Monitoring of Adenovirus Load in Stool by Real-Time PCR Permits Early Detection of Impending Invasive Infection in Patients after Allogeneic Stem Cell Transplantation

Disseminated adenovirus (AdV) infection is associated with high mortality in allogeneic stem cell transplant recipients. We have demonstrated that molecular detection of AdV in peripheral blood (PB) precedes the onset of life-threatening virus disease (Lion et al., Blood 102:1114–20, 2003). In most instances, detection of AdV in stool preceded the onset of viremia, thus raising the possibility that intestinal infections represent a common source of virus dissemination. To address this question, we have investigated 170 consecutive allogeneic transplantations in 138 pediatric patients transplanted at our center. Patients were monitored for the presence and the load of AdV in stool and in PB by a real-time PCR approach covering the entire spectrum of known human AdV serotypes. Fifty one patients (37%) tested positive in serial stool samples, revealing adenoviruses of nearly all subgenera, with strong predominance of serotypes 2 and 1 of species C. The overall risk of developing viremia in patients displaying or lacking intestinal AdV infection was 31% and 0%, respectively (p<0.0001). Among patients who had maximum AdV levels in stool ≤1×10E6 copies/g (n=29) neither experienced viremia during the post-transplant course, while the incidence of viremia in individuals with peak virus levels in stool above this threshold (n=22) was 73% (p<0.0001). In contrast to earlier observations, the recovery of T-cells including the CD4 and CD8 subsets showed no statistically significant correlation with high AdV loads in stool, occurrence of viremia or disseminated disease (p-values for CD4 and CD8 cells: 0.5833 and 0.6313). The recovery of NK cells showed a borderline-significant correlation with the above parameters (p=0.0442). Our observations indicate that serial measurement of AdV levels in stool specimens by RQ-PCR provides a parameter permitting early diagnosis of impending invasive infection. The median time span between detection of AdV load in stool above 1×10E6 copies/g and first observation of viremia was 10 days (range 0–191). Quantitative monitoring of AdV loads in stool could therefore provide a rationale for early onset of antiviral treatment in attempts to prevent progression to life-threatening systemic infection.