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Noroviruses (NoVs) as a Cause of Diarrhea in Immunocompromised Pediatric Transplant Recipients

Abstract

Background.  Case reports describe significant NoV gastroenteritis morbidity in immunocompromised hosts. Objective.  To evaluate NoV diarrhea prevalence and clinical manifestations among pediatric transplant recipients. Methods.  Solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing were enrolled. Viral RNA was extracted from stool using the QIAamp viral RNA extraction kit (QIAGEN) and amplified by real-time RT-PCR with COG primers and RING probes. NoV genotypes were determined with GSK primers. Stools were assayed at the treating physician's discretion for Clostridium difficile by real-time PCR; rotavirus by ELISA and EM; adenovirus by real-time PCR and EM; and Salmonella sp., Shigella sp., Campylobacter sp., EHEC, Cryptosporidium sp., and Giardia sp. by published methods. Clinical data was collected from medical records. After excluding tube-fed patients, NoV diarrhea and non-NoV diarrhea patients, matched by transplanted organ type, were compared. Results.  116 transplant patients (61 SOT and 55 HSCT patients) were enrolled from December 1, 2012 - September 1, 2013. NoV infection was identified in 25 (22%) transplant patients, more frequently than any other enteropathogen. All NoVs detected were genogroup II (GII) NoVs, with GII.4 NoV predominance. Compared to non-NoV diarrhea patients, NoV diarrhea patients experienced significantly more frequent ICU admission and worse renal insufficiency and weight loss. Three patients expired within 6 months of NoV diarrhea onset. One patient developed pneumatosis intestinalis. Characteristics of Transplant Patients with NoV Diarrhea and non-NoV Diarrhea NoV Diarrhea (n = 22) non-NoV Diarrhea (n = 22) P value Hospital Admission for Diarrhea (%) 12 (55) 8 (36) 0.23 ICU Admission (%) 6 (27) 0 0.02 Diarrhea duration, mean days + SD 37.2 + 69.5 15.5 + 21.0 0.27 Maximum no. stool in 24 hours, mean + SD 9.5 + 4.0 7.5 + 3.1 0.16 Serum creatinine rise (mg/dL), mean + SD 0.4 + 0.4 0.2 + 0.3 0.02 Weight loss (kg), mean + SD 2.1 + 1.8 1.0 + 1.1 <0.01 Conclusion.  NoVs are an important cause of diarrhea in transplant patients. NoVs were the most common enteric pathogen identified among pediatric transplant patients and were associated with worse clinical outcomes compared to non-NoV diarrhea. Disclosures.   M. K. Estes, Takeda Vaccines, Inc.: Consultant, Consulting fee R. L. Atmar, Takeda Vaccines, Inc: Consultant, Research grant