Review
Noroviruses: A comprehensive review☆

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Introduction

Gastroenteritis, both epidemic and sporadic, is a common cause of morbidity and mortality among persons of all ages, accounting for over 1.8 million deaths in children under 5 years of age worldwide.1 The causes of gastroenteritis include a large variety of bacteria, parasites and viruses, yet in many settings the relative contribution of these agents is unknown. Studies of gastrointestinal disease rarely test for all etiologies comprehensively, and even in those that do, 40–50% of gastroenteritis cases remain of unknown etiology. However, recent studies employing molecular methods for detection of enteric viruses are closing this diagnostic gap.2, 3 Human caliciviruses (i.e., viruses belonging to the genera Norovirus [NoV] and Sapovirus) are now recognized as a leading cause of diarrhea worldwide among persons of all ages. More widespread use of these diagnostics around the world will help elucidate the role of NoVs in different settings and improve targeting of control and treatment measures.4, 5, 6, 7 This article reviews the biologic, clinical, and epidemiologic features of NoVs and their role in the etiology of sporadic and epidemic gastroenteritis.

Section snippets

History

In 1929, Zahorsky first described “Hyperemesis hemis” or “winter vomiting disease,” an illness characterized by the sudden onset of self-limited vomiting and diarrhea that typically peaked during the colder months.8 It was not until 1972, however, that Kapikian and others discovered the etiology of this syndrome. By immune electron microscopic (IEM) examination of stools of volunteers challenged with fecal filtrates from a group of elementary school students affected by an outbreak of

Clinical and epidemiologic features

NoVs infect persons of all ages.21 Although NoV disease outbreaks are reported year-round, they peak during months with cold weather in temperate climates.22 However, recent studies have demonstrated spring and summer peaks in NoV outbreaks and diarrheal hospitalizations among children <5 years of age.23, 24 Clinical NoV infection generally has an incubation of 24–48 h and is characterized by acute onset of nausea, vomiting, abdominal cramps, myalgias, and non-bloody diarrhea. NoV illness can

Transmission

Fecal-oral spread is generally the most important mode of transmission of NoVs. Transmission through infectious vomit, both by mechanical transmission from environmental surfaces (i.e., through hand/mouth contact) and aerosolization, might account for the rapid and extensive spread of disease outbreaks in closed settings, such as hospitals, hotels, cruise ships, and day-care centers.36 Evidence of contamination of environmental surfaces with NoVs has been documented during outbreaks in

Host susceptibility, immunology, and pathogenesis

Because of the lack of an animal model and inability to cultivate NoV, most pathogenesis and immunology data is from human volunteer studies,27, 43, 44, 45 which have provided much insight into host susceptibility and development of immunity after NoV infection. Early volunteer studies showed that while infected volunteers develop immunity after a NoV challenge,27, 43, 44 immunity appeared short-lived (i.e., 6–14 weeks) and subjects who were symptomatic could be re-infected when challenged 2–3

Detection methods

Since the cloning of Norwalk virus in 1990, RT-PCR assays have been developed for detection of NoVs in clinical and environmental specimens, such as water and food.47, 48 RT-PCR assays are used widely in commercial and research laboratories allowing for detection of virus in specimens collected late in illness, when the quantity of virus is low.49 RT-PCR followed by nucleotide sequencing has been particularly useful in molecular epidemiology studies to identify point-source of infection, as

Antibody prevalence

Prevalence of antibodies to NoVs is high among children <5 years of age indicating exposure early in life55, 56, 57, 58, 59, 60, 61, 62; antibodies to NoVs are lowest during the first year of life and rise after 2 years of age.63, 64 NoV infections occur worldwide and although some studies demonstrated a greater prevalence and younger age of acquisition of antibody among children in developing countries compared with those in industrialized countries, these differences were not consistently

Outbreaks

The prevention of NoV outbreaks currently relies on identification of the mode of transmission and is interrupted by the control of contamination of food and water, maintenance of strict hygiene by food-handlers, and reduction of secondary propagation of outbreaks through person-to-person spread. Measures to avoid contamination of waters in oyster-harvesting areas (e.g., surveillance of shorelines to identify possible sites of contamination of water, prohibiting overboard dumping of fecal

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    ☆

    Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

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