Noroviruses an emerging infection Dr.T.V.Rao MD Dr.T.V.Rao MD

Viruses infecting the gut Viruses associated with gastroenteritis Rotaviruses Caliciviruses Noroviruses Sapoviruses Astroviruses adenoviruses 40, 41 Rotaviruses Sapoviruses Adenoviruses Astroviruses Noroviruses Dr.T.V.Rao MD

Viruses infecting the gut Viruses associated with systemic infections enteroviruses parechoviruses Viruses associated with infection in the immunocompromised adenovirus types 42-48 cytomegalovirus human immunodeficiency virus Dr.T.V.Rao MD

Viruses infecting the gut Presumptive enteric viruses Torovirus Coronavirus Parvovirus Picobirnavirus Aichi virus Dr.T.V.Rao MD

Noroviruses Noroviruses (formerly Norwalk agent) is an RNA virus (taxonomic family Caliciviridae) that causes approximately 90% of epidemic non-bacterial outbreaks of gastroenteritis around the world, and may be responsible for 50% of all foodborne outbreaks of gastroenteritis in the US. Noroviruses affects people of all ages. The viruses are transmitted by faecally contaminated food or water, by person-to-person contact, and via aerosolization of the virus and subsequent contamination of surfaces Dr.T.V.Rao MD

About Norovirus Norovirus Characteristics Highly contagious Multiple modes of transmission Stable in the environment Resistant to routine disinfection methods Carriers may not be symptomatic Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships, Robert E. Wheeler, MD, 2003.

Norovirus…What's in a Name? The first norovirus strain, the Norwalk agent, was discovered from an outbreak of gastroenteritis that occurred in a school in Norwalk, Ohio, in 1968. Many outbreaks with similar symptoms were later reported from other settings, such as restaurants, nursing homes, day care centers, and cruise ships. Researchers found that these outbreaks were caused by viruses that were related to the Norwalk agent, so the viruses first became known as Norwalk-like viruses. Norovirus is now the official name for this group of viruses. Dr.T.V.Rao MD

Dr.T.V.Rao MD

Mechanisms generating diversity among noroviruses Genetic Recombination Requirements co-infection of a single cell relatedness of parental strains Noroviruses endemic co-circulation of genotypes multiple infections associated with food and water borne spread environmental contamination and virus survival faecal-oral route of transmission limited heterotypic protection absence of long term immunity Dr.T.V.Rao MD

Neutral Networks: A model for NoV evolution Method of representing random neutral drift between related proteins Genotype populations that are linked by point mutation but are selectively neutral Groups are defined by epitope structure, not sequence diversity * as in Gallimore et al (2007) 3 neutral networks blue pre-2002 epidemic 2 clusters orange 2002 epidemic – 2006 7 clusters yellow 2006 epidemic 4 clusters Time Evolution Dr.T.V.Rao MD Allen DJ et al. PLoS One, 2008

2002/03 epidemic Lack of short-term herd immunity to a new variant Epidemic winter season Unusual summer activity 2002/03 epidemic Strain diversity Autum Winter Spring Summer Normal winter season Normal summer activity Normal winter season Autum Winter Spring Summer Autum Winter Spring Summer Narrowing diversity: GII4 predominates GII4 variants emerge GII4 variant is selected, out of season outbreaks occur, becomes epidemic Lack of short-term herd immunity to a new variant Return to normal season, wide diversity at the beginning, narrowing as season progresses. Population protected in the short term against variant GII4 Population susceptible to other genotypes due to short-term immune protection. GII4 dominate and have an advantage over other co-circulating genotypes. replicative advantage greater transmissibility associated with a lower infectious dose larger proportion of the population susceptible through inherited genetic factors, better survival of the virus in the environment, a mechanism that allows the virus to evade immune surveillance to some degree. Dr.T.V.Rao MD

Noroviruses Family : Caliciviridae Non-enveloped small round structured viruses (27-32 nm diameter) Genome: pos sense ssRNA ~ 7.5kb Predominantly epidemic The most common cause of outbreaks of gastroenteritis Dr.T.V.Rao MD

Spread of Noroviruses Noroviruses spread from person to person, through contaminated food or water, and by touching contaminated surfaces. Noroviruses is recognized as the leading cause of foodborne-disease outbreaks in the United States. Outbreaks can happen to people of all ages and in a variety of settings Dr.T.V.Rao MD

About Norovirus Transmission “Oral-fecal” route Food (39%) Hands, person-to-person (12%) Water (3%) Also environmental surfaces: carpets, toilets, etc. Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships, Robert E. Wheeler, MD, 2003.

Many sources spread noroviruses Noroviruses are found in the stool and vomit of infected people. People can become infected by ● Eating food or drinking liquids that are contaminated with norovirus. ● Touching surfaces or objects that are contaminated with norovirus, and then placing their hand in their mouth. ● Having direct contact with an infected person; for example, by exposure to the virus when caring for or when sharing food, drinks, or eating utensils with an infected person Dr.T.V.Rao MD

About Norovirus Food sources (i.e., food arrives contaminated) Modes of Transmission by Food Food sources (i.e., food arrives contaminated) Preparation Food handlers Customers Most at risk: ready-to-eat foods that require handling but no subsequent cooking (e.g., salads) Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships, Robert E. Wheeler, MD, 2003.

