Norovirus, sometimes referred to as the winter vomiting disease, is the most common cause of
gastroenteritis.
Infection is characterized by non-bloody
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
,
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, and
stomach pain.
[ Fever or headaches may also occur.][ Symptoms usually develop 12 to 48 hours after being exposed, and recovery typically occurs within one to three days.][ Complications are uncommon, but may include ]dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
, especially in the young, the old, and those with other health problems.[
The ]virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
is usually spread by the fecal–oral route
The fecal–oral route (also called the oral–fecal route or orofecal route) describes a particular route of transmission of a disease wherein pathogens in fecal particles pass from one person to the mouth of another person. Main causes of fecal ...
.[ This may be through contaminated food or water or person-to-person contact.][ It may also spread via contaminated surfaces or through ]air
The atmosphere of Earth is the layer of gases, known collectively as air, retained by Earth's gravity that surrounds the planet and forms its planetary atmosphere. The atmosphere of Earth protects life on Earth by creating pressure allowing f ...
from the vomit of an infected person.[ Risk factors include unsanitary food preparation and sharing close quarters.][ Diagnosis is generally based on symptoms.] Confirmatory testing is not usually available but may be performed by public health agencies during outbreaks.[
Prevention involves proper ]hand washing
Hand washing (or handwashing), also known as hand hygiene, is the act of cleaning one's hands with soap or handwash and water to remove viruses/bacteria/microorganisms, dirt, grease, or other harmful and unwanted substances stuck to the hands ...
and disinfection
A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than st ...
of contaminated surfaces. There is no vaccine
A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
or specific treatment for norovirus. Management involves supportive care such as drinking sufficient fluids or intravenous fluids.[ ]Oral rehydration solutions
Oral rehydration therapy (ORT) is a type of fluid replacement used to prevent and treat dehydration, especially due to diarrhea. It involves drinking water with modest amounts of sugar and salts, specifically sodium and potassium. Oral rehydrati ...
are the preferred fluids to drink, although other drinks without caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...
or alcohol can help.[ ]Alcohol-based hand sanitizers
Hand sanitizer (also known as hand antiseptic, hand disinfectant, hand rub, or handrub) is a liquid, gel or foam generally used to kill many viruses/bacteria/microorganisms on the hands. In most settings, hand washing with soap and water is gen ...
are not effective against the norovirus, according to the NHS information page on the subject; this is due to norovirus being a non-enveloped virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's ...
.
Norovirus results in about 685 million cases of disease and 200,000 deaths globally a year. It is common both in the developed and developing world
A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
.[ Those under the age of five are most often affected, and in this group it results in about 50,000 deaths in the developing world.][ Norovirus infections occur more commonly during winter months.][ It often occurs in ]outbreaks
In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
, especially among those living in close quarters.[ In the United States, it is the cause of about half of all ]foodborne disease
Foodborne illness (also foodborne disease and food poisoning) is any illness resulting from the spoilage of contaminated food by pathogenic bacteria, viruses, or parasites that contaminate food,
as well as prions (the agents of mad cow disease) ...
outbreaks.[ The virus is named after the city of ]Norwalk, Ohio
Norwalk is a city in the U.S. state of Ohio and the county seat of Huron County. The population was 17,012 at the 2010 census. The city is the center of the Norwalk Micropolitan Statistical Area and part of the Cleveland-Akron-Canton Combined ...
, US where an outbreak occurred in 1968.
Signs and symptoms
Norovirus infection is characterized by nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, watery diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, abdominal pain, and in some cases, loss of taste. A person usually develops symptoms of gastroenteritis 12 to 48 hours after being exposed to norovirus. General lethargy, weakness, muscle aches, headaches, and low-grade fevers may occur. The disease is usually self-limiting, and severe illness is rare. Although having norovirus can be unpleasant, it is not usually dangerous, and most who contract it make a full recovery within two to three days.[
Norovirus can establish a long term infection in people who are ]immunocompromised
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
, such as those with common variable immunodeficiency or with a suppressed immune system after organ transplantation
Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...
.[ These infections can be with or without symptoms.][ In severe cases, persistent infections can lead to norovirus‐associated ]enteropathy
Enteropathy refers to any pathology of the intestine. Although enteritis specifically refers to an inflammation of the intestine, and is thus a more specific term than "enteropathy", the two phrases are sometimes used interchangeably.
