Epidemiology and genetic diversity of invasive Neisseria meningitidis strains circulating in Portugal from 2003 to 2020.

Invasive meningococcal disease (IMD) continues to be a public health problem due to its epidemic potential, affecting mostly children. We aimed to present a detailed description of the epidemiology of IMD in Portugal, including insights into the genetic diversity of Neisseria meningitidis strains. Epidemiological analysis included data from the Portuguese National Reference Laboratory of Neisseria meningitidis during 2003 to 2020. Since 2012, N. meningitidis isolates have also been assessed for their susceptibility to antibiotics and were characterized by whole genome sequencing. During 2003-2020, 1392 confirmed cases of IMD were analyzed. A decrease in the annual incidence rate was observed, ranging from 1.99 (2003) to 0.39 (2020), with an average case fatality rate of 7.1%. Serogroup B was the most frequent (69.7%), followed by serogroups C (9.7%), Y (5.7%), and W (2.6%). Genomic characterization of 329 isolates identified 20 clonal complexes (cc), with the most prevalent belonging to serogroup B cc41/44 (26.3%) and cc213 (16.3%). Isolates belonging to cc11 were predominantly from serogroups W (77.3%) and C (76.5%), whereas cc23 was dominant from serogroup Y (65.7%). Over the past 4 years (2017-2020), we observed an increasing trend of cases assigned to cc213, cc32, and cc11. Regarding antimicrobial susceptibility, all isolates were susceptible to ceftriaxone and 61.8% were penicillin-nonsusceptible, whereas 1.4% and 1.0% were resistant to ciprofloxacin and rifampicin. This is the first detailed study on the epidemiology and genomics of invasive N. meningitidis infections in Portugal, providing relevant data to public health policy makers for a more effective control of this disease.

[Validation of the European Portuguese Version of a Pediatric Palliative Needs Assessment Tool: The Pediatric Palliative Screening Scale]. / Validação da Versão Portuguesa de um Instrumento de Avaliação de Necessidades Paliativas Pediátricas: A Pediatric Palliative Screening Scale.

INTRODUCTION: The Pediatric Palliative Screening Scale (PaPaS Scale) was designed to help professionals to identify life-limiting or life-threatening children/young people with complex chronic conditions who would benefit from pediatric palliative care and facilitate their timely and appropriate referral. The aim of this study was to translate, culturally adapt and validate the PaPaS Scale for the Portuguese pediatric population. MATERIAL AND METHODS: A quantitative methodological study involving translation, cultural adaptation and validation of a scale was performed. In the first phase, the translation and cultural adaptation of the original version of the PaPaS Scale from English to European Portuguese was undertaken. The second phase consisted of evaluating the psychometric properties of the Portuguese version of the PaPaS Scale. RESULTS: Fifty-one enquires pertaining to children/young adults with complex chronic conditions were completed and returned, the sum of the responses to the items on the scale revealed that 84.4% of the patients had an indication for referral to pediatric palliative care. The internal consistency analysis obtained a value of Cronbach's alpha above 0.80, so the scale was considered adequate for the analyzed data. In our sample, the item-total correlation values indicated that the 11 variables measured the PaPaS Scale with good reliability and unidimensionally. The confirmatory factor analysis suggested that the items were significant, consistent, and presented convergent validity globally. Only item "2.2. Treatment side effects" obtained a value below the defined threshold. CONCLUSION: The PaPaS Scale was translated and adapted to the European Portuguese version, allowing its immediate use in the Portuguese population. It will be essential to design multicentric studies to expand the knowledge about the psychometric characteristics of this scale.

