Immunochromatography Method Was Useful in Prompt Diagnosis of Potentially Fatal Norovirus Gastroenteritis After Hematopoietic Stem Cell Transplantation
Authors: Ueda Ryosuke , Hiramoto Nobuhiro , Mori Shin-Ichiro , Kurosawa Saiko , Tanaka Takashi , Tada Kohei , Kobayashi Yujin , Morikawa Noriyuki , Shinohara Akihito , Okinaka Keiji , Yamashita Takuya , Heike Yuji , Fukuda Takahiro 
Published: October 2019

Abstract
Abstract 4542

Background:
Norovirus-gastroenteritis (NV-GE) is considered as a highly transmittable disease that can lead to fatal outcomes in vulnerable populations. Therefore, prompt detection of norovirus in stool specimens is important for patients who undergo hematopoietic stem cell transplantation (HSCT). The commercially available immunochromatography kit (Denka Seiken, Tokyo, Japan) is a diagnostic tool that can easily and rapidly detect norovirus antigens with high specificity and relatively less sensitivity compared with reverse transcription polymerase chain reaction (RT-PCR). Although previous studies used RT-PCR to detect norovirus in stool, this method is not necessarily a standardized technique for the clinical use, and only limited information is available about clinical significance of norovirus infection among the HSCT recipients. Here, we report an analysis of patients with NV-GE in our HSCT unit using the immunochromatography method.

Patients and Methods:
We prospectively examined stool specimens to detect norovirus antigens in patients who developed diarrhea in our HSCT unit between December 2008 and June 2011. We also retrospectively examined stool specimens which had been collected for Clostridium difficile (CD) toxin test and frozen at –40°C between January 2007 and November 2008. During the study period, a total of 468 patients underwent HSCT (autologous 83, allogeneic 385) at our center and we tested stool specimens from 355 patients who developed diarrhea.

Results:
Norovirus was detected by the immunochromatography method in 11 patients among the HSCT recipients, and in 1 patient who died before HSCT because of disease progression. Among the 12 patients with NV-GE, 3 were retrospectively diagnosed using the frozen specimens. The CD toxin test was also positive in 1 of the 12 patients with NV-GE. The median age of the 12 patients was 56 years (range, 29–66). The median duration of symptoms was 30 days (2–134). Among the 11 patients who developed NV-GE after HSCT, primary disease included lymphoma (6 patients), acute leukemia (4 patients), and multiple myeloma (1 patient), and 9 of them were not in remission at HSCT. One patient developed NV-GE after autologous HSCT, and 10 patients after allogeneic HSCT. Among the 10 allo-HSCT recipients, 6 received grafts from unrelated bone marrow donor and 4 received grafts from related donor. Five patients received myeloablative conditioning and 5 received reduced-intensity conditioning before allo-HSCT. The median time from HSCT to the onset of symptoms was 36 days (4–93). The median time from HSCT to diagnosis of NV-GE was 37 days (11–101). At diagnosis of NV-GE, all allo-HSCT recipients were given immunosuppressive agents, and 2 of them received corticosteroids for intestinal graft-versus host disease (GVHD). The volume of diarrhea was more than 500 ml per day in 4 patients. Among 4 patients who underwent endoscopy of the lower gastrointestinal tract, intestinal GVHD was diagnosed in 2 patients by histopathology findings, whereas the other 2 patients had no evidence of intestinal GVHD, which resulted in no need for an intensification of immunosuppression. Of the 12 patients with NV-GE, 6 were alive with a median follow-up of 826 days (17–1168) after the diagnosis of NV-GE. No patients died of NV-GE, and 6 died of other causes (disease progression, 4; GVHD, 1; multiple organ failure, 1). There was no outbreak of NV-GE as we promptly implemented isolation of infected patients and enhanced hygiene strategy within an hour of collection of stool specimens in patients with diarrhea.

Conclusions:
In this study, we detected 11 patients who developed NV-GE after HSCT using the immunochromatography method. Our results suggested that this method is helpful in the differential diagnosis of patients with diarrhea after HSCT and enable us to take an appropriate and prompt preventive measure. In the future study, validation with RT-PCR and immunochromatography method is warranted among the immune-compromised populations.

Disclosures:
No relevant conflicts of interest to declare.