Time filter

Source Type

Fisicaro P.,Laboratory of Viral Immunopathology | Valdatta C.,Laboratory of Viral Immunopathology | Massari M.,Unit of Infectious Diseases | Loggi E.,University of Bologna | And 6 more authors.
Gastroenterology | Year: 2010

Background & Aims: The antiviral function of peripheral hepatitis B virus (HBV)-specific T cells can be increased in patients with chronic hepatitis B by blocking the interaction of programmed death (PD)-1 with its ligand PD-L1. However, no information is available about the effects of this blockade on intrahepatic lymphocytes. We studied T-cell exhaustion and the effects of PD-1/PD-L1 blockade on intrahepatic and circulating HBV-specific T cells in patients with chronic hepatitis B. Methods: A total of 42 patients with chronic HBV infection who underwent liver biopsy were studied. The ex vivo phenotype of peripheral and intrahepatic HBV-specific CD8+ T cells was assessed by flow cytometry with class I tetramers and antibodies to T-cell differentiation molecules. Functional recovery was evaluated by analyzing expansion and production of interferon (IFN)-γ and interleukin (IL)-2 after short-term incubation of T cells with HBV peptides in the presence of anti-PD-L1 or control antibodies. Results: Intrahepatic HBV-specific CD8+ cells expressed higher levels of PD-1 and lower levels of CD127 than their peripheral counterparts. Blockade of PD-1/PD-L1 interaction increased CD8+ cell proliferation and IFN-γ and IL-2 production by circulating intrahepatic lymphocytes, even though anti-PD-L1 had a stronger effect on intrahepatic compared with peripheral T cells. Conclusions: T-cell exhaustion by high antigen concentrations promotes HBV-specific T-cell dysfunction by affecting phenotype and function of peripheral and intrahepatic T cells. By restoring antiviral T-cell functions, not only in peripheral but also in intrahepatic lymphocytes, anti-PD-L1 might be a good therapeutic candidate for chronic HBV infection. © 2010 AGA Institute.


PubMed | Unit of Infectious Diseases., Tel Aviv University and Assaf Harofeh Medical Center
Type: Journal Article | Journal: Open forum infectious diseases | Year: 2016

Intra-abdominal infections (IAI) constitute a common reason for hospitalization. However, there is lack of standardization in empiric management of (1) anaerobes, (2) enterococci, (3) fungi, and (4) multidrug-resistant organisms (MDRO). The recommendation is to institute empiric coverage for some of these organisms in high-risk community-acquired or in healthcare-associated infections (HCAI), but exact definitions are not provided.Epidemiological study of IAI was conducted at Assaf Harofeh Medical Center (May-November 2013). Logistic and Cox regressions were used to analyze predictors and outcomes of IAI, respectively. The performances of established HCAI definitions to predict MDRO-IAI upon admission were calculated by receiver operating characteristic (ROC) curve analyses.After reviewing 8219 discharge notes, 253 consecutive patients were enrolled (43 [17%] children). There were 116 patients with appendicitis, 93 biliary infections, and 17 with diverticulitis. Cultures were obtained from 88 patients (35%), and 44 of them (50%) yielded a microbiologically confirmed IAI: 9% fungal, 11% enterococcal, 25% anaerobic, and 34% MDRO. Eighty percent of MDRO-IAIs were present upon admission, but the area under the ROC curve of predicting MDRO-IAI upon admission by the commonly used HCAI definitions were low (0.73 and 0.69). Independent predictors for MDRO-IAI were advanced age and active malignancy.Multidrug-resistant organism-IAIs are common, and empiric broad-spectrum coverage is important among elderly patients with active malignancy, even if the infection onset was outside the hospital setting, regardless of current HCAI definitions. Outcomes analyses suggest that empiric regimens should routinely contain antianaerobes (except for biliary IAI); however, empiric antienterococcal or antifungals regimens are seldom needed.


