ROTAVIRUS Dr Kamran Afzal Classified MicrobiologistEpidemiology © First identified as cause of diarrhea in 1973 © Most common cause of severe diarrhea in infants and children © Nearly universal in causing infection by 5 years of age © Spreads in settings where many children @ are together, such as daycare centres / ° Winter season highly predisposing 44k © Estimated range 3 - 5 billion infections iT up © Responsible for up to > 1.0 million diarrheal deaths each year worldwide © Adults too can get infectedChildhood Deaths due to Diarrhea Causes of under-five mortality Source: 2008 World Health Rena, WHO ARI Diarrheal Malaria Measles HIV/AIDS diseaseChildhood Deaths due to Diarrhea Malaria 525 Measles: vee ‘Other, 32% Diarrhea 19% | Malnutrition Perinatal, \ Acute Respiratory 18% Infections 18% Percentage of Deaths in Children under 5 years of ageDiarrhea Causing Agents in World Developed Countries Third World Parasites ae Other > < Rotavirus Beeteria 16% 33% ee aE ‘astenwtias Astroviras 7 AS B73. Caticyjras Adenovirus O7% Calicivieus Adenoviras 0.7% 6.2% O.7% 6.7%, Percentage of Rotavirus infection in Children under 5 years of ageUnder-5 mortality rate due to rotavirus disease per 100,000 population (<5 years of age) (1 «10 eats per 190,000 (J tte 50 deaths per 100,000. [RRR] 0te 100 deaths per 100,000 HB 2000500 deaths pes 100,000,Rotavirus - Structural features 0000 ° Reovirus (RNA) 60-80nm in size Double stranded (ds) RNA Non-enveloped virus A rotavirus has a characteristic wheel-like appearance when viewed by electron microscopy The name rotavirus is derived from Latin, meaning "wheel" Group A is important human pathogen [7 Groups (A to G)] 5 predominant strains (G1-G4, G9), account for 90% of isolates Strain G1 accounts for 73% of infectionsCharacters ° The virus is stable in the environment Relatively resistant to hand-washing agents Susceptible to disinfection * 95% ethanol, ‘Lysol’, formalin ° ° ° Very stable and may remain viable for weeks or months if not disinfectedTransmission © Transmission * Mainly person to person via fecal-oral route, fomites * Poor hygiene © Food and water-borne spread is possible © Spread via respiratory route is speculated — & 'Pathogenesis © Reservoir Human-GI tract © Communicability 2 days before to 10 days after onset Entry through mouth Replication in epithelium of small intestine Viremia uncommon 0000 Infection leads to isotonic diarrheaEntry to Exit 4, Entry 3. DiseaseViral attachment, multiplication and releaseViral attachment, multiplication and release Newvirusteaves GS) Epithelial cells wee Ones die.and fluids ee Invade healthyone: @ exit the body vP4 VP4 spikes attach: 4 A. eS Ow é ws ee 000.0 6 oO AA @.6A | | | “ esPathogenicity ° The virus infect the villi of the small intestine Gastric and colonic mucosa are not infected © Attach with the enterocytes by VP4 © They multiply in the cytoplasm of the enterocytes and damage their transport mechanisms © Damaged cell may show into lumen of the intestine and release large quantities of virus which appear in the stool © Viral excretion usually lasts for 2 - 12 days in otherwise healthy patientsMechanism of diarrhea They strip the tips of the villi thus decreasing the surface area and decreasing by more than 50% the specific absorptive capacities of the intestine Damaged cells on villi are replaced by non absorbing immature cells Watery diarrhea due to net secretion of intestinal fluid and loss of absorptive surface Activation of the enteric nervous system Role of NSP4 peptide regions as an enterotoxinClinical Features © Incubation period 1-3 days © Clinical manifestations depend on whether it is the first infection or reinfection © Present with Watery diarrhea (no blood or leukocytes) Fever, can be high grade Abdominal pain Vomiting Loss of electrolytes and fluids leading to dehydration May be fatal unless treated © First infection after age 3 months generally most severe May be asymptomatic or result in severe dehydrating diarrhea with fever and vomiting © GI symptoms generally resolve in 3 to 7 daysDehydration - leading cause of morbidity and mortality ‘Sunken Fontanelie Sunken Eyes _Clinical Syndromes ° Asymptomatic carriers © Childhood gastroenteritis » Endemic in tropics * High infectivity © Outbreaks * Day care centers ° Hospitals © Immunocompromised adults * Severe form of diarrheaComplications oo 00 ° Severe chronic diarrhea Dehydration Electrolyte imbalance Metabolic acidosis Immunodeficient children may have more severe or persistent diseaseImmunity © Antibody against VP7 and VP4, and Secretory IgA probably important for protection © First infection usually severe * First infection usually does not lead to permanent immunity » Subsequent infections generally less severe © Re-infection can occur at any age © By age 3 years, 90% of the children have serum antibodies to one or more types © Young children may suffer up to five re-infections by 2 years of ageDiagnosis ° Serology for epidemiologic studies Antigen detection in stool Antibody detection in serum ° Molecular methods © Electron Microscopy ° Culture Group A