Haemophilus influenzae Type b Vaccine Failure in Portugal: A Nationwide Multicenter Pediatric Survey.

BACKGROUND: Despite the high effectiveness of the Haemophilus influenzae type b (Hib) vaccine in preventing invasive disease (ID) in children, Hib vaccine failures (VFs) cases may still occur. This study aimed to characterize the Hib-VF cases in Portugal in a 12-year period and trying to identify the possible associated risk factors. METHODS: Prospective descriptive nationwide surveillance study. Bacteriologic and molecular studies were performed at the same Reference Laboratory. Clinical data were collected by the referring pediatrician. RESULTS: Hib was identified in 41 children with ID and 26 (63%) were considered VF. Nineteen (73%) cases occurred in children less than 5 years old; 12 (46%) occurred before the Hib vaccine booster dose at 18 months of age. Comparing the first and the last 6-year periods of the study, the incidence rate of Hib, VF and total H. influenzae (Hi) ID significantly raised ( P < 0.05). VF cases corresponded, respectively, to 13.5% (7/52) and 22% (19/88) of total Hi-ID cases ( P = 0.232). Two children died due to epiglottitis and 1 acquired sensorineural hearing loss. Only 1 child had an inborn error of immunity. The immunologic workup performed in 9 children revealed no significant abnormalities. All 25 Hib-VF strains analyzed belonged to the same clonal complex 6. CONCLUSIONS: In Portugal, more than 95% of children are vaccinated against Hib, but severe Hib-ID cases still occur. No predisposing factors were clearly identified to justify the increased number of VF in recent years. Along with continued Hi-ID surveillance, Hib colonization and serologic studies should be implemented.

The Added Value of a Multidisciplinary Clinic for Systemic Autoinflammatory Diseases.

Background: Systemic autoinflammatory diseases (SAID) are characterized by inappropriate activation of the innate immune system and include not only monogenic periodic fever syndromes but also multifactorial conditions. As SAID are rare and represent a diagnostic challenge, a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients. Objective: To describe the organization of our multidisciplinary SAID clinic and to characterize our clinical experience, highlighting the benefits of multidisciplinary team management. Methods: Our SAID clinic takes place monthly and is managed by pediatric rheumatologists closely collaborating with pediatricians specialized in infectious diseases and immunodeficiencies and one medical geneticist. Patients' data are systematically incorporated in the Rheumatic Diseases Portuguese Register (Reuma.pt). Biological samples are stored in a biobank. We describe our clinical experience based on SAID patients registered into Reuma.pt/SAID between July 2011 and June 2020. Results: We have registered 176 patients, with a median age of disease onset of 3.1 ± 4.4 years and median age at disease diagnosis of 4.7 ± 4.0 years. Most patients were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome (PFAPA) (n=133), 20 with undefined SAID (uSAID) and 13 with monogenic SAID, including familial Mediterranean fever (FMF) (n=5), tumor necrosis factor receptor-associated periodic syndrome (TRAPS) (n=1), cryopyrin-associated periodic disease (CAPS) (n=1), and hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD) (n=2). A genetic test was performed in 31 patients (18%), and in 26% of these a mutation responsible for the phenotype was found. Thirty-four patients (19%) achieved remission. Conclusion: FMF was the most common monogenic SAID and the percentage of patients with an identified causal mutation was low. A structured electronic clinical record coupled with a biobank and a multidisciplinary approach are crucial to ensure successful diagnosis and adequate follow-up of these patients.

[Case Series of 103 Children with SARS-CoV-2 Infection in Portugal]. / Série de Casos de 103 Crianças com Infeção por SARS-CoV-2 em Portugal.

INTRODUCTION: The North Lisbon University Hospital Center was activated for referral of SARS-CoV-2 infected patients on the 11th March 2020. The aim of this study is to describe the experience at the Department of Pediatrics in the approach and the clinical outcomes of infected children. MATERIAL AND METHODS: A descriptive observational study was performed. Children and adolescents (0 to 18 years) with SARS-CoV-2 infection, diagnosed in the emergency room or admitted to the Department of Pediatrics between March 11th and June 18th, were included. Hospital records and Trace COVID-19 platform were reviewed and patient caregivers were interviewed to assess follow up. RESULTS: Among 103 diagnosed children, 83% had a known previous contact with an infected patient, 43% presented fever and 42% presented respiratory symptoms. Ten percent had risk factors and 21% were aged under one year old. Ten percent were hospitalised, one needing intensive care, with paediatric inflammatory multisystem syndrome. Blood tests were performed in 9% and chest radiograph in 7%. No children required ventilation, antiviral therapy or underwent thoracic computed tomography scan. Eight percent of children returned to the emergency room and one child was hospitalised. The clinical outcome is known in 101 patients and is favourable in all. DISCUSSION: Most children had an epidemiological link and little clinical repercussion, even during the first year of life. The expected mild severity in children justified the use of established clinical criteria and recommendations for similar conditions, regarding tests and hospitalizations. No antiviral treatments were given due to lack of evidence of its benefits. CONCLUSION: This strategy contributed to a low consumption of hospital resources and proved safe in this series.

