Presentation at SAVE meet, April 2012, at Timber Trail, Himachal Pradesh

1. Influenza vaccination in children
Rationale and Opportunities
Dr Gaurav Gupta,
Pediatrician,
Member AAP, IAP,
Charak Clinics, Mohali
April 2012

2. Conflict of Interest
 Received grants from various vaccine
manufacturers including
 - Sanofi Pasteur
 - GSK
 - Abbott
(Manufacturers of different Influenza vaccines)

3. Overview
 Influenza – what is it ?
 Is it really that big a problem – World/ India/
Children ?
 Influenza vaccine – rationale for use
 What data exists regarding Influenza vaccine
safety & effectiveness, especially from India ?
 When, whom & how to vaccinate ?

4. CASE
Alisha is a 7-year-old girl brought to your Clinic by her
mother, who tells you her daughter “suddenly came
down with a bad cold.” She reports that “Alisha was
fine when she went to bed” but in the morning
suddenly became ill with vomiting, a dry cough, sore
throat, and high fever.
W H A T D O YO U T H IN K IS
T H IS ? ?

5. O f t e n m is u n d e r s t o o d a n d
u n d e r e s t im a t e d ,
In f lu e n z a is n o t ju s t “ a b a d
c o ld ” !
Annual Influenza pandemics:
influenza epidemics exceptional epidemiological events
occurring every few decades
(11–36 years)

6. C L IN IC A L F E A T U R E S &
C A S E D E F IN IT IO N
Influenza can also present as croup, bronchiolitis, pneumonia, febrile disease
mimicking bacterial sepsis
Can predispose to bacterial infections (otitis media, pneumonia, bronchiolitis)
Laboratory Confirmation required for epidemiological purposes only
JAMA 2000; 284 (13): 1740

7. Let us learn from
our past!!!

8. IN F L U E N Z A P A N D E M IC S
IN H IS T O R Y
1968 Hong Kong flu H3N2
1957 Asian flu H2N2
1933 Influenza virus isolated for the first time
1918 Spanish flu H1N1
Epidemic
reported 1889
by & 1891
H3N8 pandemic
Hippocrates
412 BC 1173-1174 Influenza-like epidemics first reported
Potter CW. A history of influenza. J Appl Microbiol 2001; 91(4):572-579.
H1N1 pandemic- 2009 being the latest faced by the globe

9. D U R IN G E A C H A N N U A L
E P ID E M IC :
 5 to 10 % of the world’s population catches influenza
i.e., 500 million people
 Including 3 to 5 million serious cases
 And 500 000 to 1 000 000 deaths each year
 Influenza does not discriminate: it affects men and
women, boys and girls of all ages, in all sectors of
the population, and in all countries

10. A F R E Q U E N T D IS E A S E
I N C H I Lproportion in young
Greatest D R E N
children
Hospital admissions for influenza, Australia, 2000-2004
40
Identified influenza virus (J10)
35
% total hospitalisations
30
25
20 2000-2004
15
10
5
0
30 29
45 44
15 14
20 19
25 24
35 34
40 39
50 49
55 54
60 59
65 64
70 69
75 74
80 79
4
4
10 9
+
<1
-8
1-
5-
85
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Age (years)
AIHW National Hospital Morbidity Database

11. IN F L U E N Z A IN IN D IA N
C H IL D R E N
Hospital based survey at AIIMS,
Delhi:
 Influenza virus isolated in 29 of 200 (14.5%) children suffering
from acute LRI
 In bronchopneumonia cases (101) the most common viral
pathogen was influenza virus (17%)
 Influenza virus infection in Delhi pediatric population peaked
from September to December
J Clin Virol. 2000; 16 (1): 41-7,

12. IN F L U E N Z A IN IN D IA N
C H IL D R E N
OPD based survey at KIPM, Chennai:
 Influenza virus isolated from 30 out of 240 (12.5%) children
suffering from acute RTI
 Influenza activity commenced in February and continued till
November, peaking in June coinciding with the onset of the
Southwest Monsoon
Indian J Med Res 2005; 121: 776-779

