What are we talking about ? A disease that affects ALL children before the age of 5 years Responsible for 5 % deaths of all children less than 5 years.

A disease that affects ALL children before the age of 5 years

Responsible for 5 % deaths of all children less than 5 years.

Rotavirus – in 4 parts Dr Gaurav Gupta Charak Clinics www.charakclinics.com DCH, DNB, MAAP, MIAP

Rotavirus – the 4 parts Virology – boring yet interesting ! Scary Statistics about Rotavirus – the Indian connection Can we clinically identify Rotavirus Diarrhea Preventing Rotavirus Diarrhea – what GSK wants me to talk about 

Virology – boring yet interesting !

Scary Statistics about Rotavirus – the Indian connection

Can we clinically identify Rotavirus Diarrhea

Preventing Rotavirus Diarrhea – what GSK wants me to talk about 

Rotavirus Virology – Part 1 Rota – means wheel-like in greek Double-stranded RNA virus

Rota – means wheel-like in greek

Double-stranded RNA virus

Rotavirus – this is how it looks!

Rotavirus Virology VERY resistant to destruction (Why is this important?) VP4 antigen: P serotype; 11 human rotaviruses VP7 antigen: G serotype; 10 human rotaviruses Commonly found strains: P[8]G1; P[8]G3; P[8]G4; and P[4]G2

VERY resistant to destruction (Why is this important?)

VP4 antigen: P serotype; 11 human rotaviruses

VP7 antigen: G serotype; 10 human rotaviruses

Commonly found strains: P[8]G1; P[8]G3; P[8]G4; and P[4]G2

Global distribution of human group A rotavirus P-G types (1989-2004) http://www.cdc.gov/ncidod/EID/vol4no4/parasharG.htm#fig%204) Other P[6]G8 Africa P[8]G5 Brazil P[11]G10 India P[6]G12 India

Are these multiple serotypes important ? NOT REALLY ! Because Natural RV infection attenuates severity of subsequent infections, regardless of serotype

NOT REALLY !

Because Natural RV infection attenuates

severity of subsequent infections, regardless

of serotype

Cumulative probability of rotavirus infection in 200 Mexican infants during the 1st 2 years of life * *Complete protection against moderate-to-severe diarrhoea NEJM 1996; 335: 1022 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Probability of rotavirus infection Age (months) 1st infection 2nd infection 3rd infection 4th infection 5th infection

Scary Statistics– Part 2 Diarrhoea is third largest cause of death in under 5 Rotavirus are the single most important cause of diarrhoea worldwide. Annually rotaviruses cause 5% of all deaths in children 527,000 deaths 80% of deaths are in infancy > 100,000 in India 39% of childhood hospitalisations for diarrhea Lancet Infect Dis 2007; 7: 56 Wkly Epidemiol Rec 2007; 82: 285 JID 2005; 192(Suppl 1) S1 EID 2006;12: 304

Diarrhoea is third largest cause of death in under 5

Rotavirus are the single

most important cause of

diarrhoea worldwide.

Annually rotaviruses cause

5% of all deaths in children

527,000 deaths

80% of deaths are in infancy

> 100,000 in India

39% of childhood

hospitalisations for diarrhea

Modified after Emerg Infect Dis 2006; 12: 304 5 million clinic visits 25 million domiciliary episodes 1 : 250 1 : 65 Event Risk of Particular Event 100,000 deaths 0.4 million hospitalisations 1 : 5 1 : 1 Estimated prevalence of rotavirus disease in India

Part 3 - Can we clinically diagnose Rotavirus gastroenteritis (RVGE)? High fever and vomiting in a 6 month to 2 year child Severe vomiting resistant to anti-emetics Followed by explosive diarrhea, severe with significant peri-anal excoriation The diarrhea can be mild to severe and generally lasts 3-9 days. Illness usually begins 3 days after exposure.

High fever and vomiting in a 6 month to 2 year child

Severe vomiting resistant to anti-emetics

Followed by explosive diarrhea, severe with significant peri-anal excoriation

The diarrhea can be mild to severe and generally lasts 3-9 days. Illness usually begins 3 days after exposure.

When is a Viral GE unlikely? Blood / WBCs in the stool Persistent high fever Persistent severe bilious vomit without diarrhea

Blood / WBCs in the stool

Persistent high fever

Persistent severe bilious vomit without diarrhea

Part 4 – Preventing rotavirus Democratic Virus – affects the entire world equally, without differentiating the rich & poor – almost 40 % of hospital admissions worldwide due to diarrhea are due to RVGE. Hand-washing and sanitation does not work due to the resistant nature of the virus. Vaccine works well

Democratic Virus – affects the entire world equally, without differentiating the rich & poor – almost 40 % of hospital admissions worldwide due to diarrhea are due to RVGE.

Hand-washing and sanitation does not work due to the resistant nature of the virus.

Vaccine works well

Vaccine development Goals of a rotavirus vaccine Aim to duplicate the degree of protection following natural infection Prevent moderate to severe disease Decrease numbers of children: Dying from rotavirus disease Admitted to hospital Presenting to health care facilities Hospital Community

Goals of a rotavirus vaccine

Aim to duplicate the degree of protection following natural infection

Prevent moderate to severe disease

Decrease numbers of children:

Dying from rotavirus disease

Admitted to hospital

Presenting to health care facilities

Hospital

Community

What vaccines are available? Rotashield (Wyeth) – Available in 1998, Animal Rhesus Monkey strain, withdrawn after 1 year due to clustering of cases of Intussusception. Rotateq (Merck) – Pentavalent Bovine Live Attenuated vaccine. > 70,000 subjects Predominantly in the United States and Finland No evidence for increased risk of intussusception

Rotashield (Wyeth) – Available in 1998, Animal Rhesus Monkey strain, withdrawn after 1 year due to clustering of cases of Intussusception.