Introdução: O Centro Hospitalar Universitário Lisboa Norte foi ativado para referência de doentes com infeção SARS-CoV-2 em 11 de março de 2020. O objetivo deste estudo é descrever a experiência do Departamento de Pediatria na abordagem e evolução clínica de crianças infetadas.Material e Métodos: Realizámos um estudo observacional descritivo. Incluímos as crianças e adolescentes (0 aos 18 anos) com infeção por SARS-CoV-2 diagnosticados na urgência e internamento do nosso departamento entre 11 de março e 18 de junho de 2020. Consultámos registos internos e a plataforma Trace COVID-19 e contactámos os cuidadores para avaliação de seguimento.Resultados: De 103 crianças diagnosticadas, 83% tiveram contacto prévio identificado com doente infetado, 43% doentes apresentaram febre e 42% sintomas respiratórios. Em 10% havia fatores de risco; 21% tinham idade inferior a um ano. Foram internadas 10% das crianças, uma em cuidados intensivos com síndrome inflamatória multissistémica pediátrica. Foi efetuada avaliação laboratorial em 9%, radiografia torácica em 7%. Nenhum recebeu suporte ventilatório, terapêutica antiviral ou realizou tomografia computorizada torácica. Foram reobservadas em serviço de urgência 8% das crianças, sendo internada uma. A evolução foi conhecida em 101 casos sendo favorável em todos.Discussão: A maioria dos doentes tinha link epidemiológico familiar e pouca repercussão clínica, mesmo no primeiro ano de vida. A menor gravidade esperada na criança motivou a adoção de critérios habituais noutros quadros clínicos semelhantes para a realização de exames complementares de diagnóstico e internamento hospitalar. Não foi administrada terapêutica antiviral em nenhum doente por se considerar haver pouca evidência de benefício.Conclusão: Esta estratégia traduziu-se num baixo consumo de recursos hospitalares e revelou-se segura nesta série.

[Correction to the article "Case Series of 103 Children with SARS-CoV-2 Infection in Portugal", published on Acta Med Port 2020 Dec;33(12):795-802]. / Errata ao artigo "Série de Casos de 103 Crianças com Infeção por SARS-CoV-2 em Portugal", publicado em Acta Med Port 2020 Dec;33(12):795-802.

On page 801, fifth, where it reads: "No início da pandemia, teorizou-se que a vacina BCG pudesse ter um efeito protetor relativamente à COVID-19,27,28 mas não se encontrou até à data evidência para tal, não estando atualmente recomendada a vacinação BCG na prevenção da COVID-19.28,29 No nosso estudo, a maioria dos doentes (76%) tinha sido vacinada. Analisámos separadamente o subgrupo de crianças nascidas após janeiro de 2016, altura em que passaram a ser vacinadas apenas as crianças pertencentes a grupos de risco.30 A taxa de vacinação neste grupo foi de 51%, sendo superior à taxa de 30,1% estimada para crianças nascidas em Portugal com um ano de idade referido a 2019.31" It should read: "No início da pandemia, teorizou-se que a vacina BCG pudesse ter um efeito protetor relativamente à COVID-19,27,28 mas não se encontrou até à data evidência para tal, não estando atualmente recomendada a vacinação BCG na prevenção da COVID-19.28 No nosso estudo, a maioria dos doentes (76%) tinha sido vacinada. Analisámos separadamente o subgrupo de crianças nascidas após janeiro de 2016, altura em que passaram a ser vacinadas apenas as crianças pertencentes a grupos de risco.29 A taxa de vacinação neste grupo foi de 51%, sendo superior à taxa de 30,1% estimada para crianças nascidas em Portugal com um ano de idade referido a 2019.30" Paper published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/14537.

