Viral Diarrhea

VIRAL DIARRHEA Gastroenteritis: Gastroenteritis is the medical term for infections causing inflammation of the stomach and intestines. Viruses are common causes of gastroenteritis  Diarrhea is a clinical syndrome of diverse etiology Background associated with many influencing factors.  It is the most frequent childhood disease second only to the respiratory infection.  The major cause of death among world’s children and the number one killer of children under five in many developing countries. ACUTE INFECTIOUS GASTROENTERITIS PUBLIC HEALTH IMPACT United States • Second most common clinical entity • Greatest clinical impact on children < 5yrs – 500,000 physician visits – 55,000 children hospitalized per year – >500 deaths per year – $1 billion in total costs Worldwide • Estimated 3-5 billion cases occur annually • 5-10 million deaths annually primarily in developing countries Definition In pediatrics, diarrhea is defined as an increase in the Fluidity Volume of stools Number relative to the usual habits of each individual Why diarrhea is more dangerous for children ? Mortality Dehydration Malnutrition If: Diarrhea + Malnutrition The RISK of DEATH is 4 fold higher than that of well nourished children Why children are highly vulnerable to diarrhea? Immature digestive system More nutrition demand Weakness of defense system The normal intestinal flora have not well built up Bottle feeding Etiology: Rotavirus Enteric adenovirus Human Calcivirus (Norovirus & Norwalk virus) Astrovirus Torovirus HSV, CMV in immunocompromised patients. Two major cause of human viral gastroenteritis are Rotavirus & Norwalk virus. Rota virus (winter diarrhea) is most common among infants & young children. Norwalk virus (summer diarrhea) affects older children & adults. They are carried in intestine of most domestic & wild animals. Astrovirus is the second most common cause of diarrhea (outpatient) in infants. Mode of transmission: Fecal – oral spread from animal to person or person to person through1. Contaminated hands 2. Contaminated food or water 3. By contact with contaminated surface or fomites. Noroviruses are most common cause of gastroenteritis outbreaks in industrialized countries. Often referred to as “winter vomiting disease”. Gastrointestinal Viruses Virus Rotaviruses: Group A, B, C Genome ds-segmented RNA Typical disease Major cause of diarrhea in children Infects adults and children Epidemic viral gastroenteritis diarrhea in children Incubation Duration 1- 3 days 24- 56 h 1- 3 days 18-24 h 5- 8 days 3-7 days 1- 3 days 12- 48 h Caliciviruses ssRNA Norwalk agents EntericAdenovi Linear dsDNA rus 40,41 7- 8 days 8-12 d Astrovirus +ssRNA Infects mainly children 1- 4 days and elderly 1- 4 d Viral Agents: Developing Countries Compared to U.S. • Comparison of viral etiologic agents of diarrhea in developing countries and the United States Etiologic agent Rotavirus Noroviruses Developing country Important U.S. Very important Probably important Important Probably important Enteric adenoviruses Minor GASTROENTERITIS VIRUSES PATHOGENETIC CHARACTERISTICS • Type of infection: acute, localized – Gastrointestinal tract is target organ • Incubation period: generally short, 1-4days – Exception is adenovirus type 40 and 41infections (7-8days) • Mechanism of transmission: person-to-person via fecal-oral route; food-and water-borne – Viruses environmentally stable • Frequency of inapparent infections: low (except Astrovirus) for primary infection; increase with re-infection (Rotavirus) • Symptomatic re-infections: common – Implies poor long-term immunity • Prolonged virus shedding: common with adenovirus; can occur with rotavirus • Illnesses often more severe in compromised hosts ROTAVIRUS- winter diarrhea • Rotavirus was first identified in 1973 from duodenal biopsies of children with diarrhea • It was also detected in stool samples. Classification Family: Reoviridae Genus: Rotavirus • Rotavirus is a naked double – stranded RNA virus with a double icosahedral capsid. Structure: • Non enveloped, icosahedral, 60-80 nm in size • It give a appearance of a wheel with radiating spokes • Double capsid (outer and inner) and a core. • Outer capsid structural proteinsVP7 (G