Sustained impairment of human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T cell response is responsible for recurrent episodes of disseminated HCMV infection in a D+R- hand transplant recipient

Human cytomegalovirus (HCMV) infection is the major viral complication in solid organ transplant recipients. Seronegative recipents (R-) of organs from seropositive donors (D+) appear to be at higher risk of developing symptomatic HCMV infection. To what extent systemic life-threatening complications can be risked for non-life-saving transplant procedures? A case report describing successful treatment of repeated episodes of active HCMV infection in a D+R- hand recipient in the absence of HCMV-specific T-cell immunity is presented. In the attempt to save both the patient and the transplanted hand, a preemptive treatment strategy was adopted with the aim to boost the constitution of the virus-specific T-cell immune response and simultaneously avoid onset of disease. Careful monitoring of HCMV load in blood and HCMV-specific T-cell immunity guided administration of repeated courses of antiviral treatment and avoided emergence of HCMV-related symptoms. Following establishment of HCMV-specific CD4+ and CD8+ T-cell response, preemptive treatment was no longer required due to sustained HCMV disappearance from blood. The patient is now well, and his hand too. In conclusion, evaluation of virus-specific T-cell immunity is of crucial importance in D+R- transplant recipients and careful monitoring of HCMV-specific T cell mediated response should always parallel monitoring of HCMV load in transplant recipients

Vaccination for seasonal influenza in patients with cancer: Recommendations of the Italian Society of Medical Oncology (AIOM)

Background: Influenza virus causes annual epidemics in the winter\u2013spring season with significant morbidity in the general population and important mortality in high-risk groups, including cancer patients. Opinions on the suitability of patients with malignancies not undergoing active treatment and in different phases of antineoplastic therapy, to receive influenza vaccination, vary considerably among oncologists, sometimes even within one center. Methods: We reviewed available data, including recommendations by national health authorities, on impact of influenza in patients with cancer and their capacity to mount protective immunological responses to vaccination, thus allowing, on behalf of Italian Association of Medical Oncology, to make suitable recommendations for the prevention and treatment of seasonal influenza. Results and discussion: Patients with cancer often have disease- or treatment-related immunosuppression, and as a consequence, they may have a suboptimal serologic response to influenza vaccination. The protective effect of the differ- ent preparations of influenza vaccines in patients with cancer has not been widely investigated, especially in adult patients harboring solid tumors. The optimal timing for administration of influenza vaccines in patients receiving chemotherapy is also not clearly defined. However, since vaccination is the most effective method, along with antiviral drugs in selected patients, for preventing influenza infection, it has to be recommended for cancer patients. Implementing vaccination of close contacts of oncology patients would be an additional tool for enhancing protection in fragile patient populations

Taeniid cestodes in a wolf pack living in a highly anthropic hilly agro-ecosystem

The Italian wolf population in human-modified landscapes has increased greatly in the last few decades. Anthropisation increases the risk of transmission of many zoonotic infections and in this context, control of taeniid cestode species needs to be addressed from a One Health perspective. Predator-prey interactions are at the root of taeniid cestode transmission, and the wolf plays a key role in the maintenance and transmission of taeniids. To date, all available data on the taeniids of wolves in Italy refer to populations living in a wild habitat. Between 2018 and 2019, we investigated taeniids in a wolf pack living in a highly anthropic hilly agro-ecosystem. Thirty-eight faecal samples were collected and analysed, 4 of which were also genetically characterised for individual wolves and belonged to three different animals. Samples collected were analysed microscopically and by molecular analysis in order to identify the taeniid species. Taeniid eggs were detected in 34.2% (13/38) of samples. Within samples positive to taeniid eggs only Echinococcus granulosus s.s. and Taenia hydatigena were identified in 26.3% and 10.5% of the samples, respectively. On microscopic examination, Capillaria spp., Ancylostomatidae and Toxocara canis eggs, Crenosoma vulpis larvae, and coccidian oocysts were also found. The combination of low biodiversity of taeniid species with a high occurrence of E. granulosus s.s. recorded in this study could be the consequence of a deeper link occurring between wolves and livestock in human-modified landscapes than in wild settings

Finite-temperature relativistic Landau problem and the relativistic quantum Hall effect

