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Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a Risk Factor for Invasive Infection
Karin Kosulin1, Bettina Berkowitsch1, Susanne Matthes2
1Children's Cancer Research Institute, Zimmermannplatz 10, 1090 Vienna, Austria.
Insights
Pre-transplant intestinal shedding of human adenovirus (HAdV) in pediatric stem cell transplant recipients significantly increases the risk of invasive HAdV infection and disease post-transplant. Early monitoring is crucial.
Area of Science:
- Virology
- Immunology
- Pediatric Hematology/Oncology
Background:
- Human adenoviruses (HAdV) are a significant cause of illness and death in pediatric stem cell transplant (HSCT) patients.
- The gastrointestinal tract is a known site for HAdV persistence, but the impact of pre-transplant intestinal shedding on invasive infection risk remains unclear.
Purpose of the Study:
- To investigate the association between pre-transplant intestinal HAdV shedding and the risk of invasive HAdV infection in pediatric HSCT recipients.
- To determine if pre-transplant HAdV shedding predicts earlier or higher levels of intestinal virus post-transplant.
Main Methods:
- Molecular monitoring of HAdV in serial stool samples using RQ-PCR in 304 pediatric HSCT candidates.
- Analysis of stool and peripheral blood specimens pre-transplant and up to 100 days post-HSCT.
Main Results:
- HAdV was detected in the stool of 42% of patients, with 42 patients shedding virus before HSCT.
- Patients with pre-transplant shedding showed a significantly earlier rise in intestinal HAdV levels above a high-risk threshold (p<0.01).
- Invasive infection occurred significantly more often in patients with pre-transplant shedding (33%) compared to those without (7%; p<0.0001).
Conclusions:
- Intestinal HAdV shedding before HSCT substantially elevates the risk of invasive infection and disseminated disease post-transplant.
- Timely HAdV monitoring and consideration of pre-emptive therapies are essential for HSCT recipients.
Abstract:
Human adenoviruses (HAdV) are a major cause of morbidity and mortality in pediatric human stem cell transplant (HSCT) recipients. Our previous studies identified the gastrointestinal tract as a site of HAdV persistence, but the role of intestinal virus shedding pre-transplant for the risk of ensuing invasive infection has not been entirely elucidated. Molecular HAdV monitoring of serial stool samples using RQ-PCR was performed in 304 children undergoing allogeneic HSCT. Analysis of stool and peripheral blood specimens was performed pre-transplant and at short intervals until day 100 post-HSCT. The virus was detected in the stool of 129 patients (42%), and 42 tested positive already before HSCT. The patients displaying HAdV shedding pre-transplant showed a significantly earlier increase of intestinal HAdV levels above the critical threshold associated with high risk of invasive infection (p<0.01). In this subset of patients, the occurrence of invasive infection characterized by viremia was significantly higher than in patients without HAdV shedding before HSCT (33% vs 7%; p<0.0001). The data demonstrate that intestinal HAdV shedding before HSCT confers a greatly increased risk for invasive infection and disseminated disease post-transplant, and highlights the need for timely HAdV monitoring and pre-emptive therapeutic considerations in HSCT recipients.
