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Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

Background: The aim of this study was to evaluate whether asymptomatic recurrent (≥2) antibody-mediated rejection (pAMR 1+), defined as diffuse capillary C4d immunostaining (rAMR) on endomyocardial biopsies (EMBs), during the first year after heart transplantation impairs left ventricular (LV) function., Methods: Fifty-four consecutive heart transplant patients who survived well (New York Heart Association ≤2 and EF≥55%) the first month after transplantation were enrolled and prospectively underwent 490 echocardiographies and EMB. Asymptomatic rAMR without histopathologic findings was evaluated as a risk factor for deterioration of graft function. Primary endpoint, assessed 1 year after transplantation, was development of LV dysfunction and/or adverse remodeling according to pre-specified echo parameters., Results: During the first year from transplantation, rAMR occurred in five patients. Recurrent AMR was associated with a significant higher risk to develop LV concentric hypertrophy (OR 3.6, 95% CI: 1.8-7.0, P=.02) or reduced lateral S' peak velocity (OR 2.3, 95% CI: 1.5-3.6, P=.03). Patients with rAMR showed significative adverse graft remodeling (ΔLV end-diastolic volume: +16±12.3 vs -0.2±14.4 mL; P=.02) and deterioration of graft function (Δlateral S' peak velocity: -3.3±3 vs -0.4±2.9 cm/s; P=.03)., Conclusions: Recurrent asymptomatic diffuse capillary C4d immunostaining may play a role in the early development of cardiac allograft adverse remodeling and dysfunction., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study investigated the epidemiology of tuberculosis in the last 16 years in the province of Pavia, Lombardy, Northern Italy. The objective was to evaluate the clinical pattern of tuberculosis in immigrant groups compared with Italians in an observational retrospective study conducted from 1998 to 2013. In all, 615 tuberculosis cases were admitted, 354 males (57.3%), median age 47-years, 425 (69.1%) Italian-born patients, 190 (30.9%) immigrants. The ratio between the immigrant group and the Italian-born group of patients increased from 1.7% to 54.5% in the study period (p=0.001). HIV was the most common comorbidity, affecting 48 patients (7.8%), followed by diabetes in 35 (5.7%) and COPD in 30 (4.9%). The overall admission-associated mortality was 5.5%. Italian-born patients were older than non-Italian born subjects and had at least one comorbidity, 162 (38.1%) and 22 (11.6%), respectively (p<0,0001). Mortality was increased among Italian-born compared with non-Italian-born patients (7.3% versus 1.6%, p=0.004). No significant variation in extra-pulmonary tuberculosis (EPTB) prevalence occurred. Considering specific form of EPTB, HIV infection was associated with an increased risk of EPTB (RR 2.02, 95%CI 1.09-3.74, p=0.026). There was a high risk of tuberculosis among immigrants, whereas a decreasing trend was consistently observed among Italian-born patients. Italian-born patients show a higher tuberculosis-associated mortality risk due to older age and comorbidities.

Background: The C1q-binding properties of donor specific antibodies (DSA) may be related to antibody-mediated rejection and poor outcome., Methods: We retrospectively studied 35 kidney transplant recipients with transplant glomerulopathy (TG) and de novo DSA (dnDSA). C1q dnDSA were measured in the serum stored at renal biopsy and the association among C1q-fixing dnDSA, C4d deposition and graft loss was examined., Results: Of the 35 patients with dnDSA and TG, 15 (42.9%) had C1q-positive dnDSA and 20 (57.1%) had C1q-negative dnDSA. Ten out of 15 patients with C1q-positive dnDSA (66.6%) and 5 with C1q-negative dnDSA (25%) had C4d positive staining renal biopsies (P=0.02), being the C1q-negative dnDSA/C4d-negative TG 42.9% of the total. The C1q-positive dnDSA group has significantly higher IgG DSA Class II MFI than the C1q-negative dnDSA group (P=0.004). Patients with C4d deposits have significantly higher IgG DSA MFI for both Class I and Class II than those without C4d deposits (P=0.02). We found a trend toward higher graft loss in the C1q-positive dnDSA group (60%) versus the C1q-negative dnDSA group (40%) without a statistical significance (P=0.31)., Conclusion: Our study provides further characterization of TG associated with dnDSA. The major part of dnDSA-associated TG was C1q-negative and the presence of C1q-fixing dnDSA did not significantly correlate with graft outcome., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) present in the urine are mainly released from cells of the nephron and can therefore provide information on kidney function. We here evaluated the presence of vesicles expressing the progenitor marker CD133 in the urine of normal subjects and of patients undergoing renal transplant. We found that EV expressing CD133 were present in the urine of normal subjects, but not of patients with end stage renal disease. The first day after transplant, urinary CD133+ EVs were present at low levels, to increase thereafter (at day 7). Urinary CD133(+) EVs significantly increased in patients with slow graft function in respect to those with early graft function. In patients with a severe pre-transplant vascular damage of the graft, CD133(+) EVs did not increase at day 7. At variance, the levels of EVs expressing the renal exosomal marker CD24 did not vary in the urine of patients with end stage renal disease or in transplanted patients in respect to controls. Sorted CD133(+) EVs were found to express glomerular and proximal tubular markers. These data indicate that urinary CD133(+) EVs are continuously released during the homeostatic turnover of the nephron and may provide information on its function or regenerative potential.

Schistosomiasis is on the rise but still difficult to treat in international travelers; it should be suspected in patients returning from endemic areas. Praziquantel (PZQ) is not effective and may aggravate symptoms. More recently, combination treatment with artemisinin derivatives have shown promising results. We report four cases of acute schistosomiasis (AS) in which several courses of combined therapy had been necessary to obtain negative serology., (© 2014 International Society of Travel Medicine.)

