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  • Gastrointestinal System

    Viral Gastroenteritis

    Dr. Durgadas Govind Naik

  • Viral gastroenteritis (stomach flu) is an inflammation of the stomach & intestine caused by virus/es. People at higher risk are: - children under age five - Old aged people, especially if they live in nursing homes - children and adults with weakened immune system - immunocompromised Lack of immunity Important Viruses that cause gastroenteritis (mcq) 1. Rotavirus 2. Norovirus (Norwalk Virus) 3. Adenovirus 4. Astrovirus 5. Sapovirus

  • Known enteric viral pathogens - Adenovirus, Rotavirus, Astrovirus and two genera of caliciviruses, namely Norovirus (Norwalk Virus) and Sapovirus. Rotavirus and Adenoviruses are predominantly causative agents of acute infantile gastroenteritis. Astrovirus, Caliciviruses (Norovirus and Sapovirus ) are collectively responsible for an estimated 87% of viral gastroenteritis cases infecting both children and adults, and occurring as both outbreaks and sporadic cases. Norovirus infection results in acute sudden-onset of vomiting (Winter Vomiting Disease UK) especially in winter.

  • ROTA VIRUS

    Most common cause of severe gastroenteritis in infants and children

    Responsible for up to 500,000 diarrheal deaths each year worldwide NOTE : A vaccine to prevent rotavirus gastroenteritis was first licensed in August 1998 but was withdrawn in 1999 because of its association with intussusception. Second-generation safe and effective vaccines were licensed in 2006 and 2008. At present these vaccines are in use .

  • Rotavirus occurs throughout the world. The incidence of rotavirus is similar in developed and developing countries, suggesting that improved sanitation alone is not sufficient to prevent the infection.

    Rotavirus is very stable and may remain viable in the environment for weeks or months if not disinfected. Rotaviruses cause infection in many animals - cows and monkeys. These animal strains are antigenically distinct from humans and they rarely cause infection in humans. Eight Groups - A, B, C, D, E, F, G and H. Rotavirus A, the most common -causes more than 90% of rotavirus infections in humans.

  • Rotavirus - double-stranded RNA virus (60-80 nm in diameter) Three concentric shells (VP 2,6,7) enclose 11 gene segments. The outermost shell with 2 important proteins VP7, or G-protein, and VP4, or P-protein. VP7 and VP4 define the serotype & provide protection. 5 Serotypes of rotavirus (G14, G9) accounts for 90% of isolates from children younger than 5 years . Of these, the G1 strain accounted for more than 75% of isolates.

  • ROTA VIRUS in Electron Microscope

  • ROTA (wheel) VIRUS

  • Mode of Transmission Fecal-oral route - close person-to-person contact - fomites (such as toys and other

    environmental surfaces contaminated by stool).

    Transmission of rotavirus through contaminated water or food appears to be uncommon.

  • Pathogenesis - Virus entry By ingestion - Viral replication occurs in small intestinal epithelium. - Up to two-thirds of children with severe rotavirus gastroenteritis show the presence of rotavirus antigen in serum (antigenemia). - Infection may result in decreased intestinal absorption of sodium, glucose, and water, - decreased levels of intestinal lactase, alkaline phosphatase, and sucrase activity, and may lead to isotonic diarrhea.

  • Osmotic diarrhea

    a form of diarrhea associated with water retention in the bowel resulting from an accumulation of nonabsorbable water-soluble substances.

    an overload of unabsorbed osmotically active

    particles will attract and retain water in bowel,

    Associated with maldigestion, malabsorption,

    overeating, excessive carbohydrates or fats.

  • 1. antibodies directed against VP4 & or VP7 can prevent viral binding and penetration,

    2. Virus induce altered metabolism malabsorptive or osmotic diarrhoea.

    3. anti-VP6 Secretory abs

    5. (NSP4), entero toxin

    4. rotavirus-specific T cells inhibit viral replication

    6. stimulate the enteric nervous system -secretory diarrhoea and increasing intestinal motility.

    7. rotavirus kills the host cell malabsorptive /osmotic diarrhoea

  • Despite its 'enteric nature', rotavirus antigens, double-stranded RNA and infectious particles have been found in the blood of children.

