Diagnóstico da infeção por Pseudomonas aeruginosa através da serologia na população pediátrica do Centro de Fibrose Quística do Hospital de Santa Maria

Tese de mestrado, Doenças Infecciosas Emergentes, Faculdade de Medicina, Universidade de Lisboa, 2015A Fibrose Quística (FQ) é a doença genética hereditária mais frequente em caucasianos. A infeção pulmonar por Pseudomonas aeruginosa é a principal causa de morbilidade e mortalidade, podendo ser difícil diagnosticar a infeção precoce em crianças. Dado que a determinação de anticorpos (Ac) apresenta elevada capacidade preditiva na deteção desta infeção, pretendeu-se neste trabalho realizar uma avaliação do método serológico em doentes do grupo pediátrico do Centro de FQ do Hospital de Santa Maria. Realizou-se um estudo retrospetivo transversal entre 2010-2011. Procedeu-se à determinação de Ac anti-P. aeruginosa utilizando um teste serológico de imunoglobulina G que inclui três proteínas de P. aeruginosa (protease alcalina, elastase, exotoxina A), considerando a cultura como referência. Analisaram-se os dados microbiológicos e clínicos dos 12 meses prévios à entrada no estudo. Foram incluídos 37 doentes (género feminino 59,5%; idade mediana 10,8 anos). A determinação de Ac anti-P. aeruginosa foi positiva em 10 doentes e negativa em 27. Todos os doentes com infeção crónica apresentaram determinação de Ac positiva, que foi negativa em todos os doentes livres de infeção. Dos 15 doentes com infeção intermitente, dois apresentaram determinação positiva. Na deteção da infeção global por P. aeruginosa, o método serológico revelou especificidade e valor preditivo do positivo de 100%, sensibilidade de 43,5% e valor preditivo do negativo de 51,9% (exatidão: 64,8%). Na deteção da infeção crónica, a especificidade, a sensibilidade, o valor preditivo do positivo e do negativo foram todos de 100% (exatidão: 100%). Os doentes com determinação positiva de Ac apresentaram z-score de índice de massa corporal significativamente inferior e pior função respiratória. Este é o primeiro trabalho realizado em Portugal, de que temos conhecimento, que avalia a determinação de Ac na infeção por P. aeruginosa. O método serológico pode ser considerado como um teste adjuvante ao exame cultural, para avaliar a infeção por P. aeruginosa num grupo de crianças e jovens com FQ.Cystic Fibrosis (CF) is the most frequent hereditary genetic disease in caucasians. Pulmonary infection by Pseudomonas aeruginosa is the main cause of morbidity and mortality, but early infection in children may be difficult to diagnose. Antibody measurements present high predictive capacity to diagnose this infection. The aim of this study was to evaluate serology in patients followed in the pediatric group of the specialized CF centre of Hospital de Santa Maria. A cross sectional retrospective analysis was performed between years 2010-2011. Antibodies against three P. aeruginosa antigens were measured (alkaline protease, elastase, exotoxin A) using an immunoglobulin G commercial serologic test. Culture was considered as reference standard. Microbiologic and clinical parameters were analyzed in the 12 months previous to serology. This study included 37 patients (59,5% girls; median age of 10,8 years). Antibody measurements against P. aeruginosa were positive in 10 patients and negative in 27. All the patients with P. aeruginosa chronic infection showed positive serology, and it was negative in all the patients free of infection. Serology was positive in two of the 15 patients with intermittent infection. Serology had 100% specificity, 43,5% sensitivity, 100% positive predictive value, 51,9% negative predictive value (accuracy: 64,8%) for global P. aeruginosa infection. For the detection of chronic infection, serology revealed 100% of specificity, sensitivity, positive predictive value, and negative predictive value (accuracy: 100%). Patients with positive serology had significant lower median body mass index z-score and worse pulmonary function. This is the first study in Portugal, that we know so far, concerning serology evaluation for the diagnosis of P. aeruginosa infection. Serology may be considered as an adjuvant to culture to evaluate P. aeruginosa infection in children and young patients with CF