PubMed | University of Pisa, Unit of Infectious Diseases, Unit of Microbiology and University of Genoa
Type: | Journal: The Journal of hospital infection | Year: 2016

Enhanced environmental cleaning practices are among the most accepted measures for controlling the spread of carbapenem-resistant Acinetobacter baumannii (CR-Ab).To evaluate the impact of heightened cleaning on an ongoing CR-Ab outbreak in a burn intensive care unit (BICU) of an Italian teaching hospital, where chlorhexidine-60% isopropyl alcohol was applied as a complementary disinfectant on high-touch surfaces.Compliance with the microbial limit proposed for the BICU by AFNOR-NF-S90-351 (20 colony-forming units/100cmDuring the standard cleaning regimen, three out of 23 samples (13%) gave results over the AFNOR limit and five (21.7%) showed unacceptable ATP levels with 100 relative light units/100cmAdding chlorhexidine-60% isopropyl alcohol as complementary disinfectant proved to be effective for reducing environmental microbial contamination, ATP levels and CR-Ab infection/colonization in patients admitted to the BICU. Real-time monitoring by ATP assay was useful for managing the cleaning schedule and reducing hospital infections, although the calculated values must be interpreted as cleanliness indicators rather than risk indicators.


PubMed | Hospital Universitario La Paz, Hospital Clinico San Carlos, Hospital Clinic Of Barcelona, Polytechnic University of Valencia and 4 more.
Type: | Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology | Year: 2016

The objective of this study was to evaluate the efficacy and safety of fidaxomicin in the real-life clinical setting. This was a retrospective cohort of patients with Clostridium difficile infection (CDI) treated with fidaxomicin in 20 Spanish hospitals between July 2013 and July 2014. Clinical cure, 30-day recurrence, 30-day mortality, sustained cure, and factors associated with the failure to achieve sustained cure were analyzed. Of the 72 patients in the cohort 41 (56.9%) had a fatal underlying disease. There were 44 (61.1%) recurrent episodes and 26 cases (36.1%) with a history of multiple recurrences. Most episodes were severe (26, 36%) or severe-complicated (14, 19.4%). Clinical cure rate was 90.3%, recurrence rate was 16.7% and three patients (4.2%) died during the follow-up period. Sustained cure was achieved in 52 cases (72.2%). Adverse events were reported in five cases (6.9%). Factors associated with the lack of sustained cure were cardiovascular comorbidity (OR 11.4; 95%CI 1.9-67.8), acute kidney failure (OR 7.4; 95%CI 1.3-43.1), concomitant systemic antibiotic treatment (OR 6.2; 95%CI 1.1-36.8), and C-reactive protein value at diagnosis (OR 1.2 for each 1mg/dl increase; 95%CI 1.03-1.3). Fidaxomicin is an effective and well tolerable treatment for severe CDI and for cases with elevated recurrence risk.


PubMed | International Science and Technology University, Karolinska Institutet, Unit of Infectious Diseases and National Institute of Allergy and Infectious Diseases
Type: Journal Article | Journal: The Journal of infectious diseases | Year: 2015

Immunity to the antigenically diverse parasite Plasmodium falciparum is acquired gradually after repeated exposure. Studies in areas of high malaria transmission have shown that asymptomatic individuals infected with multiclonal infections are at reduced risk of febrile malaria during follow-up.We assessed the relationship between the genetic diversity of clones in P. falciparum infections that persist through the dry season and the subsequent risk of febrile malaria in 225 individuals aged 2-25 years in Mali, where the 6-month malaria and dry seasons are sharply demarcated. Polymerase chain reaction-based genotyping of the highly polymorphic merozoite surface protein 2 gene was performed on blood samples collected at 5 cross-sectional surveys.In an age-adjusted analysis, individuals with multiclonal P. falciparum infections before the rainy season were at reduced risk of febrile malaria, compared with individuals who were uninfected (hazard ratio [HR], 0.28; 95% confidence interval [CI], .11-.69). In contrast, there was no significant association between risk of malaria and having 1 clone at baseline (HR, 0.71; 95% CI, .36-1.40).The results suggest that persistent multiclonal infections carried through the dry season contribute to protection against subsequent febrile malaria, possibly by maintaining protective immune responses that depend on ongoing parasite infection.