Na página 801, quinto parágrafo, onde se lê: "No início da pandemia, teorizou-se que a vacina BCG pudesse ter um efeito protetor relativamente à COVID-19,27,28 mas não se encontrou até à data evidência para tal, não estando atualmente recomendada a vacinação BCG na prevenção da COVID-19.28,29 No nosso estudo, a maioria dos doentes (76%) tinha sido vacinada. Analisámos separadamente o subgrupo de crianças nascidas após janeiro de 2016, altura em que passaram a ser vacinadas apenas as crianças pertencentes a grupos de risco.30 A taxa de vacinação neste grupo foi de 51%, sendo superior à taxa de 30,1% estimada para crianças nascidas em Portugal com um ano de idade referido a 2019.31" Deverá ler-se: "No início da pandemia, teorizou-se que a vacina BCG pudesse ter um efeito protetor relativamente à COVID-19,27,28 mas não se encontrou até à data evidência para tal, não estando atualmente recomendada a vacinação BCG na prevenção da COVID-19.28 No nosso estudo, a maioria dos doentes (76%) tinha sido vacinada. Analisámos separadamente o subgrupo de crianças nascidas após janeiro de 2016, altura em que passaram a ser vacinadas apenas as crianças pertencentes a grupos de risco.29 A taxa de vacinação neste grupo foi de 51%, sendo superior à taxa de 30,1% estimada para crianças nascidas em Portugal com um ano de idade referido a 2019.30"Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/14537.

[Live Vaccine in Children with DiGeorge/22q11.2 Deletion Syndrome]. / Vacinas Vivas em Crianças com Síndrome de DiGeorge/ Deleção 22q11.2.

INTRODUCTION: Children with DiGeorge syndrome/chromosome 22q11.2 deletion syndrome might have a variable degree of immunodeficiency, which may limit the use of live vaccines. The aim of this study was to review the adverse effects of live vaccines and possible relation with immune status in patients with DiGeorge Syndrome/partial 22q11.2 deletion syndrome. MATERIAL AND METHODS: Retrospective study with analysis of the clinical records of children with chromosome 22q11.2 deletion syndrome and DiGeorge syndrome phenotype, followed in a Primary Immunodeficiency center. Data were collected on: demographic characteristics; medical and vaccination history with live vaccines; T-CD4+ lymphocyte counts and lymphocyte proliferative responses to antigens and mitogens; adverse reactions; vaccine failure. RESULTS: Twenty three children with DiGeorge syndrome/22q11.2 deletion syndrome were included, 65.2% male, with average age at diagnosis of 11.3 months. Eighteen children (78%) received bacillus Calmette-Guérin vaccine: all with evidence of thymic activity; three presented moderate T-CD4+ lymphopenia and abnormal lymphocyte proliferative responses; one had abnormal lymphocyte proliferative responses for mitogens, four for purified protein derivative and one for tetanus toxoid. Measles, mumps and rubella vaccine was administered to 15 children, three of them with moderate immunosuppression and abnormal lymphocyte proliferative responses. Live attenuated polio vaccine was administered to 4 children without immunosuppression and the rotavirus vaccine to three children, one with moderate immunosuppression. No significant adverse reactions were reported. DISCUSSION: These data are in line with the findings of other international studies. CONCLUSION: In our sample, live vaccines were well-tolerated, even in children with moderate T-CD4+ lymphopenia and abnormal lymphocyte proliferative responses to antigens/mitogens.

Introdução: A síndrome de DiGeorge/deleção 22q11.2 pode apresentar um grau variável de imunodeficiência, condicionando a utilização de vacinas vivas. Este estudo teve como objetivo documentar os efeitos adversos de vacinas vivas e possível relação com alterações imunitárias em crianças com síndrome de DiGeorge/deleção 22q11.2 parcial. Material e Métodos: Foi realizado um estudo retrospetivo por revisão dos processos clínicos das crianças com deleção do cromossoma 22q11.2 e fenótipo de síndrome de DiGeorge, seguidos num centro de referência de imunodeficiências primárias. Foi realizada colheita de dados, incluindo: características demográficas; história médica; historial de vacinação com vacinas vivas; contagem de linfócitos T-CD4+ e respostas proliferativas linfocitárias a antigénios e mitogénios; reações adversas; falências vacinais. Resultados: Foram incluídas 23 crianças com síndrome de DiGeorge/deleção 22q11.2, 65,2% do sexo masculino e idade média de diagnóstico de 11,3 meses. Destas, 18 crianças (78%) receberam a vacina bacillus Calmette-Guérin: todas com evidência de atividade tímica; três apresentaram linfopénia T-CD4+ moderada e respostas proliferativas linfocitárias anormais; uma com respostas proliferativas linfocitárias anormais para mitogénios, quatro para derivado de proteína purificada e uma para toxóide tetânico. A vacina tríplice contra o sarampo, parotidite e rubéola foi administrada a 15 crianças, três com imunossupressão moderada e respostas proliferativas linfocitárias anormais. A vacina viva atenuada contra poliomielite foi administrada a quatro crianças sem imunossupressão e a vacina contra o rotavírus a três crianças, uma com imunossupressão moderada. Não foram reportadas reações adversas. Discussão: Estes dados estão de acordo com as conclusões de outros estudos internacionais. Conclusão: Na nossa amostra, as vacinas vivas atenuadas foram bem toleradas, incluindo em crianças com linfopénia T-CD4+ moderada e com respostas proliferativas linfocitárias a antigénios/mitogénios anormais.

