Severe chronic norovirus diarrheal disease in transplant recipients: Clinical features of an under-recognized syndrome.
BACKGROUND
Norovirus (NV) infection has been reported as a cause of severe chronic diarrhea in transplant recipients, but this entity remains under-recognized in clinical practice, leading to diagnostic delays. Transplant clinicians should become familiar with this syndrome in order to facilitate early detection and management.


METHODS
Demographic, clinical, and outcomes variables were summarized from a series of transplant recipients with positive stool NV reverse transcription polymerase chain reaction (RT-PCR) assays at Johns Hopkins in 2013-2014. Factors associated with longer duration of symptoms were compared using random forest analysis.


RESULTS
Thirty-one of 193 (16%) transplant recipients who were tested for NV had positive stool RT-PCRs. Symptoms included diarrhea (100%), nausea/vomiting (58%), abdominal pain (52%), and wasting (35%). Acute kidney injury occurred in 23%, and persisted in 21% after 6 months. Median duration of diarrheal symptoms was 4 months (range, <1-20) and 11/31 (35.4%) patients had relapses after improvement. Wasting, incompatible kidney transplant status, and plasmapheresis were associated with longer diarrhea durations. Treatments included nitazoxanide (in 74%), reduction of immunosuppression (58%), and intravenous immunoglobulin (32%). Six patients died, but no deaths were attributed to NV.


CONCLUSIONS
It is important for clinicians to recognize that NV can cause severe chronic diarrhea in transplant recipients. In this series, receipt of a human leukocyte antigen- and/or blood type-incompatible kidney transplant, and plasmapheresis were associated with longer symptom duration.
Division of Infectious Disease, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Robin K
RK
Avery
Division of Transplantation, Department of Surgery, Johns Hopkins University, Baltimore, MD, USA.
Bonnie E
BE
Lonze
Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Edward S
ES
Kraus
Division of Infectious Disease, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Kieren A
KA
Marr
Division of Transplantation, Department of Surgery, Johns Hopkins University, Baltimore, MD, USA.
Robert A
RA
Montgomery
D000328:Adult; D000368:Aged; D017250:Caliciviridae Infections / Q000453:epidemiology / Q000821:virology*; D002908:Chronic Disease; D003967:Diarrhea / Q000453:epidemiology / Q000821:virology*; D004751:Enteritis / Q000453:epidemiology / Q000821:virology*; D005243:Feces / Q000821:virology; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000302:isolation & purification*; D012367:RNA, Viral / Q000302:isolation & purification; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D066027:Transplant Recipients; D014180:Transplantation / Q000009:adverse effects*; D055815:Young Adult
D012367:RNA, Viral
diarrhea; incompatible kidney transplant; norovirus; viral infections