View
4.130
Download
0
Category
Preview:
DESCRIPTION
Rotavirus - Simplified Virology, Statistics, Symptoms, Vaccination & Common FAQs with specific reference to India.
Citation preview
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.
Rotavirus – in 4 parts
Dr Gaurav GuptaCharak Clinics
www.charakclinics.comDCH, DNB, MAAP, MIAP
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
Rotavirus Virology – Part 1
• Rota – means wheel-like in greek• Double-stranded RNA virus
Rotavirus – this is how it looks!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
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
Cumulative probability of rotavirus infection in 200 Mexican infants during the 1st 2 years of life
1.01.0
0.90.9
0.80.8
0.70.7
0.60.6
0.50.5
0.40.4
0.30.3
0.20.2
0.10.1
11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414 1515 1616 1717 1818 1919 2020 2121 2222 2323 2424
Pro
bab
ility
of
rota
viru
s in
fect
ion
Pro
bab
ility
of
rota
viru
s in
fect
ion
Age (months)Age (months)
1st infection1st infection
2nd infection2nd infection
3rd infection3rd infection
4th infection4th infection
5th infection5th infection
*
*Complete protection againstmoderate-to-severe diarrhoea
NEJM 1996; 335: 1022
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
diarrheaLancet Infect Dis 2007; 7: 56 Wkly Epidemiol Rec 2007; 82: 285 JID 2005; 192(Suppl 1) S1 EID 2006;12: 304
Modified after Emerg Infect Dis 2006; 12: 304
5 million clinic visits
25 million domiciliaryepisodes
1 : 250
1 : 65
EventRisk 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.
When is a Viral GE unlikely?
• 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
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
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
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
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
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
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.
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.
Common Questions1. 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?
Let us ERADICATE
the thought of viral
diarrhea
Recommended