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1.
N Engl J Med ; 387(21): 1957-1968, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36346079

RESUMEN

BACKGROUND: Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins. METHODS: We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication. RESULTS: The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4). CONCLUSIONS: In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.).


Asunto(s)
Antivirales , Hepatitis B Crónica , Oligonucleótidos Antisentido , ARN Viral , Humanos , Antivirales/efectos adversos , Antivirales/uso terapéutico , ADN Viral/sangre , Antígenos e de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos Antisentido/efectos adversos , Oligonucleótidos Antisentido/uso terapéutico , Resultado del Tratamiento , ARN Viral/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , Inyecciones Subcutáneas
2.
J Cell Mol Med ; 28(7): e18226, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38501860

RESUMEN

More than 3 years after the start of SARS-CoV-2 pandemic, the molecular mechanisms behind the viral pathogenesis are still not completely understood. Long non-coding RNAs (lncRNAs), well-known players in viral infections, can represent prime candidates for patients' risk stratification. The purpose of the current study was to investigate the lncRNA profile in a family cluster of COVID-19 cases with different disease progression, during the initial wave of the pandemic and to evaluate their potential as biomarkers for COVID-19 evolution. LncRNA expression was investigated in nasopharyngeal swabs routinely collected for diagnosis. Distinct expression patterns of five lncRNAs (HOTAIR, HOTAIRM1, TMEVPG1, NDM29 and snaR) were identified in all the investigated cases, and they were associated with disease severity. Additionally, a significant increase in the expression of GAS5-family and ZFAS1 lncRNAs, which target factors involved in the inflammatory response, was observed in the sample collected from the patient with the most severe disease progression. An lncRNA prognostic signature was defined, opening up novel research avenues in understanding the interactions between lncRNAs and SARS-CoV-2.


Asunto(s)
COVID-19 , ARN Largo no Codificante , Humanos , COVID-19/epidemiología , COVID-19/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Biomarcadores/metabolismo , Progresión de la Enfermedad
3.
Eur J Clin Microbiol Infect Dis ; 42(8): 981-992, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37318601

RESUMEN

Existing literature about peritoneal tuberculosis (TBP) is relatively insufficient. The majority of reports are from a single center and do not assess predictive factors for mortality. In this international study, we investigated the clinicopathological characteristics of a large series of patients with TBP and determined the key features associated with mortality. TBP patients detected between 2010 and 2022 in 38 medical centers in 13 countries were included in this retrospective cohort. Participating physicians filled out an online questionnaire to report study data. In this study, 208 patients with TBP were included. Mean age of TBP cases was 41.4 ± 17.5 years. One hundred six patients (50.9%) were females. Nineteen patients (9.1%) had HIV infection, 45 (21.6%) had diabetes mellitus, 30 (14.4%) had chronic renal failure, 12 (5.7%) had cirrhosis, 7 (3.3%) had malignancy, and 21 (10.1%) had a history of immunosuppressive medication use. A total of 34 (16.3%) patients died and death was attributable to TBP in all cases. A pioneer mortality predicting model was established and HIV positivity, cirrhosis, abdominal pain, weakness, nausea and vomiting, ascites, isolation of Mycobacterium tuberculosis in peritoneal biopsy samples, TB relapse, advanced age, high serum creatinine and ALT levels, and decreased duration of isoniazid use were significantly related with mortality (p < 0.05). This is the first international study on TBP and is the largest case series to date. We suggest that using the mortality predicting model will allow early identification of high-risk patients likely to die of TBP.


Asunto(s)
Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Isoniazida , Cirrosis Hepática , Antituberculosos/uso terapéutico
4.
BMC Infect Dis ; 23(1): 639, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37770836

RESUMEN

BACKGROUND: Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM). MATERIALS/METHODS: This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018. RESULTS: Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3-5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34). CONCLUSIONS: Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.


Asunto(s)
Meningitis , Vancomicina , Humanos , Vancomicina/uso terapéutico , Meropenem/uso terapéutico , Cefepima/uso terapéutico , Ceftazidima/uso terapéutico , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Meningitis/tratamiento farmacológico , Bacterias , Staphylococcus , Atención a la Salud , Ampicilina
5.
Euro Surveill ; 28(47)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37997666

RESUMEN

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.


Asunto(s)
COVID-19 , Humanos , Adulto , COVID-19/epidemiología , COVID-19/prevención & control , Vacuna BNT162 , ARN Viral , SARS-CoV-2 , Eficacia de las Vacunas , Hospitalización , Europa (Continente)/epidemiología
6.
Euro Surveill ; 28(47)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37997665

RESUMEN

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.


