Effects of visceralising leishmania on the spleen, liver, and bone marrow: A pathophysiological perspective

The leishmaniases constitute a group of parasitic diseases caused by species of the protozoan genus Leishmania. In humans it can present different clinical manifestations and are usually classified as cutaneous, mucocutaneous, and visceral (VL). Although the full range of parasite—host interactions remains unclear, recent advances are improving our comprehension of VL pathophysiology. In this review we explore the differences in VL immunobiology between the liver and the spleen, leading to contrasting infection outcomes in the two organs, specifically clearance of the parasite in the liver and failure of the spleen to contain the infection. Based on parasite biology and the mammalian immune response, we describe how hypoxia-inducible factor 1 (HIF1) and the PI3K/Akt pathway function as major determinants of the observed immune failure. We also summarize existing knowledge on pancytopenia in VL, as a direct effect of the parasite on bone marrow health and regenerative capacity. Finally, we speculate on the possible effect that manipulation by the parasite of the PI3K/Akt/HIF1 axis may have on the myelodysplastic (MDS) features observed in VL. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Inflammatory bowel disease exacerbation associated with Epstein-Barr virus infection

BACKGROUND: Epstein-Barr virus infection is associated with inflammatory bowel disease, but its role as a pathogenetic or exacerbating factor remains unclear. OBJECTIVE: The aim of this study was to evaluate the association between Epstein-Barr virus infection and inflammatory bowel disease, particularly in regard to exacerbation of disease activity. DESIGN: This was a nonrandomized crosssectional study in subgroups of patients with inflammatory bowel disease compared with a control group with noninflammatory disease. SETTINGS AND PATIENTS: Participants were patients treated for ulcerative colitis or Crohn's disease and individuals undergoing evaluation for noninflammatory disease recruited from 2 urban adult gastrointestinal referral centers in Greece. Main Outcome Measures: Diagnosis of inflammatory bowel disease was based on standard clinical and endoscopic criteria. Demographic and clinical characteristics of all participants were recorded. Whole blood samples and fresh tissue samples from biopsy of intestinal sites were obtained from each participant. The presence of Epstein-Barr virus was determined by amplifying the LMP1 gene of the virus in blood and intestinal tissue samples. RESULTS: The study comprised 94 patients with inflammatory bowel disease (63 with ulcerative colitis and 31 with Crohn's disease) and 45 controls with noninflammatory disease. Of the 94 patients, 67 (71.3%) had disease exacerbation and 27 (28.7%) were in remission. The prevalence of Epstein-Barr virus genome was significantly higher in patients than in controls for intestinal tissue (44 patients, 46.8% vs 6 controls, 13.3%; p = 0.001), but not for whole blood (24 patients, 25.5% vs 9 controls, 20%; p = 0.3). The viral genome was found significantly more frequently in intestinal samples from patients with disease exacerbation compared with patients in remission (38 patients with exacerbation, 56.7% vs 6 patients in remission, 22.2%; p = 0.001), but no significant difference was found for whole blood (18 patients with exacerbation, 26.8% vs 6 patients in remission, 22.2%; p = 0.79). Neither disease exacerbation nor the presence of virus genome was related to demographic or clinical characteristics. LIMITATIONS: The exact location of Epstein-Barr virus in the intestinal tissues could not be specified because morphological data by immunohistochemistry or in situ hybridization were not available. CONCLUSIONS: Although causality could not be determined, the significantly higher prevalence of Epstein-Barr virus in intestinal tissue from patients with inflammatory bowel disease compared with controls and in patients with exacerbation compared with patients in remission suggests a potential viral involvement in the severity of inflammatory bowel disease. These findings merit further investigation in view of a potential for usefulness of antiviral therapy against Epstein-Barr virus infection in patients with exacerbation of inflammatory bowel disease. © The ASCRS 2013

Characterization of Enterobius vermicularis in a human population, employing a molecular-based method from adhesive tape samples

Human infection with the parasitic nematode Enterobius vermicularis occurs worldwide, particularly in children. Although its prevalence may exceed 35% in some parts of the world, molecular studies of E. vermicularis in humans are limited. The aim of the present study was to investigate the genetic variation within E. vermicularis in a human population. For this purpose, 77 adhesive tape samples taken from Greek children infested with E. vermicularis were tested. New primers were designed to amplify a segment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of E. vermicularis from adhesive tape samples. Thirty-six amplicons were sequenced and eleven different haplotypes were identified. All sequences clustered within the type previously characterized (type B), only reported to date from captive chimpanzees. To the best of our knowledge, this is the first study of E. vermicularis genotypes from a human population. © 2011 Elsevier Ltd

Evolution of multidrug-resistant Acinetobacter baumannii clonal lineages: a 10 years study in Greece (2000-2009).

