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each year worldwide NOTE : A vaccine to prevent rotavirus gastroenteritis was first licensed in August 1998 but was withdrawn in 1999 because of its association with intussusception.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 (G1–4, 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 102°F (39°C). 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 norovirus gastroenteritis includes the following: Oral fluid and electrolyte replacement: Generally adequate for the treatment of norovirus infections Intravenous fluid and electrolyte resuscitation: May be necessary in cases of severe volume depletion Antiemetics: For relief of nausea and vomiting Analgesics: For relief of myalgias and headache Antiperistaltic agents: Should generally be avoided in cases of infectious diarrhea but can be considered in patients with severe diarrhea

Adenovirus – ds DNA virus ,

70-90 nm, icosahedral capsid. 52 serotypes of adenovirus cause various diseases/syndrome Major syndromes : (1) acute respiratory disease (ARD), (2) pharyngoconjunctival fever (3) epidemic keratoconjunctivitis (4)acute hemorrhagic cystitis

(5) gastroenteritis (40,41)

(6) adenoviral infections in immunocompromised hosts.

Gastroenteritis (most commonly associated with serotypes 40 and 41, but others may be involved) Fever and watery diarrhea are usually limited to 1-2 weeks. Mesenteric adenitis and intussusception have been associated with nonenteric adenovirus serotypes (ie, types 1, 2, 3, 5, 6).

Gastroenteritis: Patients with severe gastroenteritis may have signs of dehydration.

Laboratory Diagnosis Adenovirus infections can be identified using antigen detection by

1.ELISA, 2. PCR 3. Virus isolation 4. Serology. Adenovirus typing is usually done by hemagglutination-inhibition and/or neutralization with type-specific antisera or by molecular methods. Primary monkey kidney cells - isolation of Ad 40 and Ad41 strains

Astrovirus Astroviruses - nonenveloped viruses, 28 to 30 nm in diameter single-stranded RNA viruses known to cause a less severe form of viral gastroenteritis than that caused by other enteric pathogens. Infection occurs as both sporadic cases and in outbreaks, predominantly affecting young children, although infection has been documented in all age groups Astroviruses are reportedly the most common viral agent associated with diarrhea in immunosuppressed adults.

ELISA - in vitro diagnostic detection of human astrovirus & is better than Electron Microscopy