    The role of these systemic antigens and/or virus in the pathogenesis of rotavirus-induced disease is currently unknown

  • Rotavirus Immunity Antibody against VP7 and VP4 probably important for protection First infection usually does not lead to permanent immunity Reinfection can occur at any age Subsequent infections generally less severe

  • Clinical Features Incubation Period : Usually less than 48 hours. Clinical manifestations vary - depend on first infection or reinfection. Infection may be - asymptomatic, - self-limited watery diarrhea, - severe dehydrating diarrhea with fever and vomiting. Up to one-third of infected children may have a temperature greater than 102F (39C). The gastrointestinal symptoms generally resolve in 3 to 7 days. The clinical features and stool characteristics of rotavirus diarrhea are nonspecific, and similar illness may be caused by other pathogens. As a result, confirmation of a diarrheal illness as rotavirus requires laboratory testing.

  • Rotavirus Complications - Severe diarrhea - Dehydration - Electrolyte imbalance - Metabolic acidosis - Immunodeficient children may have more severe or persistent disease

  • Laboratory Diagnosis : Most Common : Detection of rotavirus antigen in stool by enzyme-linked immunoassay (EIA). These kits are simple to use, inexpensive, and very sensitive. Latex Agglutination Other techniques - electron microscopy, - polymerase chain reaction, - nucleic acid hybridization, - sequence analysis, and culture

  • Management Supportive care in infants with rotavirus infection: Maintaining hydration: Key issue for children who are not dehydrated; selection of an appropriate fluid is crucial small, frequent feedings work better in infants who are vomiting; after resolution of vomiting, administer standard soy-based infant formula Administering supplemental feedings of oral maintenance solutions to infants with excessive fluid losses antiemetics for vomiting children older than 6 months

  • RV5 (RotaTeq) is a live oral vaccine Merck 2006. RV5 contains five live attenuated strains Three Doses - 2, 4, and 6 months

    RV1 (Rotarix), a live oral vaccine GlaxoSmithKline, 2008. RV1 contains one live attenuated strain Two Doses - 2, 4 months The vaccination series for both vaccines may be started as early as 6 weeks of age. The minimum interval between doses is 4 weeks. No rotavirus vaccine should be administered to infants older than 8 months of age. Both vaccines donot contain preservative or thimerosal.

    Vaccines

  • Rotavirus Vaccine Efficacy Both Vaccines are safe and effective Any rotavirus gastroenteritis: 75%-85% Severe gastroenteritis: 85%-98% Both vaccines significantly reduced physician visits for diarrhea, and reduced rotavirus-related hospitalization.

  • Norovirus, (formerly Norwalk virus), is the most common cause of epidemic nonbacterial gastroenteritis in the world. It's also called the "winter vomiting bug" because it's more common in winter Norovirus (27 nm), genome is composed of a linear, positive-sense RNA Illness spreads rapidly in closed and crowded environments, such as hospitals, nursing homes, day-care centers, schools, cruise ships and restaurants. - prolonged viral shedding, - its ability to survive in the environment, - Very Low infective dose (10-100 viral particles)

  • Mode of Transmission

  • Recurrent infections can occur throughout life because of the great diversity of norovirus strains and the lack of cross-strain or long-term immunity. Infection is characterized by damage to the microvilli in the small intestine. Blunted villi but the mucosa and epithelium remain intact.

    Increased epithelial cell apoptosis and damage to tight junction proteins.

    Diarrhea is induced by D-xylose and fat malabsorption Severe Vomiting is related to virus-mediated changes in gastric motility and delayed gastric emptying.

  • CLINICAL FEATURES OF NOROVIRUS INFECTION incubation period of 48 h - Asymptomatic Infection - Symptomatic Nausea and vomiting Watery diarrhea Abdominal cramps Headaches Low-grade fever is common Myalgias and malaise Dominant symptoms of norovirus infection are vomiting and diarrhea Norovirus infection-associated illness may also be more prolonged and severe inimmunocompromised individuals ( 3 days to years)

  • ELISA , RT PCR, Rapid Immunochromatography Assay test Immune electron microscopy: Immune serum is used to aggregate virus in stool samples to aid detection Antigen detection immunoassay: Has high sensitivity but low specificity because of reactivity with antigenic variants and homologous viruses Nucleic acid amplification: Highly sensitive and specific Serum antibody titers can be detected within 2 weeks of illness. During norovirus infection, immunoglobulin M (IgM) to norovirus has been found to be more specific than IgG. Multiplex PCR/RT-PCR tests for diarrheal pathogens- rotavirus A, adenovirus 40/41,Giardia, Cryptosporidium, Entamoeba histolytica, Campylobacter,C. difficile toxin A/B, Salmonella, Shigella, Vibrio cholerae, Escherichia coli O157:H7, ET E.coli, EH E.coli.

  • Treatment of norovir

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