Introduction: So far, data on the effect of a (val-)ganciclovir-based antiviral chemoprophylaxis on the incidence of post-transplant EBV primary infection are lacking. Methods: In the framework of a prospective, multicenter trial in 106 pediatric RTx patients, we therefore performed a cohort analysis investigating the influence of (val-)ganciclovir, with or without cytomegalovirus hyperimmunoglobulin (CMV-IgG), on the incidence of EBV viremia during the first year post-transplant. 28/80 (35%) patients with known donor (D)/recipient (R) EBV serostatus bore a high risk (D+/R-) of EBV primary infection. Results: 17/28 (61%) high-risk patients developed EBV primary infection, defined as positive EBV viremia and/or EBV seroconversion, and 10/17 (59%) exhibited clinical symptoms (n=6 flu-like, n=2 infectious mononucleosis, n=2 PTLD). 4/17 (24%) patients with high, persistent EBV viremia (6.5 ± 4.9 × 104 genomes/ml) nevertheless remained asymptomatic; 3/17 (18%) were asymptomatic with low-level EBV viremia. (Val-)ganciclovir prophylaxis was associated with a significant reduction of EBV primary infection incidence in D+/R- patients (9/20 on vs. 8/8 without (val-)ganciclovir, p=0.01). Whereas at 5 months post-transplant no patient in the control group remained EBV primary infection-free, 75% of the prophylaxis group did not develop EBV primary infection; the rate of EBV primary infection-free patients at 12 months post-transplant was 55% (Fig. 1). An additive effect of CMV-IgG could not be shown (p=0.64). Type and intensity of immunosuppression, quantified according to the modified Vasudev score, had no effect either on the incidence of EBV primary infection or on the level or persistence of EBV viral load or clinical symptoms.Figure: [EBV Prophylaxis]Conclusion: Chemoprophylaxis with (val-)ganciclovir is associated with a significantly reduced incidence of EBV primary infection in high-risk pediatric kidney transplant patients.

Introduction: So far, it is unclear why some patients exhibit pronounced acute clinical EBV-related symptoms during post-transplant EBV primary infection, whilst others remain asymptomatic despite a high, persistent EBV viral load, over months or years. A genetic predisposition is likely. Methods: In the framework of a prospective, multicenter trial among 106 pediatric kidney allograft recipients (aged 11.1 ± 5.9 years), we therefore analyzed the prevalence of HLA class I and II alleles and a potential association of HLA alleles with the development of a symptomatic EBV infection (flu-like symptoms or infectious mononucleosis (IM)) in the first year post-transplant. Results: Patients expressing HLA-DR7 bore a significantly increased risk of developing a symptomatic EBV infection (univariate regression analysis: OR 4.77; 95%-CI 1.60-14.2; p=0.005; multivariate analysis: Fig. 1). The prevalence of the HLA-DR7 allele amounted to 25%. Having a comparable EBV risk constellation, HLA-DR7-positive patients suffered significantly more often (9/26 (35%)) a symptomatic EBV infection than HLA-DR7-negative recipients (8/80 (10%); p=0.008). Asymptomatic patients with a high EBV viral load tended to express HLA-DR7 less frequently than symptomatic patients with a high EBV viral load (3/17 (18%) vs. 6/11 (55%), p=0.095).Figure: [EBV HLA]Conclusions: Pediatric renal transplant recipients expressing HLA-DR7 develop significantly more often a symptomatic EBV infection than HLA-DR7-negative patients, possibly as a consequence of a pronounced immune response which, in the long run, may protect against PTLD. Indeed, HLA-DR7 induces a T helper cell reaction through presentation of EBNA1 (1) and is known to be a protective factor against the development of PTLD (2).

The detection of light from optical fibers is required in a variety of particle detector types like fiber trackers or sampling calorimeters. Instead of using classical photo sensors like PMTs or SiPMs and associated readout electronics, we propose to combine Single Photon Sensitive Avalanche Diodes (SPADs) and CMOS readout electronics on the same silicon die. We have developed, fabricated and initially characterized such a ‘Digital SiPM’ solution. In order to provide a high flexibility in fiber diameters and positions, our architecture allows for assigning the individual SPADs to programmable ‘groups’ which are routed to chip pins. The purely digital output signals provide the timing by the rising edge and an amplitude information by the pulse width. The first available chip has been successfully used to detect light of individual fibers from a fiber bundle. The proposed concept could significantly reduce the mechanical and electronic complexity as well as the cost of fiber readouts and possibly improve their performance.