Emergência da tuberculose muitirresistente e extensivamente resistente : caracterização em co-infectados por VIH e em imunocompetentes

Tese de doutoramento, Medicina (Doenças Infecciosas e Parasitárias), Universidade de Lisboa, Faculdade de Medicina, 2017A tuberculose multirresistente (TB MR) e a tuberculose extensivamente resistente (TB ER) são um importante problema de Saúde Pública, em Portugal. No nosso País, a TB MR e a TB ER começaram a ser identificadas na década de 90 do século passado e, desde então, emergiram em indivíduos co-infectados por vírus da imunodeficiência humana (VIH) e em imunocompetentes, com particular incidência na região de Lisboa. No entretanto, pouco se sabe sobre a sua prevalência real na cidade, as características demográficas e clínicas dos doentes, a contribuição dos toxicodependentes e dos imigrantes ou de outros grupos populacionais para a sua dimensão, se resultam de má adesão ao tratamento ou de transmissão primária, qual é a importância da reinfecção e da co-infecção, quais são os padrões de resistência dominantes, quais são as possibilidades de cura ou qual é a origem e as características das estirpes de M. tuberculosis envolvidas. Em 311 doentes (237 co-infectados por VIH e 74 imunocompetentes), admitidos no Serviço de Doenças Infecciosas, do Hospital de Curry Cabral (HCC), de 1993 a 2012, com o diagnóstico de TB MR ou de TB ER, na sua maioria de nacionalidade portuguesa (80,7%) e residentes no distrito de Lisboa (89,4%), fez-se um estudo misto (retrospectivo e prospectivo) e comparativo entre aqueles dois grupos de doentes. Para tal, avaliaram-se as suas características epidemiológicas e clínicas, de diagnóstico, de resposta à terapêutica e de evolução e, a partir das culturas, ainda, disponíveis, fez-se a caracterização genética das estirpes isoladas de M .tuberculosis. Para os genótipos identificados foram, de igual modo, diferenciadas as mesmas características. Naquele período de tempo (1993 a 2012) verificou-se que a prevalência conjunta de TB MR e TB ER, entre o total de doentes com tuberculose (TB), foi elevada (12,7%) e, por outro lado, a sua incidência média anual (11,2%), foi superior à reportada pelas autoridades de saúde para o mesmo período, em Portugal (valor máximo de 3,1% em 2000) e que, embora mostrando tendência para diminuir e estabilizar, depois de 2007, em valor próximo de 3%, permaneceu mais elevada do que no resto do País (0,6%, em 2012). Nesta amostra, os co-infectados por VIH foram o principal grupo de doentes afectados pela TB MR e TB ER, com uma incidência média anual de 13,2% vs 8,7% em imunocompetentes, contudo, enquanto nos anos 90 a doença afectou, sobretudo, co-infectados e toxicodependentes, com história de má adesão ao tratamento (TB MR ou TB ER secundária), os quais, nessa época, disseminaram a doença em meio hospitalar e na comunidade, nos últimos anos (2006 a 2011), a incidência foi semelhante ou maior em imunocompetentes e foi maior a proporção de casos de TB MR ou de TB ER primária. Na globalidade dos doentes deste estudo, 60,7% dos casos de TB MR e TB ER resultou de transmissão primária. A doença atingiu, sobretudo, grupos etários jovens e uma proporção importante de imigrantes imunocompetentes e, numa percentagem relevante dos doentes, não se identificaram factores de risco para TB, nem história de TB anterior, fazendo supor um elevado potencial de transmissão na comunidade. Entre os doentes de Lisboa identificou-se o padrão típico na TB MR, caracterizado por resistência à isoniazida (INH), à rifampicina (RMP), ao etambutol (EMB) e à estreptomicina (SM), que foi comum a co-infectados por VIH e a imunocompetentes, com ou sem história de TB prévia. Este facto é sugestivo de transmissão activa entre os dois grupos de doentes e, provavelmente, de co-infectados por VIH para imunocompetentes, porque entre estes foi maior o número dos que nunca haviam tido TB. A sobreposição verificada nos padrões de resistência e o facto da maioria dos doentes não ter história de TB prévia sugere, de igual modo, que a maioria dos casos resultou de infecção primária ou de reinfecção recente e, em consequência, de transmissão na comunidade e não de reactivação. Nos doentes com TB MR e TB ER, a taxa de resistência individual aos restantes antibacilares testados foi muito elevada (superior a 60% para qualquer dos fármacos de 1ª linha e às fluoroquinolonas e superior a 48% para os injectáveis de 2ª linha), condicionando o sucesso terapêutico e prevendo a evolução para a tuberculose totalmente resistente (TB TR), potencialmente, intratável, a qual, também, foi identificada na amostra deste estudo. Não se encontraram diferenças de apresentação clínica, laboratorial ou radiológica, as quais permitissem suspeitar, atempadamente, do diagnóstico, mas detectaram-se responsabilidades que podem ser repartidas pelos clínicos, pela negligência dos doentes e pelos atrasos na informação dos resultados do diagnóstico, que contribuíram