Objectives: To analyse the evolution and genetic relatedness of Acinetobacter baumannii clonal lineages in Greece during a 10 year period. Methods: The study included 94 randomly selected A. baumannii clinical isolates recovered from 2000 to 2009 in eight tertiary Greek hospitals. Carbapenem MICs were determined by agar dilution. PCR was applied for carbapenemase genes. Isolates were typed by PFGE and tri-locus sequence typing (3LST), and 25 were also typed by multilocus sequence typing (MLST) developed by the Institut Pasteur, followed by e-Burst analysis. Results: All isolates were multidrug-resistant (MDR); 54 (57.4%) were non-susceptible to imipenem and/or meropenem. The blaOXA-58 gene was identified in 51 (94.4%) carbapenem-non-susceptible and 15 (37.5%) carbapenem- susceptible isolates; other carbapenemase genes were not detected. Eight different PFGE types were identified. Sequence typing revealed previously characterized 3LST groups (1, 2, 4 and 5) and MLST types (STs) (1, 2, 15, 45 and 54) and the novel STs 85 (in two distant hospitals) and 86. Eight novel 3LST alleles were identified. Fifty-two (55.3%) isolates were assigned to 3LST group 1 and ST2 or ST45, both corresponding to international clonal complex 2 (CC2). Thirty-one (33.0%) isolates were assigned to 3LST group 2 and ST1 (CC1). From 2000 to 2004 63% of isolates belonged to 3LST group 2, but from 2005 to 2009 87.5% of isolates belonged to 3LST group 1; this shift was accompanied by an increase in carbapenem resistance from 43.5% to 64.6% of isolates. Conclusions: The emergence of MDR A. baumannii in Greece was associated with CC1 and CC2, which are disseminated worldwide, often harbouring the blaOXA-58 gene. Novel 3LST alleles and STs were also detected, underlining an evolutionary divergence in Greece

Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases of intrauterine fetal death: Association with pathological findings

There are previous indications that transplacental transmission of cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and 2 (HSV-1/2) cause fetal infections, which may lead to fetal death. In a prospective case-control study we examined the incidence of these viruses in intrauterine fetal death and their association with fetal and placenta pathological findings. Molecular assays were performed on placenta tissue extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and HSV-1/2 genomes. Formalin-fixed, paraffin-embedded liver, spleen and placenta tissues of fetal death cases were evaluated histologically. Thirty-four percent of placental specimens taken from intrauterine fetal deaths were positive for any of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV-1/2, respectively), whereas only 6% of those taken from full term newborns were positive (P = 0.0017). No dual infection was observed. This difference was also observed when fetal deaths with a gestational age <20 weeks or a gestational age >20 weeks were compared with the controls (P = 0.025 and P = 0.0012, respectively). Intrauterine death and the control groups differed in the detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more pronounced in a gestational age >20 weeks (P = 0.03). Examination of the pathological findings among the PCR-positive and PCR-negative fetal deaths revealed that hydrops fetalis and chronic villitis were more common among the former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an association was detected between viral infection and fetal death, which was more pronounced in the advanced gestational age. Fetal hydrops and chronic villitis were evidently associated with viral DNA detection in cases of intrauterine death. © 2008 Wiley-Liss, Inc

Evolution of multidrug-resistant Acinetobacter baumannii clonal lineages: A 10 year study in Greece (2000-09)