__TOC__
Type ...
, intestinal villous atrophy, and malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...
.
Virology
Transmission
Noroviruses are transmitted directly from person to person (62–84% of all reported outbreaks) and indirectly via contaminated water and food. They are extremely contagious, and fewer than twenty virus particles can cause an infection (some research suggests as few as five). Transmission can be aerosolized
Aerosolization is the process or act of converting some physical substance into the form of particles small and light enough to be carried on the air i.e. into an aerosol. Aerosolization refers to a process of intentionally oxidatively converting a ...
when those stricken with the illness vomit, and can be aerosolized by a toilet flush when vomit or diarrhea is present; infection can follow eating food or breathing air near an episode of vomiting, even if cleaned up. The viruses continue to be shed
A shed is typically a simple, single-story roofed structure that is used for hobbies, or as a workshop in a back garden or on an allotment. Sheds vary considerably in their size and complexity of construction, from simple open-sided ones de ...
after symptoms have subsided and shedding can still be detected many weeks after infection.
Vomiting, in particular, transmits infection effectively and appears to allow airborne transmission
Airborne or aerosol transmission is transmission of an infectious disease through small particles suspended in the air. Infectious diseases capable of airborne transmission include many of considerable importance both in human and veterinary ...
. In one incident, a person who vomited spread infection across a restaurant, suggesting that many unexplained cases of food poisoning may have their source in vomit. In December 1998, 126 people were dining at six tables; one person vomited onto the floor. Staff quickly cleaned up, and people continued eating. Three days later others started falling ill; 52 people reported a range of symptoms, from fever and nausea to vomiting and diarrhea. The cause was not immediately identified. Researchers plotted the seating arrangement: more than 90% of the people at the same table as the sick person later reported becoming ill. There was a direct correlation between the risk of infection of people at other tables and how close they were to the sick person. More than 70% of the diners at an adjacent table fell ill; at a table on the other side of the restaurant, the infection rate was still 25%. The outbreak was attributed to a Norwalk-like virus (norovirus). Other cases of transmission by vomit were later identified.
In one outbreak at an international scout jamboree in the Netherlands, each person with gastroenteritis infected an average of 14 people before increased hygiene measures were put in place. Even after these new measures were enacted, an ill person still infected an average of 2.1 other people. A US Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) study of 11 outbreaks in New York State lists the suspected mode of transmission
In electronics and telecommunications, modulation is the process of varying one or more properties of a periodic waveform, called the ''carrier signal'', with a separate signal called the ''modulation signal'' that typically contains informatio ...
as person-to-person in seven outbreaks, foodborne in two, waterborne in one, and one unknown. The source of waterborne outbreaks may include water from municipal supplies, wells, recreational lakes, swimming pools, and ice machines.
Shellfish
Shellfish is a colloquial and fisheries term for exoskeleton-bearing aquatic invertebrates used as food, including various species of molluscs, crustaceans, and echinoderms. Although most kinds of shellfish are harvested from saltwater envir ...
and salad ingredients are the foods most often implicated in norovirus outbreaks. Ingestion of shellfish that has not been sufficiently heatedunder poses a high risk for norovirus infection. Foods other than shellfish may be contaminated by infected food handlers. Many norovirus outbreaks have been traced to food that was handled by only one infected person.
Between March and August 2017, in Quebec, Canada, there was an outbreak of norovirus that sickened more than 700 people. According to an investigation by Canada's CFIA Food Control Agency, the culprit was frozen raspberries imported from Harbin Gaotai Food Co Ltd, a Chinese supplier, and then Canadian authorities issued a recall on raspberries products from Harbin Gaotai.
Classification
Noroviruses (NoV) are a genetically diverse group of single-stranded positive-sense RNA
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the contex ...
, non- enveloped viruses belonging to the family ''Caliciviridae
The ''Caliciviridae'' are a family of "small round structured" viruses, members of Class IV of the Baltimore scheme. Caliciviridae bear resemblance to enlarged picornavirus and was formerly a separate genus within the picornaviridae. They are p ...
''. According to the International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to ap ...
, the genus ''Norovirus'' has one species, which is called ''Norwalk virus''.[
Noroviruses can genetically be classified into at least seven different genogroups (GI, GII, GIII, GIV, GV, GVI, and GVII), which can be further divided into different genetic clusters or ]genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
s.