This paper presents a study of the free energy and particle density of the relativistic Landau problem, and their relevance to the quantum Hall effect. We study first the zero temperature Casimir energy and fermion number for Dirac fields in a 2+1-dimensional Minkowski space-time, in the presence of a uniform magnetic field perpendicular to the spatial manifold. Then, we go to the finite-temperature problem, with a chemical potential, introduced as a uniform zero component of the gauge potential. By performing a Lorentz boost, we obtain Hall's conductivity in the case of crossed electric and magnetic fields.Comment: Final version, to appear in Journal of Physics A: Mathematical and Genera

Cytomegalovirus Management in Solid Organ Transplant Recipients: A Pre-COVID-19 Survey From the Working Group of the European Society for Organ Transplantation

Infections are leading causes of morbidity/mortality following solid organ transplantation (SOT) and cytomegalovirus (CMV) is among the most frequent pathogens, causing a considerable threat to SOT recipients. A survey was conducted 19 July–31 October 2019 to capture clinical practices about CMV in SOT recipients (e.g., how practices aligned with guidelines, how adequately treatments met patients’ needs, and respondents’ expectations for future developments). Transplant professionals completed a ∼30-minute online questionnaire: 224 responses were included, representing 160 hospitals and 197 SOT programs (41 countries; 167[83%] European programs). Findings revealed a heterogenous approach to CMV diagnosis and management and, sometimes, significant divergence from international guidelines. Valganciclovir prophylaxis (of variable duration) was administered by 201/224 (90%) respondents in D+/R− SOT and by 40% in R+ cases, with pre-emptive strategies generally reserved for R+ cases: DNA thresholds to initiate treatment ranged across 10–10,000 copies/ml. Ganciclovir-resistant CMV strains were still perceived as major challenges, and tailored treatment was one of the most important unmet needs for CMV management. These findings may help to design studies to evaluate safety and efficacy of new strategies to prevent CMV disease in SOT recipients, and target specific educational activities to harmonize CMV management in this challenging population

Clinically-based determination of safe DNAemia cutoff levels for preemptive therapy or human cytomegalovirus infections in solid organ and hematopoietic stem cell transplant recipients

Transplantation Centers using human cytomegalovirus (HCMV) antigenemia-based preemptive therapy will need to replace in the near future the antigenemia assay with a more standardized and automatable assay, such as a molecular assay quantifying HCMV DNA in blood (DNAemia). Thus, in view of replacing antigenemia with clinically safe cutoff values, DNAemia levels corresponding to antigenemia cutoffs guiding HCMV preemptive therapy were determined retrospectively in solid organ and hematopoietic stem cell transplant recipients (HSCTR) using an "in-house" quantitative PCR (QPCR) method. Since preemptive therapy had prevented appearance of HCMV disease in all patients tested, DNA cutoffs determined retrospectively had to be considered as safe clinically as antigenemia cutoffs used prospectively. However, in solid organ transplant recipients (SOTR), initiating preemptive therapy upon an antigenemia cutoff of 100 pp65-positive leukocytes, a DNAemia cutoff of 300,000 copies/ml blood had positive and negative predictive values of >90%, indicating that a DNAemia cutoff could achieve, in terms of prevention of HCMV disease, the same clinical results as the antigenemia cutoff. In HSCTR, initiating preemptive therapy upon first antigenemia positivity, a DNAemia cutoff of 10,000 copies/ml blood had a positive predictive value of >90%, indicating that the great majority of patients treated under the antigenemia guidance would have been treated also using this DNA cutoff. On the other hand, the negative predictive value of 28.6% indicated that two out of three HSCTR had been treated under the antigenemia guidance having the same levels of viral DNA as the untreated patients. The data suggest that a quantitative cutoff could be adopted as a guiding criterion for preemptive therapy also in HSCTR. Regression analysis allowed to determine the DNAemia (corresponding to QPCR) cutoff values for two commercial assays tested both in solid organ and HSCTR. Retrospective DNAemia cutoff values will be verified for safety in prospective trial

Miscarriage following dengue virus 3 infection in the first six weeks of pregnancy of a dengue virus-naive traveller returning from Bali to Italy, April 2016