Introdução: A Pediatric Palliative Screening Scale (PaPaS Scale) foi desenhada para ajudar os profissionais a identificar as crianças/jovens com doença crónica complexa, limitante ou ameaçadora da vida que beneficiariam de cuidados paliativos pediátricos e facilitar referenciação atempada e apropriada. O objetivo deste estudo foi traduzir, adaptar culturalmente e validar a PaPaS Scale para a população pediátrica portuguesa. Material e Métodos: Realizou-se um estudo metodológico quantitativo de tradução, adaptação cultural e validação de uma escala. Numa primeira fase, procedeu-se à tradução e adaptação cultural da versão original da PaPaS Scale de inglês para português europeu. A segunda fase consistiu na avaliação das propriedades psicométricas da versão portuguesa da Escala PaPaS. Resultados: Numa amostra de 51 questionários referentes a crianças/jovens com doença crónica complexa, a soma das respostas aos itens da escala revelou que 84,4% dos doentes tinham indicação para ser referenciados aos cuidados paliativos pediátricos. Na análise de consistência interna obteve-se um valor do alfa de Cronbach superior a 0,80, pelo que se pôde considerar a escala como adequada aos dados analisados. De facto, os valores de correlação item-total indicaram que as 11 variáveis mediram com boa fiabilidade e de forma unidimensional a escala PaPaS. Na análise fatorial confirmatória, os resultados obtidos indicaram que globalmente os itens eram significativos, consistentes e apresentaram validade convergente. Apenas o item "2.2. Efeitos secundários do tratamento" obteve um valor abaixo do limiar definido. Conclusão: A PaPaS Scale foi traduzida e adaptada para a versão em português europeu, o que permite a sua utilização imediata na população portuguesa. Torna-se importante o desenho de estudos, preferencialmente multicêntricos, que aprofundem as características psicométricas desta escala.

Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature.

Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups­healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.

Eficácia de um programa de enfermagem de reabilitação, à distância, para a pessoa pós enfarte agudo do miocárdio centrado na autogestão do exercício físico / Efficacy of a distance rehabilitation nursing program for people after acute myocardial infarction centered on self-management of physical exercise

Enquadramento: O Enfarte Agudo do Miocárdio é uma das, mais importantes, causas de diminuição da capacidade funcional e da qualidade de vida. A Reabilitação Cardíaca, sendo, uma das recomendações terapêuticas, não farmacológicas, e, com a componente central focada no exercício físico, é uma ferramenta essencial, possibilitando a redução das limitações físicas e psicológicas, fomentando a adoção de um estilo de vida saudável. O exercício físico é um componente dos programas de Enfermagem de reabilitação que pode ser implementado de forma preventiva ou reabilitadora por Enfermeiros Especialistas em Reabilitação. Objetivos: Avaliar a eficácia de um programa de enfermagem de reabilitação, à distância, para a pessoa pós enfarte agudo do miocárdio centrado na autogestão do exercício físico; na qualidade de vida; na capacidade funcional e na atividade física da pessoa pós Enfarte Agudo do Miocárdio. Metodologia: Desenvolveu-se um estudo quase experimental com uma amostra com 30 doentes numa unidade coronária intensiva de um hospital central em Portugal, organizados em grupo de controlo e experimental, 22 do sexo masculino e 8 do sexo feminino, com uma média de idades de 58,8 anos, sujeitos a um programa de reabilitação fase I, durante o internamento, aos quais foram aplicados: questionário sociodemográfico; IPAQ; EQ-5D-3L, Índice de Lawton-Brody e Índice de Barthel. Foi, também, entregue um folheto, onde constam os exercícios que fazem parte do treino de exercício físico a realizar no domicílio. Uma semana após a alta, foi realizada a intervenção específica de enfermagem de reabilitação dirigida ao grupo experimental, um follow-up telefónico, onde foram reforçados ensinos sobre o exercício físico. Um mês após alta, a todos os elementos da amostra, foram aplicados, todos os instrumentos do primeiro momento. Resultados: Confirma-se a hipótese 1, de que a intervenção melhora a atividade física. Quanto à hipótese 2, não existe evidência estatística da influência direta da intervenção sobre a qualidade de vida (p> 0,05). Apesar de não se observar a influência direta da intervenção, observa-se a presença de um efeito significativo da intervenção sobre a qualidade de vida através da atividade física, confirmando a hipótese 5 (p <0,05). Conclusão: O programa de intervenção revelou-se efetivo, potenciando a adesão ao exercício físico dos doentes pós enfarte agudo do miocárdio com substancial incremento da sua qualidade de vida. Verificando-se, desta forma, um impacto positivo na vida destes doentes.