para longos tempos de doença oculta, não diagnosticada (mediana de 77 dias), que favoreceram a disseminação da TB na comunidade e que comprometeram, de igual modo, o sucesso terapêutico e o prognóstico, particularmente no grupo dos co-infectados por VIH. A taxa de cura dos doentes com TB MR e TB ER foi de 13,4% para os co-infectados e de 62,9% para os imunocompetentes e o tempo mediano de sobrevivência, após o diagnóstico, foi, respectivamente, de 4,6 meses e de 91 meses. A caracterização genética de 92 estirpes de M. tuberculosis, provenientes de igual número de doentes, mostrou que pertencem a uma família designada, no início dos anos 90, de Lisboa e que são as mais prevalentes e as principais responsáveis pela epidemia que ocorre na cidade. Dois clusters (76,1% de todas as estirpes caracterizadas), designados por cluster Lisboa (56,5% das estirpes) e por cluster B (19,6% das estirpes), com homologia acima de 85%, disseminaram-se, de início em meio hospitalar, sobretudo entre co-infectados por VIH e toxicodependentes (causaram uma epidemia nosocomial naquele Serviço de Doenças Infecciosas, em 1995 e 1996, em que o estudo genético comprovou a reinfecção e co infecção por estirpes diferentes). De seguida, espalharam-se na comunidade e para fora do País e continuaram a ser, até 2012, os clusters mais identificados, sendo os responsáveis pelo maior número de casos de TB MR e TB ER da cidade, agora, sobretudo primária e entre imunocompetentes. Os padrões de resistência mais prevalentes, em cada cluster, coincidiram, também, com os mais identificados nos doentes ao longo do estudo, sendo de assinalar que, quatro das estirpes estudadas eram de TB TR. As estirpes pertencentes a estes dois clusters associaram-se a taxas menores de cura (21,7% no cluster Lisboa e 25% no cluster B) e a tempos medianos mais baixos de sobrevivência (7,1 meses no cluster Lisboa e 6,2 meses no cluster B) do que os de outras estirpes e o seu comportamento epidemiológico e clínico assemelhou-se ao de estirpes, caracterizadas, também, por mortalidade elevada e rapidez de progressão, como a célebre estirpe Beijing. Por fim, assinale-se a identificação, na amostra, de duas estirpes Beijing, o que comprova o risco de introdução periódica de novas estirpes de M. tuberculosis no nosso meio, o que pode vir a dificultar o controlo da epidemia. O conjunto dos dados obtidos neste estudo ajuda a perceber as razões e características da epidemia, a entender a cadeia epidemiológica entre co-infectados por VIH e imunocompetentes e a conhecer as estirpes responsáveis pela TB MR e TB ER, em Lisboa, contribuindo para se adequarem as medidas de prevenção e de terapêutica da TB à realidade do meio.Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant (XDR-TB) are a major public health issue, in Portugal. In our country, MDR-TB and XDR-TB were first reported in the last decade of the past century and, since then, emerged among immunocompetents and human immunodeficiency virus (HIV) coinfected individuals, with particular incidence in the region of Lisbon. Meanwhile, little is known about their real prevalence, the demographic and clinical features of the patients, the relative weight of injecting-drug users, immigrants or other specific groups on the global burden of the disease, whether they represent the outcome of poor adherence to treatment or primary transmission, what the importance of reinfection and coinfection, the dominating resistance patterns, the real cure rates or the origin and particular features of the Mycobacterium tuberculosis strains involved. A mixed retrospective and prospective comparative study was done involving 311 patients (237 HIV-coinfected and 74 immunocompetents) admitted to the Infectious Diseases Department of Hospital de Curry Cabral, between 1993 and 2012, who were diagnosed with MDR-TB or XDR-TB. The majority were portuguese (80,7%) and lived in the district of Lisbon (89,4%). Epidemiological, clinical and diagnosis features, response to treatment and prognosis were assessed among the two population groups, and genetic characterization of the isolated Mycobacterium tuberculosis strains was performed from those cultures that were still available. For the different genotypes identified, the same characteristics were assessed. In the study period (1993 to 2012), the joint prevalence of MDR and XDR-TB among the total of tuberculosis (TB) cases was found to be high (12,7%). Additionally, its average annual incidence (11,2%) was found to be superior to that reported by the national health authorities for the same time period, in Portugal (maximum of 3,1% in 2000) and, despite showing, since 2007, a trend towards a decline and stabilization around 3%, it remained higher than in the rest of the country (0,6% in 2012). In the present sample, the HIV coinfected were the main group affected by MDR-TB and XDR-TB, with a average annual incidence of 13,2% versus 8,7% in immunocompetents. However, while