Adenovirus Infection in Hematopoietic and Solid Organ Paediatric Transplant Recipients: Treatment, Outcomes, and Use of Cidofovir

Abstract

Background: human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in transplant recipients, due to their immune status. Among drugs currently available, cidofovir (CDF) is the most prescribed. Methods: Retrospective study of hAdV infection in paediatric transplant recipients from a tertiary paediatric centre, describing characteristics, management, and outcomes, and focused on the role of CDF. Results: 49 episodes of infection by hAdV were detected during a four-year period: 38 episodes in patients that received allogeneic hematopoietic stem cell transplantation (77.6%) and 11 in solid organ transplant recipients (22.4%). Twenty-five patients (52.1%) were symptomatic, presenting mainly fever and/or diarrhoea. CDF was prescribed in 24 patients (49%), with modest results. CDF use was associated with the presence of symptoms resulting in lower lymphocyte count, paediatric intensive care unit admission, and high viral load. Other therapeutic measures included administration of intravenous immunoglobulin, reducing immunosuppression, and T-lymphocyte infusion. Despite treatment, 22.9% of patients did not resolve the infection and there were three deaths related to hAdV infection. All-cause mortality was 16.7% (8 episodes) by 30 days, and 32.7% (16 episodes) by 90 days, of which, 3 episodes (3/16, 18.8%) were attributed to hAdV directly. Conclusions: hAdV infection had high morbidity and mortality in our series. CDF use is controversial, and available therapeutic options are limited. Transplant patients with low lymphocyte count are at higher risk of persistent positive viremias, and short-term survival of these patients was influenced by the resolution of hAdV infection.

Respiratory adenovirus infections in children: a focus on Africa

“…HAdV can cause severe and fatal disease in both immunocompetent and immunocompromised hosts, particularly in the pediatric under-5 population [ 6 , 39 ]. Among immunocompromised patients, infection is most frequently described in hematopoietic stem cell transplant recipients and solid organ transplant recipients [ 15 , 39 ].…”

“…HAdV can cause severe and fatal disease in both immunocompetent and immunocompromised hosts, particularly in the pediatric under-5 population [ 6 , 39 ]. Among immunocompromised patients, infection is most frequently described in hematopoietic stem cell transplant recipients and solid organ transplant recipients [ 15 , 39 ]. A South African study comparing LRTI cause in hospitalized under-5 children living and not living with HIV showed a significantly higher proportion of adenovirus infections in children living with HIV (32 vs. 27%, P = 0.013) [ 40 ].…”

“…Intravenous immunoglobulin has been used to treat acute myocarditis, pneumonia (in immunocompromised patients), and disseminated disease due to adenovirus [ 27 , 39 ]. Glucocorticoids have also been used in patients with adenovirus-associated pneumonia; early administration may improve treatment success and reduce inpatient mortality [ 27 , 48 ].…”

“…Cidofovir has emerged as the currently preferred antiviral agent for treatment of adenoviral disease, although it is only available intravenously. Cidofovir-related nephrotoxicity and myelotoxicity is a concern, and has been described in high-risk hematopoietic stem cell transplant patients [ 15 , 39 ], However, only a minority of immunocompetent children treated with cidofovir seem to develop nephrotoxicity. Recently, brincidofovir, an oral formulation lipid conjugate of cidofovir, has been reported to have good oral bioavailability, and reduced nephrotoxicity and bone marrow toxicity compared with cidofovir [ 48 ].…”

A quick algorithmic review on management of viral infectious diseases in pediatric solid organ transplant recipients

“…There are no clinical trials supporting the use of cidofovir in pediatric patients, and there are only a few retrospective studies with controversial results ( 93 – 96 ). In a more recent study about the use of cidofovir for the treatment of adenovirus infection in hematopoietic and solid organ pediatric transplant recipients, the benefits of cidofovir could not be established ( 96 ). Cidofovir can be administered in two ways: 1 mg/kg three times per week for 2 weeks or 5 mg/kg per week for 2 weeks, followed by maintenance therapy with 5 mg/kg every other week ( 91 , 97 ).…”