Asunto(s)
COVID-19 , Neumonía , Humanos , Adulto , COVID-19/prevención & control , Vacunas contra la COVID-19 , Eficacia de las Vacunas , SARS-CoV-2 , Hospitalización , Europa (Continente)/epidemiología , ARN Mensajero
7.
Emerg Infect Dis ; 27(5): 1482-1485, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33900182

RESUMEN

We describe a series of severe neuroinvasive infections caused by Toscana virus, identified by real-time reverse transcription PCR testing, in 8 hospitalized patients in Bucharest, Romania, during the summer seasons of 2017 and 2018. Of 8 patients, 5 died. Sequencing showed that the circulating virus belonged to lineage A.


Asunto(s)
Infecciones por Bunyaviridae , Virus de Nápoles de la Fiebre de la Mosca de los Arenales , Humanos , Rumanía
8.
Eur J Clin Microbiol Infect Dis ; 38(9): 1753-1763, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31187307

RESUMEN

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).


Asunto(s)
Endocarditis/epidemiología , Infecciones Relacionadas con Prótesis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica/microbiología , Bacterias/aislamiento & purificación , Endocarditis/microbiología , Endocarditis/mortalidad , Endocarditis Bacteriana , Femenino , Mortalidad Hospitalaria , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Válvula Mitral/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Estafilocócicas , Estreptococos Viridans , Adulto Joven
9.
Euro Surveill ; 24(10)2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30862335

RESUMEN

We report nine travellers with confirmed chikungunya virus infection, returning from tourist areas of Thailand to Sweden, Switzerland, the United Kingdom, Romania, Israel and France, diagnosed in January and February 2019. These sentinel tourists support the intensification of chikungunya virus circulation in Thailand and highlight the potential for importation to areas at risk of local transmission.


Asunto(s)
Aedes/virología , Fiebre Chikungunya/diagnóstico , Virus Chikungunya/aislamiento & purificación , Brotes de Enfermedades , Vigilancia de Guardia , Viaje , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Artralgia/tratamiento farmacológico , Artralgia/etiología , Fiebre Chikungunya/tratamiento farmacológico , Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Europa (Continente) , Fiebre/tratamiento farmacológico , Fiebre/etiología , Humanos , Masculino , Persona de Mediana Edad , Medio Oriente , Mosquitos Vectores , Reacción en Cadena en Tiempo Real de la Polimerasa , Tailandia/epidemiología , Adulto Joven
10.
Liver Int ; 38(4): 602-610, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28816020

RESUMEN

BACKGROUND: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/virología , 2-Naftilamina , Adulto , Anciano , Anciano de 80 o más Años , Anilidas/uso terapéutico , Carbamatos/uso terapéutico , Ciclopropanos , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Lactamas Macrocíclicas , Modelos Logísticos , Compuestos Macrocíclicos/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prolina/análogos & derivados , Estudios Prospectivos , Ribavirina/uso terapéutico , Rumanía , Sulfonamidas/uso terapéutico , Respuesta Virológica Sostenida , Uracilo/análogos & derivados , Uracilo/uso terapéutico , Valina
11.
MMWR Morb Mortal Wkly Rep ; 67(11): 340-341, 2018 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-29565840

RESUMEN

Yellow fever virus is a mosquito-borne flavivirus that causes yellow fever, an acute infectious disease that occurs in South America and sub-Saharan Africa. Most patients with yellow fever are asymptomatic, but among the 15% who develop severe illness, the case fatality rate is 20%-60%. Effective live-attenuated virus vaccines are available that protect against yellow fever (1). An outbreak of yellow fever began in Brazil in December 2016; since July 2017, cases in both humans and nonhuman primates have been reported from the states of São Paulo, Minas Gerais, and Rio de Janeiro, including cases occurring near large urban centers in these states (2). On January 16, 2018, the World Health Organization updated yellow fever vaccination recommendations for Brazil to include all persons traveling to or living in Espírito Santo, São Paulo, and Rio de Janeiro states, and certain cities in Bahia state, in addition to areas where vaccination had been recommended before the recent outbreak (3). Since January 2018, 10 travel-related cases of yellow fever, including four deaths, have been reported in international travelers returning from Brazil. None of the 10 travelers had received yellow fever vaccination.


Asunto(s)
Brotes de Enfermedades , Enfermedad Relacionada con los Viajes , Fiebre Amarilla/diagnóstico , Adulto , Brasil/epidemiología , Resultado Fatal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fiebre Amarilla/epidemiología
12.
Emerg Infect Dis ; 23(4): 574-581, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28322689

RESUMEN

We characterized influenza B virus-related neurologic manifestations in an unusually high number of hospitalized adults at a tertiary care facility in Romania during the 2014-15 influenza epidemic season. Of 32 patients with a confirmed laboratory diagnosis of influenza B virus infection, neurologic complications developed in 7 adults (median age 31 years). These complications were clinically diagnosed as confirmed encephalitis (4 patients), possible encephalitis (2 patients), and cerebellar ataxia (1 patient). Two of the patients died. Virus sequencing identified influenza virus B (Yam)-lineage clade 3, which is representative of the B/Phuket/3073/2013 strain, in 4 patients. None of the patients had been vaccinated against influenza. These results suggest that influenza B virus can cause a severe clinical course and should be considered as an etiologic factor for encephalitis.


