Allogeneic Hematopoietic Stem Cell Transplantation and Norovirus Gastroenteritis: A Previously Unrecognized Cause of Morbidity

Roddie, Claire; Paul, Joel; Benjamin, Reuben; Gallimore, Christopher; Xerry, Jacqueline; Gray, Jim; Peggs, Karl S.; Morris, Emma; Thomson, Kirsty; Ward, Katherine N.

doi:10.1086/605557

Cited by 143 publications

(138 citation statements)

References 23 publications

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“…However, the frequency of their detection, as well as the detection of other enteric pathogens, was clearly lower than that observed in kidney transplant recipients at the time of the diarrhea episode. Interestingly, the mean cycle threshold values of Norovi- rus detection by Ridagene Norovirus I & II were 27.1 and 23.6 (not shown) in kidney transplant recipients at the time of the diarrhea episode and in the control groups, respectively, contradicting the hypothesis of a link between high viral load and the disease, which is still debated (29,32,33).…”

Section: Discussionmentioning

confidence: 90%

Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays

Coste¹,

Vuiblet

Moustapha

et al. 2013

J Clin Microbiol

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Diarrhea is a frequent complication after kidney transplantation, ascribed to adverse effects of the immunosuppressive therapy in case of negative microbiological examination of the stools. The aim of this study was to improve the microbiological diagnosis by implementing molecular tests. Fifty-four severe diarrhea events that occurred in 49 adult kidney transplant recipients from September 2010 to November 2011 were investigated. One or several enteric pathogens were detected in 13 (23%) stool samples using classical microbiological methods versus 39 (72%) for the seven commercially available multiplex PCR assays used retrospectively (P ‫؍‬ 0.006). Interestingly, molecular diagnosis identified 15 multiple infections compared to none using classical techniques. The primary pathogens detected were enteropathogenic Escherichia coli (EPEC) (n ‫؍‬ 15; 38%), Campylobacter spp. (n ‫؍‬ 15; 38%), and Norovirus (n ‫؍‬ 14; 36%). Specificities for Campylobacter and Norovirus infection diagnosis were 75 and 100%, respectively, by comparison to reference methods. Based on molecular findings, a cyclosporine-mycophenolate mofetil combination was identified as a risk factor for developing Norovirus-induced diarrhea. Norovirus infections were also responsible for higher weight loss than all the other causes of diarrhea. In samples from asymptomatic immunocompromised and immunocompetent patients, EPEC but not Norovirus and Campylobacter infections were detected at a frequency similar to that observed in symptomatic kidney transplant recipients. In conclusion, molecular tools significantly improved the detection of single and multiple enteric infections by comparison to classical techniques and could quickly become the key element in the management of severe acute diarrhea in transplant recipients.

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Section: Discussionmentioning

confidence: 90%

Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays

Coste¹,

Vuiblet

Moustapha

et al. 2013

J Clin Microbiol

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“…Noroviruses are an important cause of gastroenteritis in immunocompromised individuals (44,45), who are at increased risk for severe disease outcomes (1,44). Recent vaccine trials utilizing a VLP-based vaccine approach support the idea that efficacious vaccines that elicit short-term protection in some healthy individuals can be generated, but vaccines may not protect immunocompromised populations, making development of therapeutics that effectively treat or prevent norovirus infections a top health priority.…”

Section: Discussionmentioning

confidence: 99%

Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses

Debbink

Lindesmith

Ferris

et al. 2014

J Virol

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Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic GII.4 strains. However, while some capsid protein residues are under positive selection and undergo patterned changes in sequence variation over time, the relationships between genetic variation and antigenic variation remains unknown. Based on previously published GII.4 strains from a chronically infected individual, we synthetically reconstructed virus-like particles (VLPs) representing early and late isolates from a small-bowel transplant patient chronically infected with norovirus, as well as the parental GII.4-2006b strain. We demonstrate that intrahost GII.4 evolution results in the emergence of antigenically distinct strains over time, comparable to the variation noted between the chronologically predominant GII.4 strains GII.4-2006b and GII.4-2009. Our data suggest that in some individuals the evolution that occurs during a chronic norovirus infection overlaps with changing antigenic epitopes that are associated with successive outbreak strains and may select for isolates that are potentially able to escape herd immunity from earlier isolates. IMPORTANCENoroviruses are agents of gastrointestinal illness, infecting an estimated 21 million people per year in the United States alone. In healthy individuals, symptomatic infection typically resolves within 24 to 48 h. However, symptoms may persist for years in immunocompromised individuals, and development of successful treatments for these patients is a continuing challenge. This work is relevant to the design of successful norovirus therapeutics for chronically infected patients; provides support for previous assertions that chronically infected individuals may serve as reservoirs for new, antigenically unique emergent strains; and furthers our understanding of genogroup II, genotype 4 (GII.4) norovirus immune-driven molecular evolution.

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“…Twelve allogeneic HSCT recipients with norovirus infection had onset of diarrhea for 0.25 to 6 months prior to diagnosis (55). Eleven patients were receiving immunosuppressive therapy, including two who received it for presumed GVHD (which proved to be absent).…”

Section: Figmentioning

confidence: 99%

Norovirus

2015

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SUMMARY Norovirus, an RNA virus of the family Caliciviridae , is a human enteric pathogen that causes substantial morbidity across both health care and community settings. Several factors enhance the transmissibility of norovirus, including the small inoculum required to produce infection (<100 viral particles), prolonged viral shedding, and its ability to survive in the environment. In this review, we describe the basic virology and immunology of noroviruses, the clinical disease resulting from infection and its diagnosis and management, as well as host and pathogen factors that complicate vaccine development. Additionally, we discuss overall epidemiology, infection control strategies, and global reporting efforts aimed at controlling this worldwide cause of acute gastroenteritis. Prompt implementation of infection control measures remains the mainstay of norovirus outbreak management.

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Allogeneic Hematopoietic Stem Cell Transplantation and Norovirus Gastroenteritis: A Previously Unrecognized Cause of Morbidity

Abstract: Noroviruses are a hitherto unsuspected cause of prolonged morbidity and mortality in adults after allogeneic HSCT. The use of reverse-transcriptase polymerase chain reaction to detect high viral load levels in feces distinguishes norovirus gastroenteritis from gut GVHD.

Cited by 143 publications

References 23 publications

Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays

Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays

Within-Host Evolution Results in Antigenically Distinct GII.4 Noroviruses

Norovirus

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