Noroviruses commonly isolated in cases of acute gastroenteritis belong to two genogroups: genogroup I (GI) includes Norwalk virus, Desert Shield virus and Southampton virus; and II (GII), which includes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaii virus and Snow Mountain virus.[
Most noroviruses that infect humans belong to genogroups GI and GII.]
Noroviruses from genogroup II, genotype 4 (abbreviated as GII.4) account for the majority of adult outbreaks of gastroenteritis and often sweep across the globe.
Recent examples include US95/96-US strain, associated with global outbreaks in the mid- to late-1990s; Farmington Hills
Farmington Hills is a city in Oakland County, Michigan, Oakland County in the U.S. state of Michigan. Part of the affluent suburbs northwest of Metro Detroit, Detroit, Farmington Hills is the second most-populated city in Oakland County, after Tro ...
virus associated with outbreaks in Europe and the United States in 2002 and in 2004; and Hunter virus which was associated with outbreaks in Europe, Japan and Australasia. In 2006, there was another large increase in NoV infection around the globe. Reports have shown a link between the expression of human histo-blood group antigen
A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrate ...
s (HBGAs) and the susceptibility to norovirus infection. Studies have suggested the capsid
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
of noroviruses may have evolved from selective pressure
Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...
of human HBGAs. HBGAs are not however the receptor or facilitator of norovirus infection. In fact, co-factors such as bile salts
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.
Primary b ...
may facilitate the infection, making it more intense when introduced during or after the initial infection of the host tissue. Bile salts are produced by the liver in response to eating fatty foods, and they help with the absorption of consumed lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s. It is not yet clear as to at what specific point in the Norovirus replication cycle bile salts facilitate infection: penetration, uncoating, or maintaining capsid stability.
The protein MDA-5 may be the primary immune sensor that detects the presence of noroviruses in the body. Some people have common variations of the MDA-5 gene that could make them more susceptible to norovirus infection.
Structure
Viruses in Norovirus are non-enveloped, with icosahedral
In geometry, an icosahedron ( or ) is a polyhedron with 20 faces. The name comes and . The plural can be either "icosahedra" () or "icosahedrons".
There are infinitely many non- similar shapes of icosahedra, some of them being more symmetrica ...
geometries. Capsid
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
diameters vary widely, from 23 to 40 nm in diameter. The larger capsids (38–40 nm) exhibit T=3 symmetry and are composed of 180 VP1 proteins. Small capsids (23 nm) show T=1 symmetry, and are composed of 60 VP1 proteins. The virus particles demonstrate an amorphous surface structure when visualized using electron microscopy.
Genome
Noroviruses contain a linear, non-segmented, positive-sense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context ...
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
of approximately 7.5 kilobases, encoding a large polyprotein which is cleaved into six smaller non-structural proteins (NS1/2 to NS7) by the viral 3C-like protease (NS6), a major structural protein ( VP1) of about 58~60 kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
and a minor capsid protein ( VP2).
The most variable region of the viral capsid is the P2 domain
Domain may refer to:
Mathematics
*Domain of a function, the set of input values for which the (total) function is defined
**Domain of definition of a partial function
**Natural domain of a partial function
**Domain of holomorphy of a function
* Do ...
, which contains antigen-presenting sites and carbohydrate-receptor binding regions.
Evolution
Groups 1, 2, 3, and 4 last shared a common ancestor
Common descent is a concept in evolutionary biology applicable when one species is the ancestor of two or more species later in time. All living beings are in fact descendants of a unique ancestor commonly referred to as the last universal comm ...
in AD 867.[Kobayashi M, Matsushima, Y, Motoya T, Sakon N, Shigemoto N, Okamoto-Nakagawa R ''et al.'' (2016) Molecular ecolution of the capsid gene in human norovirus genogroup II. Sci Rep 6:29400] The group 2 and group 4 viruses last shared a common ancestor in approximately AD 1443 (95% highest posterior density 1336–1542 AD).[Ozaki K, Matsushima Y, Nagasawa K, Motoya T, Ryo A, Kuroda M, Katayama K, Kimura H (2018) Molecular evolutionary analyses of the RNA-dependent RNA polymerase region in Norovirus genogroup II Front Microbiol] Several estimates of the evolution rate have been made varying from 8.98 × 10−3 to 2.03 × 10−3 substitutions per site per year.
The estimated mutation rate
In genetics, the mutation rate is the frequency of new mutations in a single gene or organism over time. Mutation rates are not constant and are not limited to a single type of mutation; there are many different types of mutations. Mutation rates ...
(1.21 to 1.41 substitutions per site per year) in this virus is high even compared with other RNA viruses.
In addition, a recombination hotspot Recombination hotspots are regions in a genome that exhibit elevated rates of recombination relative to a neutral expectation. The recombination rate within hotspots can be hundreds of times that of the surrounding region. Recombination hotspots re ...
exists at the ORF1-ORF2 (VP1) junction.
Replication cycle
Viral replication
Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome an ...
is cytoplasmic. Entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Positive-stranded RNA virus transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
is the method of replication. Translation takes place by leaky scanning
Leaky scanning is a mechanism used during the initiation phase of eukaryotic translation that enables regulation of gene expression. During initiation, the small 40S ribosomal subunit (as a 43S PIC) "scans" or moves in a 5' --> 3' direction along ...
and RNA termination-reinitiation. Humans and other mammals serve as the natural host. Transmission routes are fecal-oral and contamination.
Pathophysiology
When a person becomes infected with norovirus, the virus replicates within the small intestine
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...
. The principal symptom is acute gastroenteritis, characterized by nausea, forceful vomiting, watery diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, and abdominal pain, that develops between 12 and 48 hours after exposure, and lasts for 24–72 hours. Sometimes there is loss of taste, general lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
, weakness, muscle aches, headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
, cough
A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three ph ...
, and/or low-grade fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
. The disease is usually self-limiting.
Severe illness is rare; although people are frequently treated at the emergency ward, they are rarely admitted to the hospital. The number of deaths from norovirus in the United States is estimated to be around 570–800 each year, with most of these occurring in the very young, the elderly, and persons with weakened immune systems. Symptoms may become life-threatening in these groups if dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
or electrolyte imbalance
Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...
is ignored or not treated.
Diagnosis
Specific diagnosis of norovirus is routinely made by polymerase chain reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR) assays or quantitative PCR
A real-time polymerase chain reaction (real-time PCR, or qPCR) is a laboratory technique of molecular biology based on the polymerase chain reaction (PCR). It monitors the amplification of a targeted DNA molecule during the PCR (i.e., in real ...
assays, which give results within a few hours. These assays are very sensitive and can detect as few as 10 virus particles.
Tests such as ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
that use antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against a mixture of norovirus strains are available commercially, but lack specificity and sensitivity.
Prevention
After infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
, immunity
Immunity may refer to:
Medicine
* Immunity (medical), resistance of an organism to infection or disease
* ''Immunity'' (journal), a scientific journal published by Cell Press
Biology
* Immune system
Engineering
* Radiofrequence immunity desc ...
to the ''same'' strain of the virus – the genotype – protects against reinfection for between 6 months to 2 years. This immunity does not fully protect against infection with the other diverse genotypes of the virus.
In Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
, norovirus is a notifiable disease
A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. In the case of live ...
. In both the US and the UK it is not notifiable.
Hand washing and disinfectants
Hand washing with soap and water is an effective method for reducing the transmission of norovirus pathogens. Alcohol rubs (≥62% isopropyl alcohol
Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group ( chemical formula ) it is the s ...
) may be used as an adjunct, but are less effective than hand-washing, as norovirus lacks a lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
viral envelope
A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes.
Numerous human pathogenic viruses in circulation are encase ...
. Surfaces where norovirus particles may be present can be sanitised with a solution of 1.5% to 7.5% of household bleach in water, or other disinfectants effective against norovirus.
Health care facilities
In health-care environments, the prevention of nosocomial infection
A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is so ...
s involves routine and terminal cleaning
Terminal cleaning is the thorough cleaning of a room after use, used in healthcare environments to control the spread of infections.
Justification
Nosocomial infections claim approximately 90,000 lives in the United States annually. When patie ...
. Nonflammable alcohol vapor in CO2 systems is used in health care environments where medical electronics would be adversely affected by aerosolized chlorine or other caustic compounds.
In 2011, the CDC published a clinical practice guideline addressing strategies for the prevention and control of norovirus gastroenteritis outbreaks in health-care settings. Based on a systematic review of published scientific studies, the guideline presents 51 specific evidence-based
Evidence-based practice (EBP) is the idea that occupational practices ought to be based on scientific evidence. While seemingly obviously desirable, the proposal has been controversial, with some arguing that results may not specialize to indiv ...
recommendations, which were organized into 12 categories: 1) patient cohorting and isolation precautions, 2) hand hygiene, 3) patient transfer and ward closure, 4) food handlers in healthcare, 5) diagnostics, 6) personal protective equipment, 7) environmental cleaning, 8) staff leave and policy, 9) visitors, 10) education, 11) active case-finding, and 12) communication and notification. The guideline also identifies eight high-priority recommendations and suggests several areas in need of future research.
Vaccine trials
LigoCyte announced in 2007 that it was working on a vaccine and had started phase 1 trials. The company has since been taken over by Takeda Pharmaceutical Company
The is a Japanese multinational pharmaceutical company, with partial American and British roots. It is the largest pharmaceutical company in Asia and one of the top 20 largest pharmaceutical companies in the world by revenue (top 10 followin ...
. , a bivalent (NoV GI.1/GII.4) intramuscular vaccine had completed phase 1 trials. In 2020 the phase 2b trials were finished. The vaccine relies on using a virus-like particle
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural pro ...
that is made of the norovirus capsid proteins in order to mimic the external structure of the virus. Since there is no RNA in this particle, it is incapable of reproducing and cannot cause an infection.
Persistence
The norovirus can survive for long periods outside a human host depending on the surface and temperature conditions: it can survive for weeks on hard and soft surfaces, and it can survive for months, maybe even years in contaminated still water. A 2006 study found the virus remained on surfaces used for food preparation seven days after contamination.
Detection in food
Routine protocols to detect norovirus in clams and oysters by reverse transcription polymerase chain reaction are being employed by governmental laboratories such as the Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) in the US.
Treatment
There is no specific medicine to treat people with norovirus illness. Norovirus infection cannot be treated with antibiotics because it is a virus. Treatments aim to avoid complications by measures such as the management of dehydration
The management of dehydration typically involves the use of oral rehydration solution (ORS). Standard home solutions such as salted rice water, salted yogurt drinks, vegetable and chicken soups with salt can be given. Home solutions such as water ...
caused by fluid loss in vomiting and diarrhea,[ and to mitigate symptoms using ]antiemetics
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may be ...
and antidiarrheals.
Epidemiology
Norovirus causes about 18% of all cases of acute gastroenteritis worldwide. It is relatively common in developed countries and in low-mortality developing countries (20% and 19% respectively) compared to high-mortality developing countries (14%). Proportionately it causes more illness in people in the community or in hospital outpatients (24% and 20% respectively) as compared with hospital inpatients (17%) in whom other causes are more common.
Age and emergence of new norovirus strains do not appear to affect the proportion of gastroenteritis attributable to norovirus.[
Norovirus is a common cause of epidemics of gastroenteritis on ]cruise ship
Cruise ships are large passenger ships used mainly for vacationing. Unlike ocean liners, which are used for transport, cruise ships typically embark on round-trip voyages to various ports-of-call, where passengers may go on tours known as "s ...
s. The CDC through its Vessel Sanitation Program records and investigates outbreaks of gastrointestinal illness—mostly caused by norovirus—on cruise ships with both a US and foreign itinerary; there were 12 in 2015, and 10 from 1 January to 9 May 2016. An outbreak may affect over 25% of passengers, and a smaller proportion of crew members.
Human genetics
Epidemiological studies have shown that individuals with different ABO(H) (histo-blood group
A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates ...
) phenotypes are infected with NoV strains in a genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
-specific manner. GII.4 includes global epidemic strains and binds to more histo-blood group antigens than other genogroups. FUT2
Galactoside 2-alpha-L-fucosyltransferase 2 is an enzyme that in humans is encoded by the ''FUT2'' gene. It affects the secretor status of ABO antigens.
Approximately 20% of Caucasians are non-secretors due to the G428A (rs601338) and C571T (rs4 ...
fucosyltransferase
A fucosyltransferase is an enzyme that transfers an L-fucose sugar from a GDP-fucose (guanosine diphosphate-fucose) donor substrate to an acceptor substrate. The acceptor substrate can be another sugar such as the transfer of a fucose to a core G ...
transfers a fucose
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...
sugar to the end of the ABO(H) precursor in gastrointestinal cells and saliva glands. The ABH-antigen produced is thought to act as a receptor for human norovirus: A non-functional fucosyltransferase
A fucosyltransferase is an enzyme that transfers an L-fucose sugar from a GDP-fucose (guanosine diphosphate-fucose) donor substrate to an acceptor substrate. The acceptor substrate can be another sugar such as the transfer of a fucose to a core G ...
FUT2 provides high protection from the most common norovirus strain, GII.4.
Homozygous carriers of any nonsense mutation in the FUT2 gene are called ''non-secretors
Secretor status refers to the presence or absence of water-soluble ABO blood group antigens in a person's bodily fluids, such as saliva, tears, breast milk, urine, and semen. People who secrete these antigens in their bodily fluids are referred ...
'', as no ABH-antigen is produced. Approximately 20% of Caucasians are non-secretors due to G428A and C571T nonsense mutations in FUT2 and therefore have strong – although not absolute – protection from the norovirus GII.4. Non-secretors can still produce ABH antigens in erythrocytes, as the precursor is formed by FUT1. Some norovirus genotypes (GI.3) can infect non-secretors.
History
The norovirus was originally named the "Norwalk agent" after Norwalk, Ohio
Norwalk is a city in the U.S. state of Ohio and the county seat of Huron County. The population was 17,012 at the 2010 census. The city is the center of the Norwalk Micropolitan Statistical Area and part of the Cleveland-Akron-Canton Combined ...
, in the United States, where an outbreak of acute gastroenteritis occurred among children at Bronson Elementary School in November 1968 (although an outbreak had already been discovered in 1936 in Roskilde, Denmark, where it is commonly known as "Roskilde syge" or "Roskilde illness"). In 1972, electron microscopy on stored human stool samples identified a virus, which was given the name "Norwalk virus". Numerous outbreaks with similar symptoms have been reported since. The cloning
Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, cl ...
and sequencing of the Norwalk virus genome showed that these viruses have a genomic organization consistent with viruses belonging to the family Caliciviridae
The ''Caliciviridae'' are a family of "small round structured" viruses, members of Class IV of the Baltimore scheme. Caliciviridae bear resemblance to enlarged picornavirus and was formerly a separate genus within the picornaviridae. They are p ...
. The name "norovirus" (''Norovirus'' for the genus) was approved by the International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to ap ...
(ICTV) in 2002. In 2011, however, a press release and a newsletter were published by ICTV, which strongly encouraged the media, national health authorities and the scientific community to use the virus name Norwalk virus, rather than the genus name Norovirus, when referring to outbreaks of the disease. This was also a public response by ICTV to the request from an individual in Japan to rename the Norovirus genus because of the possibility of negative associations for people in Japan and elsewhere who have the family name "Noro". Before this position of ICTV was made public, ICTV consulted widely with members of the Caliciviridae Study Group and carefully discussed the case.
In addition to "Norwalk agent" and "Norwalk virus", the virus has also been called "Norwalk-like virus", "small, round-structured viruses" (SRSVs), Spencer flu and "Snow Mountain virus". Common names of the illness caused by noroviruses still in use include "Roskilde illness", "winter vomiting disease", "winter vomiting bug", "viral gastroenteritis", and "acute nonbacterial gastroenteritis".
See also
* Norovirus cis-acting replication element In molecular biology, the Norovirus cis-acting replication element (CRE) is an RNA element which is found in the coding region of the RNA-dependent RNA polymerase in Norovirus. It occurs near to the 5′ end of the RNA dependant RNA polymerase g ...
* Norovirus GII.4 Sydney
References
External links
Norovirus (vomiting bug) NHS
Norovirus infections
Global network and database noroviruses
CDC Viral Gastroenteritis FAQs
Center for Disease Control and Prevention of Food Illness Fact Sheet
"Norovirus in Healthcare Facilities Fact Sheet"
CDC, released December 21, 2006
tips from CDC for cruise vacationers
Virus Pathogen Database and Analysis Resource (ViPR): Caliciviridae
3D macromolecular structures of Noroviruses from the EM Data Bank(EMDB)
ICTV Report: ''Caliciviridae''
{{Baltimore classification
Virus genera
Foodborne illnesses
Healthcare-associated infections
Vomiting
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