DR ANURADHA

8/9/2019 DR ANURADHA

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y Rotavirus -leading cause of diarrhoeahosptalization in children in the developedworld.1

y Approx. 70-80% of diarrhoeal episodes indeveloped countries due to rotavirus disease

y Accounts for 25 million clinical visits ,2millionhospitalisation and

y More than 600,000 childhood deaths annuallyworldwide.2.

1.Emerg. Inf Dis ,1998,4;561-70

2.Emerg. Inf Dis,2003,9;562-70



Epidemiology in

India Extensively studied c.f other vaccines

Large number of epidemiological studies

from different parts of our country Potential vaccine can be evaluated against

available epidemiological data and its

actual efficacy can be predicted/assesed



EPIDEMIOLOGY ( INDIA)

y Overall strain distribution varied from one location toanother ,year to year,and between Community and Hospitalcohort.

y Newer strains are emergingy E.g G6(Pune),G8(Vellore)and Kolkata, G3P[8]from western

India ,G12 for Delhi.y In Neonates rotavirus causes mostly asymptomatic

infection.y Neonatal rotavirus strains(naturally attenuated) possible

candidate virus for vaccine.. 116E, a G9P[11] rotavirus isolatedfrom neonatal nurseries in Delhi and I321, a G10P[11] rotavirusdescribed from Bangalore

Indian J Med Res. 2003Aug;118:59-67.



HOSPITALISED CHILDREN

(INDIA)11

CENTRE YEAR AGE TESTING HOSPITAL

DELHI10 1987-1988

<5yrs ELISA 15.3

DELHI 1982-

1992

<5yrs ELISA 6%-45%

DELHI 1998-2001

<5yrs ELISA 13.5-23.5

CHANDIGARH

1982-1985

<5yrs ELISA 15.9%

NORTH NK <5yrs ELISA 19.0%

WESTERN 1984-1996

<5yrs ELISA 21%-28.2%

EASTERN(Di

brugarh)

1999-

2000

<5yrs ELISA 23.3%

SOUTH 1988- <5 rs ELISA 11.2%-27.1%



HOSPITALISED CHILDREN

(INDIA)11

CENTRE YEAR AGE TESTING HOSPITAL

DELHI10 1987-1988

<5yrs ELISA 15.3

DELHI 1982-1992

<5yrs ELISA 6%-45%

DELHI 1998-

2001

<5yrs ELISA 13.5-23.5

CHANDIGARH

1982-1985

<5yrs ELISA 15.9%

NORTH NK <5yrs ELISA 19.0%

WESTERN 1984-1996

<5yrs ELISA 21%-28.2%

EASTERN(Dibrugarh)

1999-2000

<5yrs ELISA 23.3%

SOUTH 1988-

2004

<5yrs ELISA 11.2%-27.1%



Overall distribution of Gtypes in India (studies

from 1990-2004).



Overall distribution of P types in India

(studies from 1990-2004)



EPIDEMIOLOGY ( INDIA)

y Overall strain distribution varied from one location toanother ,year to year,and between Community and Hospitalcohort.

y Newer strains are emergingy E.g G6(Pune),G8(Vellore)and Kolkata, G3P[8]from western

India ,G12 for Delhi.y In Neonates rotavirus causes mostly asymptomatic

infection.y Neonatal rotavirus strains(naturally attenuated) possible

candidate virus for vaccine.. 116E, a G9P[11] rotavirus isolatedfrom neonatal nurseries in Delhi and I321, a G10P[11] rotavirusdescribed from Bangalore

Indian J Med Res. 2003Aug;118:59-67.



VACCINE PREPARATIONS

y ROTASHIELD (a tetravalent rhesus human reassortantrotavirus vaccine- 1998)Withdrawn in 1999 due to fear of intussusception

y ROTATEQ (Bovine, live Pentavalent,Oral)

y ROTARIX (Human ,Monovalent, Live, Oral)*

y NEONATAL ROTAVIRUS VACCINE (underdevelopment in India)

*Available in India at present*



ROTARIX

y Live,attenuated,human rotavirus (HRV)vaccine,containing the RIX4414 strain ofG1P[8] specificity12,developed from the

parent vaccine strain 89-12.13-15

y 2 doses are Immunogenic.

y 1 mL contains at least 106 median Cell

Culture Infective Dose (CCID50) ofy ROTARIX contains no preservatives.

y IgA antibodies denotes seroconversion.