Two transplant candidates sensitized during pregnancy by a B*44:02 mismatch showed antibodies that reacted with an epitope defined by the 145R+82LR eplet pair shared by all Bw4 antigens in single allele Luminex panels except B13. Both eplets are on one or more alleles of the antibody producer and according to HLAMatchmaker, they are considered intralocus and interlocus matches which should not induce antibodies. The recently developed nonself-self paradigm for HLA epitope immunogenicity has offered a ready explanation why the pair of self-145R and self-82LR eplets on B*44:02 induced specific antibodies. This finding is consistent with the concept that alloantibody responses originate from B-cells with self-HLA immunoglobulin receptors., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The effect of B cell cross-match (XM) was investigated in 680 first deceased-donor kidney transplants in a single centre from 1990 to 1999: 74 transplants presented a B-positive XM (Group 1) 606 had a B-negative XM (Group 2). The absence in Group 1 of weak/low-titre anti-HLA Class I antibodies was assured blocking anti-Class I reactivity by treating B cells with non-cytotoxic anti-beta2 microglobulin (alphabeta2 M) serum before XM. Graft survivals up to 5 years were not significantly different; some differences were nevertheless observed: HLA-A,B,DR mismatches influenced graft outcome in Group 1: patients with 0-2 mismatches had better survival than patients with 3-4. When analysed according DR mismatch, patients with 1 mismatch had worse graft survival than well matched patients (p<0.05). No significant difference depending on HLA match was observed in Group 2. Early acute rejection rate was similar in the Groups except the rejection episodes after one year: Group 1 had significantly more. 61/74 patients of Group 1 were retrospectively analysed for anti-HLA-DR,DQ reactivity: only 11/61 had anti-HLA-DR or DQ antibodies (3/11 were donor specific); graft survival and rejections were not significantly different in the patients with and without anti-HLA Class II antibodies. Anti-donor B cell reactivity, at XM, once excluded the presence of weak/low-titre anti-HLA Class I antibodies, did not influence first kidney graft survival.

Context: The first national quality control (QC) program of histocompatibility serum testing was performed in Italy in 2002., Objective: To monitor the performance of HLA typing laboratories while meeting the accreditation requirements of the European Federation for Immunogenetics (EFI), which require HLA typing laboratories to participate in external QC of their crossmatch and antibody analyses., Design: The Turin Transplant Immunology Service was asked to organize a QC survey of 17 HLA typing laboratories in Italy. Each laboratory received 12 serum specimens and 6 blood samples and was required to perform 36 crossmatches and 12 serum antibody specificity determinations., Settings: Data of participating centers were compared to establish whether EFI requirements were satisfied., Results: In crossmatch analysis, the results of 32 of 36 crossmatches reached the 75% consensus target, with all the participating laboratories meeting the standards of the EFI. In antibody analysis, only 7 of 17 laboratories met the EFI standards., Conclusion: The first Italian QC program shows that the participating laboratories obtained consistent results in crossmatching, whereas the results were less satisfactory in the determination of serum antibody specificity, where consensus was reached only with monospecific sera and antibody-negative samples.

The measurement of precursor frequencies of donor anti-recipient cytotoxic T lymphocytes (CTL-p) has been shown to predict the incidence and the severity of acute graft-versus-host disease (aGVHD) in unrelated donor bone marrow transplantation (BMT). In HLA-identical sibling BMT, where aGVHD is most likely caused by minor histocompatibility antigen mismatches, this assay did not appear to be sensitive enough to provide similar predictive information. In this study, the CTL-p frequencies and the incidence and severity of aGVHD in 51 onco-hematological patients transplanted from HLA-identical siblings were compared. Sibling donors were selected on the basis of HLA identity using serological typing for HLA-A, B, C antigens, whereas HLA-DRB was tested by molecular analysis. Sibling identity was also confirmed by DNA heteroduplex analyses. Fifteen out of 21 (71%) patients with high precursor frequency (>1:100 x 10(3)) and 12 out of 30 (40%) with low precursor frequency (<1:100 x 10(3)) experienced clinically significant (II-IV) aGVHD. A significant correlation (P = 0.04) between CTL-p frequency and severe aGVHD was demonstrated. Moreover there was a positive trend for a high frequency response according to an increasing grade of aGVHD, which was statistically significant (P = 0.04). In our experience the CTL-p assay is a helpful predictive test for aGVHD in HLA-identical sibling BMT, indicating high risk patients possibly requiring additional prophylaxis.

The selection of a kidney graft recipient should be made not only taking into account biological and clinical parameters, for assuring the maximum possible clinical success; the ethical objective to allow every patient equal opportunity of receiving a transplant should also be pursued. In every waiting list of transplant candidates a proportion of patients remains in the list for a particularly long time. The present analysis aimed to find out the factors associated with a prolonged waiting time, in order to allow the implementation of patient selection criteria able to balance unfavourable factors. The analysis of the waiting list of our kidney transplant centre allowed to observe that blood group 0, anti-HLA immunisation, presence of rare HLA antigens and, at a lesser extent, HLA homozygosity are associated with a longer waiting time for a kidney transplant.

The frequency of HLA alleles at HLA-DR and DQ loci, and that of the related HLA-D specificities, were estimated in the Italian population. 109 healthy unrelated subjects, born in several Italian regions and living in the district of Torino, were studied. DNA typing was achieved by the restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta, DQ alpha and beta genes, hybridizing specific probes with TaqI digested DNAs. The present study allowed to define in more detail the HLA class II polymorphisms in the Italian population.