Rotaviruses can be cultured in monkey kidney cells © HistopathologySerology ° Antigen detection in stool ELISA, LA (Group A Rotavirus), ICT © Antibody detection ELISA can detect antibodies and establish rise in titers © Serology for epidemiologic studiesMicroscopy (EM) Demonstration of Virus in stool helps in early disease Electron Microscopy has made the identification simpler Non-Group A viruses alsoPCR/Genotyping © Genotyping is most 12345678 9" sensitive method for detection of Rotavirus NA from stool specimensHistopathology Mature enterocytes lining the tips of intestinal villi are affected Villous atrophy and blunting Infiltration of lamina propria with mononuclear cells Death of the mature enterocytes Repopulation of the villous tips with immature secretory cells » Crypt hyperplasiaTreatment © Treatment of Gastroenteritis is supportive © Correction of loss of water and electrolytes remain the goal treatment © Failure for prompt correction of dehydration leads to Acidosis Shock Death © Lesser deaths if effective fluid replacement therapy is timely initiated eace £88Fluid Replacement © Management consists of replacement of fluids (ORS) and restoration of Electrolyte balance ° Oral rehydration therapy is highly effective in reducing morbidity and mortality © Severe dehydration needs parental administration of fluidsUNICEF / WHO O.R.S. 050 oO 0 Sodium Chloride 3.5 grams Sodium Bicarbonate 2.5 grams Potassium Chloride 1.5 grams Glucose 20 grams To be dissolved in one liter of clean drinking waterPrevention and Control © In view of fecal-oral route of transmission, significant control measures are » Waste water management ° Safe drinking water supplies * Sanitation ° Basic measures * Keep your hands clean * Wash hands often with soap and warm water after using the toilet, diapering and before preparing or eating food x © VaccineVaccine ° A live, oral, pentavalent, human-bovine re-assortant vaccine ° Administered at 2, 4, and 6 months of age RotaTeq™ Rotarix™ Human Animal ‘A a Re-assortant Tissue Culture => Created by genetic re-assortment of human and bovine antigensRecommended Vaccination Bich Fanti a monta 6 mone Oman TE MoE TEmORE TE Ma te 8 Bats 6 3 6 iiComponents of Control Uae Pe taai ETE LT breastfeeding© The following viruses spread by fecal-oral route EXCEPT: a- Poliovirus b- Hepatitis D virus c- Hepatitis A virus d- Norwalk agent e- Rota virus© The following viruses spread by fecal-oral route EXCEPT: a- Poliovirus b- Hepatitis D virus c- Hepatitis A virus d- Norwalk agent e- Rota virus© The most important consideration in the treatment of diarrhea is: antibiotic therapy antiviral therapy antispasmotic therapy fluid and salts replacement vaccine therapy mooO@>© The most important consideration in the treatment of diarrhea is: antibiotic therapy antiviral therapy antispasmodic therapy fluid and salts replacement vaccine therapy mooO@>mop > Rotavirus is a common cause of diarrhea in children. Nearly all children have been infected by the virus by what age? 1 year old 2 years old 3 years old 4 years old 5 years oldmoO p> Rotavirus is a common cause of diarrhea in children. Nearly all children have been infected by the virus by what age? 1 year old 2 years old 3 years old 4 years old 5 years old© All of the following can cause primary viral diarrhea EXCEPT: Rotavirus Norwalk virus Adenovirus Epstein-Barr virus Astrovirus moom>© All of the following can cause primary viral diarrhea EXCEPT: Rotavirus Norwalk virus Adenovirus Epstein-Barr virus Astrovirus moom>moop7 > Besides watery stools, which of these symptoms also may occur during diarrhea? Abdominal pain Bloating Nausea Fever All of the abovemoo > Besides watery stools, which of these symptoms also may occur during diarrhea? Abdominal pain Bloating Nausea Fever All of the aboveVirus Types ° Viral gastroenteritis Rotavirus Caliciviruses (Norovirus) Adenovirus Astrovirus Others (Torovirus, coronavirus,pestivirus) © Viral colitis CytomegalovirusViral Agents Causing Gastroenteritis Associated with gastroenteritis *Rotaviruses eAdenoviruses 40/41 °Caliciviruses *Norwalk like viruses or SRSV (Small Round Structured Viruses) Astroviruses . *SRV (Small Round Viruses) — *Coronaviruses ¢TorovirusesEnteric pathogens cause diarrhea LA several different mechanisms 1. Stimulation of net fluid 3. Mucosal destruction and and electrolyte secretion increased permeability Sieh 4. Nutrient malabsorption CHO malabsorption CHO 2. Increased propulsive musele contractionsDiarrhea Classification © Pathophysiology Osmotic Secretory Exudation Abnormal motility © Duration Acute (< 6 weeks) Chronic (> 6 weeks)Osmotic diarrhea ° Def: Increased amounts of poorly absorbed, osmotically active solutes in gut lumen Interferes with reabsorption of water © Solutes are ingested magnesium sorbitol malabsorption of food © mucosal injury, lactase deficiencySecretory diarrhea ° Excess secretion of electrolytes, fluid across mucosa © Usually coupled with decrease in absorption © Watery, high-volume diarrhea with dehydration © Enterotoxins Cholera, E. coli, food poisoning, Rotavirus, Norwalk virus