in the 90s the disease mainly affected HIV-coinfected patients and injecting-drug users, with a past history of poor adherence to treatment regimens (secondary MDR or XDR-TB) and who were responsible for disease spread both in the hospital setting and in the community, in recent years (2006 to 2011) the incidence was similar or even higher among immunocompetents, and the relative proportion of primary MDR and XDR-TB cases was also higher. Considering the whole period of the study, 60,7% of the cases of MDR and XDR-TB resulted from primary transmission. The disease mainly affected young age groups and an important proportion of immunocompetent immigrants and, in a significant percentage of patients no past history or traditional risk factors for TB were found, suggesting a high potential for transmission in the community. Among this group of patients from Lisbon, the classical resistance pattern for MDR-TB was observed, characterized by resistance to isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), which was present in both HIV-coinfected and immunocompetent patients, regardless of past history of TB. This fact suggests active transmission between these two patient groups and, probably, from HIV-coinfected to immunocompetent patients, since the proportion of patients with no previous history of TB was higher among the latter. The overlapping patterns of resistance and the absence of past history of TB in the majority of patients also suggests that most cases resulted from primary infection or recent reinfection and, consequently, from ongoing transmission in the community instead of reactivation. In this group of MDR and XDR-TB patients, a very high individual resistance rate to other anti-tuberculous drugs was observed (above 60% for first-line drugs plus fluoroquinolones, and above 48% for second-line injectable agents), limiting the therapeutic success and anticipating the progression to totally drug-resistant tuberculosis (TDR-TB), potentially incurable, which was also identified in the present study. No significant differences in the clinical, laboratory or radiological presentation that could allow for a timely suspicion of the diagnosis were found. Shared responsabilities between physicians, delay in diagnosis communication and patient carelessness were identified, though, which accounted for prolonged hidden, undiagnosed disease (median of 77 days), favoured dissemination in the community and hampered therapeutic outcome and prognosis, particularly among HIV-coinfected patients. Cure rate for MDR-TB and XDR-TB patients was 13,4% in the HIV-coinfected and 62,9% in the immunocompetent group, and the median survival time after diagnosis was 4,6 and 91 months, respectively.Genetic characterization of 92 Mycobacterium tuberculosis strains, from the same number of patients, showed that they belong to a family denominated, in the early 90s, as Lisbon, and that they are the most prevalent and main responsible for the ongoing epidemics in the city. Two clusters (76,1% of the characterized strains), designated Lisbon cluster (56,5% of the strains) and B cluster (19,6% of the strains), with genetic homology above 85%, initially disseminated in the intra-hospital setting, mainly among HIV-coinfected and injecting-drug users (causing a nosocomial epidemics in the aforementioned Infectious Diseases Department, in 1995 and 1996, where the genotypic testing proved reinfection or coinfection with different strains). Later, these clusters spread in the community and abroad, and continued to be, until 2012, the most commonly identified ones, accounting for the majority of MDR and XDR-TB cases in the city, nowadays consisting mainly on primary infection among immunocompetents. Most prevalent resistance patterns for each cluster overlap, with those most commonly observed in the patients of this study. Remarkably, four strains corresponded to TDR-TB cases. Strains included in these two clusters were associated with lower cure rates (21,7% for the Lisbon cluster and 25% for the cluster B) and lower median survival times (7,1 months for the Lisbon cluster and 6,2 months for the cluster B) than other strains, and their clinical and epidemiological behavior resembled that one of strains characterized by fast disease progression and high mortality rates, such as the renowned Beijing strain. Finally, worth mentioning, two Beijing strains were identified in the sample of this study, which proves the ongoing risk of periodic introduction of new Mycobacterium tuberculosis strains in our setting, which might limit the ability to control the epidemics. The data obtained in this study is a valuable help to recognize the causes and characteristics of the epidemics, to understand the epidemiological chain between HIV-coinfected and immunocompetents and to identify the strains responsible for MDR and XDR-TB in Lisbon, contributing to the adaptation of TB preventive and therapeutic measures

