical and Therapeutic Approach to Hospitalized COVID-19 Patients: A Pediatric Cohort in Portugal.

INTRODUCTION: Coronavirus disease 2019, or COVID-19, in children is usually a mild disease, but severe illness has been reported. Currently, the therapy benefits of antiviral experimental drugs are still uncertain. The main aim of this study is to describe the experience of a level III hospital regarding therapeutic management of hospitalized children with COVID-19 and to characterize clinical features and evolution. MATERIAL AND METHODS: This is a descriptive study of patients with COVID-19 in a level III pediatric hospital in Portugal between March and June 2020. Experimental drugs were administered according to the best scientific evidence at the time as 'off-label use'. RESULTS: Among 200 children with SARS-CoV-2 infection, 37 were admitted due to COVID-19. Median age was one year (23 days - 18 years), 43% had comorbidities and 20/37 (54%) received antiviral therapy. Hydroxychloroquine was administered in 13 patients, in monotherapy or combined with lopinavir/ritonavir or azithromycin. Lopinavir/ritonavir was administered in eight patients and three children were treated with remdesivir. The patients who were treated had pneumonia (14), multisystem inflammatory syndrome in children (2), sepsis (2), myocarditis (1), acute respiratory distress syndrome (1), and mild illness with comorbidities (3). Other therapies included methylprednisolone and immunoglobulin (3), enoxaparin (2), antibiotics (16), oxygen (7), corticosteroids, and other inhaled therapy (16). DISCUSSION: Several treatment approaches have been proposed for severe COVID-19, even though none of them had been proven effective or approved for small children. Currently, remdesivir is approved for children aged above 12 years-old. Although 54% of our patients were treated with antivirals, it is important to understand that the favorable clinical evolution could be related with the natural course of the disease. CONCLUSION: A significant proportion of our population presented severe and critical disease, was hospitalized and received treatment according to the most recent data, although most patients had mild disease. COVID-19 treatment in children is a clinical challenge and clinical trials are urgently needed.

Introdução: A infeção SARS-CoV-2 em idade pediátrica cursa maioritariamente com doença ligeira. No entanto, pode ocorrer doença grave, ainda que com menor frequência. Atualmente, os benefícios das terapêuticas antivirais experimentais ainda são incertos. O objetivo deste estudo consiste em descrever a experiência de um hospital terciário no tratamento de crianças internadas por COVID-19 e caracterizar a clínica e evolução. Material e Métodos: Estudo descritivo em doentes até aos 18 anos de idade, internados com COVID-19 num hospital pediátrico de nível III em Portugal, de março a junho de 2020. Os fármacos antivirais foram administrados em regime de off-label. Resultados: Identificaram-se 200 casos de infeção SARS-CoV-2, dos quais 37 foram internados com COVID-19. A idade mediana foi de um ano (23 dias - 18 anos), 43% apresentavam comorbilidades e 20/37 (54%) receberam terapêutica antiviral. A hidroxicloroquina foi administrada em 13 doentes em monoterapia ou associada a lopinavir/ritonavir ou azitromicina. O lopinavir/ritonavir foi utilizado em oito doentes e três doentes receberam remdesivir. O tratamento antiviral foi aplicado a doentes com pneumonia (14), sépsis (2), síndrome inflamatório multisistémico pediátrico (2), síndrome dificuldade respiratória aguda (1), miocardite (1) e crianças com doença ligeira e comorbilidades (3). Realizaram-se também outras terapêuticas que incluíram metilprednisolona e imunoglobulina (3), enoxaparina (2), antibióticos (16), oxigenoterapia (7) e broncodilatadores e corticoides inalados (16). Discussão: Diversas abordagens terapêuticas têm sido sugeridas para casos graves de COVID-19, embora nenhuma seja até à data considerada eficaz, ou esteja aprovada em crianças pequenas. Atualmente, o remdesivir está aprovado para idades superiores a 12 anos. Apesar de 54% dos nossos doentes terem sido tratados com antivirais, é importante compreender que a evolução favorável poderá ter estado associada à evolução natural da doença. Conclusão: Uma percentagem significativa da população apresentou doença grave a crítica, com necessidade de internamento e tratamento, este último definido com base nas recomendações da comunidade científica à data, embora a maioria apresentasse doença ligeira. O tratamento da COVID-19 em idade pediátrica é um desafio, sendo urgente realizar ensaios clínicos relativos a esta matéria.

Outbreak of acute respiratory infection among infants in Lisbon, Portugal, caused by human adenovirus serotype 3 and a new 7/3 recombinant strain.

Human adenoviruses (AdVs) typically cause mild illnesses in otherwise healthy hosts. We investigated a pediatric outbreak of acute respiratory infection with fatal outcomes that occurred in Lisbon, Portugal, in 2004. Biological specimens were collected from 83 children attending two nurseries, a kinesiotherapy clinic, and the household of a nanny. Adenovirus infection was confirmed in 48 children by PCR and virus isolation. Most (96%) isolates were classified as being of subspecies B1. Phylogenetic analysis of fiber and hexon gene sequences revealed that most infants were infected with AdV serotype 3 (AdV3) strains. Infants attending one nursery harbored a new recombinant strain containing an AdV serotype 7 hexon and serotype 3 fiber (AdV7/3). Both the AdV3 and the AdV7/3 strains caused fatal infections. Two different serotype 3 strains were circulating in Lisbon in 2004, and the new AdV7/3 recombinant type originated from only one of those strains. These results demonstrate that recombination leads to the emergence of new adenovirus strains with epidemic and lethal potential.

Recurrent maternal CMV infection associated with symptomatic congenital infection: results from a questionnaire study in Portugal.

OBJECTIVE: Human cytomegalovirus (CMV) is the most widespread agent of congenital infection in humans and is still a challenging issue. Despite lower rates of vertical transmission being associated with recurrent infection when compared with primary infection, the first still represents the majority of congenital infections worldwide. Based on data from active reporting, we explored the influence of maternal primary/non-primary infection both on the presentation and outcome of congenital CMV infection in early childhood. DESIGN: Infants with positive viruria during the first 3 weeks of life were reported through the Portuguese Paediatric Surveillance Unit. PATIENTS: Infants born between 2006 and 2011 with confirmed congenital CMV infection. METHODS: Maternal infection was considered primary if CMV IgG seroconversion occurred during pregnancy or low avidity IgG was documented; it was considered non-primary if positive IgG was documented before pregnancy or high avidity CMV IgG was present early in pregnancy. Follow-up questionnaires were sent up to 6 years of age. RESULTS: Forty confirmed cases of congenital CMV infection were reported (6.6:105 live births, 95% CI 4.81 to 8.92); 22 out of 40 were asymptomatic. The odds for non-primary maternal infection if the offspring was symptomatic at birth were 6.2 (95% CI 1.2 to 32.27). CONCLUSION: The reported number of confirmed cases of congenital CMV infection was much lower than expected. Under-reporting and missed diagnosis were considered possible reasons. Non-primary maternal infections were associated with symptomatic congenital CMV infection in the offspring. Maternal recurrent infections can have a significant impact on the total number of symptomatic infections in Portugal.