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 virusDR.T.V.RAO MD 3
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 surfacesDR.T.V.RAO MD 5
ABOUT NOROVIRUS Norovirus Characteristics • Highly contagious • Multiple modes of transmission • Stable in the environment • Resistant to routine disinfection methods • Carriers may not be symptomaticAdapted from Strategies for Norovirus Infection Control Aboard Cruise Ships, Robert E. Wheeler, MD, 2003.
NOROVIRUS…WHATS 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 7
Mechanisms generating diversity among noroviruses Genetic Recombination Requirements• co-infection of a single cell• relatedness of parental strainsNoroviruses• 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 immunityDR.T.V.RAO MD 9
Neutral Networks: A model for NoV evolutionMethod of representing random neutral drift between related proteinsGenotype populations that are linked by point mutation but are selectively neutralGroups are defined by epitope structure, not sequence diversity Motif Year S Domain P2 Domain Epidemiological Number of Site A Site B 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Variant* Cluster Variant Strains SHD N-N 1 10 3 v2 A 14 pre-2002 SHD S-N 1 2 v2 B 3 THD NSN 1 1 v1 C 2 THN NGT 2 4 v2 D 6 2002 TRT STA 1 v1 E 1 epidemic TRT SST 1 1 v2 F 2 through to SRN STT 1 v6 G 1 2006 TQN STT 10 4 2 v3 H 16 TQN NTT 9 v3 I 9 TQE STT 9 v2, v4 J 9 TQE NTT 1 v8 K 2006 1 TQE SAT 1 v4 L epidemic 1 TQH STT 1 v3 M 1 * as in Gallimore et al (2007) n= 66 3 neutral networks blue pre-2002 epidemic 2 clusters orange 2002 epidemic – 2006 7 clusters yellow 2006 epidemic 4 clusters DR.T.V.RAO MD 10 Allen DJ et al. PLoS One, 2008
Strain diversity 2002/03 epidemic Autum Winter Spring Summer Autum Winter Spring Summer Autum Winter Spring Summer Unusual Epidemic winter season Normal Normal winter season Normal winter season summer summer activity activity Narrowing diversity: GII4 predominates GII4 variants emerge GII4 variant is selected, out of season outbreaks occur, becomes epidemic Return to normal season, wide diversity at the beginning, narrowing as season progresses. Lack of short-term herd immunity to a new variant •Population protected in the short term against variant GII4 •Population susceptible to otherGII4 dominate and have an advantage over other co-circulating genotypes. genotypes due to short-term immune• replicative advantage protection.• 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 11
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 12
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 settingsDR.T.V.RAO MD 13
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 personDR.T.V.RAO MD 15
ABOUT NOROVIRUS 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 moreAdapted 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 personDR.T.V.RAO MD 18
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 19
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 20
ABOUT NOROVIRUS Norovirus Infection Symptoms • Vomiting • Diarrhea • Nausea • Abdominal cramps • Headache, muscle aches • Fever (minority) • Dehydration • Up to 30% may be asymptomaticAdapted 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 fatigueDR.T.V.RAO MD 22
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 23
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 ofDR.T.V.RAO MD 24 an outbreak.
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 25
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 26
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 27
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 28
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 29
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