Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients

Abstract

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled 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. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1 – 324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

Epidemiology of Norovirus Infection Among Immunocompromised Patients at a Tertiary Care Research Hospital, 2010–2013

“…In our cohort, norovirus and C difficile were the most commonly detected enteric pathogens, with prevalence rates of 13% and 16%, respectively. Our findings are consistent with studies conducted in similar populations: among solid organ and hematopoietic stem cell transplant recipients, norovirus was identified in 25 (22%) of 116 pediatric patients and was the most common enteric pathogen identified [18]. In a cohort of 62 children with primary immune deficiencies, norovirus was the most common pathogen identified, found in up to 17.7% of patients systematically screened [19].…”

“…Considering that formerly dominant GII.4 variants were detected in our cohort, it is possible that a number of these patients were infected years ago. Clearance and reinfection with a new norovirus has been reported in immunocompromised patients [18], so continued monitoring of our patient cohort with molecular tools will be needed to better define the extent of this risk.…”

“…Noroviruses are increasingly recognized as an important cause of gastroenteritis in immunocompromised patients [18–23]. Patients with deficient immune responses resulting from a congenital disorder, immunosuppressive therapy, cancer treatment, or human immunodeficiency virus (HIV) infection may become chronically infected, with prolonged virus shedding and illness.…”

Identification and Characterization of Single-Chain Antibodies that Specifically Bind GI Noroviruses

“…In the case of exceptionally crowded living environments, such as the Reliant Park Complex housing >27,000 individuals during Hurricane Katrina in 2005, the availability of rapid diagnostics becomes increasingly essential for infection control [40]. At the individual level, rapid norovirus detection with an approved POCT would enable appropriate care of patients with increased vulnerability, such as transplant recipients, and prevent the administration of inappropriate treatments such as antibiotics that can further complicate symptoms [6,41]. Economically, norovirus costs society approximately $60.3 billion globally every year, including direct healthcare costs and lost productivity [42].…”

“…Further, the standard diagnostic assays present significant limitations that hinder their ability to identify infection in order to inform effective prevention strategies, especially at the point-of-care. These shortcomings in detection can lead to otherwise preventable outbreaks, while immunocompromised and other especially vulnerable patients who become infected by norovirus can suffer from chronic symptoms and inappropriate treatments [6]. To ameliorate the effects of norovirus in people, developing improved diagnostics can help to prevent outbreaks and inform appropriate clinical responses that will protect sensitive patient populations.…”