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1.
N Engl J Med ; 387(8): 679-691, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35866746

RESUMO

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.


Assuntos
Saúde Global , Mpox , Adulto , Exantema/etiologia , Feminino , Febre/etiologia , Saúde Global/estatística & dados numéricos , Humanos , Masculino , Mpox/epidemiologia , Mpox/terapia , Monkeypox virus
2.
Euro Surveill ; 29(21)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38785087

RESUMO

An outbreak of hepatitis A is ongoing in Portugal, with 71 confirmed cases from 7 October 2023 to 24 April 2024. Most cases are male, aged 18-44 years, with many identifying as men who have sex with men (MSM) and reported as suspected sexual transmission. Phylogenetic analysis identified the subgenotype IA, VRD 521-2016 strain, last observed in an MSM-associated multi-country outbreak in 2016 to 2018. We wish to alert colleagues in other countries to investigate potential similar spread.


Assuntos
Surtos de Doenças , Genótipo , Hepatite A , Homossexualidade Masculina , Filogenia , Humanos , Masculino , Portugal/epidemiologia , Hepatite A/epidemiologia , Hepatite A/transmissão , Homossexualidade Masculina/estatística & dados numéricos , Adulto , Adolescente , Adulto Jovem , Vírus da Hepatite A/genética , Vírus da Hepatite A/isolamento & purificação , Vírus da Hepatite A/classificação , Pessoa de Meia-Idade , Comportamento Sexual , Feminino , Busca de Comunicante
3.
Clin Infect Dis ; 77(5): 740-748, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37288954

RESUMO

BACKGROUND: Integrase strand transfer inhibitor-based regimens are recommended for first-line therapy in human immunodeficiency virus type 2 (HIV-2). Nonetheless, dolutegravir (DTG) clinical trial data are lacking. METHODS: We conducted a phase 2, single-arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen that included DTG in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naive adults receive DTG in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of patients who achieved a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+ T-cell count and in CD4/CD8 ratio at week 48. RESULTS: A total of 30 patients were enrolled (22 women; median age, 55 years). At baseline, 17 (56.7%) individuals were viremic (median, pVL 190 copies/mL; interquartile range [IQR], 99-445). The median CD4 count was 438 cells/µL (IQR, 335-605), and the CD4/CD8 ratio was 0.8. Three patients discontinued the study. At week 48, all participants (27) had pVL <40 copies/mL. No virological failures were observed. Mean changes in CD4 count and CD4/CD8 ratio at week 48 were 95.59 cells/µL (95% confidence interval [CI], 28-163) and 0.32 (95% CI, .19 to .46). The most common drug-related adverse events were headache and nausea. One participant discontinued due to central nervous system symptoms. No serious adverse events were reported. CONCLUSIONS: DTG plus 2 NRTIs is safe and effective as first-line treatment for PWHIV-2 with a tolerability profile previously known. No virological failures were observed that suggest a high potency of DTG in HIV-2 as occurs in HIV-1. CLINICAL TRIALS REGISTRATION: M NCT03224338.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Fármacos Anti-HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-2 , Inibidores da Transcriptase Reversa/efeitos adversos , Resultado do Tratamento , Carga Viral , Masculino
4.
Emerg Infect Dis ; 28(5): 1068-1071, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35447057

RESUMO

We report a case of rickettsiosis caused by Rickettsia monacensis in an immunocompetent 67-year-old man in Portugal who had eschar, erythematous rash, and an attached Ixodes ricinus tick. Seroconversion and eschar biopsy led to confirmed diagnosis by PCR. Physicians should be aware of this rare rickettsiosis, especially in geographic regions with the vector.


Assuntos
Ixodes , Infecções por Rickettsia , Rickettsia , Idoso , Animais , Humanos , Ixodes/microbiologia , Masculino , Portugal , Rickettsia/genética , Infecções por Rickettsia/diagnóstico , Infecções por Rickettsia/tratamento farmacológico , Infecções por Rickettsia/microbiologia
5.
HIV Med ; 23(6): 585-598, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34889022

RESUMO

OBJECTIVES: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non-liver malignancies in people living with HIV (PLWH). METHODS: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. RESULTS: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person-years of follow-up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94-8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47-12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV-positive versus HBV-negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00-1.51]. Compared to HBV-negative individuals, HBsAg-positive/HBV-DNA-positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00-1.89) and NHL (aIRR 2.57; 95% CI 1.16-5.68). There was no significant association between HBV and lung or anal cancer. CONCLUSIONS: We found increased rates of nonliver malignancies in HBsAg-positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV-positive subjects with chronic HBV infection.