We report miscarriage following dengue virus (DENV)-3 infection in a pregnant woman returning from Bali to Italy in April 2016. On her arrival, the woman had fever, rash, asthenia and headache. DENV RNA was detected in plasma and urine samples collected the following day. Six days after symptom onset, she had a miscarriage. DENV RNA was detected in fetal material, but in utero fetal infection cannot be demonstrated due to possible contamination by maternal blood

Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients

<p>Abstract</p> <p>Background</p> <p>Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only.</p> <p>Methods</p> <p>The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described.</p> <p>Results</p> <p>Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 10⁵PBMC in one patient and > 1,000 copies EBV DNA/1 × 10⁵PBMC in two patients.</p> <p>Conclusion</p> <p>A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD.</p

Epidemiological and molecular characteristics of HPEV infection in children&lt;6 months hospitalized with symptoms of sepsie-like illness, northen Italy, 2015-2018

BACKGROUND. Human parechoviruses (HPeVs) are widespread pathogens belonging to the Picornaviridae family and currently divided into 19 genotypes. HPeV infections can be associated with severe clinical manifestations, such as sepsis-like illness, particularly in youngest children. The epidemiological and molecular characteristics of HPeV infections observed in children &lt;6 months hospitalized with symptoms of sepsis-like illness were investigated. METHODS. From January 1st, 2015, to December 31st, 2018, clinical samples (cerebrospinal fluid samples and/or blood samples) were collected for diagnosis of HPeV infection from 193 patients (median age: 21 days, range: 1 day - 6 months) hospitalized with symptoms of sepsis-like illness, in two hospitals of Northern Italy. HPeV-RNA was detected by real-time RT-PCR (target 5\u2019UTR) and a portion of HPeV VP3/VP1 junction (nt. 2159\u20132458) was sequenced for typing and molecular characterization. RESULTS. 14% (27/193) of patients with symptoms of sepsis-like illness tested HPeV-positive. 26/27 (96.3%) HPeV-cases were &lt;3 months and 20/27 (74.1%) &lt;1 month. HPeV-positive cases were detected throughout the study period, mainly (12/27; 44.4%) during the summertime (June-August). 17/27 (63%) HPeV-positive samples were molecularly characterized: 16 resulted HPeV-3 and 1 HPeV-5. CONCLUSIONS. HPeV infection was identified in 14% of children &lt;6 months with symptoms of sepsis-like illness. Almost all HPeV infections were detected in children &lt;3 months and mainly during the summertime; almost all molecularly characterized HPeV belonged to type 3. Including HPeV molecular detection in routine diagnostic tests would allow estimating the burden of HPeV infection and improving clinical management of pediatric patients

Genome Characterisation of Enteroviruses 117 and 118 : A New Group within Human Enterovirus Species C

The more than 120 genotypes of human enteroviruses (HEVs) reflect a wide range of evolutionary divergence, and there are 23 currently classified as human enterovirus C species (HEV-C). Two new HEV-C (EV-C117 and EV-C118) were identified in the Community-Acquired Pneumonia Pediatric Research Initiative (CAP-PRI) study, and the present paper describes the characterisation of the complete genome of one EV-C117 strain (LIT22) and two EV-C118 (ISR38 and ISR10) strains. The EV-C117 and EV-C118 5'UTR sequences were related to those of EV-C104, EV-C105 and EV-C109, and were slightly shorter than those of other HEV A-D species. Similarity plot analyses showed that EV-C117 and EV-C118 have a P1 region that is highly divergent from that of the other HEV-C, and phylogenetic analyses highly supported a monophyletic group consisting of EV-C117, EV-C118, EV-C104, EV-C105 and EV-C109 strains. Phylogenetic, Simplot and Bootscan analyses indicated that recombination was not the main mechanism of EV-C117 and EV-C118 evolution, thus strengthening the hypothesis of the monophyletic origin of the coding regions, as in the case of other HEV-C. Phylogenetic analysis also revealed the emergence of a new group within HEV-C that is divided into two subgroups. Nucleotide and amino acid identity in VP1 sequences have been established as useful criteria for assigning new HEV types, but analysis of the complete P1 region improves resolutio