Distinguishing Kingella kingae from Pyogenic Acute Septic Arthritis in Young Portuguese Children.

(1) Background: We aim to identify clinical and laboratorial parameters to distinguish Kingella kingae from pyogenic septic arthritis (SA). (2) Methods: A longitudinal, observational, single-centre study of children < 5 years old with microbiological positive SA admitted to a paediatric hospital from 2013−2020 was performed. Clinical and laboratorial data at admission and at 48 h, as well as on treatment and evolution, were obtained. (3) Results: We found a total of 75 children, 44 with K. kingae and 31 with pyogenic infections (mostly MSSA, S. pneumoniae and S. pyogenes). K. kingae affected younger children with low or absent fever, low inflammatory markers and a favourable prognosis. In the univariate analyses, fever, septic look, CRP and ESR at admission and CRP at 48 h were significantly lower in K. kingae SA. In the multivariate analyses, age > 6 months ≤ 2 years, apyrexy and CRP ≤ 100 mg/L were significative, with an overall predictive positive value of 86.5%, and 88.4% for K. kingae. For this model, ROC curves were capable of differentiating (AUC 0.861, 95% CI 0.767−0.955) K. kingae SA from typical pathogens. (4) Conclusions: Age > 6 months ≤ 2 years, apyrexy and PCR ≤ 100 mg/L were the main predictive factors to distinguish K. kingae from pyogenic SA < 5 years. These data need to be validated in a larger study.

Genomic surveillance of Neisseria meningitidis serogroup W in Portugal from 2003 to 2019.

In recent years, a change in the epidemiology of meningococcal disease caused by Neisseria meningitidis serogroup W (MenW) has been observed worldwide, with the emergence of new sublineages associated with a higher rate of fatal cases. The present study intends to describe the epidemiology of invasive meningococcal disease (IMD) due to MenW in Portugal between 2003 and 2019, and to genetically characterize population structure. Despite MenW has a low incidence in Portugal, having almost disappeared from 2008 to 2015, since 2016, the number of MenW cases has been steadily increasing at a rate of ~ twofold per year, with more than 80% of the characterized isolates belonging to clonal complex 11 (cc11). Core-genome phylogeny of 25 Portuguese (PT) MenW isolates showed a strain clustering mainly either with the Original UK or the UK 2013 sublineages. Our study also reported for the first time the presence of distinct prophages with a notable overrepresentation of an ~ 32-35-kb PS_1-like prophage found in MenW cc11 genomes. The presence of the PS_1-like prophage in almost all 4723 cc11 genomes selected from Neisseria PubMLST database regardless of the capsular group they belong to suggests an ancestral acquisition of this mobile element prior to capsular switching events. Overall, by mimicking the scenario observed worldwide, this study reinforces the importance of a close monitoring of MenW disease, especially from cc11, in order to promptly adapt the vaccination plan for IMD control in Portugal. Moreover, future studies are needed to understand the putative contribution of prophages to fitness and virulence of PT MenW strains.

Seroprevalence of meningococcal serogroup C bactericidal antibodies in the Portuguese population, a decade after vaccine introduction in the National Immunisation Programme.