Non-COVID-19 respiratory viral infection

Implemented control measures brought about by the coronavirus disease 2019 (COVID-19) pandemic have changed the prevalence of other respiratory viruses, often relegating them to a secondary plan. However, it must not be forgotten that a diverse group of viruses, including other human coronaviruses, rhinoviruses, respiratory syncytial virus, human metapneumoviruses, parainfluenza and influenza, continue to be responsible for a large burden of disease. In fact, they are among the most common causes of acute upper and lower respiratory tract infections globally. Viral respiratory infections can be categorised in several ways, including by clinical syndrome or aetiological agent. We describe their clinical spectrum. Distinctive imaging features, advances in microbiological diagnosis and treatment of severe forms are also discussed.info:eu-repo/semantics/publishedVersio

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study

During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2·26, 95% CI 1·90 to 2·70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0·86, 95% CI 0·84 to 0·89; 2 to <5 years IRR 0·80, 95% CI 0·78 to 0·82; 5 to <12 years IRR 0·68, 95% CI 0·67 to 0·70; 12 to 18 years IRR 0·72, 95% CI 0·70 to 0·74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1·30, 95% CI 1·16 to 1·45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1·10, 95% CI 1·08 to 1·12; emergent and very urgent triage IRR 1·53, 95% CI 1·49 to 1·57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258

Colonização por Staphylococcus aureus resistente à meticilina: Que impacto na morbilidade de doentes pediátricos com fibrose quística?

Resumo: Introdução: Ao Staphylococcus aureus resistente à meticilina (MRSA) é classicamente reconhecido um papel patogénico no âmbito da fibrose quística (FQ).Objectivos: Avaliação da evolução da prevalência e incidência da colonização por MRSA, impacto clínico no ano após o primeiro isolamento, factores de risco e padrão de resistência antimicrobiana.Métodos: Estudo retrospectivo dos doentes pediátricos colonizados por MRSA seguidos no centro de FQ do Hospital de Santa Maria de 2003 a 2007.Resultados: O MRSA foi isolado em secreções respiratórias de 12 dos 60 doentes seguidos durante este período (colonização crónica em 3 doentes). A idade média à data do primeiro isolamento foi de 9 anos e 10 meses e o tempo médio entre o diagnóstico de FQ e a aquisição de MRSA de 5 anos e 7 meses.Verificou-se um aumento da prevalência e incidência de colonização por MRSA, com um máximo atingido em 2007 (prevalência 14,3% e incidência 8,9%). Quatro doentes cumpriram antibioticoterapia profiláctica antiestafilocócica com flucloxacilina.No ano após o primeiro isolamento de MRSA, constatou-se um aumento do número de dias de internamento em 4 doentes (2 com colonização crónica) e deterioração da função pulmonar em 5, incluindo a totalidade dos doentes com colonização crónica. Apenas um doente apresentou diminuição de percentil de índice de massa corporal.As resistências mais frequentemente encontradas foram à rifampicina e à clindamicina.Conclusões: Este estudo revelou ocorrência de deterioração clínica relevante em doentes com colonização crónica por MRSA, reforçando a importância da implementação de estratégias eficazes e precoces de erradicação.Rev Port Pneumol 2010; XVI (4): 527-542 Abstract: Background: Methicillin-resistant Staphylococcus aureus (MRSA) plays a well-recognised pathogenic role in cystic fibrosis (CF).Aims: To evaluate the prevalence and incidence of colonisation by MRSA, clinical impact of MRSA colonisation (year after first MRSA isolation), risk factors and pattern of antimicrobial resistance.Methods: Retrospective review of paediatric CF patients colonised with MRSA followed-up at the CF Unit of Hospital de Santa Maria 2003-2007.Results: Twelve of the 60 patients followed-up during this period were MRSA-positive at some time (chronic colonisation in 3 patients). Mean age at acquisition was 9 years 10 months and mean time interval between CF diagnosis and MRSA acquisition 5 years 7 months.An important rise in MRSA colonisation prevalence and incidence was observed, with the highest rate seen in 2007 (prevalence 14.3% and incidence 8.9%).Four patients had received anti-staphylococcal prophylaxis with flucloxacillin.An increase in the total number of in-patient days was observed in four patients (two with chronic colonisation). Deterioration in lung function was seen in five patients (including the three patients with chronic colonisation). Only one patient had a decrease in body mass index percentile. Resistance to clindamycin and rifampin was the most frequently seen.Conclusions: This study revealed significant clinical deterioration in patients with chronic colonisation by MRSA, reinforcing the importance of effective and timely decolonisation strategies.Rev Port Pneumol 2010; XVI (4): 527-542 Palavras-chave: Fibrose quística, MRSA, erradicação, Key-words: Cystic fibrosis, MRSA, decolonisatio

