presentación

1. 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.

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

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

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

5. Rotavirus – this is how it looks!
Rotavirus – this is how it looks!

7. 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

8. 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

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

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

11. 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

14. 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

16. 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.

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

19. 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

20. 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

21. 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

22. Vaccines based upon human rotaviruses
• A live-attenuated monovalent human rotavirus vaccine (RotarixR
) 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

23. RotarixR
RotaTeqTM
Origin Human monovalent
P[8]G1
Bovine-human pentavalent
P[8] G1-G4
Oral doses 2 3
Efficacy (95% CI)
any disease
severe
hospitalisation
Severe disease (95% CI)
G1
G2
G3
G4
G9
All cause gastro admissions
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)
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)
Post 1st
dose shedding 50-80% 9%
NEJM 2006; 354: 11 + 23

24. 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

25. 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.

26. 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.

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

28. Let us ERADICATE
the thought of viral
diarrhea