Outcomes of human adenovirus infection and disease in a retrospective cohort of pediatric solid organ transplant recipients

Abstract

Information about HAdV infection in SOT recipients is limited. We aimed to describe HAdV infection epidemiology and outcomes in a single‐center retrospective cohort during the era of PCR availability. SOT recipients transplanted at the CHOP 2004‐2013 were followed up for 180 days post‐transplant. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. HAdV disease was defined by organ‐specific radiologic and/or laboratory abnormalities. No HAdV surveillance protocols were employed during the study period; testing was solely per clinician discretion. Progression of HAdV infection was defined as HAdV disease or ≥1‐log viral load increase since a corresponding site's first positive specimen. Of the assembled 425 SOT recipients, 227 (52.6%) had ≥1 HAdV PCR. Twenty‐four (10.6%) had ≥1 HAdV‐positive PCR. HAdV‐positive subjects were younger than uninfected subjects (2.0 years vs 6.5, P = 0.001). Infection incidence rates were highest in liver recipients (15.3%), followed by heart (8.6%), kidney (8.3%), and lung (4.2%). Four subjects (16.7%) met HAdV disease criteria at virus detection. Five subjects (20.8%) had progression of HAdV infection. All‐cause mortality rates in positive and negative subjects were 0% and 3.9%, respectively. HAdV infection was infrequently detected in SOT recipients. Over one‐third of HAdV‐positive patients met disease criteria at detection or had infection progression, but none died. This low all‐cause mortality raises questions about benefits of HAdV surveillance. Larger multicenter studies are needed to assess incidence variance by center and comparative effectiveness of therapeutic interventions.

Adenovirus persistence, reactivation, and clinical management

“…The putative implication of HAdVs in human cancer therefore continues posing an intriguing enigma. There is convincing evidence, however, that persistent HAdV infection can serve as a source for viral reactivation during phases of severe immunosuppression, including particularly the allogeneic stem cell transplantation (SCT) setting and, to some extent, also the solid organ transplantation setting [19][20][21][22][23][24]. The occurrence of HAdV reactivation in SCT recipients may be associated with life-threatening clinical manifestations.…”

“…Although a high prevalence of HAdV sequences has been documented in a variety of malignant neoplasms including, for example, mantle cell lymphoma, oligodendroglioma, glioblastoma, or ependymoma [10,18], it was not possible thus far to provide clear indications for a causal relationship between HAdV infection and tumorigenicity in humans. There is convincing evidence, however, that persistent HAdV infection can serve as a source for viral reactivation during phases of severe immunosuppression, including particularly the allogeneic stem cell transplantation (SCT) setting and, to some extent, also the solid organ transplantation setting [19][20][21][22][23][24]. There is convincing evidence, however, that persistent HAdV infection can serve as a source for viral reactivation during phases of severe immunosuppression, including particularly the allogeneic stem cell transplantation (SCT) setting and, to some extent, also the solid organ transplantation setting [19][20][21][22][23][24].…”

Brincidofovir for the treatment of human adenovirus infection in pediatric solid organ transplant recipients: A case series

“…In SOT patients, HAdV can be acquired as a primary infection from horizontal transmission or as a reactivation of a latent infection in the setting of immunosuppression. HAdV infections have been documented in pediatric liver, kidney, lung, and heart transplant recipients with variability in incidence based on the organ group 5‐9 . Infection is most common in the immediate post‐transplant time period with varying severity of infection ranging from asymptomatic disease to disseminated disease with multiorgan dysfunction, graft failure, and death.…”

“…Brincidofovir has been successfully used in the treatment of refractory cases of severe HAdV which failed to respond to cidofovir, but its current use is restricted to investigational and compassionate indications. 8,11 Herein, we describe four cases of HAdV disease complicated by AKI in pediatric SOT patients (two kidney, one dual kidney-liver, and one liver) that were treated with brincidofovir through IRB-approved compassionate-use exemption.…”

“…This can be difficult in patients early after transplant who are at higher risk of allograft rejection with decreased immunosuppression. Several antiviral medications, including ganciclovir, cidofovir, vidarabine, and ribavirin, have been used to treat patients with disseminated disease and those at risk of graft loss or death 8,11. Limitations such as drug toxicity, varying success of drug therapy, and lack of data from prospective, controlled, or comparative trials make treatment decisions difficult 1.…”