Flu Vaccine – Does it work for Indian Children?

Dr. Gaurav Gupta, Practising Pediatrician

Member AAP, IAP Charak Clinics, Mohali, Punjab

Today’s discussion

Is there effective Flu Surveillance in India ?Though vaccine available in India since 2004,

is it safe in Indian pediatric population? Is the flu vaccine clinically effective in Indian

context ?What is the public perception of Flu vaccine in

India?

Ours is the first set of studies from India

Karnataka

Andhra Pradesh

Maharashtra

Orissa

Gujarat

Rajasthan

Madhya Pradesh

Uttar Pradesh

Jharkhand

Jammu Kashmir

Punjab

Chattisgarh

Uttaranchal

Himachal Pradesh

Haryana

Bihar

New Delhi

Tamil NaduKerala

West Bengal

Sikkim

Arunachal Pradesh

Assam Nagaland

Manipur

Tripura

Mizoram

Meghalaya

• Location: Chennai (22Location: Chennai (22ndnd Feb- Feb-2222ndnd March 2008) March 2008) Total Sample Collected : 55

Samples Total No. of Sample +ve : 23

Samples % + ve : 41.82 % +ve Influenza A :13 Samples (56.5%) Influenza B : 10 Samples (43.3%)

MONTHLY INFLUENZA ACTIVITY REPORTED BY-INDIAN SENTINEL DOCTOR’S NETWORK FEB-MAR 2008

No Report

• Location: Delhi ( Jan- Mar 2008 )Location: Delhi ( Jan- Mar 2008 ) Total Sample Collected :86 samples Total No. of Sample +ve :12 Samples % +ve :14%+ve Influenza A/H1N1 : 6 Samples Influenza B : 4 Samples Not determined but +ve : 2 Samples

Source: Sentinel Doctor’s Network,March 2008

> 10 % positvity

> 40% positivity

WHO National Influenza Center(as of April 2011)Pune (NIV),Kasauli (CRI)& Mumbai (Haffkine Institute)

Choice of vaccine strains procedure

Hannoun C. Role of international networks for the surveillance of influenza. Eur Journal of Epidemiol 1994;10:459-61

Sentinel Doctors

National influenza Centers(112 national laboratories in over 80

countries)

World Health Organisation

(WHO - Geneva)

Collaborating Reference Centers for Research against influenza

(London, Atlanta, Melbourne and Tokyo)

Vaccine Manufacturers

Global Influenza Surveillance Network

Indian Scenario:Reality

No robust data in public domain on annual Influenza cases and deaths in Indian scenario*

Influenza vaccine is in Indian market since 2004

There is no published data on safety, tolerability and effectiveness of Influenza vaccine in Indian children**

8

*India to compile database for influenza. Available from: URL: http://www.livemint.com/2009/05/31215156/India-to-compile-database-on-s.html. Accessed on 22 May, 2010.**Joseph L Mathew. Influenza vaccination for children in India. Indian Pediatrics. 2009 ;46:304-307.

Private pediatric outpatient (clinical) setting

Aims of the study - Clinical Effectiveness of Seasonal Flu vaccine in

preventing ILI 1, 2

Safety & Tolerability of the Seasonal Flu Vaccine 3

KAP Survey of Caregivers of children given the Seasonal Flu Vaccine

1. WSPID, Nov 2011, Melbourne, Poster Presentation.2. ISPOR Asia Conference, September 2010, Thailand, Poster Presentation.3. Singh H, Gupta G, Tiwari P. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).

Differentiating Vaccine Efficacy from Vaccine Effectiveness

In the clinical development of a vaccine, an efficacy study asks the question, "Does the vaccine work?"

In contrast, an effectiveness study asks the question "Does vaccination help people?"

Methodology-Clinical Effectiveness Study

16

Methodology-Clinical Effectiveness Study

17

Continued…..

Methodology-Clinical Effectiveness Study

18

Continued…..

Overall ResultsVaccinated (198) vs Unvaccinated Cohort (397)

# Parameter RR CIp value

VE (%)

1 ILI0.65

0.49-0.84

0.001 35

2 ARI0.98

0.96-1.01

0.88

3

Unsch. Visit

0.750.52-0.99

0.003 25

4

Absenteeism

0.970.70-1.32

0.86

Clinical Effectiveness of Influenza vaccine-1

Sr.No

Parameters Odds Ratio CI VE % P-value

1 Influenza like illness

0.58 0.24-0.92 42 0.009

2 Visits to Physician 0.71 0.33-1.09 29 0.039

Fully vaccinated cohort (n=154) vs. Unvaccinated cohort (n=330)*

Conclusion: Influenza vaccine is effective in reducing the ILI and visits to physician for ARI in fully vaccinated Indian children as compared to unvaccinated children.

*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.