Gazzola L.,University of Milan | Cicconi P.,University of Milan | Ripamonti D.,Unit of Infectious Diseases | Di Filippo E.,Unit of Infectious Diseases | And 5 more authors.
HIV Clinical Trials | Year: 2014

Objectives: To assess the outcome of a dual regimen combining darunavir/ritonavir plus etravirine in a cohort of antiretroviral therapy (ART)-experienced patients. Methods: A retrospective analysis was performed on all ART-experienced patients starting a darunavir/ritonavir plus etravirine regimen at the 3 clinics. Patients were stratified according to HIV RNA detectability (≥40 copies/mL) at baseline. Two efficacy endpoints were evaluated by Kaplan-Meier and Cox multivariable models: virological failure (confirmed HIV RNA ≥40 copies/mL after 6 months) and therapeutic failure (including virological failure and treatment discontinuation for any reason). Results: Sixty-eight patients were included in the study. They had a median of 10.8 years on ART and 5 previous ART regimens; 61.3% showed primary protease inhibitor (PI) mutations and 70% showed previous non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure. HIV RNA was detectable in 34 (50%) patients. The median observation period was 21 (interquartile range [IQR], 11.9-25.1) months. After 24 months, 75.1% of the patients were still on the study regimen and 88.8% remained free from virological failure. Although a higher therapeutic failure rate was reported in patients with detectable viremia at baseline, only the immunological status revealed an independent predictive role. No differences in virological failure were observed according to HIV RNA detectability at baseline; a higher number of previous ART regimens was the only predictor. Discontinuation due to adverse events occurred in 5.9%. Conclusions: Darunavir/ritonavir plus etravirine regimen proved virological efficacy and safety in heavily pretreated patients with a high rate of virological success, even in patients who switched during virological failure. © 2014 Thomas Land Publishers, Inc.


Di Sabatino D.,Instituto Zooprofilattico Sperimentale Dellabruzzo E Del Molise G Caporale | Lorusso A.,Instituto Zooprofilattico Sperimentale Dellabruzzo E Del Molise G Caporale | Di Francesco C.E.,Unit of Infectious Diseases | Gentile L.,Veterinary Services | And 7 more authors.
PLoS ONE | Year: 2014

Canine distemper virus (CDV) infection is a primary threat affecting a wide number of carnivore species, including wild animals. In January 2013, two carcasses of Apennine wolves (Canis lupus) were collected in Ortona dei Marsi (L'Aquila province, Italy) by the local Veterinary Services. CDV was immediately identified either by RT-PCR or immunohistochemistry in lung and central nervous tissue samples. At the same time, severe clinical signs consistent with CDV infection were identified and taped (Videos S1-S3) from three wolves rescued in the areas surrounding the National Parks of the Abruzzi region by the Veterinary Services. The samples collected from these symptomatic animals also turned out CDV positive by RT-PCR. So far, 30 carcasses of wolves were screened and CDV was detected in 20 of them. The sequencing of the haemagglutinin gene and subsequent phylogenetic analysis demonstrated that the identified virus belonged to the CDV Arctic lineage. Strains belonging to this lineage are known to circulate in Italy and in Eastern Europe amongst domestic dogs. To the best of our knowledge this is the first report of CDV Arctic lineage epidemics in the wild population in Europe. © 2014 Di Sabatino et al.


De Socio G.V.L.,Santa Maria Hospital | Bonfanti P.,Luigi Sacco Hospital | Martinelli C.,Unit of Infectious Diseases | Ricci E.,Luigi Sacco Hospital | And 6 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2010

Objective: An attenuation of the physiological day-night blood pressure (BP) reduction is an important predictor of cardiovascular (CV) events and death. We compared circadian BP profile in treatment-naive HIV-infected patients and in healthy control subjects. Methods: Fifty-two antiretroviral therapy-naive HIV-infected patients (85% men, age 39 ± 11 years, BP 125/78 ± 11/9 mm Hg) and 156 age- and BP-matched HIV-negative controls (85% men, age 39 ± 10 years, BP 125/78 ± 9/7 mm Hg) underwent 24-hour BP monitoring. Subjects with a nocturnal reduction of systolic BP <10% were defined as "nondippers." Results: Nighttime BP was higher in HIV-infected subjects (113/69 ± 11/9 vs 109/67 ± 8/6 mm Hg, P = 0.008/0.005). Nocturnal systolic/diastolic BP reduction was 8.8/13.2% in HIV-positive patients and 11.7/17.2% in HIV negative (P = 0.002/0.001). The prevalence of "nondippers" was 35% and 15%, respectively (P = 0.003). In multivariate analysis, nocturnal systolic BP fall was negatively associated to HIV infection (β = -0.22, P = 0.001). HIV viral load, low CD4 cell count, and AIDS progression risk were all related with a flattened day-night BP profile (P < 0.01). Conclusions: HIV infection per se negatively affects circadian BP rhythm. These findings, obtained in subjects without major CV risk factors and antiretroviral naive, suggest that day-night BP changes may play a role in the HIV-related increase in CV risk. © 2010 by Lippincott Williams & Wilkins.


