Norovirus Gastroenteritis in Immunocompromised Patients

Robert J. Leggiadro, MD


Pediatr Infect Dis J. 2013;32(4):388 

In the United States, noroviruses are the single most common cause of acute gastroenteritis in adults that results in a visit to the hospital emergency department, and they are second only to rotavirus as a major cause of severe diarrhea in infants and young children. In developing countries, noroviruses are estimated to cause more that 200,000 deaths annually among children younger than 5 years of age, and it is predicted that these viruses will become the predominant cause of diarrhea in all age groups worldwide once rotavirus infection is controlled by vaccination. Noroviruses are increasingly recognized as an important cause of chronic gastroenteritis in immunocompromised patients, as reflected by the growing number of clinical case reports. This review summarizes recent developments in norovirus research that are relevant to the prevention and management of norovirus gastroenteritis in immunocompromised patients.

Noroviruses are small, nonenveloped viruses with a single-stranded RNA genome that make up the genus norovirus of the family Caliciviridae. They are divided into 6 major genogroups designated GI through GVI. GI and GII contain the majority of norovirus strains associated with human diseases and are further divided into about 30 genotypes. A single genotype, GII.4, has been associated with majority of global outbreaks since the mid-1990s, when active surveillance with molecular diagnostic techniques were initiated.

Prolonged norovirus and illness have been reported in persons who are immunocompromised as a result of congenital immunodeficiency, immunosuppressive therapy for the purpose of maintaining an organ allograft, cancer chemotherapy and infection with HIV. Immunocompromised patients can be exposed to noroviruses from many sources, including family members, healthcare workers, contaminated food or water and the environment (including nosocomial sources). The overall incidence of norovirus gastroenteritis in hospital and community settings has not yet been determined. An increasing number of studies show that immunosuppressive therapy is a risk factor for norovirus infections.

Noroviruses are highly resistant to harsh environmental conditions, and the infectious oral dose is estimated to be <20 viral particles. In immunocompetent adults, norovirus gastroenteritis is characteristically acute (24 to 48 hours in duration) and self- limiting, but in immunocompromised adults, the disease can become chronic and can persist for weeks to years. A marked predominance of wintertime norovirus infections has been widely described in the general population, and common names are winter-vomiting disease and stomach flu.

It is not yet clear whether noroviruses are transmissible to immunocompetent adults from patients with chronic viral shedding, the latter having been proposed as a possible reservoir of novel genetic variants. Surveillance studies suggest that most nosocomial norovirus infections are acquired in the community; nosocomial outbreaks in which persons with immunodeficiency disorders are the source are rare. It is difficult to diagnose norovirus gastroenteritis on the basis of clinical features alone. Diarrhea is a common complication in transplant recipients; gastroenteritis develops in 80% of patients who have undergone hematopoietic stem-cell transplantation, as a result of conditioning therapy, graft-versus-host disease (GVHD), drugs or infectious agents. However, symptoms of acute norovirus disease can include diarrhea, fever and projectile vomiting, in contrast to the characteristic combination of diarrhea and nausea (without vomiting), observed in GVHD.

Noroviruses are shed in stool, and norovirus-specific antigens and RNA can be detected in stool samples. Regular or quantitative real-time RT-PCR assay is the most widely used laboratory method for diagnosing norovirus gastroenteritis, but several other assays are now available. Computed tomography has been reported to aid in discriminating between norovirus infection and GVHD because norovirus-infected patients have pronounced bowel-wall edema restricted to the small intestine, which is infrequently seen in patients with intestinal cytomegalovirus infections or GVHD.

Comment: Currently the treatment of patients with norovirus gastroenteritis is supportive and focuses on prevention and reversal of dehydration. Chronic norovirus infection in transplant recipients may also require the adjustment of immunosuppressive therapy during prolonged illness. The incidence of norovirus gastroenteritis in patients being treated with different types of immunosuppressive agents will require more study. Widespread use of diagnostic assays and continued research will help clarify the precise disease burden and epidemiologic features of norovirus infection in this population and will improve the clinical care of those infected.