BACKGROUND: The incidence of invasive meningococcal disease due to serogroup C (MenC) decreased in Portugal since the introduction of the conjugate vaccine (MCC) in the free market in 2001 and in the National Immunisation Plan in 2006. Considering the potential waning of the antibody response reported in the literature, the different vaccination schemes that were used in our country over the past decade, and that Neisseria meningitidis serogroup C continues to circulate, the Portuguese population may currently be at increased risk of infection. In the absence of national data, we evaluated the seroprotection level of the Portuguese population against MenC, in order to identify the protected fraction of the population and ponder on the necessity of a booster dose of the MCC vaccine. METHODS: We measured serum bactericidal antibody levels against MenC in a representative sample of the population (n = 1500) aged 2-64 years who participated in the 2015/2016 National Serological Survey. RESULTS: A total of 31.1% (466/1500, 95%CI: 29-33%) of the individuals studied were protected against MenC. The geometric mean titre was 6.5. The proportion of seroprotected was particularly low in children aged 2-4 years (<16%) who received a single dose of the vaccine at 12 months of age (vaccination strategy since 2012). The proportion of seroprotected was higher (44.7% to 53.5%) in adolescent and young adults (15-24 years of age), resulting from vaccination during the catch-up campaign at 5-15 years of age. The highest protection rates were observed when the vaccine was administered during adolescence. CONCLUSION: The small fraction of population seroprotected, combined with the already known waning effect of the antibody response over time, may indicate that the Portuguese population will become progressively more exposed to the risk of infection. Taking in consideration our results, we recommend to change the current vaccination strategy and introduce a booster dose of the MCC vaccine during adolescence.

Kingella kingae Displaced S. aureus as the Most Common Cause of Acute Septic Arthritis in Children of All Ages.

BACKGROUND: Acute septic arthritis (SA) still remains a challenge with significant worldwide morbidity. In recent years, Kingella kingae has emerged and treatment regimens have become shorter. We aim to analyze trends in SA etiology and management and to identify risk factors for complications. METHODS: Longitudinal observational, single center study of children (<18 years old) with SA admitted to a tertiary care pediatric hospital, from 2003 to 2018, in 2 cohorts, before and after implementation of nucleic acid amplification assays (2014). Clinical, treatment and disease progression data were obtained. RESULTS: A total of 247 children were identified, with an average annual incidence of 24.9/100,000, 57.9% males with a median age of 2 (1-6) years. In the last 5 years, a 1.7-fold increase in the annual incidence, a lower median age at diagnosis and an improved microbiologic yield (49%) was noticed. K. kingae became the most frequent bacteria (51.9%) followed by MSSA (19.2%) and S. pyogenes (9.6%). Children were more often treated for fewer intravenous days (10.7 vs. 13.2 days, P = 0.01) but had more complications (20.6% vs. 11.4%, P = 0.049) with a similar sequelae rate (3.7%). Risk factors for complications were C-reactive protein ≥80 mg/L and Staphylococcus aureus infection, and for sequelae at 6 months, age ≥4 years and CRP ≥ 80 mg/L. CONCLUSIONS: The present study confirms that K. kingae was the most common causative organism of acute SA. There was a trend, although small, for decreasing antibiotic duration. Older children with high inflammatory parameters might be at higher risk of sequelae.

Association of Use of a Meningococcus Group B Vaccine With Group B Invasive Meningococcal Disease Among Children in Portugal.