DOSES and Schedule

y Two 1-ml doses ,1st

dose -6wk age & upto 12 wk age.

y INTERVAL-at least 4 wks between the doses.

y Lyophilized vaccine to be reconstituted with liquid diluent prior to

administration

y Dose may be repeated at the same visit If the infant spits out orregurgitates

CONTRAINDICATED in uncorrected Congenital malformation of GIT.

CAUTION -Hypersensitivity to any of the vaccine components orprevious vaccine dose.

Safety and Efficacy in Immunocompromised infants -Unknown



Rotarix trial study

y 6-13 weeks (max age 4 months at the time of 2nd dose)

y 31673 infants in HRV group

y 31552 infants in placebo groupy 2 doses at 4-8 weeks interval

y OPV either before or after 15 days of HRVvaccine

y Safety profile up to 31 days after 2nd dose

y Efficacy profile in a subset from 15 days after 2nd dose up to 1 year age



Results(Safety)

y Intussusception not increased overplacebo

Within 31 days of any dose 6 7

Within 1 year of first dose 9 16

yOverall Deaths(56) in vaccine group morethan in the placebo(43) group

yPneumonia deaths significantly more

Cause ??



Results (Efficacy)

Severe Rota virus GE 85%

Rota virus associated hospitalisation

85% Diarrhea Hospitalisation of any cause 42%

Same G1 P8 Serotype 90.8%

Different G but same P8 87.3% Different G and different P 41%



Results (overview)

y Effective and safe but

y Safety above 4 months ? (Natural incidence of intussception low below 4 months)

y Increased Pneumonia deaths ??

y Simultaneous administration with OPV ±couldefficacy be compromised ?

y Efficacy against Different serotypes much lower

y Actual efficacy in India ???

Many serotypes not same as vaccine strainsDifferent in different areas, and in different years

Newer strains



CONCLUSIONS

Studies needed to asses efficacy in

India in different regions

Till then cannot be recommended for general use or parents be informed

accordingly

Simultaneous administration of OPVbe avoided (May compromise efficacy)



THANK YOU

v1v2



Slide 18

v1 vijay, 10/24/2008

v2 vijay, 10/24/2008



CHARACTERISTICS

ROTARIX ROTATEQ

INFANTS-NO. N N

AGE 6-13 wk old 6-12 wk old

ORAL POLIO At least 2wk before or after Excl. if recd. 42 days prior 1st dose

OTHER VACCINES

As per schedule As per schedule

STUDY PARAMETERS

PRIMARY GO AL

SAFETY assess risk ofINTUSSUSCEPTION andother side effects

Vaccine would not increase the riskof intussusception c 42dafter any dose.

EFFICACY Prevent SEVERE ROTAVIRUS

GE

Prevent wild type G1-G4 rotavirus

GE 14 or more d after completionSECONDARYGO ALS

Against severe GE(vesikariscale)

Severe G1-G4 rotavirus GE

Against sp. Serotypes Efficacy through 2nd season

Hospit. due to Rotavirus GE Red .in no. of hospitalisation andED visits

Severe GE of any cause _____



ROTATEQROTATEQ

Live,oral, pentavalent , five humanbovine reassortant rotaviruses,WC3 bovine strain viral surface proteins, human rotavirusserotypes G1, G2, G3, G4, and P[8]

liquid sodium and phosphate buffer at an aggregate viral titer of

approximately 6.7×107 to 12.4×107 infectious units per dose

three 2-ml oral doses of vaccine at 2, 4,6 mo.



EFFICACY

PROTECTON AGAINST

-Wildtype G1G4 rotavirus gastroenteritis

-Severe gastroenteritis, 98.0 percent

-Protection against rotavirus

gastroenteritis of any severity, 74.0percent

-Persisted through a second rotavirusseason & to gastroenteritis of any severity



ADVERSE

EFFECTS INTUSSUSCEPTION(RR 1.6)

FEVER(40%)

VOMITING(12.8%)

DIARROHEA(19.7%)

HEMATOCHEZIA(0.6%)



UNSOLICITED ADVERSEEFECTS

fussiness/irritability(52%),

cough/runny nose(28%),

infants temperature(25%), loss of appetite(25%),

vomiting(13%), or

diarrhea(4%) on a daily basis

DR ANURADHA

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