Colonização por Staphylococcus aureus resistente à meticilina: Que impacto na morbilidade de doentes pediátricos com fibrose quística? The impact of methicillin-resistant Staphylococcus aureus colonisation on paediatric cystic fibrosis patients’morbidity

Introdução: Ao Staphylococcus aureus resistente à meticilina (MRSA) é lassicamente reconhecido um papel patogénico no âmbito da fibrose quística (FQ). Objectivos: Avaliação da evolução da prevalência e incidência da colonização por MRSA, impacto clínico no ano após o primeiro isolamento, factores de risco e padrão de resistência antimicrobiana. Métodos: Estudo retrospectivo dos doentes pediátricos colonizados por MRSA seguidos no centro de FQ do Hospital de Santa Maria de 2003 a 2007. Resultados: O MRSA foi isolado em secreções respiratórias de 12 dos 60 doentes seguidos durante este período (colonização crónica em 3 doentes). A idade média à data do primeiro isolamento foi de 9 anos e 10 meses e o tempo médio entre o diagnóstico de FQ e a aquisição de MRSA de 5 anos e 7 meses. Verificou-se um aumento da prevalência e incidência de colonização por MRSA, com um máximo atingido em 2007 (prevalência 14,3% e incidência 8,9%). Quatro doentes cumpriram antibioticoterapia profiláctica antiestafilocócica com flucloxacilina. No ano após o primeiro isolamento de MRSA, constatou -se um aumento do número de dias de internamento em 4 doentes (2 com colonização crónica) e deterioração da função pulmonar em 5, incluindo a totalidade dos doentes com colonização crónica. Apenas um doente apresentou diminuição de percentil de índice de massa corporal. As resistências mais frequentemente encontradas foram à rifampicina e à clindamicina.Conclusões: Este estudo revelou ocorrência de deterioração clínica relevante em doentes com colonização crónica por MRSA, reforçando a importância da implementação de estratégias eficazes e precoces de erradicação.Background: Methicillin-resistant Staphylococcus aureus (MRSA) plays a well-recognised pathogenic role in cystic fibrosis (CF). Aims: To evaluate the prevalence and incidence of colonisation by MRSA, clinical impact of MRSA colonisation (year after first MRSA isolation), risk factors and pattern of antimicrobial resistance. Methods: Retrospective review of paediatric CF patients colonised with MRSA followed-up at the CF Unit of Hospital de Santa Maria 2003-2007. Results: Twelve of the 60 patients followed-up during this period were MRSA-positive at some time (chronic colonisation in 3 patients). Mean age at acquisition was 9 years 10 months and mean time interval between CF diagnosis and MRSA acquisition 5 years 7 months. An important rise in MRSA colonisation prevalence and incidence was observed, with the highest rate seen in 2007 (prevalence 14.3% and incidence 8.9%). Four patients had received anti-staphylococcal prophylaxis with flucloxacillin. An increase in the total number of in-patient days was observed in four patients (two with chronic colonisation). Deterioration in lung function was seen in five patients (including the three patients with chronic colonisation). Only one patient had a decrease in body mass index percentile. Resistance to clindamycin and rifampin was the most frequently seen. Conclusions: This study revealed significant clinical deterioration in patients with chronic colonisation by MRSA, reinforcing the importance of effective and timely decolonisation strategies