Importance: A 4-component meningococcus group B vaccine (4CMenB) is the only vaccine in use to prevent group B invasive meningococcal disease in young children, but no matched controlled studies have evaluated it. Objective: To determine the association between receipt of 4CMenB and invasive group B meningococcal disease. Design, Setting, and Participants: Matched incidence density case-control study. Patients presenting from October 2014 to March 2019 were ascertained, with follow-up until death or discharge (last follow-up in June 2019) in 31 pediatric services in Portugal. Children and adolescent residents in Portugal with laboratory-confirmed invasive meningococcal disease were included. Controls, usually 2 per case, with unrelated conditions who were at the same hospital at the same time were matched for sex, age, and residence. Exposures: Immunization with 4CMenB, ascertained from the national database (2-4 doses are recommended, depending on age). Main Outcomes and Measures: The primary outcome was group B invasive meningococcal disease in fully vaccinated cases compared with controls. The secondary outcomes were all serogroup invasive meningococcal disease in fully vaccinated cases compared with controls and group B and all serogroup invasive meningococcal disease in cases compared with controls who received at least 1 vaccine dose. Results: Of 117 patients with invasive meningococcal disease, 98 were eligible for inclusion and 82 had group B invasive meningococcal disease; 69 were old enough to have been fully vaccinated and considered protected. Among these 69 cases, the median (interquartile range) age was 24 (4.5-196) months, 42 were male, and the median (interquartile range) duration of hospitalization was 8 (0-86) days. Five of 69 cases (7.2%) and 33 of 142 controls (23.1%) were fully vaccinated (difference, -16.0% [95% CI, -26.3% to -5.7%]; odds ratio [OR], 0.21 [95% CI, 0.08-0.55]). For all serogroup invasive meningococcal disease, 6 of 85 cases (7.1%) and 39 of 175 controls (22.3%) were fully vaccinated (difference, -15.2% [95% CI, -24.3% to -6.1%]; OR, 0.22 [95% CI, 0.09-0.53]). For group B disease, 8 of 82 cases (9.8%) and 50 of 168 controls (29.8%) received at least 1 vaccine dose (difference, -20.0% [95% CI, -30.3% to -9.7%]; OR, 0.18 [95% CI, 0.08-0.44]) and for all serogroup invasive meningococcal disease, 11 of 98 cases (11.2%) and 61 of 201 controls (30.3%) received at least 1 vaccine dose (difference, -19.1% [95% CI, -28.8% to -9.5%]; OR, 0.23 [95% CI, 0.11-0.49]). Conclusions and Relevance: During the first 5 years of vaccine availability in Portugal, vaccination with 4CMenB was less likely among children who developed invasive meningococcal disease compared with matched controls without invasive meningococcal disease. These findings may help inform the use of the 4CMenB vaccine in clinical practice. Trial Registration: ISRCTN Identifier: ISRCTN10901628.

Lung abscess due to Neisseria meningitidis serogroup X-unexpected virulence of a commensal resulting from putative serogroup B capsular switching.

To report the first case of a lung abscess caused by Neisseria meningitidis (Nm) and to genetically characterize the rare underlying capsule switching event. The strain (PT NmX) was subjected to whole genome sequencing, and a comparative gene-by-gene analysis was performed based on 1605 N. meningitidis core loci that constitute the MLST core-genome scheme (cgMLST) V1.0. All ~ 9,600 genomes available on Neisseria PubMLST (until 30th November 2019) from all serogroups were used to better identify the genome make-up of the PT NmX strain. This strain was found to be highly divergent from other NmX reported worldwide and to belong to a new sequence type (ST-14273), with the finetype X: P1.19,15-1:F5-2. Moreover, it revealed a closer genetic proximity to strains from serogroup B than to other serogroups, suggesting a genome backbone associated with serogroup B, while it presents a capsule synthesis region derived from a NmX strain. We describe a new hybrid NmB/X isolate from a noninvasive meningococcal infection, causing lung abscess. Despite capsular switching events involving serogroup X are rare, it may lead to the emergence of pathogenic potential. Studies should continue to better understand the molecular basis underlying Neisseria strains' ability to spread to body compartments other than the tissues for which their tropism is already known.

A rare cause of vertebral osteomyelitis: the first case report of rat-bite fever in Portugal

Abstract Rat-bite fever is a rarely diagnosed illness caused by Streptobacillus moniliformis . Although this disease is distributed worldwide, there have been few cases reported in Europe. Here, we report a case of vertebral osteomyelitis and sternoclavicular septic arthritis caused by S. moniliformis in a Portuguese patient previously bitten by a rat. Laboratory diagnosis was performed using molecular identification. This is the first case report of rat-bite fever in Portugal. The case described here serves as a reminder for physicians to consider this diagnosis in patients who have developed fever syndromes after being in contact with rodents.

A rare cause of vertebral osteomyelitis: the first case report of rat-bite fever in Portugal.

Rat-bite fever is a rarely diagnosed illness caused by Streptobacillus moniliformis . Although this disease is distributed worldwide, there have been few cases reported in Europe. Here, we report a case of vertebral osteomyelitis and sternoclavicular septic arthritis caused by S. moniliformis in a Portuguese patient previously bitten by a rat. Laboratory diagnosis was performed using molecular identification. This is the first case report of rat-bite fever in Portugal. The case described here serves as a reminder for physicians to consider this diagnosis in patients who have developed fever syndromes after being in contact with rodents.