Genetic variants of the IFITM3 gene reveal a potential modifier of influenza severity

As epidemias de gripe representam um sério problema de saúde pública com elevados custos económicos. Foi sugerido que um dos alelos do gene IFITM3 (rs12252-C) constitui um impor tante fator de risco de base populacional para as formas graves da gripe por infeção pelo vírus A(H1N1)pdm09. Analisámos variantes do IFITM3 associadas à gravidade da doença em doentes por tugueses (n=41). Foram identificados sete SNPs no amplicão de 352bp do IFITM3 em torno do rs12252. De acordo com HapMap, o SNP rs34481144 per tence ao mesmo bloco de desequilíbrio de ligação (LD) que rs12252, e está em LD com rs6421983. A associação negativa com formas sintomáticas graves em relação a ligeiras obser vada para o alelo rs34481144-A é sugestiva de um efeito protetor no modelo de hereditariedade dominante. Para além disso, o haplótipo Hap4 com rs34481144-A, e sem o rs12252-C, mostrou estar significativamente associado a gripe sintomaticamente ligeira. Por outro lado, apesar de a um nível de significância limiar, o haplótipo Hap1 com rs34481144-G, sem rs12252-C, mostrou-se associado à gripe com sintomatologia grave. Em comparação com a população por tuguesa em geral, foram obser vadas diferenças significativas nas frequências do alelo possivelmente protetor rs34481144-A no grupo com sintomatologia grave, do Hap1 deletério no grupo com sintomatologia ligeira e do Hap4 protetor no grupo com doença grave. A proporção de casos com sintomas graves que poderiam ser evitados se todos os indivíduos da população apresentassem o alelo protetor rs34481144-A foi estimada em 56% e 64%, respetivamente na população em geral e no grupo de indivíduos com doença ligeira. A implicação destas variantes nos fenótipos da doença necessita de estudos de validação, nomeadamente de natureza funcional.Influenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a strong population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed IFITM3 variants for association to influenza severity in Por tuguese patients (n=41). Seven SNPs, within the 352bp IFITM3 amplicon around rs12252, were identified. According to HapMap SNP rs34481144 belongs to the same linkage disequilibrium (LD) block as rs12252, and is in strong LD with rs6421983. A negative association with severe relative to mild disease was obser ved for allele rs34481144-A, indicating a protective ef fect under the dominant model. Moreover, haplotype Hap4 with rs34481144-A, not including rs12252-C, was significantly associated to mild influenza. Conversely, although with borderline significance, haplotype Hap1 with rs34481144-G, not including rs12252-C, was associated to severe disease. Moreover, in comparison to the general Por tuguese population, statistical significant dif ferences in the frequencies of the protective allele rs34481144-A in the severe disease group, the deleterious Hap1 in the mild disease group and the protective Hap4 in the severe disease group, were obser ved. The population attributable risk (PAR) for the targeted rs34481144 allele or genotype was of 55.91% and 64.44% in the general population and the mildly infected individuals, respectively. Implication of these variants in disease phenotype needs fur ther validation, namely through functional analysis.Este trabalho foi financiado pela Fundação Luso-Americana para o Desenvolvimento (LACR Award program - 2007) e pela Fundação para a Ciência e Tecnologia (FCT), Portugal, (POCTI/ESP/44826/2002), com a comparticipação dos fundos da Comunidade Europeia (FEDER).info:eu-repo/semantics/publishedVersio

Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting.

BACKGROUND: Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades. RESULTS: In the present study we have genotyped and sequenced the genomes of 56 Mycobacterium tuberculosis isolates recovered mostly from Lisbon. The genotyping data revealed three major clusters associated with MDR-TB, two of which are associated with XDR-TB. Whilst the genomic data contributed to elucidate the phylogenetic positioning of circulating MDR-TB strains, showing a high predominance of a single SNP cluster group 5. Furthermore, a genome-wide phylogeny analysis from these strains, together with 19 publicly available genomes of Mycobacterium tuberculosis clinical isolates, revealed two major clades responsible for M/XDR-TB in the region: Lisboa3 and Q1 (LAM).The data presented by this study yielded insights on microevolution and identification of novel compensatory mutations associated with rifampicin resistance in rpoB and rpoC. The screening for other structural variations revealed putative clade-defining variants. One deletion in PPE41, found among Lisboa3 isolates, is proposed to contribute to immune evasion and as a selective advantage. Insertion sequence (IS) mapping has also demonstrated the role of IS6110 as a major driver in mycobacterial evolution by affecting gene integrity and regulation. CONCLUSIONS: Globally, this study contributes with novel genome-wide phylogenetic data and has led to the identification of new genomic variants that support the notion of a growing genomic diversity facing both setting and host adaptation

The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients

<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the <it>env </it>C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2–4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity</p> <p>Results</p> <p>The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites.</p> <p>Conclusion</p> <p>The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size limiting the number of virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope recognition by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design.</p

HIV infection: time from diagnosis to initiation of antiretroviral therapy in Portugal, a multicentric study

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).The benefits of antiretroviral therapy (ART) for persons living with HIV (PLWH) are well established. Rapid ART initiation can lead to improved clinical outcomes. Portugal has one of the highest rates of new HIV diagnoses in the European Union, and an average time until ART initiation above the recommendations established by the national guideline according to data from the first two years after its implementation in 2015, with no more recent data available after that. This study aimed to evaluate time from the first hospital appointment until ART initiation among newly diagnosed HIV patients in Portugal between 2017 and 2018, to investigate differences between hospitals, and to understand the experience of patient associations in supporting the navigation of PLWH throughout referral and linkage to the therapeutic process. To answer to these objectives, a twofold design was followed: a quantitative approach, with an analysis of records from five Portuguese hospitals, and a qualitative approach, with individual interviews with three representatives of patient associations. Overall, 847 and 840 PLWH initiated ART in 2017 and in 2018, respectively, 21 days (median of the two years) after the first appointment, with nearly half coming outside the mainstream service for hospital referral, and with observed differences between hospitals. In 2017–2018, only 38.0% of PLWH initiated ART in less than 14 days after the first hospital appointment. From the interviews, barriers of administrative and psychosocial nature were identified that may hinder access to ART. Patient associations work to offer a tailored support to patients’ navigation within the health system, which can help to reduce or overcome those potential barriers. Indicators related to time until ART initiation can be used to monitor and improve access to specialized care of PLWH.info:eu-repo/semantics/publishedVersio

Using genomics to understand the origin and dispersion of multidrug and extensively drug resistant tuberculosis in Portugal.

Portugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR- and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach

Anal Cancer in HIV Patients - Experience at Hospital de Curry Cabral

Introdução: Os homens que têm sexo com homens, particularmente os infectados pelo vírus da imunodeficiência humana (VIH) têm risco aumentado de cancro anal. Ao contrário da maior parte das doenças oportunistas e/ou definidoras de SIDA, os dados são contraditórios no que diz respeito ao efeito da terapêutica antirretrovírica, não sendo claro o impacto da supressão virológica e reconstituição imunitária na evolução da infecção por vírus do papiloma humano (HPV) e prevenção das neoplasias associadas. Actualmente é já recomendada a vacinação de doentes com infecção por VIH contra o HPV; os programas de rastreio do cancro anal, recomendados por algumas organizações, carecem ainda de validação definitiva da sua eficácia.Material e Métodos: Os autores fizeram um estudo retrospectivo dos casos de cancro anal diagnosticados entre 2000-2015 em doentes com infecção por VIH em seguimento no serviço de Infecciologia do Hospital de Curry Cabral, em Lisboa. São avaliadas as características clínicas e epidemiológicas dos doentes com cancro do canal anal ao longo de um período de quinze anos.Resultados: O cancro anal foi diagnosticado em dez doentes, maioritariamente homens HSH, com infecção por VIH com uma duração média de 15,1 anos, com contagem média de linfócitos TCD4+ de 441 células/uL. O diagnóstico foi mais frequentemente realizado no estádio III e o tratamento mais frequente foi cirúrgico, ocasionalmente conjugado com radioterapia. Faleceram 4 doentes.Conclusões: São necessários programas de rastreio consensuais do cancro anal, a par da necessidade de reforço da vacinação contra o HPV nos homens, nomeadamente nos homens que têm sexo com homens, com ou sem infecção por VIH.Introduction: Men who have sex with men, particularly those infected by human immunodeficiency virus (HIV), have an increased risk of anal cancer. Unlike most opportunistic or AIDS-defining events, data have been contradictory regarding impact of antiretroviral therapy, viral suppression and immunologic reconstitution on HPV infection prevention and related cancers. Vaccination against human papillomavirus (HPV) is presently recommended in all HIV-infected patients, whereas there is still an on-going debate about the need for anal cancer screening programmes.Material and methods: The authors performed a retrospective study of anal cancer cases diagnosed between 2000-2015 in HIV patients on follow up at the Infectious Diseases Unit at Hospital de Curry Cabral, in Lisbon. We present the clinical and epidemiological characteristics of anal cancer cases throughout a fifteen-year period.Results: Anal cancer was diagnosed in ten patients, most of them MSM, HIV-infected for an average time of 15.1 years, with an average TCD4+ cell count of de 441 cells/uL. Anal cancer diagnosis was more frequently performed at stage III and treatment most frequently involved surgery, occasionally with radiotherapy. Four patients died.Conclusion: There is a need for consensual anal cancer screening programs, along with a need to reinforce HPV vaccination in men, particularly men who have sex with men, regardless of HIV infection

Ensaio de cravação pneumática de pino para avaliação da resistência à compressão de juntas de assentamento de alvenaria estrutural

Ensaios não destrutivos têm sido propostos e usados para avaliação das condições de alvenarias estruturais, para controle de qualidade e propriedades dos materiais in loco. Entretanto, a maioria dos métodos funciona apenas para argamassas com baixa resistência à compressão (&lt; 4,0 MPa) ou servem apenas para avaliação qualitativa, além de não serem práticos para uso em campo, demandando muito tempo para a realização das avaliações. Em função disso, um pinador pneumático foi utilizado para avaliar a profundidade de penetração de pinos de aço e correlacioná-la com a resistência à compressão de argamassas em laboratório. O trabalho mostrou que há uma boa correlação entre a profundidade de cravação de pinos e a resistência à compressão das argamassas, além de ser um ensaio prático, rápido e fácil de ser realizado in loco

Clinical and epidemiological features of hospitalized and ambulatory patients with human monkeypox infection: a retrospective observational study in Portugal

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Monkeypox, a neglected and re-emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.The writing of this manuscript received the support of Fundação para a Ciência e a Tecnologia, grant numbers UIDB/04295/2020 and UIDP/04295/2020info:eu-repo/semantics/publishedVersio