15. D IF F E R E N C E S B E T W E E N
IN F L U E N Z A V A C C IN E S
V a c c in e Im m u n o g e n i R e a c t o g e n
C o m p o s it io n
typ e c it y ic it y
Whole-virus
Whole virus +++ +++
(no longer used)
Surface, nucleocapsid &
Split virion
matrix proteins
+++ +
Subunit Surface proteins ++ ++
Surface proteins &
Virosomal ++ +
virosomes
Surface proteins &
Adjuvanted +++ ++
adjuvant
Nasal Live attenuated +++ +++
+ (Low) ++ (Medium) +++ (High)
A ijJ Pham R 20 8
mor P. r es. 0 ;25(6):1256- .
1273

16. R A T IO N A L E F O R C H IL D H O O D
V A C C IN A T IO N
 All children are at substantially
increased risk for influenza-related
hospitalisations
 As well as reducing the risk to their own
health, it reduces influenza infection in
their contacts
 May also reduce influenza infections in
adults by interfering with the
circulation of the virus in the
community
 Annual influenza vaccine is widely
recommended for children at high risk

17. C H IL D R E N A R E P R IM A R Y
VE C TO R S
Other Family members
children and other close contacts
Children
Day care, preschool
and school-age
Community
including high-risk populations
1. Glezen WP, et al. N Engl J Med. 1978;298:587-592.
2. Weycker D, et al. Vaccine. 2005;23:1284-1293.

18. V A C C IN A T IO N IN P R E -
S C H O O L C Influenza D R E N
Reduction in H I L related Morbidity
URIs LRIs
(Acute Bronchitis,
Influenza A A.O.M (Pharyngitis,Croup)
Wheezing, Pneumonia)
83% 36% 33% 22%
Studies confirm effectiveness of Influenza vaccination
in Pre-School Children
1. Neuzil KM et al Pediatr Infect Dis J, 2001: 20:733-40.
2. Heikkinen T et al.Influenza vaccination in the prevention of acute otitis media in children: Am J Dis Child 1991;45:445-8
3. Pediatric Infect Disease J 2006:25;5;401-404
4. New England J Med 2000; 342:225-31

19. V A C C IN A T IO N IN S C H O O L -
G O I NDirect & Indirect L D Rof Influenza Vaccination
G C H I Benefits E N
Missed No. of antibiotic Maternal work Paternal work
School Days Rxs absenteeism absenteeism
48% 32% 33% 43%
Studies confirm Influenza vaccination in School-Going Children to be:
• Not only effective in reducing the sufferings
• But also a Cost Saving proposition
1. Principi N et al. socioeconomic impact of influenza on healthy children and their families Pediatr Infect Dis J 2003; 22:S2007-10.

20. IN F L U E N Z A V A C C IN A T IO N
A M O N G C H IL D R E N –
Respiratory-Related MorbidityC T IUnvaccinated 5- to 17-Year-Old
P R O T E Among O N O F
Household Contacts of Study Children
C O N TA C TS
Contacts of Control Children (N=31) Contacts of Vaccinated Children (N=28)
45
Percent of Individuals
40
35
30
25
20 72%
15
91%
10 88%
88% 100%
5
0
Missed School Physician Visits Earache Antibiotic Use Adults Missed
Work
All comparisons significant (p <0,05)
JAMA 2000;284:1677-84

22. Indian Scenario:Reality
 Limited 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**
*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.
22
**Joseph L Mathew. Influenza vaccination for children in India. Indian Pediatrics. 2009 ;46:304-307.

24. 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
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).

25. Methodology-Clinical Effectiveness Study
25

26. Continued…..
Methodology-Clinical Effectiveness Study
26

27. Clinical Effectiveness of Influenza
vaccine-1
Fully vaccinated cohort (n=154) vs. Unvaccinated cohort (n=330)*
Sr.N Parameters Odds Ratio CI VE % P-value
o
1 Influenza like 0.58 0.24-0.92 42 0.009
illness
2 Visits to Physician 0.71 0.33-1.09 29 0.039
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.

28. Clinical Effectiveness of Influenza
vaccine-2
Age-wise efficacy for prevent of ILI*
Sr.N Age group (no.) Odds CI P-value VE %
o Ratio
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
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.

29. 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 ILI 0.65 0.48-0.86 0.003 35
2 Unsch. Visit 0.74 0.51-0.99 0.007 26
Fully 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.

30. Safety and Tolerability of Influenza
vaccine-1
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).

31. Conclusion
 Flu vaccine is effective in reducing ILI &
unscheduled visits to doctor. No effect of partial
vaccination
 It is safe & well tolerated by healthy Indian
children.