protein) VP4 (viral hemagglutinin or P protein) • Inner capsid structural proteins – VP6 VP1,2,3 • Inner core contains the genome that has double stranded RNA in 11 segments. Types: • Seven different groups (A-G) & 2 subgroups based on antigenic specificity to VP6 (inner capsid structural protein). • Human pathogens belong to groups A,B & C • Group A virus with either subgroup I or II are common. • Serotypes: • 14 human G serotypes (specified by VP7) • Group A subtypes 1, 2, 3, 4 (main human pathogens) (Further 7 subtypes) also infect animals (monkey, calf, mouse) • Group B - Infects pigs and rats Found to cause extensive outbreaks in China in past decade • Group C - Infects Pigs (Occasionally Man) • Group D - Infects birds • Group E - Infects pigs Properties: Virus is acid-labile but stable in the environment It is susceptible to disinfection with 95% ethanol. Pathogenesis: Affected host cells are mature enterocytes lining the middle and upper end of the intestinal villi in the small intestine. Infectious particle is thought to be an “intermediate subviral particle”(ISVP) which is generated after removal of of the outer capsid. Virions enter the host cell by endocytosis. Viral replicates in the host cytoplasm. Mechanism of watery diarrhea has been thought to be due to cell dysfunction/ death. Pathogenesis • Group A: Main pathogen of infantile diarrhea • Group B : Cause epidemic adult diarrhea • Group C: Cause human or animal sporadic diarrhea Epidemiology: World wide in distribution In US 20-40 deaths per year and >50,000 hospitalizations per year. It is seen during winter months in US Infects children at a young age. Older infants and young children tend to be more symptomatic with diarrhea. Mode of transmission: Fecal-oral route Through fomites Contaminated water Contagiousness: Contagious period starts before onset of diarrhea to a few days after end of diarrhea. Nosocomial cases and outbreaks are known to occur Asymptomatic infections are common, in adults Severe infections seen in young, elderly, immune compromised hosts. Group A infections are most common Group B has been associated with out breaks in china Group C is responsible for sporadic cases of diarrhea in infants around the world. Clinical features: • Incubation period: <4 days • Fever can be high grade (>102°F in 30%) • Nausea and vomiting precede diarrhea. • Diarrhea is usually watery (no blood or leukocytes), lasting 3-9 days, but longer in malnourished and immune deficient individuals. • Necrotizing enterocolitis and hemmorrhagic gastroenteritis is seen in neonates. • Dehydration is the main contributor to mortality. • Secondary malabsorption of lactose and fat, and chronic diarrhea are possible. Diagnosis: Specific antigens in stool specimen recommended by WHO • Antigen-detection in stool-by ELISA (uses a monoclonal antibody). • Latex agglutination is used for rapid. • Culture – group A can now be cultured in monkey kidney cells. Treatment: • Supportive rehydration Prevention of spread: Hand washing Disinfection of surfaces, toilets, toys etc. VaccinesRotashield, a live tetravalent rhesus-human ressortant vaccine was first used in infants in Aug. 1998. – now not in use because of reports of intussusception. RotaTeq® (Merck) is a new live pentavalent human-bovine reassortant vaccine. It confers protection that lasts for at least 2 yrs. Human Calciviruses: Members of the family- Calciviridae. Now classified into genera –Norovirus Sapovirus based on antigenic differences. Norwalk virus was first detected in stools of patients with gastroenteritis in Norwalk, Ohio in 1972. Structure: • Non - enveloped, single stranded RNA virus • Size- 27-35 nm in size • Two morphologic 1. Atypical, small round structured viruses (SRSVs):• Members of Norovirus group. • They have rough, feathery edge, but no internal pattern 2. Typical, spiked appearing viruses:• Members of Sapovirus group. • Cup shaped depression on surface Clinical Symptoms: Mode of transmission: Contaminated food or water. Incubation: 1-2 days Duration: 2-3 days • Abrupt onset of – Nausea Vomiting Abdominal cramping Watery diarrhea • Other symptoms: Headache Fever Malaise Outbreaks seen in institutions, cruise ships etc. Epidemiology: • World wide distribution. • Higher seroprevalence in developing countries. • 23 million annually • All ages affected • Occurs year around • “Summer diarrhea” or “Winter vomiting disease” • The virus are most often associated with epidemics outbreaks of waterborne, food-borne and shell-associated gastroenteritis • Institutional, and community-wide outbreaks • Asymptomatic infection (>30% cases) can result in transmission of infection. Diagnosis: • Analysis of stool or suspected food material. • State public health laboratories mainly use realtime RTPCR of stool samples. • Serology is used for epidemiologic purposes. • Commercial ELISA is thought to have poor sensitivity. Control CDC recommends disinfection with bleach solution. Astro virus: First described in relation to an outbreak of gastroenteritis in 1975, by direct electron microscopy. Family: Astrovirdiae Genus: Astrovirus It contains 8 human species. Structure: Small ssRNA, non enveloped virus. Size: 27-32 nm Capsid consists of 3 structural proteins arranged to create a 5 or 6 pointed star. Clinical features: Illness milder than Rotavirus Mode of transmission: Person to person via – Fecal – oral route Ingestion of aerosolized vomitus Indirectly: contamination of sea-food/water contaminated fomites. Incubation period: 1-4 days Duration: < 5 days Symptoms: Diarrhea Headache Nausea Low grade fever Vomiting Epidemiology: • Worldwide • Mainly affects children infants and young children <7 yrs of age. • Community impact uncertain • Often asymptomatic • Mild illness in adults • Out breaks have been seen in child-care centers. Diagnosis: • Electron microscopy (EM) useful • Enzyme Immunoassay (EIA) test can be done • RT-PCR is used by research laboratories. Treatment • Fluid and electrolyte replacement Enteric Adenovirus: Family: Adenoviridae These are the second commonest cause of viral diarrhea in young children. • ds DNA, non-enveloped. • Size: 70 - 75 nm • There are six groups of adenovirus. The enteric adenovirus belongs to group F • 2 Serotypes “enteric serotypes ” are : 40 and 41 • Causes diarrheal disease in infants and children <4 yrs of age. Adenovirus 40/41 Clinical manifestation: Mode of transmission: Feco-oral spread Incubation period: 8 - 10 days Duration: 8 - 12 days • Watery diarrhea predominates • It lasts longer than other viral gastroenteritis 5-12 days. • Vomiting and fever may occur, but are mild. Epidemiology: • Second leading cause of cases (5-20%) and hospitalizations in infants • Occurs year around; no seasonal peak • Predominates in late fall and winter • Asymptomatic or mild illness in older children, adults Diagnosis: Latex-agglutination test ELISA EM Torovirus • Family: Coronaviridae • Genus: Torovirus Virus belonging to Coronavirus family are round, pleomorphic, enveloped virus. Size: 120 to 140 nm in diameter. Virus also exhibits surface spike proteins that are club-shaped and are evenly dispersed all over the surface. A nucleocapsid is present and is rod-shaped with helical symmetry of variable sizes Core is “doughnut shaped” Clinical features: Diarrhea Diagnosis: Electron microscope 1. A 36 yr old man enjoyed a meal of raw oysters. Twenty four hours later he became ill, with sudden onset of vomiting, diarrhea and headache. The most likely cause of his gastroenteritis is A. Astrovirus B. Hepatitis A virus C. Norwalk virus D. Rotavirus group A E. Echovirus 2. This virus is the most important cause of gastoenteritis in infants and young children. It causes infections that are often severe and may be life-threatening, especially in infants. A. Echovirus B. Norwalk virus C. Rotavirus group A D. Orbivirus E. Parvovirus 3. Since rotavirus infections can be serious, a vaccine would be beneficial. Which of the following is most correct regarding a rotavirus vaccine? A. A killed human rotavirus group A vaccine is in use in US. B. A live attenuated vaccine was withdrawn from use because of reports of intussusception C. Vaccine development is complicated by rapid antigenic variation by the virus D. Available antiviral drugs make a vaccine unnecessary E. Vaccine development is complicated because the virus cannot be grown in cell culture. • References: • MIMS-2nd edition- chapter 20