Assuntos
Infecções por HIV , Hepatite B Crônica , Hepatite B , Neoplasias , DNA Viral , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Humanos , Neoplasias/complicações
6.
Clin Infect Dis ; 70(10): 2131-2140, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31504296

RESUMO

BACKGROUND: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. METHODS: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). RESULTS: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. CONCLUSIONS: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.


Assuntos
Carcinoma Hepatocelular , Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos
7.
Immunogenetics ; 70(3): 169-177, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28842783

RESUMO

Influenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed the population genetics of IFITM3 variants in the Portuguese general population (n = 200) and Central Africans (largely Angolan) (n = 148) as well as its association to influenza severity in Portuguese patients (n = 41). Seven SNPs, within the 352 bp IFITM3 amplicon around rs12252, were identified. SNP distributions in the Portuguese appeared at an intermediate level between the Africans and other Europeans. According to HapMap, 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 observed for allele rs34481144-A, indicating a protective effect 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 Portuguese population, statistical significant differences 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 observed. 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 further validation, namely through functional analysis as is discussed.


Assuntos
Genética Populacional , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/genética , Proteínas de Membrana/genética , Proteínas de Ligação a RNA/genética , Adulto , África Central/epidemiologia , Alelos , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Portugal/epidemiologia , Proteínas de Ligação a RNA/imunologia , Fatores de Risco , Índice de Gravidade de Doença
8.
Ann Hepatol ; 17(2): 335-338, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29469037

RESUMO

Hepatitis E in industrialized countries is mainly associated with genotype 3 hepatitis E virus (HEV) and normally causes a sporadic self-limiting disease in immunocompetent individuals. Unlike genotype 3, genotypes 1 and 2 circulate in developing countries, produce severe disease and occur in the epidemic form. Hepatitis E occurring in travellers returning from endemic areas in developing countries is not a novel epidemiological occurrence, however the vast majority of cases remain to be genetically studied. The present study describes two cases of severe acute hepatitis E that required hospitalization for 6 and 9 days in two individuals of Indian nationality that had recently migrated to Portugal to work. The retrieved HEV sequences both belonged to genotype 1 and had a high degree of nucleotide sequence identity, clustering with strains isolated in India and Nepal, in 2013 and 2014. Confirmed HEV genotypes of increased pathogenicity like genotype 1 are being introduced into otherwise naïve populations of industrialized countries such as European countries with consequences difficult to predict. As far as we know the present study is the first in Portugal to describe and genetically characterize imported cases of hepatitis E infection caused by HEV genotype 1.


Assuntos
DNA Viral/genética , Vírus da Hepatite E/genética , Hepatite E/virologia , Adulto , Emigrantes e Imigrantes , Emigração e Imigração , Genótipo , Hepatite E/diagnóstico , Hepatite E/terapia , Vírus da Hepatite E/patogenicidade , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Portugal , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Euro Surveill ; 23(21)2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29845931

RESUMO

BACKGROUND: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection. AIM: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA < 500 copies/mL) across Europe and explored temporal trends. METHODS: In three cross-sectional analyses in 2004-05, 2009-10 and 2014-15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression. RESULTS: Overall, the percentage of people on ART increased from 2004-05 (67.8%) to 2014-15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004-05, 87.7% in 2014-15). However, the rate of improvement over time varied significantly between regions (p < 0.01). In 2014-15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014-15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13-0.21) in Eastern Europe. CONCLUSIONS: Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Disparidades em Assistência à Saúde/estatística & dados numéricos , Resposta Viral Sustentada , Carga Viral/efeitos dos fármacos , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Falha de Tratamento
10.
Clin Infect Dis ; 64(10): 1413-1421, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28329090

RESUMO

BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fraturas Ósseas/etiologia , Infecções por HIV/complicações , Osteonecrose/etiologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Contagem de Linfócito CD4 , Estudos de Coortes , Coinfecção/epidemiologia , Coleta de Dados , Europa (Continente)/epidemiologia , Feminino , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/virologia , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etnologia , Fraturas Ósseas/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose/epidemiologia , Osteonecrose/virologia , Análise de Regressão , Fatores de Risco , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
11.
BMC Genomics ; 15: 991, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25407810