Fisicaro P.,Laboratory of Viral Immunopathology | Valdatta C.,Laboratory of Viral Immunopathology | Massari M.,Unit of Infectious Diseases | Loggi E.,University of Bologna | And 8 more authors.
Gastroenterology | Year: 2012

Background & Aims: In patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, antiviral functions of T cells are impaired; these might be increased by blocking T-cell co-inhibitory pathways, such as preventing interaction between the receptor programmed death (PD)-1 and its ligand, PD-L1. We attempted to optimize the restoration of T-cell functions in patients with chronic HBV or HCV infection with a combination of reagents that block PD-1 interaction with PD-L1 and stimulate T-cell signaling via CD137, a member of the tumor necrosis factor-receptor family. Methods: We assessed the effects of CD137 stimulation (via CD137L), alone or in combination with antibodies that block PD-1 interaction with PD-L1 (anti-PD-L1), on proliferation and production of interferon-γ and interleukin-2 by intrahepatic and peripheral T cells from patients with chronic HBV or HCV infection. We also analyzed expression of different co-stimulatory molecules on virus-specific CD8+ and forkhead box P3+CD4+ cells by flow cytometry. Results: Incubation of intrahepatic T cells with CD137L and anti-PD-L1 increased their responses to HBV, but not HCV. However, HCV-specific T cells isolated from peripheral blood were sensitive to these reagents. Virus-specific T cells from some, but not all patients, had increased responses to anti-PD-L1 when CD137L was added because in some cases the combination of anti-PD-L1 and CD137L overstimulated T cells, leading to their inhibition. Intrahepatic HBV- and HCV-specific CD8+ T cells had different costimulatory profiles; liver cells from patients with chronic HBV infection had a higher proportion of forkhead box P3+ regulatory T cells, with higher levels of PD-1, compared with liver cells from patients with chronic HCV infection. Conclusions: A combination of reagents that prevent interaction between PD-1 and its ligand and activate CD137 signaling increase responses of intrahepatic HBV-specific T cells and circulating HCV-specific T cells. This strategy might be developed to increase T-cell responses to these viruses in patients with chronic hepatitis B or C, and tailoring the dose of CD137L administered will help optimize results. © 2012 AGA Institute.


PubMed | Unit of Infectious Diseases, University of Naples Federico II and Instituto Superiore Of Sanita
Type: Journal Article | Journal: Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive | Year: 2016

Hepatitis A virus is a widely occurring disease, with different prevalence rates between countries in the North and West and those in the South and East. In Italy endemicity is low/medium, but not homogeneously distributed: in the northern/central regions a large hepatitis A outbreak due to genotype IA, related to the consumption of contaminated mixed frozen berries, occurred between 2013 and 2014, whereas in southern Italian regions recurrent outbreaks of hepatitis A, due to the IB genotype, still result from consumption of raw seafood. In 2014 an uncommon genotype IA strain was isolated from five patients (2 adults and 3 children) with hepatitis A, living in the surroundings of Naples (Campania) who did not have any of the most common risk factors for hepatitis A in Italy, such as consumption of raw shellfish or frozen berries, or travel to endemic countries. Moreover, based on the analysis of viral sequences obtained, this strain differed from several others in the national database, which had been recently isolated during Italian outbreaks. This case report reinforces the need to implement both information campaigns about the prevention of hepatitis A and vaccination programmes in childhood; in addition, it would be suitable to sequence strains routinely not only during large outbreaks of hepatitis A in order to obtain a more detailed national database of HAV strains circulating in Italy.

Loading Unit of Infectious Diseases collaborators
Loading Unit of Infectious Diseases collaborators