Fatal Meningitis in Patient with X-Linked Chronic Granulomatous Disease Caused by Virulent Granulibacter bethesdensis.

Granulibacter bethesdensis is a pathogen reported to cause recurrent lymphadenitis exclusively in persons with chronic granulomatous disease. We report a case of fatal meningitis caused by a highly virulent G. bethesdensis strain in an adolescent in Europe who had chronic granulomatous disease.

Genetic Meningococcal Antigen Typing System (gMATS): A genotyping tool that predicts 4CMenB strain coverage worldwide.

BACKGROUND: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. METHODS: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. RESULTS: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. CONCLUSIONS: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates.

[Klebsiella pneumoniae from K1 and Hypervirulent Clone ST23: First Documented Case in Portugal]. / Klebsiella pneumoniae do Serotipo K1 e do Clone Hipervirulento ST23: Primeiro Caso Documentado em Portugal.

The hypervirulent K1 serotype Klebsiella pneumoniae is responsible for a new invasive syndrome, typically associated to hepatic abscesses with extra-hepatic complications. Initially described in Taiwan, it has significantly spread to several Asian countries and more recently to Europe and North America, thus constituting an emerging and global problem. The authors describe a case report of a 64-years-old portuguese caucasian woman without any previous diseases or epidemiological risk factors such as trips or contact with Asian products or population, diagnosed with a pyogenic liver abscess with pleural effusion caused by this hyper-virulent strain. A successful clinical cure was achieved after the etiological identification and treatment with antimicrobial therapy combined with catheter drainage. This is the first identification of hypervirulent Klebsiella pneumonia ST 23 clone in Portugal in the context of an invasive syndrome.

A estirpe híper-virulenta Klebsiella pneumoniae serotipo K1 é responsável por uma síndrome invasiva infeciosa, caracterizada por abcessos hepáticos com manifestações extra-hepáticas. Inicialmente identificada em Taiwan, tem aumentado significativamente em vários países da Ásia, e mais recentemente na Europa e América do Norte, conferindo a esta entidade um caracter emergente e global. Os autores apresentam o caso clinico de uma mulher de 64 anos, caucasiana, portuguesa, sem antecedentes pessoais ou epidemiológicos como viagens ou exposição a produtos asiáticos, na qual foi diagnosticada, abcesso hepático piogénico complicado de derrame pleural por esta estirpe híper-virulenta. Após conhecimento do diagnóstico e instituição de terapêutica antibiótica combinada com drenagem percutânea, foi possível a resolução do caso clínico com sucesso. Este caso permitiu a identificação do primeiro caso de síndroma invasiva infeciosa, por Klebsiella pneumoniae do clone híper-virulento ST23 documentado em Portugal.

Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Portugal.

OBJECTIVE: Although the incidence of meningococcal disease has been declining over the past decade in Portugal MenB meningococci is still an important cause of meningitis and sepsis. The aim of this study was to estimate the strain coverage of the 4CMenB vaccine in Portugal in order to support health policies for prevention and control of meningococcal disease. METHODS: Since 2002 the clinical and laboratory notification of meningococcal disease is mandatory in Portugal. National database includes since then all confirmed cases notified to the reference laboratory or to the Directorate of Health. Strains included in this study were all the invasive MenB isolated from the 1st July 2011 to the 30th June 2015, sent to the reference laboratory. To predict the vaccine strain coverage of the 4CMenB the expression and cross-reactivity of the surface antigens fHbp, NadA, NHBA were assessed by the Meningococcal Antigen Typing System (MATS) whereas PorA typing was performed by sequencing. The presence of at least one antigen with a Relative Potency (RP) greater than its MATS-positive bactericidal threshold RP value or the presence of PorA VR2 = 4 was considered to be predictive for a strain to be covered by the 4CMenB vaccine. RESULTS: The estimated 4CMenB strain coverage in Portugal was 67.9%. The percentage of strain coverage in each of the four epidemiological years ranged from 63.9% to 73.7%. Strains covered by one antigen represent 32.1% of the total of isolates, 29.2% of strains were covered by two antigens and 6.6% by three antigens. No strain had all the four antigens. Antigens that most contributed for coverage were NHBA and fHbp. Data from Portugal is in accordance with the MATS predicted strain coverage in five European countries (England and Wales, France, Germany, Italy and Norway) that pointed to 78% coverage for strains collected in the epidemiological year 2007-2008.