Propionibacterium Acnes: Cause of Cerebrospinal Fluid Shunt Infection.

Infection after implantation of ventriculo-peritoneal shunts is associated with significant morbidity and mortality. We describe a 9-year-old girl with Propionibacterium acnes shunt infection with negative cerebrospinal fluid cultures, diagnosed by broad-range 16S-rRNA gene polymerase chain reaction. This case supports the use of this molecular diagnostic technique in shunt infections, where the offending pathogens are difficult to culture using traditional methods.

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/µL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/µL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

Congenital malaria in a European country.

A newborn of 26 days, born in Lisbon, Portugal, presented with fever, anaemia and thrombocytopaenia. She was admitted considering neonatal sepsis, but Plasmodium vivax was identified in the second peripheral blood smear performed. Parenteral quinine was started with good evolution. Despite clinicians' unfamiliarity with congenital malaria in non-endemic areas, this diagnosis, although rare, should not be forgotten in the evaluation of newborns/infants born to women from endemic areas or with recent trip to these areas.

[Periodic fever with aphthous stomatitis, pharyngitis and adenitis: report of 21 cases]. / Síndrome PFAPA (febre periódica, estomatite aftosa, faringite, adenite): análise retrospectiva de 21 casos.

INTRODUCTION: PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis) is a benign sporadic syndrome of unknown cause and an important diagnosis to consider in the child with recurrent fever and tonsillitis. OBJECTIVES: To describe the presentation, age of onset, time until diagnosed, episode duration, frequency of typical and atypical symptoms, clinical course after diagnosis and response to treatment in a case series of children with PFAPA. METHODS: Case series of children with PFAPA referred to our consult over an eight-year period (from May 2001 to May 2009). Data were collected from medical records and telephone calls. RESULTS: We included 21 patients with PFAPA, with age of onset between 6 months and 5 years (median 24 months). Diagnosis was established 4 months to 3 years after onset of crises (median 24 months). Episodes recurred every 2 to 6 weeks (median 30 days), and consisted in 3 to 10 days (median 4,5 days) of fever (21/21), pharyngitis (21/21), cervical adenitis (19/21), and aphthous stomatitis (16/21). Atypical symptoms were reported sporadically and without clinical severity: abdominal pain (8 patients), nauseas/vomits (3 patients), arthralgia (3 patients), hepatosplenomegaly (1 patient), lactose intolerance (1 patient). Eighteen patients received treatment with one dose of prednisolone with rapid symptomatic relief. In two patients subsequent crises became more frequent for a short period of time and then returned to monthly periodicity. Seven treated patients experienced less frequent episodes and in four of them this occurred after diagnosis but before first dose of prednisolone. In the three untreated patients the crises bécame rare and treatment was not prescribed. Tonsillectomy was performed in two patients and in one the monthly episodes reappeared five months after the procedure. DISCUSSION: In spite including a small number of patients, our case series is similar to others in the literature regarding most clinical aspects. PFAPA syndrome should be considered even in the absence of all clinical criteria. Correct and timely diagnosis does not require and obviates unnecessary diagnostic tests. The outcome after symptomatic therapy with corticosteroids and family reassurance was generally good and we do not recommend tonsillectomy as a first line treatment in this syndrome.

Two siblings with periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome.

PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis) is a benign sporadic syndrome of unknown cause. We report 2 siblings diagnosed with this syndrome. The second case started crisis simultaneously with recurrence of crisis after a 3-year free interval in her brother. This temporal relation suggests environmental factor acting in genetically predisposed children.