Characteristics of pneumococci causing disease in adults in Portugal in a time of private use of pneumococcal conjugate vaccines in children

Invasive pneumococcal disease (IPD) and non-invasive pneumococcal pneumonia (NIPP) are important causes of morbidity and mortality worldwide, particularly among young children, the elderly and the immunocompromised. Two types of vaccines are available to prevent pneumococcal disease, but these target a limited number of the 97 pneumococcal serotypes described so far. One type is a strictly polysaccharide-based vaccine, which includes 23 serotypes and is primarily indicated for adults (23-valent pneumococcal polysaccharide vaccine, PPV23, targeting serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F). The other type are pneumococcal conjugate vaccines (PCVs). Three PCVs have been licensed to date: a 7-valent formulation (PCV7), which covers serotypes 4, 6B, 9V, 14, 18C, 19F and 23F; a 10-formulation (PCV10), which includes all serotypes of PCV7, plus serotypes 1, 5 and 7F; and a 13-valent formulation (PCV13), which targets all serotypes of PCV10 and also serotypes 3, 6A and 19A. PCV7 became available in the USA in 2000 and in Europe in 2001. Several studies reported that the use of PCV7 in children was followed by decreases in the incidence of PCV7-type IPD in children. Since PCV7 reduced colonization due to the vaccine serotypes and because children are the main reservoirs of pneumococci in the community, PCV7 serotypes became less transmitted from children to the remaining population, with this resulting in decreases in the incidence of PCV7-type IPD also in non-vaccinated people, including adults (herd protection). However, at the same time, increases in the incidence of IPD due to particular non-PCV7 serotypes occurred in children and adults. In Portugal, PCV7 was used in children between 2001 and 2009, but was not included in the national immunization program. The uptake of PCV7 was initially low (43% in 2004), but increased steadily (75% in 2008). In mid-2009 and early-2010, PCV10 and PCV13, respectively, became available for children, with PCV13 replacing PCV7. PCV10 and PCV13 were given through the private market until June 2015, when PCV13 was included in the national immunization program for children. During the availability of PCV10 and PCV13 outside the national immunization program, PCV13 was the most frequently used PCV. Even though PPV23 and PCV13 are also available for adults, in Portugal, adult pneumococcal vaccination is estimated to be low. The studies presented in this thesis aimed to evaluate the characteristics of pneumococci causing adult IPD and adult NIPP in Portugal in a time of private PCVs use in children in the country. The isolates were collected by an epidemiological surveillance network, in work since 1999, which includes several laboratories throughout the country. All isolates analyzed were collected from adult patients (≥ 18 yrs). For the characterization of adult IPD isolates we determined the serotype and antimicrobial susceptibility of isolates responsible for adult IPD between 2009 and 2014 (n = 2428). The results were compared with previously published data from the same network (1999-2008, n = 2182). Adult IPD isolates were also characterized by Multi Locus Sequence Typing (MLST) and regarding the presence and type of two pilus islands (PI-1 and PI-2). For this characterization, 50% of adult IPD isolates recovered from 2008 to 2011 (n = 871), from each serotype, were randomly chosen. For the characterization of adult NIPP isolates, we determine the serotype and antimicrobial susceptibility of a collection of isolates responsible for adult NIPP between 1999 and 2015 (n = 2735). Previous studies from this epidemiological surveillance network, which analyzed the serotypes of adult IPD isolates recovered between 1999 and 2008, found that in Portugal there was a significant decrease in the proportion of PCV7 serotypes in adult IPD in the post-PCV7 period (from 30.3% in 1999-2003 to 16.4% in 2008, p < 0.001), accompanied by increases in the proportion of specific non-PCV7 serotypes (serotypes 1, 7F and 19A). When analyzing adult IPD data from 2009 to 2014, we found further changes in the serotype distribution of pneumococci causing adult IPD. Comparing adult IPD isolates recovered in 2009-2011 with those recovered in 2012- 2014, a new but small decrease in the representation of PCV7 serotypes in adult IPD was noted (from 19% to 14%, p = 0.003). In what concerns the overall proportion of PCV13 serotypes, it peaked in 2008 (70%) and then started a significant and gradual decline until 2014 (38%, p < 0.001), the last year analyzed. Since PCV10 and PCV13 became available in Portugal only in mid-2009 and early-2010, respectively, the initial decline in the overall proportion of PCV13 serotypes was independent of childhood vaccination. The PCV13 serotypes that decreased the most from 2008 to 2011 were serotypes 1 (from 10.7% in 2009 to 4.1% in 2011, p < 0.001) and 5 (from 2.0% in 2008 to 0% in 2011, p = 0.003). The early decreases of these two serotypes may be associated with long term fluctuations and outbreaks, described elsewhere. Other serotypes, instead, decreased when a herd effect with the use of PCV13 in children was expected. This was the case of serotype 7F (from 8.2% in 2012 to 2.7% in 2014, p < 0.001) and 19A (from 9.7% in 2012 to 5.6% in 2014, p = 0.027). In the post-PCV13 period, there were also significant increases in some of the serotypes not covered by PCV13 (i.e. serotypes 8, 15A, 20 and 22F). In what concerns antimicrobial resistance, and considering current Clinical Laboratory Standards Institute (CLSI) breakpoints, in 2012-2014, o.5% of the isolates were considered penicillin non-susceptible pneumococci (PNSP) and 17% erythromycin resistant pneumococci (ERP). Regarding the characterization of adult IPD isolates by MLST we found high genetic diversity, with 206 different sequence types (STs) detected. The STs represented 80 different clonal complexes (CCs), but the six more frequent CCs accounted for half of the isolates (CC156, CC191, CC180, CC306, CC62 and CC230). Most of the STs detected related to STs described in other countries. We found the changes in serotypes occurring in adult IPD following PCV7 use in children were mostly driven by the expansion of previously circulating clones or to decreases in most of the lineages expressing a given serotype. Concerning the presence and type of PI-1 and PI-2, only a small proportion of isolates was positive for any of the PIs (31.9%). Most of the isolates expressing PCV7 serotypes presented PI-1 (87.9%), while PI-2 positive isolates were mainly found among isolates expressing serotypes 1 and 7F, which are serotypes included in PCV10 and PCV13. In what concerns the characterization of adult NIPP isolates, we found significant declines in the proportion of vaccines serotypes following the use of PCVs in children, although these declines were less marked than those occurring in adult IPD. In adult NIPP, the proportion of PCV7 serotypes declined from 31% in 1999-2003 to 11% in 2011 (p < 0.001), while the overall proportion of PCV13 serotypes declined from 44% in 2010 to 30% in 2015 (p < 0.001). When considering the 2012-2015 period, and according to current CLSI breakpoints, 1% of adult NIPP isolates were PNSP and 21.7% were ERP. Comparison of NIPP serotypes with IPD serotypes identified associations of several serotypes with either disease presentation. The studies presented in this thesis showed that in Portugal in the time of PCVs use in children outside the national immunization program there were several changes in the characteristics of pneumococci causing disease in adults. While some of the changes suggested herd protection with the use of PCVs in children, others were independent. The inclusion of PCV13 in the national immunization program for children in June 2015 may be further reducing the importance of PCV13 serotypes in adult IPD and adult NIPP. However, increases of particular non-PCV13 serotypes in adult IPD are concerning and should be monitored. Continued IPD and NIPP epidemiological surveillance is important due to different serotype distribution and dynamics of pneumococci causing each disease presentation