Clinical Effectiveness of Influenza vaccine-2

Sr.No

Parameters Odds Ratio

CI P-value

1 Influenza like illness 0.69 0.39-0.99 0.20

2 Visits to Physician 0.64 0.29-1.01 0.64

Partially vaccinated cohort (n=16) vs. Unvaccinated cohort (n=330)*

Conclusion: Partially vaccinated children had no significant protection against ILI and visits to physician as compared to unvaccinated children.

*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.

# ILI Parameters Present study Ritzwoller et al*

1 Fully vaccinated vs. Unvaccinated

OR (CI) 0.58 (0.24-0.92) 0.77 (0.66-0.90)

P value P=0.009 <0.001

VE% 42% 23%

2 Partially vaccinated vs. Unvaccinated

OR(CI) 0.69 (0.39-0.99)

0.93 (0.82-1.04)

P value 0.20 <0.01

VE% NA 7%

*Ritzwoller DP, Bridges CB, Shetterly S, Yamasaki K, Kolczak M, France EK. Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8 years of age, with 1 vs 2 doses. Pediatrics.

2005;116:153-159.

Clinical Effectiveness of Influenza vaccine-3

Sr.No

Age group (no.)

Odds Ratio

CI P-value

VE %

1 6 m – 3 y (78) 0.57 0.46-1.31 0.55

2 3 y – 9 y (64) 0.48 0.17-0.72 0.002 52 %

3 9 y – 18 y (28) 0.69 0.39-1.03 0.06

Age-wise efficacy for prevent of ILI*

Conclusion: Children aged 3-9 year had the best protection rates against ILI as compared to unvaccinated children.

*Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.

Authors' conclusionsInfluenza vaccines are efficacious in children older than two but little evidence is available for children under two. There was a marked difference between vaccine efficacy and effectiveness.This version first published online: January 25. 2006Last assessed as up-to-date: September 30. 2007

Results_(Comparison of 2009-10 v/s 2010-11)

Comparison of VE in 2 years in our center

Fully vaccinated (154) vs Unvaccinated Cohort (330) (2010-11)

# Parameter RR CI p value VE (%)

1 ILI0.65

0.48-0.86

0.003 35

2

Unsch. Visit

0.740.51-0.99

0.007 26Fully vaccinated (101) vs Unvaccinated Cohort (141) * (2009-10)

# Parameter RR CI p value VE (%)

1 ILI 0.57 0.32-0.09 0.05 43

2

Unsch. Visit 0.43 0.22-0.09 0.007 57

* Singh H, Gupta G, Tiwari P. Clinical effectiveness of the 2009-2010 seasonal influenza vaccine among healthy Indian children. ISPOR 4th Asia Pacific Conference, Phuket, Thailand.

Singh H, Gupta G, Tiwari P. Safety and tolerability of trivalent inactivated influenza (TIV) vaccine in healthy Indian children. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).

*Singh H, Gupta G, Tiwari P. Safety and tolerability of trivalent inactivated influenza (TIV) vaccine in healthy Indian children. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).

Reactions after vaccination

The Present Study Delore et al*

Local reactions (Inj. site tenderness)

>6-35 months

8.5 % 6-36 months 8.6 %

3-9 years 24.1 % 3-10 years 32.1 %

>9-18 years 46.6 % - -

Systemic reaction>6-35

months

26.7 % 6-36 months 21.2 %

3-9 years 13.3 % 3-10 years 4.3 %

>9-18 years 6.6 % - -

*Delore V, Salamand C, Marsh G, Arnoux S, Pepin S and Saliou P. Long-term clinical trial safety experience with the

inactivated split influenza vaccine, Vaxigrip®. Vaccine 2006; 24 : 1586-1592.

Hurdles to Flu vaccination

Hurdles to Flu vaccination

Lack of awareness among pediatricians and physicians regarding influenza vaccine

Lack of awareness in parents/patients

# Knowledge of parents of vaccinated children

Percentage

1 Influenza is a serious problem and influenza vaccine prevents influenza

90%

2 Starting of winters is right time to get influenza vaccine

61%

3 Pediatrician is source of information about influenza vaccine

99%

4 Children and elderly with complications can be given influenza

15%

5 Influenza vaccine is an annual vaccine

76%

#Practices of parents of

vaccinated childrenPercentage

1 Parents want to take Influenza vaccine next year also 48%

2 Find that influenza vaccine was not very effective and don’t want to get their child vaccinated next year 16%

3 Influenza vaccine prevents all ailments like cough or cold or runny nose or fever 28%

4 Health of the child was much better than before 44%

ConclusionFlu vaccine is effective in reducing ILI &

unscheduled visits to doctor. No effect of partial vaccination

It is safe & well tolerated by healthy Indian children.

KAP – Awareness of flu vaccine is present, many parents feel that it is effective and would like to take annual doses.

ConclusionsMore studies with larger sample size to

establish efficacy

Identify sub-groups if age in which it is more effective

Further research for more effective & single dose Influenza vaccine

The European vaccine study involved an antibody that neutralizes all the influenza-A subtypes.

Research Team Himmat Singh Rahul Renuka Dr. Gaurav Gupta Prof. Pramil Tiwari