Asunto(s)
Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/virología , Virus de la Influenza B , Gripe Humana/complicaciones , Gripe Humana/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades del Sistema Nervioso Central/epidemiología , Enfermedades del Sistema Nervioso Central/mortalidad , Niño , Femenino , Humanos , Gripe Humana/epidemiología , Gripe Humana/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rumanía/epidemiología , Adulto Joven
13.
Cureus ; 16(6): e62970, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38912074

RESUMEN

Introduction Chronic hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, including depression. This study aimed to determine the prevalence of depression in treatment-naive HCV patients and explore its potential association with liver fibrosis severity. Methodology A consecutive cohort of 50 treatment-naive HCV patients without coinfections was enrolled over six months. Depression was assessed using the Hamilton Depression Rating Scale (HAM-D), and the liver fibrosis stage was evaluated using Fibroscan elastography. Results The cohort comprised 62% females (n=31) and 38% males (n=19), with ages ranging from 27 to 76 years. HAM-D scores indicated mild depression in 78% (n=39) and moderate depression in 16% (n=8) of patients. Notably, patients with mild depression displayed varying degrees of liver fibrosis (F0, F1, and F2), while all patients with moderate depression had advanced fibrosis (F3). Based on the multiple regression model, fibrosis was a statistically significant independent predictor with an unstandardized regression coefficient (B) of 3.115 (p=0.007). Conclusions Our findings point to a high prevalence of depression in treatment-naive HCV patients. Interestingly, there might be a link between depression severity and the stage of liver fibrosis, with advanced fibrosis potentially associated with more severe depression.

14.
Vaccines (Basel) ; 12(6)2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38932392

RESUMEN

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies, and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. Overall, 29.8% of PLWH had no SARS-CoV-2 serologic markers; they displayed significantly lower CD4 counts and higher HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (p = 0.0003), anti-S IgA (p < 0.0001) and lack of neutralizing activity against the Omicron variant (p < 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immune responses but retained specific cellular immunity.

15.
Antibiotics (Basel) ; 13(5)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38786163

RESUMEN

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (Cr-Kpn) is becoming a growing public health problem through the failure of adequate treatment. This study's objectives are to describe the sources of Cr-Kpn in our hospital over 22 months, associating factors with the outcome of Cr-Kpn-positive patients, especially those with NDM+OXA-48-like (New Delhi Metallo-ß-Lactamase and oxacillinase-48), and the effectiveness of the treatments used. METHODS: A retrospective observational cohort study including all hospitalized patients with Cr-Kpn isolates. We reported data as percentages and identified independent predictors for mortality over hospital time through multivariate analysis. RESULTS: The main type of carbapenemases identified were NDM+OXA-48-like (49.4%). The statistical analysis identified that diabetes and co-infections with the Gram-negative, non-urinary sites of infection were factors of unfavorable evolution. The Cox regression model identified factors associated with a poor outcome: ICU admission (HR of 2.38), previous medical wards transition (HR of 4.69), and carbapenemase type NDM (HR of 5.98). We did not find the superiority of an antibiotic regimen, especially in the case of NDM+OXA-48-like. CONCLUSIONS: The increase in the incidence of Cr-Kpn infections, especially with NDM+OXA-48-like pathogens, requires a paradigm shift in both the treatment of infected patients and the control of the spread of these pathogens, which calls for a change in public health policy regarding the use of antibiotics and the pursuit of a One Health approach.