Personality and attachment in the homeless: a systematic review

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2022Introdução: As pessoas em situação de sem-abrigo apresentam uma elevada prevalência de psicopatologia, incluindo perturbações da personalidade. Dada a associação entre perturbações da personalidade e vinculação, e a potencial importância destes dois temas na compreensão das pessoas sem-abrigo, o objetivo deste estudo foi o de rever todos os artigos que analisaram as perturbações da personalidade e a vinculação nas pessoas sem-abrigo. Métodos: Nesta revisão usaram-se critérios de inclusão amplos, de modo a incluir todos os estudos sobre vinculação nos sem abrigo e todos os estudos sobre personalidade nos sem-abrigo, que tenham avaliado a distribuição de pelo menos três perturbações da personalidade. Um total de 213 estudos foram analisados por título e resumo, dos quais 63 foram escolhidos para leitura do texto completo. Destes, 14 artigos obedeceram aos critérios de inclusão, tendo sido incluídos nesta revisão sistemática. Resultados: Dos 14 artigos incluídos, seis estudos avaliaram as perturbações da personalidade e oito estudos avaliaram a vinculação. As perturbações da personalidade revelaram-se muito frequentes nas pessoas sem-abrigo, ocorrendo em 64% a 79% das amostras. As perturbações da personalidade paranoide, borderline, evitante e anti-social foram as mais comummente identificadas, embora as suas frequências tenham variado entre os estudos. Os artigos sobre vinculação diferiram nos métodos usados e nos resultados obtidos. Ainda assim, observou-se uma predominância dos estilos de vinculação insegura nas pessoas sem-abrigo (62% a 100% das amostras). Conclusões: A elevada prevalência das perturbações da personalidade e dos estilos de vinculação insegura nos sem-abrigo pode ter um impacto negativo nas estratégias de intervenção planeadas para ajudar estas pessoas. Esta revisão sistemática demonstrou que a literatura disponível sobre as perturbações da personalidade e a vinculação nos sem-abrigo é escassa, e que mais estudos são necessários sobre estes dois temas.Background: Homeless people present high rates of psychopathology, including personality disorders. Given the link between personality disorders and attachment and the potential importance of these two traits for understanding homeless populations, our aim was to review all studies focusing on personality disorders and attachment in the homeless. Methods: We used broad inclusion criteria to include all studies focusing on attachment and on at least three personality disorders in the homeless. Overall, 213 studies were screened through title and abstract. Of these, 63 were chosen for full-text assessment. A total of 14 articles met eligibility criteria and were included. Results: Six studies evaluated personality in the homeless and eight studies focused on attachment in the homeless. In general, reports suggest personality disorders are highly frequent in the homeless, with frequencies ranging between 64% and 79% for any personality disorder. The most common personality diagnoses were paranoid, borderline, avoidant and antisocial personality disorders, but their frequencies varied greatly between studies. Attachment reports differed in the methods used and presented diverse results and correlates. Even so, insecure types of attachment dominated in the homeless in the few studies showing this analysis (accounted for 62% to 100% of the samples). Conclusions: The high prevalence of personality disorders and insecure types of attachment in the homeless may impact intervention strategies for the homeless. The available literature focusing on attachment and the full assessment of personality disorders in the homeless is scarce. The present review supports the need for more research on these two topics