Objectives: To analyse the evolution and genetic relatedness of Acinetobacter baumannii clonal lineages in Greece during a 10 year period. Methods: The study included 94 randomly selected A. baumannii clinical isolates recovered from 2000 to 2009 in eight tertiary Greek hospitals. Carbapenem MICs were determined by agar dilution. PCR was applied for carbapenemase genes. Isolates were typed by PFGE and tri-locus sequence typing (3LST), and 25 were also typed by multilocus sequence typing (MLST) developed by the Institut Pasteur, followed by e-Burst analysis. Results: All isolates were multidrug-resistant (MDR); 54 (57.4%) were non-susceptible to imipenem and/or meropenem. The blaOXA-58 gene was identified in 51 (94.4%) carbapenem-non-susceptible and 15 (37.5%) carbapenem-susceptible isolates; other carbapenemase genes were not detected. Eight different PFGE types were identified. Sequence typing revealed previously characterized 3LST groups (1, 2, 4 and 5) and MLST types (STs) (1, 2, 15, 45 and 54) and the novel STs 85 (in two distant hospitals) and 86. Eight novel 3LST alleles were identified. Fifty-two (55.3%) isolates were assigned to 3LST group 1 and ST2 or ST45, both corresponding to international clonal complex 2 (CC2). Thirty-one (33.0%) isolates were assigned to 3LST group 2 and ST1 (CC1). From 2000 to 2004 63% of isolates belonged to 3LST group 2, but from 2005 to 2009 87.5% of isolates belonged to 3LST group 1; this shift was accompanied by an increase in carbapenem resistance from 43.5% to 64.6% of isolates. Conclusions: The emergence of MDR A. baumannii in Greece was associated with CC1 and CC2, which are disseminated worldwide, often harbouring the blaOXA-58 gene. Novel 3LST alleles and STs were also detected, underlining an evolutionary divergence in Greece. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Dissemination of clinical isolates of Klebsiella oxytoca harboring CMY-31, VIM-1, and a new OXY-2-type variant in the community

The aim of the present study was to investigate the epidemiological link of multidrug-resistant Klebsiella oxytoca isolates causing community-onset infections among patients attending our outpatient department and to investigate the underlying resistance mechanisms. The isolates were tested by agar dilution MICs, phenotypic carbapenemase testing, enterobacterial repetitive intergenic consensus-PCR, and pulsed-field gel electrophoresis (PFGE). PCR assays and nucleotide sequencing were employed for the identification of bla gene types and the mapping of the integron-containing metallo-β-lactamase (MBL) gene. During the study period (January 2005 to April 2007), nine broad-spectrum cephalosporin-resistant K. oxytoca clinical isolates were prospectively collected from separate outpatients with urinary tract infections. In all cases, the patients had been hospitalized or exposed to health care facilities during the preceding year. Molecular typing revealed that all isolates belonged to the same K. oxytoca clonal type, which contained five PFGE subtypes. A novel chromosomal OXY-2 β-lactamase type variant (OXY-2-9) was detected in all isolates, but no mutations in the promoter region justifying blaOXY gene overproduction were detected. In addition, all isolates harbored the plasmidic CMY-31 (LAT-4) AmpC cephalosporinase, while three of them harbored VIM-1 MBL in a class 1 integron structure. This is the first study to present the dissemination in the community of multidrug-resistant K. oxytoca isolates causing extrahospital infections. Copyright © 2011, American Society for Microbiology. All Rights Reserved

Antibody response following a two-dose mrna vaccination regimen, in health care workers of a tertiary hospital in athens, greece

We analyzed the antibody responses of 564 hospital workers in Athens, Greece, after vaccination with two doses of the BNT162b2 (Comirnaty®; BioNTech and Pfizer) mRNA COVID-19 vaccine. A greater antibody increase was observed in women, younger age groups, previously infected individuals and personnel working in COVID-19 clinics. Notably, individuals with a prior COVID-19 infection mounted a significantly higher antibody titer following the first dose than the rest of the population; the same was true for those working in COVID-19 clinics, even without history of previous infection. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Pseudomonas aeruginosa bacteraemia in patients with hematologic malignancies: risk factors, treatment and outcome

Our aims were to identify factors associated with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) in patients with hematological malignancies and evaluate the outcome of the affected patients. Consecutive patients with hematological malignancies who developed PA BSI were identified. Subsequently, two case–control studies were performed to evaluate the risk factors (i) for PA BSI and (ii) for carbapenem resistant (CR) PA BSI. Patients' outcome was evaluated at 28 days after the onset of bacteraemia. A total of 64 patients with PA BSI (45 caused by CS and 19 by CR organisms) and 128 without PA BSI were enrolled. Patients with rapidly fatal disease, steroid use, neutropenia or prior surgery were more likely to develop PA BSI, whereas patients with previous hospitalization and prior use of fluoroquinolones were more likely to develop CR PA BSI. The 28-day mortality rate was 35.9%. Severity of sepsis was the only independent predictor of adverse outcome. © 2017 Elsevier Inc