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Seropositive Donors (seropositive + donor)

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Medical Sciences	60%

Selected Abstracts

Primary CMV Infections Are Common in Kidney Transplant Recipients After 6 Months Valganciclovir Prophylaxis

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010
I. Helanterä
Prolonging cytomegalovirus (CMV) prophylaxis in CMV seronegative recipients of a kidney from CMV seropositive donor (D+/R,) may reduce the incidence of late infections. We analyzed late-onset primary CMV infections after 6 months valganciclovir prophylaxis. Data from all CMV D+/R, kidney transplant recipients between January 2004 and December 2008 at our center were analyzed. Patients with a functioning graft at 6 months after transplantation who received 6 months of valganciclovir prophylaxis 900 mg once daily were included (N = 127). CMV was diagnosed with quantitative PCR. Prophylaxis was completed in 119 patients. Prophylaxis was stopped at 3,5 months due to leukopenia or gastrointestinal side effects in eight patients. Late-onset primary CMV infection developed in 47/127 (37%) patients median 244 days after transplantation (range 150,655) and median 67 days after the cessation of prophylaxis (range 1,475). Four infections were asymptomatic. In others, symptoms included fever (N = 28), gastrointestinal symptoms (nausea, vomiting, diarrhea) (N = 24), respiratory tract symptoms (N = 12), and hepatopathy (N = 6). Median peak viral load was 13500 copies/mL (range 400,2 831 000). Recurrent CMV infection developed in 9/47 (19%) patients. No significant risk factors for CMV infection were identified. Symptomatic primary CMV infections were commonly detected also after prolonged valganciclovir prophylaxis. [source]

Prevention of toxoplasmosis in transplant patients

CLINICAL MICROBIOLOGY AND INFECTION, Issue 12 2008
F. Derouin
Abstract Toxoplasmosis is a life-threatening opportunistic infection that affects haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. Its incidence in these patients is closely related to the prevalence of toxoplasmosis in the general population, which is high in Europe. In SOT recipients, toxoplasmosis results mainly from transmission of the parasite with the transplanted organ from a Toxoplasma -seropositive donor to a Toxoplasma -seronegative recipient. This risk is high in cases of transplantation of organs that are recognized sites of encystation of the parasite, e.g. the heart, and is markedly lower in other SOT recipients. Clinical symptoms usually occur within the first 3 months after transplantation, sometimes as early as 2 weeks post transplant, and involve febrile myocarditis, encephalitis or pneumonitis. In HSCT recipients, the major risk of toxoplasmosis results from the reactivation of a pre-transplant latent infection in seropositive recipients. The median point of disease onset is estimated at 2 months post transplant, with <10% of cases occurring before 30 days and 15,20% later than day 100. Toxoplasmosis usually manifests as encephalitis or pneumonitis, and frequently disseminates with multiple organ involvement. Diagnosis of toxoplasmosis is based on the demonstration of parasites or parasitic DNA in blood, bone marrow, cerebrospinal fluid, bronchoalveolar lavage fluid or biopsy specimens, and serological tests do not often contribute to the diagnosis. For prevention of toxoplasmosis, serological screening of donors and recipients before transplantation allows the identification of patients at higher risk of toxoplasmosis, i.e. seropositive HSCT recipients and mismatched (seropositive donor/seronegative recipients) SOT recipients. Preventing toxoplasmosis disease in those patients presently relies on prophylaxis via prescription of co-trimoxazole. [source]

Regulatory T cell activity in primary and persistent Epstein,Barr virus infection

JOURNAL OF MEDICAL VIROLOGY, Issue 5 2009
P.J. Wingate
Abstract Regulatory T cells (Treg) provide a balance to immune T cell activation thereby protecting the body from pathogen-induced immunopathology. Several persistent viruses induce Treg that subvert protective immune mechanisms and promote viral persistence. Epstein,Barr virus (EBV) generally infects children subclinically and persists thereafter, but primary infection in early adulthood may cause immunopathological damage manifest as infectious mononucleosis. In this study the role of Treg was investigated in acute infectious mononucleosis and healthy EBV seropositive donors. The proportion of CD4+CD25high T cells in blood from infectious mononucleosis patients was significantly lower than in seropositive donors (P,=,0.05). Using the FOXP3 marker for Treg the same frequency and extra-follicular distribution of Treg was noted in infectious mononucleosis and control tonsils. Regulatory cytokines, interleukin (IL)-10 and transforming growth factor (TGF)-,, were significantly raised in infectious mononucleosis compared to seropositive donor plasma (P,=,0.0001, P,=,0.0004 respectively) although levels of IL-10 peaked earlier in infectious mononucleosis than TGF-,. Previous studies identified EBV latent membrane protein (LMP)-1-induced Treg activity [Marshall et al. (2003): J Immunol 170:6183,6189; Marshall et al. (2007): Brit J Haematol 139:81,89], and in this study a significant reduction in interferon-, production was found from infectious mononucleosis but not seropositive donor lymphocytes after stimulation with a recall antigen when LMP-1 peptide PRG was added (P,=,0.03). It is possible that Treg are important in controlling primary EBV infection to a subclinical level in most cases and that infectious mononucleosis represents a failure of this protective mechanism. J. Med. Virol. 81:870,877, 2009. © 2009 Wiley-Liss, Inc. [source]

Cytomegalovirus in transplantation , challenging the status quo

CLINICAL TRANSPLANTATION, Issue 2 2007
Jay A Fishman
Abstract:, Background:, Cytomegalovirus (CMV) infection of solid organ transplant (SOT) recipients causes both ,,direct'' and ,,indirect'' effects including allograft rejection, decreased graft and patient survival, and predisposition to opportunistic infections and malignancies. Options for CMV prevention include pre-emptive therapy, whereby anti-CMV agents are administered based on sensitive viral assays, or universal prophylaxis of all at-risk patients. Each approach has advantages and disadvantages in terms of efficacy, costs, and side effects. Standards of care for prophylaxis have not been established. Methods:, A committee of international experts was convened to review the available data regarding CMV prophylaxis and to compare preventative strategies for CMV after transplantation from seropositive donors or in seropositive recipients. Results:, Pre-emptive therapy requires frequent monitoring with subsequent treatment of disease and associated costs, while universal prophylaxis results in greater exposure to potential toxicities and costs of drugs. The advantages of prophylaxis include suppressing asymptomatic viremia and prevention of both direct and indirect effects of CMV infection. Meta analyses reveal decreased in mortality for patients receiving CMV prophylaxis. Costs associated with prophylaxis are less than for routine monitoring and pre-emptive therapy. The optimal duration of antiviral prophylaxis remains undefined. Extended prophylaxis may improve clinical outcomes in the highest-risk patient populations including donor-seropositive/recipient-seronegative renal transplants and in CMV-infected lung and heart transplantation. Conclusions:, Prophylaxis is beneficial in preventing direct and indirect effects of CMV infection in transplant recipients, affecting both allograft and patient survival. More studies are necessary to define optimal prophylaxis regimens. [source]