Deciphering an Adenovirus F41 outbreak in hematopoietic stem cell transplant paediatric recipients by whole genome sequencing

ABSTRACT

Human adenovirus (HAdV) represent a major cause of mortality and morbidity in pediatric recipients of allogeneic hematopoietic stem cells transplantation (HSCT). HAdV F type 41 (HAdV-F41) infections in HSCT patients are scarce whereas HAdV-F41 circulates commonly in healthy individuals. Between March and July 2018, HAdV-F41 infections were identified in four children (A, B, C and E) with allogeneic HSCT and one child before HSCT (D) at Robert Debré hospital, Paris, France. We report the clinical course of HAdV-F41 infection and the phylogenetic investigation to identify inter-patient transmission.

HAdV DNA was quantified in stool and plasma samples by real-time PCR. HAdV type was determined by sequencing of the fiber and hexon genes. Phylogenetic investigation was done with whole genome sequences obtained by next generation sequencing.

HAdV loads in stool samples ranged from 6.60 to 10.10 log₁₀ copies/ml. HAdV-F41 detection in plasma was observed in four patients but no disseminated disease was reported. Two patients died, but no death was attributed to HAdV. While sequencing limited to fiber gene suggested a cluster with four patients, phylogenetic analysis with whole genome sequencing and HVR7 revealed a cluster including three patients (C, D and E), suggesting an inter-patient transmission and two other independent infections.

HAdV-F41 levels in stool specimens of pediatric HSCT patients are high and represent a risk of inter-patient transmission. Whole genome sequencing helped to identify related cases. Prompt detection of HAdV in stool and control measures are warranted to limit any risk of nosocomial transmission.