Acute hemorrhagic edema of infancy: a vasculitis with good prognosis

Aims: To report two cases of acute hemorrhagic edema of infancy, a rare vasculitis characterized by purpuric skin lesions and peripheral edema without systemic involvement (excluding fever), which has a sudden onset and an usually benign course, with spontaneous resolution. Cases description: The authors describe two cases of male infants, 11 and 12 months old, who were admitted to the emergency department with fever and progressively worsening purpuric lesions. The diagnosis of acute hemorrhagic edema of infancy was made by exclusion and sustained by the fact that, despite the impressive skin presentation, both infants had a good general state and presented the classic triad of this entity: fever, peripheral edema, and purpuric lesions on the face, ears and extremities. Both boys presented total regression of the lesions in about one week, without sequelae. Conclusions: There are just over 100 cases of hemorrhagic edema of infancy reported worldwide. The rarity of this vasculitis may be due to underdiagnosis or mistaken diagnosis of other leukocytoclastic vasculitis, mostly Henoch-Schönlein purpura. In addition to this, there are other conditions to consider in the differential diagnosis, such as meningococcemia, Kawasaki disease and erythema multiforme, which have similarities, but at the same time distinctive features that allow to exclude them. Timely diagnosis of acute hemorrhagic edema of childhood is crucial to avoid unnecessary therapies and supplementary tests, as well as to reassure the family about the good prognosis of the disease

Edema hemorrágico agudo da infância: uma vasculite com bom prognóstico = Acute hemorrhagic edema of infancy: a vasculitis with good prognosis

Objetivos: Relatar dois casos de edema hemorrágico agudo da infância, que consiste numa vasculite rara, caracterizada por lesões cutâneas purpúricas e edema periférico, sem envolvimento sistêmico (excetuando-se a febre), que tem início súbito, curso benigno e evolui espontaneamente para a cura. Descrição dos casos: Os autores apresentam dois casos de crianças do sexo masculino, com 11 e 12 meses de idade, que foram atendidos no serviço de urgência por febre e lesões purpúricas exuberantes de agravamento progressivo. O diagnóstico de edema hemorrágico agudo da infância foi feito por exclusão e sustentado pelo fato de que, apesar da impressionante apresentação cutânea, ambos os lactentes apresentavam um ótimo estado geral e a tríade clássica desta entidade: febre, edema e lesões purpúricas da face, orelhas e extremidades. Houve regressão total das lesões cutâneas em aproximadamente uma semana, sem sequelas em ambos os casos. Conclusões: Existem pouco mais de 100 casos publicados mundialmente de edema hemorrágico agudo da infância. A raridade dessa vasculite pode dever-se a um subdiagnóstico ou diagnóstico equivocado de outras vasculites leucocitoclásticas, principalmente a Púrpura de HenochSchönlein. Além desta, existem outras doenças a considerar no diagnóstico diferencial, como meningococemia, doença de Kawasaki e eritema multiforme, que apresentam similaridades, mas ao mesmo tempo características distintas que permitem excluí-las. É fundamental o diagnóstico oportuno do edema hemorrágico agudo da infância, de modo a evitar exames complementares e terapêuticas desnecessárias, além de tranquilizar a família quanto ao bom prognóstico da doenç

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system

Background Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. Methods We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. Results In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI −100–−54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from −97% (95% CI −100– −47%; p=0.0005) to −36% (95% CI −79–7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14–0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20–0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25–0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31–0.97); p=0.038) were independently associated with reducing bronchiolitis. Conclusions Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis