are one of the leading causes of acute gastroenteritis in all age groups, in both immunocompetent and immunocompromised individuals and have been associated with outbreaks in hospitals, schools, and cruise ship. This is the first viral agent identified as the cause of acute gastroenteritis. Norovirus was previously known as Norwalk virus as it was identified in stool samples collected during a school outbreak in Norwalk.
VIRUS
It belongs to the family Caliciviridae and genus Norovirus. It is a single stranded, positive sense RNA virus contained within a non-enveloped protein coat having cup-shaped depressions.
Norovirus genus is divided into six genogroups (GI to GVI) and >40 genotypes based on the amino acid sequence of the VP1 capsid protein. Genogroup I, II and IV cause infection in humans. Genogroup II causes maximum number of cases followed by GI and GIV.
EPIDEMIOLOGY
In developing countries, noroviruses cause »2,00,000 deaths every year in children below 5 years of age. In developed countries, it is responsible for »64,000 severe diarrheal cases each year and in USA it is considered as the single most important cause of acute gastro enteritis in adults requiring hospitalization.
Infection can occur throughout the year but more during cold dry months of winter. Because of more incidences during winter, previously it was known as “winter vomiting disease”.
Modes of Transmission
Humans are the only natural host of human noroviruses. Transmission of virus occurs through feco-oral route. Like rotavirus, it also has a high potency to spread which is mainly because of:
• Low infectious dose
• High secondary attack rate >30%
• Spread of virus mainly occurs through person to person contact, fomites, droplets and environmental contamination.
• Long duration of virus shedding: Starts before onset of symptoms and prolongs after cessation of diarrhea.
• Capacity to survive in adverse environ mental conditions:
– Wide range of temperature: Freezing up to 60°C
– Survives in vegetables, oysters and can be transmitted through raw vegetables or fruits or improperly cooked food.
– Survives in drinking water, environmental surfaces.
• Repeated infection can occur in the same individual due to lack of long-lasting protective antibody and high genetic diversity.
Outbreaks
Norovirus infection predominantly occurs as outbreaks. This can be due to food- borne, water borne, and outbreak in health care setting.
Foodborne outbreak: Fruits and oysters get contaminated with noroviruses when treated with contaminated water. These food items when eaten raw or improperly cooked, can lead to infection. Food items like raspberry, lettuce, shellfish have been implicated in various norovirus outbreaks. Transmission through food can also occur through preparation of food by infected food handler.
Waterborne outbreaks: Several waterborne outbreaks due to norovirus have been reported. Discharge of waste water into river and various water bodies are thought to play important role in contaminating the water. Outbreaks have been linked to drinking water sources as well as recreational water.
Outbreaks in closed settings like day care centers, school and health care settings are common due to noroviruses. This is mainly due to ability of the virus to survive in environment for a long period, low infectious dose and also susceptibility of individuals. Spread of virus occurs through person to person contact, fomites and also through aerosol generated while vomiting.
Sporadic disease due to norovirus also occurs commonly, second only to rotavirus in children. This is commonly seen amongst the family members or in family clusters.
CLINICAL FEATURES
Norovirus affects all age groups. Average incubation period is 2 days (10–50 hours). Clinical symptoms in most of the cases start with sudden onset of vomiting and diarrhea, vomiting is more common in children and diarrhea is more common in adults. In general, symptoms are mild and self-limiting in nature and resolve within 1–3 days. In extremes of age, the disease may be severe with fatal outcome. Outbreak with severe disease has been more commonly associated with GII.4 strains than non-GII.4. Old age (> 85 years) is more significantly associated with fatal outcome.
Norovirus can also cause asymptomatic infection. This is more commonly seen in children of developing countries. However, asymptomatic infection also has been reported in children of developed countries and in adults.
In immunocompromised individuals, more specifically in hematopoietic stem cell and solid organ transplant recipients, symptoms are more severe and lasts for a prolong period. Excretion of virus may occur for a long period.
DIAGNOSIS
Diarrheal stool sample collected within 48-72 hours of symptom onset is preferred. Vomitus also can be used as an alternative sample.
Antigen detection: Antigen detection of GI and GII genogroups in stool sample is commonly employed for diagnosis. Several ELISA systems are commercially available. Specificity of these tests is high (85 to 100%), however, the sensitivity is variable and has been reported 40 to 80% in various studies.
Rapid immunochromatographic test: Several commercially available rapid tests are available for GI and GII antigen detection in stool samples. These tests have good specificity of >80% but suffers from variable sensitivity ranging from < 50 to 80%. Advantage of these tests is applicability in field setting.
Molecular test: Conventional reverse transcriptase PCR (RT-PCR) and real-time PCR have been developed for detection of viral RNA from clinical samples as well as from food and water. These tests also can be used for genotyping and further for sequencing, thus employed for outbreak investigation. Molecular tests are presently considered as the reference test for diagnosis of norovirus infection.
Multiplex PCR/RT-PCR: Presently commercial multiplex RT-PCR tests are available for detection of acute gastroenteritis agents which includes viral, bacterial and parasitic pathogens. The sensitivity of >95 for detection of GI and GII noroviruses has been reported by various studies with specificity of 100%.
TREATMENT AND PREVENTION
Management of diarrhea and vomiting follows the standard treatment protocol of oral/ intravenous fluid and electrolyte maintenance.
Avoiding the contaminated food and hand ling by infected food handler is not a practical solution for prevention of norovirus outbreaks.
Maintenance of personal hygiene, hand hygiene, environmental disinfection and eating properly cooked food are the key measures to prevent the spread of norovirus.
VACCINE
Due to high prevalence of norovirus infection both in children and adults and its potential to cause outbreaks have given a thought for development of vaccine for this virus.
Vaccines containing GI and bivalent vaccine containing GI and GII.4 in the form of virus like particles (VLP) have been tried in humans with reduction in the number of vomiting and diarrhea in the vaccine group.
High genetic diversity, lack of knowledge in viral immunity, and inability to cultivate the virus are the major problems associated with the development of vaccine against noroviruses.
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