16.
Trop Med Infect Dis ; 9(4)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38668534

RESUMEN

Pegylated interferon alpha 2a continues to be used for the treatment of chronic hepatitis D. The reported on-treatment virologic response varies between 17 and 47%, with relapses in more than 50% of these patients. No stopping rules have been defined, and the duration of the treatment is not clearly established, but it should be between 48 and 96 weeks. In total, 76 patients with compensated liver disease treated with peg-interferon according to the Romanian National protocol for the treatment of hepatitis D were retrospectively included. The duration of treatment was up to 96 weeks, with the following stopping rules: less than a 2 log HDV RNA decrease by week 24 and less than a 1 log decrease every 6 months afterwards. Six months after stopping the treatment, it can be restarted for unlimited cycles. The inclusion criteria were aged above 18, HBs Ag-positive, HDV RNA detectable, ALT above ULN and/or liver fibrosis at least F1 at liver biopsy, or Fibrotest and/or Fibroscan higher than 7 KPa and/or inflammation at least A1 at liver biopsy or Fibrotest. We monitored our patients for a total period of 4 years (including those that repeated the cycle). After the first 6 months of treatment, 27 patients (35.5%) had a greater than 2 log HDV RNA decrease, 19 of them achieving undetectable HDV RNA. Seventeen patients (22.3%) had undetectable HDV RNA 24 weeks after stopping 96 weeks of treatment, and none relapsed in the following 2 years. Of these 17 patients, 6 were cirrhotic, and 4 had F3. Undetectable HDV RNA at 24 weeks was the only parameter that predicted a long-term suppression of HDV RNA. In 49 patients, the treatment was stopped after 6 months according to protocol, but it was restarted 6 months later. Five of these patients finished a 48-week course of treatment; none achieved undetectable HDV RNA. During the first course of therapy, 45 patients had at least one moderate adverse reaction to treatment. In one patient, the treatment was stopped due to a serious adverse event (osteomyelitis). Treatment doses had to be reduced in 29 patients. The virologic response at week 24 can select the patients who will benefit from continuing the treatment from those who should be changed to another type of medication when available.

17.
J Travel Med ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38951998

RESUMEN

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

18.
Influenza Other Respir Viruses ; 18(2): e13255, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38403302

RESUMEN

We conducted a multicentre hospital-based test-negative case-control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: -23-36); 20% (95% CI: -4-39) against A(H3N2) and 56% (95% CI: 22-75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Neumonía , Adulto , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estaciones del Año , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Estudios de Casos y Controles , Eficacia de las Vacunas , Europa (Continente)/epidemiología , Hospitalización , Hospitales , Vacunación
19.
AIDS Res Hum Retroviruses ; 39(11): 616-620, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37756367

RESUMEN

Monkeypox virus (mpox), a double-stranded DNA virus belonging to the Orthopox genus, can affect vulnerable anatomic sites, including the eyes, causing a monkeypox-related ophthalmic disease. The mpox virus may enter the eye via autoinoculation and cause multiple problems from mild lesions including conjunctivitis, blepharitis, keratitis, to severe ones such as corneal ulcers, corneal scarring, and rarely loss of vision. The aim of this article is to aggregate from an ophthalmologic point of view what is presently known about mpox-related ophthalmic disease (mpoxROD) and to present a particular case of a 41-year-old, white, bisexual, HIV positive male, with severe ocular complications. This article presents the first reported case in Romania, of severe mpoxROD, with clinically relevant information for infectious disease doctors and especially for ophthalmologists.


Asunto(s)
Infecciones por VIH , Seropositividad para VIH , Mpox , Médicos , Masculino , Humanos , Adulto , Rumanía
20.
Travel Med Infect Dis ; 53: 102583, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37207977

RESUMEN

BACKGROUND: The COVID-19 pandemic resulted in a sharp decline of post-travel patient encounters at the European sentinel surveillance network (EuroTravNet) of travellers' health. We report on the impact of COVID-19 on travel-related infectious diseases as recorded by EuroTravNet clinics. METHODS: Travelers who presented between January 1, 2019 and September 30, 2021 were included. Comparisons were made between the pre-pandemic period (14 months from January 1, 2019 to February 29, 2020); and the pandemic period (19 months from March 1, 2020 to September 30, 2021). RESULTS: Of the 15,124 visits to the network during the 33-month observation period, 10,941 (72%) were during the pre-pandemic period, and 4183 (28%) during the pandemic period. Average monthly visits declined from 782/month (pre-COVID-19 era) to 220/month (COVID-19 pandemic era). Among non-migrants, the top-10 countries of exposure changed after onset of the COVID-19 pandemic; destinations such as Italy and Austria, where COVID-19 exposure peaked in the first months, replaced typical travel destinations in Asia (Thailand, Indonesia, India). There was a small decline in migrant patients reported, with little change in the top countries of exposure (Bolivia, Mali). The three top diagnoses with the largest overall decreases in relative frequency were acute gastroenteritis (-5.3%), rabies post-exposure prophylaxis (-2.8%), and dengue (-2.6%). Apart from COVID-19 (which rose from 0.1% to 12.7%), the three top diagnoses with the largest overall relative frequency increase were schistosomiasis (+4.9%), strongyloidiasis (+2.7%), and latent tuberculosis (+2.4%). CONCLUSIONS: A marked COVID-19 pandemic-induced decline in global travel activities is reflected in reduced travel-related infectious diseases sentinel surveillance reporting.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Humanos , Vigilancia de Guardia , Viaje , Pandemias , Enfermedad Relacionada con los Viajes , COVID-19/epidemiología , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/diagnóstico , Europa (Continente)/epidemiología , Tailandia
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