Rotateq (Merck) – Pentavalent Bovine Live Attenuated vaccine.

> 70,000 subjects

Predominantly in the United States and Finland

No evidence for increased risk of intussusception

Vaccines based upon human rotaviruses A live-attenuated monovalent human rotavirus vaccine (Rotarix R ) P[8]G1 > 63,000 infants Predominantly in 11 countries from Latin America No evidence for increased risk of intussusception Efficacy for rotavirus disease 85% against severe rotavirus disease (81% after 1 dose) 100% against the most severe dehydrating episodes Protective efficacy against severe disease Homotypic G1 serotype 92% Homotypic P[8] non-G1 serotype 88% NEJM 2006; 354: 11

A live-attenuated monovalent human rotavirus vaccine (Rotarix R ) P[8]G1

> 63,000 infants

Predominantly in 11 countries from Latin America

No evidence for increased risk of intussusception

Efficacy for rotavirus disease

85% against severe rotavirus disease (81% after 1 dose)

100% against the most severe dehydrating episodes

Protective efficacy against severe disease

Homotypic G1 serotype 92%

Homotypic P[8] non-G1 serotype 88%

9% NEJM 2006; 354: 11 + 23 50-80% Post 1 st dose shedding N = 68,038 74 (67,79) 95 (91,97) 96 (90,98) 95 (92,97) 88 (<0,99) 93 (49,99) 89 (52,98) 100 (67,100) 59 (52,65) N = 20,169 ND 85 (72,92) 85 (70,94) 92 (74,98) 41 (-72,94) 88 (8,100) - 91 (62,99) 42 (29,53) Efficacy (95% CI) any disease severe hospitalisation Severe disease (95% CI) G1 G2 G3 G4 G9 All cause gastro admissions 3 2 Oral doses Bovine-human pentavalent P[8] G1-G4 Human monovalent P[8]G1 Origin RotaTeq TM Rotarix R

Other vaccine candidates Human-bovine reassortants Bovine rotavirus tetravalent (BRV-TV) vaccine: G1-G4 Adding G8 + G9 Brazil, China and India Naturally occurring human-bovine reassortants Delhi (116E) neonatal strain P[10]G9 single bovine VP4 gene Vellore (I321) neonatal strain P[11]G10 Bovine strain with 2 human-derived NSPs Recently shown to be non-protective Human neonatal rotavirus strains Some strains appear naturally attenuated and protective Melbourne neonatal RV3 strain P[6]G3 Low immunogenecity, but protective against disease in a small study JID 2006; 194: 370 Vaccine 2006; 24: 5817 Vaccine 2002; 20: 2950

Human-bovine reassortants

Bovine rotavirus tetravalent (BRV-TV) vaccine: G1-G4

Adding G8 + G9

Brazil, China and India

Naturally occurring human-bovine reassortants

Delhi (116E) neonatal strain P[10]G9 single bovine VP4 gene

Vellore (I321) neonatal strain P[11]G10

Bovine strain with 2 human-derived NSPs

Recently shown to be non-protective

Human neonatal rotavirus strains

Some strains appear naturally attenuated and protective

Melbourne neonatal RV3 strain P[6]G3

Low immunogenecity, but protective against disease in a small study

Cost Effectiveness of Rota Vaccine A CMC Vellore study shows that average diarrhea hospitalization costs Rs. 4,000/- to 5,000/- Rotavirus is a dehydrating diarrhea , with significant chances of doctor visit and hospitalization. Vaccine is almost 90-100 % effective against severe RV diarrhea & hospitalization.

A CMC Vellore study shows that average diarrhea hospitalization costs Rs. 4,000/- to 5,000/-

Rotavirus is a dehydrating diarrhea , with significant chances of doctor visit and hospitalization.

Vaccine is almost 90-100 % effective against severe RV diarrhea & hospitalization.

Remember ….. Largest number of death in the WORLD due to Rotavirus occur in India. (More than 300 children/ day) ORS is less likely to be effective in Rotavirus, due to increased tendency for vomiting, and destruction of intestinal villi by RV causing malabsorption of glucose, sodium and potassium.

Largest number of death in the WORLD due to Rotavirus occur in India. (More than 300 children/ day)

ORS is less likely to be effective in Rotavirus, due to increased tendency for vomiting, and destruction of intestinal villi by RV causing malabsorption of glucose, sodium and potassium.

Common Questions What is the maximum age for first dose? What if the child vomits? Can it be given with OPV/ Breast feed/ other vaccines? How to best administer the vaccine? Can Rotarix cause Intussusception? Can we give one dose in children between 5-6 month? After 6 months? How to counsel parents regarding this vaccine? What are the contraindications for Rotavirus vaccine?

What is the maximum age for first dose?

What if the child vomits?

Can it be given with OPV/ Breast feed/ other vaccines?

How to best administer the vaccine?

Can Rotarix cause Intussusception?

Can we give one dose in children between 5-6 month? After 6 months?

How to counsel parents regarding this vaccine?

What are the contraindications for Rotavirus vaccine?

Let us ERADICATE the thought of viral diarrhea

Let us ERADICATE

the thought of viral

diarrhea