RESUMO

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.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Evolução Molecular , Variação Genética , Genoma Bacteriano , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacologia , Proteínas de Bactérias/genética , Mapeamento Cromossômico , Biologia Computacional , Loci Gênicos , Instabilidade Genômica , Genômica , Genótipo , Humanos , Mutação INDEL , Testes de Sensibilidade Microbiana , Repetições Minissatélites , Filogenia , Polimorfismo de Nucleotídeo Único , Portugal/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
12.
Acta Med Port ; 37(1): 46-50, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36919988

RESUMO

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria. Cellulosimicrobium cellulans is a gram-positive bacterium from the order Actinomycetales that rarely causes human disease. The diagnosis is based on the clinical presentation and identification of the causative microorganism. We present a short literature review regarding the case report of a young man diagnosed with actinomycetoma due to Cellulosimicrobium cellulans and who received treatment with an association of amikacin and sulfamethoxazole/ trimethoprim (Welsh regimen).


Assuntos
Actinomycetales , Micetoma , Masculino , Humanos , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Antibacterianos/uso terapêutico , Guiné-Bissau , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
13.
Cureus ; 16(1): e51532, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38304681

RESUMO

Tuberculous meningitis (TBM) presents a complex clinical scenario, often marked by delayed recognition and high mortality. Our case involves a 27-year-old woman from Nepal with no significant medical history, presented with a two-week history of fatigue, altered consciousness, dizziness, vomiting, fever, holocranial headache, and photophobia. Initial examination revealed signs consistent with meningitis, including fever, hypertensive state, prostration, bilateral exophthalmos, sixth cranial nerve paresis, and positive Kernig/Brudzinski signs. Cerebrospinal fluid (CSF) exhibited characteristics typical of TBM: turbidity, lymphocytic-predominant pleocytosis, low glucose, and elevated protein. The patient was promptly started on meningeal doses of vancomycin, ceftriaxone, and acyclovir. However, persistent fever, neurological deterioration, and signs of increased intracranial pressure led to the decision to initiate conventional empiric treatment of tuberculosis (TB) with isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) and dexamethasone 1 week before cultural positivity for Mycobacterium tuberculosis of CSF. The case underscores the importance of considering TBM in patients from endemic regions, interpreting CSF findings, and initiating empirical treatment in critical scenarios, contributing to a positive patient outcome despite the diagnostic challenges.

14.
Acta Med Port ; 37(5): 323-333, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38325411

RESUMO

INTRODUCTION: Information about pan-genotypic treatments for hepatitis in Portugal is scarce. We aimed to evaluate the effectiveness and safety of glecaprevir plus pibrentasvir (GLE/PIB) treatment for hepatitis C virus (HCV) infection in real-world clinical practice. METHODS: An observational prospective study was implemented in six hospitals with 121 adult HCV patients who initiated treatment with GLE/PIB between October 2018 and April 2019, according to clinical practice. Eligible patients had confirmed HCV infection genotype (GT) 1 to 6 and were either treatment-naïve or had experience with interferon-, ribavirin- or sofosbuvir-based regimens, with or without compensated cirrhosis. Baseline sociodemographic and safety data are described for the total population (N = 115). Effectiveness [sustained virologic response 12 weeks after treatment (SVR12)] and patient-reported outcomes are presented for the core population with sufficient follow-up data (n = 97). RESULTS: Most patients were male (83.5%), aged < 65 years (94.8%), with current or former alcohol consumption (77.3%), illicit drug use (72.6%), and HCV acquisition through intravenous drug use (62.0%). HIV co-infection occurred in 22.6% of patients. The prevalence of each GT was: GT1 51.3%, GT2 1.7%, GT3 30.4%, GT4 16.5%, and GT5.6 0%. Most patients were non-cirrhotic (80.9%) and treatment-naïve (93.8%). The SVR12 rates were 97.9% (95% CI: 92.8 - 99.4), and > 95% across cirrhosis status, GT, illicit drug use, alcohol consumption, and HCV treatment experience. The adverse event rate was 2.6%, and no patient discontinued treatment due to adverse events related to GLE/PIB. CONCLUSION: Consistent with other real-world studies and clinical trials, treatment with GLE/PIB showed high effectiveness and tolerability overall and in difficult-to-treat subgroups (ClinicalTrials.gov: NCT03303599).


