Primary Epstein–Barr virus infection, seroconversion, and post‐transplant lymphoproliferative disorder in seronegative renal allograft recipients: a prospective cohort study

Hosseini-Moghaddam, Seyed M; Alhomayeed, Bader; Soliman, Nancy; Weir, Matthew A.; House, Andrew A.

doi:10.1111/tid.12533

Cited by 15 publications

(12 citation statements)

References 29 publications

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“…The cause of these late infections remains unclear, and we do not know if they can be caused by the intermittent expulsion of the virus from infected family members (as frequently occurs in childhood infections) or by sexual habits (as is common in adolescence and youth). In seronegative adults over 34 years of age who undergo transplant procedures, seroconversions occur even with seronegative donors, suggesting the existence of these other routes of infection …”

Section: Discussionmentioning

confidence: 99%

Impact of Epstein‐Barr virus serological status on clinical outcomes in adult patients with inflammatory bowel disease

Francisco

Castaño-García

Martínez-González

et al. 2018

Aliment Pharmacol Ther

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Section: Discussionmentioning

confidence: 99%

Impact of Epstein‐Barr virus serological status on clinical outcomes in adult patients with inflammatory bowel disease

Francisco

Castaño-García

Martínez-González

et al. 2018

Aliment Pharmacol Ther

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“…Interestingly among patients with EBV‐seronegative donors 60% experience primary infection. A recent published cohort of EBV‐seronegative kidney recipients including EBV D−/R− sero‐status, found identical results, suggesting an alternative transmission pathway . However, absence of increased risk of PTLD has been shown in this population .…”

Section: Discussionmentioning

confidence: 54%

“…The antiviral drugs used are only active on EBV lytic replication . In EBV‐seronegative recipients transplanted with an organ from a seropositive donor, primary infection occurred in a vast majority of recipients . Even if it is an original and nonphysiological situation (EBV being transmitted via donor passenger lymphocytes instead of oropharyngeal shedding) EBV lytic replication probably occurred which could explain some antiviral drug effects.…”

Section: Discussionmentioning

confidence: 99%

Impact of antiviral prophylaxis in adults Epstein-Barr Virus-seronegative kidney recipients on early and late post-transplantation lymphoproliferative disorder onset: a retrospective cohort study

et al. 2018

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Post-transplantation lymphoproliferative disorder (PTLD) pathogenesis is related to EBV infection. Mismatch with the donor (EBV D+/R-) is the main risk factor for both early PTLD (<1 year post-transplantation) and late (>1 year). In these at-risk patients, the role of antiviral prophylaxis for preventing PTLD remains controversial. We analyzed the impact of antiviral drugs given to prevent CMV disease in a monocentric retrospective cohort of 73 adult kidney or kidney-pancreas EBV-seronegative recipients, transplanted between 01/01/2000 and 01/01/2016. Thirty-seven (50.7%, prophylaxis group) received (val-)aciclovir or (val-)ganciclovir for 3-6 months and 36 (49.3%, no-prophylaxis group) received no-prophylaxis. Mean follow-up was 69 ± 7.2 months in the prophylaxis group and 91 ± 10.3 months in the no-prophylaxis group. Monitoring of EBV PCR revealed that prophylaxis delayed primary infection at 100 days (43% vs. 84%, P = 0.02). Early PTLD incidence was not different between groups (4/37 vs. 4/36, P = 0.99). Concerning late events, EBV-related neoplasia incidence was significantly lower in treated patients among whom no cases were observed, while in the no-prophylaxis group 6 cases were reported (P = 0.02). Despite a weak level of evidence our study suggests that antiviral prophylaxis could prevent late onset PTLD.

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“…EBV infection in transplant recipients may be a primary infection or a reactivation of a prior latent infection [8,18]. Primary infection occurs mainly via exchange of saliva or sharing household items from close-contacts, transplantation of kidney from a seropositive donor in a seronegative recipient or through blood transfusions [19,20]. Reactivation occurs in those with latent EBV and then undergo active viral multiplication in the setting of immunosuppression post-RT.…”

Section: Discussionmentioning

confidence: 99%

Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation

et al. 2020

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Background: Epstein–Barr virus (EBV) infection is associated with significant morbidity and mortality in renal transplant (RT) recipients. The spectrum of illness ranges from infectious mononucleosis (IM) to post-transplant lymphoproliferative disorder (PTLD). In association with clinical signs and symptoms, virus-specific serology and heterophile antibody tests are widely used in confirming the diagnosis of IM in the general population. However, these tests may have a limited role in immunosuppressed RT recipients from seropositive donor, especially in children who were EBV-seronegative prior to the transplant. The aim of this study is to evaluate the utility of these tests in the early diagnosis of IM in this subset of patients. Methods: This is a case study with a review of literature. Results: Here, we present a 14-year-old male with hemophilia B who presented with fever, fatigue, sore throat, palatal petechial rash, exudative tonsillitis and cervical lymphadenopathy 3 months post-RT. He was EBV seronegative prior to RT and received a deceased donor kidney transplant from a seropositive donor. Induction was done with Thymoglobulin and maintenance immunosuppression consisted of tacrolimus and mycophenolate. Initial heterophile antibody test (monospot) was negative, but became positive at 5 months and remained positive at 9 months follow-up post-RT. EBV viral capsid antigens (VCA) IgM and IgG, early antigen (EA) and nuclear antigen (EBNA) were all negative at the time of presentation. VCA IgM and IgG both became positive at 5 months and peaked at 9 months follow-up, however the EA and EBNA remained negative. EBV viral load as measured by polymerase chain reaction (PCR) was negative for the first 3 months post-RT but became positive at presentation, peaked at 6 months and started declining thereafter. Peripheral blood smear examination showed no absolute and atypical lymphocytosis. Cytomegalovirus PCR in the blood and throat culture for streptococcus were negative. There was no splenomegaly. He was managed conservatively with intravenous fluids, bed rest, antipyretics and reduction of immunosuppression. Conclusions: EBV serological markers have a limited role in the early diagnosis of EBV-IM following RT in prior seronegative children. Initial heterophile antibody test may also be negative, and hence a repeat test may be necessary. Once becoming positive, the VCA IgM may remain persistently elevated for prolonged duration. In addition to the suppressed cellular immunity secondary to immunosuppression, humoral response to viral infections is also delayed in transplant recipients, especially in the early transplant period. Hence, routine monitoring with PCR is superior to serology in diagnosing IM early and monitoring the EBV infection post-RT for timely evaluation and management.

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Primary Epstein–Barr virus infection, seroconversion, and post‐transplant lymphoproliferative disorder in seronegative renal allograft recipients: a prospective cohort study

Cited by 15 publications

References 29 publications

Impact of Epstein‐Barr virus serological status on clinical outcomes in adult patients with inflammatory bowel disease

Impact of Epstein‐Barr virus serological status on clinical outcomes in adult patients with inflammatory bowel disease

Impact of antiviral prophylaxis in adults Epstein-Barr Virus-seronegative kidney recipients on early and late post-transplantation lymphoproliferative disorder onset: a retrospective cohort study

Limited Utility of Serology and Heterophile Test in the Early Diagnosis of Epstein–Barr Virus Mononucleosis in a Child after Renal Transplantation

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