Infecção pneumocócica invasiva no adulto em Portugal em 2008 e 2009

Tese de mestrado. Biologia (Microbiologia Aplicada). Universidade de Lisboa, Faculdade de Ciências, 2011Streptococcus pneumoniae é um microrganismo patogénico do Homem, responsável por elevadas taxas de morbilidade e mortalidade em todo o mundo. A epidemiologia da infecção pneumocócica tem sido fundamental para avaliar a adaptação deste microrganismo à pressão imposta pela vacinação e uso de antibióticos. Esta tese teve como objectivo caracterizar feno e genotipicamente uma colecção de 425 estirpes de pneumococos responsável por infecção invasiva em adultos (18 a 64 anos de idade), em 2008 e 2009, em Portugal. Visto que no período em análise esteve disponível a vacina anti-pneumocócica conjugada 7-valente (PCV7), pretendeu-se ainda comparar estes resultados com os referentes ao período pré-vacinal de modo a avaliar o possível impacto da vacinação das crianças, na população pneumocócica que afecta os adultos. A caracterização fenotípica consistiu na serotipagem e determinação das taxas de susceptibilidade a diferentes classes de antimicrobianos, e a caracterização genotípica consistiu na determinação dos perfis de macrorestrição, obtidos por electroforese em gel de campo pulsado (PFGE), e perfis de Multi Locus Sequence Typing (MLST) e ainda na detecção da presença e distribuição das ilhas de patogenecidade que codificam para os pili tipo 1 (PI-1) e 2 (PI-2). Os serotipos 1, 3, 7F, 14 e 19A foram os mais frequentes, tendo provocado cerca de 50% das infecções. A não susceptibilidade à penicilina e eritromicina foi observada em 16,7% e em 14,6% das estirpes, respectivamente. Os complexos clonais CC306, CC156, CC191, CC62, CC180 e CC230 surgiram em aproximadamente metade das estirpes analisadas por MLST. As ilhas de patogenicidade PI-1 e PI-2 foram identificadas em 13,3% e em 28% das estirpes, respectivamente. Entre o período pré-vacinal e o analisado neste trabalho observou-se uma diminuição significativa da proporção de infecções provocadas pelo serotipo 4, um aumento significativo, para cerca do dobro, da não susceptibilidade à eritromicina e uma emergência de linhagens genéticas pré-existentes.Streptococcus pneumoniae is a human pathogen responsible for high rates of morbidity and mortality worldwide. The epidemiology of pneumococcal infections has been critical to evaluate the adaptation of this microorganism to the pressure imposed by vaccination and antimicrobial use. The aim of this thesis was to characterize pheno and genotypically a collection of 425 pneumococcal strains responsible for invasive pneumococcal disease in adults (with 18 to 64 years old), in 2008 and 2009, in Portugal. A pneumococcal 7-valent conjugate vaccine (PCV7) was available in this period and so, this thesis also aims to compare these results with the ones obtained in the pre-vaccine era, to evaluate the possible impact that vaccinating children with this vaccine might have had in the adult pneumococcal population. Phenotypic characterization consisted in serotyping and in antimicrobial susceptibility profiling of the bacterial isolates, while the genotypic characterization consisted in the determination of the macrorestriction profiles, obtained by Pulsed Field Gel Electrophoresis (PFGE), and Multi Locus Sequence Typing (MLST) profiles and also in the detection of the presence and distribution of the pathogenecity islands that encode pilus like structures, PI-1 and PI-2. Serotypes 1, 3, 7F, 14 and 19A were the most frequent, being responsible for almost 50% of all infections. Penicillin and erythromycin non-susceptibility were detected in 16,7% and 14,6% of the bacterial isolates, respectively. Clonal complexes CC306, CC156, CC191, CC62, CC180 and CC230 appeared in almost half of strains analyzed by MLST. Pathogenicity islands PI-1 and PI-2 were identified in 13,3% and 28% of all isolates. Between the pre-vaccine period and the one analyzed in this study, the proportions of serotype 4 infections have significantly decreased, erythromycin non-susceptibility has significantly doubled, and an emergence of the already existent genetic lineages occurred