Assuntos
Antivirais , Benzimidazóis , Combinação de Medicamentos , Hepatite C Crônica , Pirrolidinas , Quinoxalinas , Sulfonamidas , Humanos , Masculino , Feminino , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Quinoxalinas/uso terapêutico , Quinoxalinas/efeitos adversos , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Idoso , Portugal , Resposta Viral Sustentada , Resultado do Tratamento , Adulto , Leucina/análogos & derivados , Leucina/uso terapêutico , Hepacivirus/genética , Lactamas Macrocíclicas , Ácidos Aminoisobutíricos
15.
Lancet HIV ; 11(5): e321-e332, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38621392

RESUMO

BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. METHODS: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. FINDINGS: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction=0·46 for hypertension; pinteraction=0·31 for dyslipidaemia). INTERPRETATION: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.


Assuntos
Índice de Massa Corporal , Dislipidemias , Infecções por HIV , Hipertensão , Tenofovir , Tenofovir/análogos & derivados , Humanos , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Hipertensão/epidemiologia , Hipertensão/induzido quimicamente , Estudos Prospectivos , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Pessoa de Meia-Idade , Adulto , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Alanina/efeitos adversos , Austrália/epidemiologia , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Europa (Continente)/epidemiologia , Fatores de Risco , Quimioterapia Combinada/efeitos adversos
16.
Front Public Health ; 12: 1336845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500732

RESUMO

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto , Homossexualidade Masculina , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Portugal/epidemiologia , Europa (Continente)
17.
Acta Med Port ; 36(4): 304, 2023 Apr 03.
Artigo em Português | MEDLINE | ID: mdl-37029642

RESUMO

On page 210, lines 9 and 10, where it reads (in red): "(...) confirming stage IV diffuse large B-cell lymphoma NOS, type CCG (...)" It should read (in bold): "(...) confirming stage IV diffuse large B-cell lymphoma NOS, type GCB (...)" Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/16873.


Na página 210, linhas 9 e 10 onde se lê (a vermelho): "(...) confirming stage IV diffuse large B-cell lymphoma NOS, type CCG (...)" Deverá ler-se (a negrito): "(...) confirming stage IV diffuse large B-cell lymphoma NOS, type GCB (...)" Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/16873.

18.
Infect Dis Rep ; 15(2): 171-179, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36960970

RESUMO

We report a fatal case of disseminated mpox infection that progressed over more than three months in an HIV-infected patient with acquired immunodeficiency syndrome (AIDS). Mucocutaneous, pleuropulmonary, central nervous system, and gastrointestinal involvement was documented. This course of disease resembles progressive vaccinia, a formerly reported disease caused by uncontrolled replication of smallpox vaccination orthopoxviruses in immunosuppressed patients. Severe small bowel involvement jeopardized normal oral tecovirimat and antiretroviral therapy absorption. This problem prompted the use of full parenteral antiretrovirals and endovenous cidofovir. Although a remarkable decrease in HIV viral load occurred in six days, mpox infection continued to progress, and the patient died of septic shock. This case offers new clinical insights on the presentation of severe disease in AIDS patients. Moreover, this case alerts for the need for prompt therapy initiation in patients at risk of ominous clinical progression.

19.
Nat Med ; 29(10): 2509-2517, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37696933

RESUMO

Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early in Portugal. We estimated a 62% infection reporting rate and that 1.3% of the population of men who have sex with men in Portugal were infected. We infer the critical role played by sexual networks and superspreader gatherings, such as sauna attendance, in the dissemination of mpox virus. Overall, our findings highlight genomic epidemiology as a tool for the real-time monitoring and control of mpox epidemics, and can guide future vaccine policy in a highly susceptible population.


Assuntos
Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Portugal/epidemiologia , Homossexualidade Masculina , Surtos de Doenças , Análise por Conglomerados
20.
Med Mycol Case Rep ; 38: 21-24, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36203541

RESUMO

Invasive fungal infections caused by Candida species are increasingly observed in immunosuppressed patients. Candida albicans is the more often identified species and neurocandidiasis is associated with high mortality rates. Diagnosis and treatment of these infections are frequently challenging. We report a case of central nervous system infection caused by Candida famata in an HIV-1 infected patient. To our best knowledge this is just the second published case of neural infection by this agent.

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