Methylotroph Infections and Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013.

Neisseria meningitidis or meningococcus is divided into 12 distinct serogroups of which A, B, C, W, X, and Y are medically most important and cause health problems in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Globally, serogroup A has been prevalent in the African "meningitis belt" whereas serogroup B and C have predominated in Europe. In a paper published earlier in this journal (1) , an increase in serogroup Y invasive meningococcal disease (IMD) in some European countries was reported based on the epidemiological data for 2010, 2011 and 2012. Here, we report additional data from 30 European countries indicating that high or increased serogroup Y disease levels have continued in 2013 in certain regions of Europe. In the Western and Central Europe, there were no major changes in the proportion of serogroup Y IMD cases in 2013 compared to 2012. In the Scandinavian countries, proportion of serogroup Y disease remained high, ranging from 26% to 51% in 2013. This was in contrast to Baltic, Eastern and most Southern European countries, where the proportion of serogroup Y IMD was low similarly to previous years. For the last 2 decades, the mean age of patients affected by serogroup Y was 41 y for 7 countries from which data was available and 50% of cases were in patients aged 45 to 88 y. The age distribution of serogroup Y was bimodal and did not change significantly despite the increase of the total number and the proportion of serogroup Y IMD in some European regions.

Meningococcal serogroup Y emergence in Europe: high importance in some European regions in 2012.

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. (1)(,) (2) Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.

Use of hybrid chitosan membranes and human mesenchymal stem cells from the Wharton jelly of umbilical cord for promoting nerve regeneration in an axonotmesis rat model.

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to assess the effect on nerve regeneration, associating a hybrid chitosan membrane with non-differentiated human mesenchymal stem cells isolated from Wharton's jelly of umbilical cord, in peripheral nerve reconstruction after crush injury. Chromosome analysis on human mesenchymal stem cell line from Wharton's jelly was carried out and no structural alterations were found in metaphase. Chitosan membranes were previously tested in vitro, to assess their ability in supporting human mesenchymal stem cell survival, expansion, and differentiation. For the in vivo testing, Sasco Sprague adult rats were divided in 4 groups of 6 or 7 animals each: Group 1, sciatic axonotmesis injury without any other intervention (Group 1-Crush); Group 2, the axonotmesis lesion of 3 mm was infiltrated with a suspension of 1 250-1 500 human mesenchymal stem cells (total volume of 50 µL) (Group 2-CrushCell); Group 3, axonotmesis lesion of 3 mm was enwrapped with a chitosan type III membrane covered with a monolayer of non-differentiated human mesenchymal stem cells (Group 3-CrushChitIIICell) and Group 4, axonotmesis lesion of 3 mm was enwrapped with a chitosan type III membrane (Group 4-CrushChitIII). Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index, static sciatic index, extensor postural thrust, and withdrawal reflex latency. Stereological analysis was carried out on regenerated nerve fibers. Results showed that infiltration of human mesenchymal stem cells, or the combination of chitosan membrane enwrapment and human mesenchymal stem cell enrichment after nerve crush injury provide a slight advantage to post-traumatic nerve regeneration. Results obtained with chitosan type III membrane alone confirmed that they significantly improve post-traumatic axonal regrowth and may represent a very promising clinical tool in peripheral nerve reconstructive surgery. Yet, umbilical cord human mesenchymal stem cells, that can be expanded in culture and induced to form several different types of cells, may prove, in future experiments, to be a new source of cells for cell therapy, including targets such as peripheral nerve and muscle.