32. WH O M TO
VA C C IN A T E ? ? ?

33. IN F L U E N Z A V A C C IN E
R E C O M M E N D A T IO N S :
P E D IA T R IC A G E -G R O U P S
• All healthy • In all high
• All healthy • All healthy
children 6-59 risk children
children 6-23 children 6-59
months >6 months
months months
• All high risk
• All high risk • All high risk
children >6
children >6 children >6
months
months months
• All school
• Children in • Children in
going
close contact close contact
children
with high risk with high risk
adults adults

34. Recommendation on influenza vaccine. Available at:http://www.iapindia.org/component/content/article/315
. Accessed on: 16 April 2012

35. H O W TO
VA C C IN A T E ? ? ?

36. Vaccination Schedules
Age group Dosage (im/sc) No. of doses
6-35 months 0.25 ml 1 or 2*
3-8 years 0.5 ml 1 or 2*
> 9 years 0.5 ml 1
* 2 doses at least 1 month apart for children receiving vaccine for the first time

38. WH E N TO
VA C C IN A T E ? ? ?

39. WH O
R E C O M M E N D A T IO N S
 The World Health Organization (WHO)
convenes technical consultations in
February and September each year to
recommend viruses for inclusion in
influenza vaccines for the northern and
southern hemispheres, respectively.
 For countries in equatorial regions,
epidemiological considerations influences
which recommendation (February or
September) individual national and
regional authorities consider more
appropriate.
WHO Influenza Vaccine Recommendations

40. Global surveillance network:
106 Member countries
136 NIC
6 WHO CCS
4 ERLS
11 H5 Ref Labs

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

42. IN F L U E N Z A C IR C U L A T IO N
Influenza virus circulationD I A June-August
I N I N peaks in

43. In d ia 2 0 0 9 (samples submitted nil to
minimal from 1999-2008)
Influenza virus circulation peaks in June-August
Number of Samples positive for Influenza/week
J F M A M J J A S O N D
Data source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN)

44. I n d i a 2 0 10
Influenza virus circulation peaks in June-August
D J F M A M J J A S O N D
Data source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN)

45. India 2011
J J A S
Influenza virus circulation peaks in June-August

47. IN F L U E N Z A V IR U S E S
C IR C U L A T E IN D E L H I
T H R O U G H O U T T H E YE A R
Scientists from the All India Institute of
Medical Sciences (AIIMS) have cautioned
that different types of flu viruses widely
circulate in the national Capital
throughout the year causing Influenza
Like Illness (ILI).
The conclusion was drawn after a joint
study was conducted by AIIMS, Center
for Disease Control and Prevention,
Atlanta and National Institute of Virology,
Pune for three years. The study has
http://indiatoday.intoday.in/story/influenza-viruses-circulate-in-delhi-throughout-the-year/1/179252.html

48. IA P R E C O M M E N D A T IO N S
2 0 11

49. P r o c e s s o f In f lu e n z a
R e c o m m e n d a t io n s a n d
V a c cINTERNATIONAL SURVEILLANCE NETWORK
in e A v a ila b ilit y
VACCINE MANUFACTURER
F M A M J J A S O N D J F M
WHO PRODUCTION
(Northern hemisphere)
WHO PRODUCTION
(Southern hemisphere)
Choice of strains VACCINE on time
Chalumeau HP. Vaccine manufacture at the time of a pandemic influenza. European journal of epidemiology
1994;10: 487-490

50. Exciting Future ahead ?

51. Q U A D R IV A L E N T L IV E
IN F L U E N Z A V A C C IN E
FDA NEWS RELEASE
For Immediate Release: Feb. 29, 2012
FDA approves first quadrivalent vaccine to prevent
seasonal influenza
The first quadrivalent live attenuated
vaccine to prevent seasonal influenza has
been approved by FDA. FluMist Quadrivalent
(MedImmune), will be available for the
2013-2014 flu season. This too will be
administered as a nasal spray. The vaccine is
indicated for individuals ages 2 years
through 49 years. FluMist Quadrivalent will
contain 2 strains of influenza A and 2 strains
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm294057.htm

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

53. S UMMARY AND
C O N C L U S IO N
 Influenza is a significant problem in most
developing countries including India, causing
mild  serious disease, causing severe
morbidity & mortality
 Influenza spreads from children to adults
 Influenza vaccine is safe & effective in Indian
children.
 Yearly use of vaccines can decrease the
impact of Influenza.