Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation

Abstract

Norovirus (NV) infections are a frequent cause of gastroenteritis (GE), but data on this disease in immunocompromised patients are limited. We analyzed an NV outbreak, which affected immunosuppressed patients in the context of chemotherapy or HSCT. On recognition, 7 days after admission of the index patient, preventive measures were implemented. Attack rates were only 3% (11/334) and 10% (11/105) among patients and staff members, respectively. The median duration of symptoms was 7 days in patients compared with only 3 days in staff members (P = .02). Three patients died of the NV infection. Commonly used clinical diagnostic criteria (Kaplan-criteria) were unsuitable because they applied to 11 patients with proven NV-GE but also to 15 patients without NV-GE. With respect to the therapeutic management, it is important to differentiate intestinal GVHD from NV-GE. Therefore, we analyzed the histopathologic patterns in duodenal biopsies, which were distinctive in both conditions. Stool specimens in patients remained positive for NV-RNA for a median of 30 days, but no transmission was observed beyond an asymptomatic interval of 48 hours. NV-GE is a major threat to patients with chemotherapy or HSCT, and meticulous measures are warranted to prevent transmission of NV to these patients.

Figure 1

Kaplan-Meier curves showing the disease duration in NV GE. The symptom durations in 11 patients and 11 staff members with NV gastroenteritis are displayed.

Figure 2

Abdominal CT scan of a patient with NV GE. Extensive bowel edema in a patient with NV GE acquired during BEAM conditioning chemotherapy for autologous HSCT. The bowel wall edema was restricted to the small intestine, and the colon showed only a moderate dilation.

Figure 3

Sequential duodenal biopsies from a patient with allogeneic HSCT. (A) Duodenal biopsy with severe GVHD showing partial loss of surface epithelium (H&E) and increased numbers of apoptotic crypt epithelial cells (inset: cleaved caspase-3 staining showing apoptotic epithelial cells at the base of crypts). (B) Predominance of CD8⁺ T cells in the lamina propria with focal infiltration of the crypt epithelium (immunohistochemistry, APAAP method). (C) In contrast, duodenal biopsy in the same patient during NV infection shows villous blunting (H&E) and only a slight increase of apoptotic epithelial cells at the tip of the villi (inset: cleaved caspase-3) and (D) a massive increase of intraepithelial CD8⁺ T cells pronounced in the surface epithelium. Original magnifications, ×200 and ×600 (inset). Microscope: Olympus AX70 (Olympus); numeric aperture of objective lenses: ×20, 0.70 mm; ×60, 1.40. Stains: H&E (panels A and C); APAAP and streptavidin AP (panels B and D, inset). Camera: JVC KY-F70 (JVC); acquisition software: DISKUS; and software used for image processing: Adobe Photoshop 7.0 (Adobe Systems).