High frequency of polyoma BK virus shedding in the gastrointestinal tract after hematopoietic stem cell transplantation: a prospective and quantitative analysis

Abstract

The polyoma BK virus (BKV) remains latent after primary infection and may reactivate during immunosuppression. The uroepithelium is the main latency site defined. This study addressed whether the gastrointestinal tract might be another latency site. To test this hypothesis, we prospectively quantified fecal BKV by quantitative PCR reaction in 40 patients undergoing hematopoietic SCT (HSCT). Urinary BKV was similarly quantified. Fecal BKV excretion was positive in 16/40 patients, of whom 10 were transient (<3 consecutively positive samples), six were persistent (> or =3 consecutively positive samples) and three were persistent with peaking (> or =10(3)-fold increase in viral load over baseline, reaching 5.11 x 10(6), 4.68 x 10(7) and 2.75 x 10(8) copies/sample at 14, 14 and 21 days post-HSCT, respectively). Urinary BKV excretion was positive in 25/40 patients. Fecal BKV excretion was significantly correlated with that of the urine (P=0.036) and was significantly associated with allogeneic HSCT (P=0.037) and persistent and peaking of urinary BKV excretion (P<0.001). Binary logistic regression showed that BKV viruria was the only significant risk factor for fecal BKV excretion (P=0.021). Fecal BKV excretion occurred in 40% patients undergoing HSCT, implicating the gastrointestinal tract as a BKV latency site.

Figure 1

Fecal BK virus (BKV) excretion in 15 patients undergoing hematopoietic SCT (HSCT). The number at each time point represented the logarithm of the BKV copies/stool sample (∼0.5 g of fecal material). For example, 3+ represented 10³ copies and 5+ represented 10⁵ copies. (–) denoted negativity for BKV. T=transiently positive (<3 consecutive positive samples; note that there might be ⩾nonconsecutive positive samples); P=persistently positive (⩾3 consecutive positive samples); PP=persistent positive with peaking (⩾3-log increase over baseline).

Figure 2

Patterns of fecal and urinary BKV excretion. (a) Three patients developed concomitant fecal and urinary BKV peaking. (b) Sixteen patients developed urinary but not fecal BKV peaking. (c) Twenty-one patients developed neither urinary nor fecal BKV peaking. Each data point represented mean results of BKV excretion at each time point for all the patients in that group. Therefore, although some patients in patterns b and c never had quantifiable fecal BKV, the stool line did not touch baseline. Each error bar represented one s.d. BKV, BK virus.

Figure 3

Correlation between fecal and urinary BKV excretion. The patterns were divided into transient (<3 consecutively positive samples during HSCT), persistent (⩾3 consecutively positive samples) and persistent with peaking (⩾10³-fold increase from baseline). Each point represented data from an individual patient. The types of BKV excretion in fecal and urinary samples were significantly correlated (Kendall's Tau-b correlation coefficient 0.488, P<0.01). The encircled points denoted 10 patients with positive BKV viruria, but no detectable fecal BKV excretion. BKV, BK virus; HSCT, hematopoietic SCT.