About Norovirus Norovirus Infection Infectious dose of 10-100 virus particles 24-48 hour incubation period 12-60 hour duration of illness A “mild” and short-lived illness Treatment may indicate IV fluids Viral shedding of 3 weeks or more Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships, Robert E. Wheeler, MD, 2003.

Outbreaks of Noroviruses Outbreaks of noroviruses infection often occur in closed or semi-closed communities, such as long-term care facilities, overnight camps, hospitals, prisons, dormitories, and cruise ships where the infection spreads very rapidly either by person-to-person transmission or through contaminated food. Many noroviruses outbreaks have been traced to food that was handled by one infected person Dr.T.V.Rao MD

Outbreaks Related to Norovirus and Food Handlers Outbreaks of Norovirus gastroenteritis have occurred in places where people have consumed water and/or food prepared or handled by others, including:   Restaurants Cruise ships Nursing homes Hospitals Schools Banquet halls Summer camps Family dinners. Dr.T.V.Rao MD

Predisposition with noroviruses After infection, immunity to noroviruses is usually incomplete and temporary. There is an inherited predisposition to infection, and individuals with blood type O are more often infected, while blood types B and AB can confer partial protection against symptomatic infection. Dr.T.V.Rao MD

About Norovirus Norovirus Infection Symptoms Vomiting Diarrhea Nausea Abdominal cramps Headache, muscle aches Fever (minority) Dehydration Up to 30% may be asymptomatic Adapted from Strategies for Norovirus Infection Control Aboard Cruise Ships, Robert E. Wheeler, MD, 2003.

Usual symptoms with Norovirus infection Symptoms of Norovirus infection usually include Diarrhea Vomiting Nausea Stomach cramping Other, less common symptoms may include Low-grade fever Chills Headache Muscle aches General sense of fatigue Dr.T.V.Rao MD

Can cause sever dehydration Severe dehydration can be serious. The best way to prevent dehydration is to drink plenty of liquids. The most helpful fluids for this purpose are oral rehydration fluids. Other drinks that do not contain caffeine or alcohol can also help with mild dehydration. However, these drinks may not replace important nutrients and minerals that are lost due to vomiting and diarrhea. Dr.T.V.Rao MD

Making a Norovirus Diagnosis in Special Cases In special cases, for example, when there is an outbreak of gastroenteritis, there is a need to identify Norovirus as the cause of the illness. In these cases, Norovirus can often be found in stool samples of infected persons by using special tests. Sometimes, blood tests that check for Norovirus antibodies are also performed when the stool tests are inconclusive or were not done. Food handlers will often be asked for a stool sample, or even a blood sample, to help investigate the cause of an outbreak. Dr.T.V.Rao MD

Diagnosis of noroviruses infections Diagnostic procedures for NV are based on the detection of virus in stool samples by (immune) transmission electron microscopy (TEM), antigen ELISA, or polymerase chain reaction (PCR). In our study, a total of 244 stool samples obtained from 227 patients between March and May 2002 were tested by TEM, antigen ELISA and in-house PCR. Our data showed that PCR has the highest sensitivity (94.1%), followed by TEM (58.3%), and ELISA (31.3%), while specificity was highest for TEM (98.0%), followed by ELISA (94.9%), and PCR (92.4%). All three methods tested (TEM, ELISA and PCR) are useful for epidemiological investigations in gastroenteritis outbreaks; however, to maximize diagnostic validity for individual cases, at least two of the methods should be combined. Ref Laboratory diagnosis of Norovirus: which method is the best? Rameau HF, Strummer M Buxbaum S, Walczok A Preiser W Doerr HW. Dr.T.V.Rao MD

No specific treatment or vaccine for Norovirus infection There is no vaccine to prevent Norovirus infection, although this is an area of active research. ● There is no specific drug to treat people with Norovirus illness. ● Rehydration is important for infected people—they must drink plenty of liquids to replace fluid lost through vomiting and diarrhea. In some cases, fluid may need to be given intravenously. Dr.T.V.Rao MD

Practice proper hand hygiene: Practice proper hand hygiene: Wash your hands carefully with soap and water, especially after using the toilet and changing diapers and always before eating or preparing food. Alcohol-based hand sanitizers (containing at least 62% ethanol) may be a helpful addition to hand washing, but they are not a substitute for washing with soap and water. Dr.T.V.Rao MD

Other measures to prevent spread Take care in the kitchen: Carefully wash fruits and vegetables, and cook oysters and other shellfish thoroughly before eating them. Do not prepare food while infected: People who are infected with Norovirus should not prepare food for others while they have symptoms and for 3 days after they recover from their illness. Dr.T.V.Rao MD

Other measures to prevent spread Clean and disinfect contaminated surfaces: After an episode of illness, such as vomiting or diarrhea, immediately clean and disinfect contaminated surfaces by using a bleach-based household cleaner as directed on the product label or a solution made by adding 5–25 tablespoons of household bleach to 1 gallon of water. Wash laundry thoroughly: Immediately remove and wash clothing or linens that may be contaminated with vomit or fecal matter. Handle soiled items carefully—without agitating them— to avoid spreading virus. They should be laundered with detergent at the maximum available cycle length and then machine dried. Dr.T.V.Rao MD

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