Influenza vaccination in childrenRationale and Opportunities

Dr Gaurav Gupta,Pediatrician,

Member AAP, IAP,Charak Clinics, Mohali

April 2012

Conflict of Interest

Received grants from various vaccine manufacturers including - Sanofi Pasteur - GSK - Abbott

(Manufacturers of different Influenza vaccines)

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 ?

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.

WHAT DO YOU THINK IS THIS??

Often misunderstood and underestimated,

Influenza is not just “a bad cold”!

Annual influenza epidemics

Influenza pandemics: exceptional epidemiological events

occurring every few decades(11–36 years)

CLINICAL FEATURES & CASE DEFINITION

JAMA 2000; 284 (13): 1740

Laboratory Confirmation required for epidemiological purposes only

Influenza can also present as croup, bronchiolitis, pneumonia, febrile disease mimicking bacterial sepsis

Can predispose to bacterial infections (otitis media, pneumonia, bronchiolitis)

Let us learn from our past!!!

412 BC

1918

1933

1957

1968

Asian flu H2N2

Hong Kong flu H3N2

Influenza virus isolated for the first time

Spanish flu H1N1Epidemic reported

by Hippocrates

1173-1174 Influenza-like epidemics first reported

Potter CW. A history of influenza. J Appl Microbiol 2001; 91(4):572-579.

1889 & 1891 H3N8 pandemic

INFLUENZA PANDEMICS IN HISTORY

H1N1 pandemic- 2009 being the latest faced by the globe

DURING EACH ANNUAL EPIDEMIC:

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

AIHW National Hospital Morbidity Database

Hospital admissions for influenza, Australia, 2000-2004

Greatest proportion in young children

Identified influenza virus (J10)

0

5

10

15

20

25

30

35

40

Age (years)

% t

ota

l h

osp

ital

isat

ion

s

2000-2004

A FREQUENT DISEASE IN CHILDREN

INFLUENZA IN INDIAN CHILDREN

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,

INFLUENZA IN INDIAN CHILDREN

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

Vaccine type CompositionImmunogenici

tyReactogenici

tyWhole-virus

(no longer used)

Whole virus +++ +++

Split virionSurface,

nucleocapsid & matrix proteins

+++ +

Subunit Surface proteins ++ ++

Virosomal Surface proteins &

virosomes ++ +

Adjuvanted Surface proteins &

adjuvant +++ ++

Nasal Live attenuated +++ +++

+ (Low) ++ (Medium) +++ (High)

DIFFERENCES BETWEEN INFLUENZA VACCINES

Amorij JP. Pharm Res. 2008;25(6):1256-1273.

RATIONALE FOR CHILDHOOD VACCINATION 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 of serious or complicated influenza infection globally

CHILDREN ARE PRIMARY VECTORS

1. Glezen WP, et al. N Engl J Med. 1978;298:587-592.2. Weycker D, et al. Vaccine. 2005;23:1284-1293.

Family members and other close contacts

Other children

ChildrenDay care, preschool

and school-age

Communityincluding high-risk populations

VACCINATION IN PRE-SCHOOL CHILDREN

Studies confirm effectiveness of Influenza vaccination

in Pre-School Children

Influenza A A.O.MURIs(Pharyngitis,Croup)

83% 33%36%

LRIs(Acute Bronchitis,Wheezing, Pneumonia)

22%

Reduction in Influenza related Morbidity

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;45:445-83. Pediatric Infect Disease J 2006:25;5;401-4044. New England J Med 2000; 342:225-31

VACCINATION IN SCHOOL-GOING CHILDREN

Missed School Days

No. of antibiotic Rxs

Maternal workabsenteeism

48% 33%32%

Paternal workabsenteeism

43%

Studies confirm Influenza vaccination in School-Going Children to be:

• Not only effective in reducing the sufferings

• But also a Cost Saving proposition

Direct & Indirect Benefits of Influenza Vaccination

1. Principi N et al. socioeconomic impact of influenza on healthy children and their families Pediatr Infect Dis J 2003; 22:S2007-10.

INFLUENZA VACCINATION AMONG CHILDREN – PROTECTION OF

CONTACTS

JAMA 2000;284:1677-84

Respiratory-Related Morbidity Among Unvaccinated 5- to 17-Year-Old Household Contacts of Study Children

0

5

10

15

20

25

30

35

40

45

Missed School Physician Visits Earache Antibiotic Use Adults MissedWork

Contacts of Control Children (N=31) Contacts of Vaccinated Children (N=28)

Per

cent

of

Indi

vidu

als

All comparisons significant (p <0,05)

72%

91%88%

88% 100%

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**

22

*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

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).

Methodology-Clinical Effectiveness Study

25

Methodology-Clinical Effectiveness Study

26

Continued…..

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

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.

Comparison of VE in 2 years in our centerFully 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 0.05 432 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.

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).

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.

WHOM TO VACCINATE???

INFLUENZA VACCINE RECOMMENDATIONS:

PEDIATRIC AGE-GROUPS

• All healthy

children 6-23

months

• All high risk

children >6

months

• Children in

close contact

with high risk

adults

• In all high

risk children

>6 months

• All healthy

children 6-59

months

• All high risk

children >6

months

• Children in

close contact

with high risk

adults

• All healthy

children 6-59

months

• All high risk

children >6

months

• All school

going

children

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

HOW TO VACCINATE???

Vaccination Schedules

* 2 doses at least 1 month apart for children receiving vaccine for the first time

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

WHEN TO VACCINATE???

WHO RECOMMENDATIONS

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.

In most of the countries using influenza vaccine, the vaccination starts before the onset of peak influenza season, with the latest available stain of vaccine.

WHO Influenza Vaccine Recommendations

Global surveillance network:

106 Member countries136 NIC6 WHO CCS4 ERLS11 H5 Ref Labs

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

INFLUENZA CIRCULATION IN INDIAInfluenza virus circulation peaks in June-August

India 2009 (samples submitted nil to minimal from 1999-2008)

J F M A M J J A S O N D

Data source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN)

Influenza virus circulation peaks in June-August

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India 2010

J F M A M J J A S O N DD

Data source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN)

Influenza virus circulation peaks in June-August

India 2011

Influenza virus circulation peaks in June-August

J J A S

INFLUENZA VIRUSES CIRCULATE IN DELHI THROUGHOUT THE YEAR

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 revealed that Influenza viruses are circulating throughout the year and their types and subtypes vary remarkably. The influenza surveillance was undertaken from 2007 to 2010.

http://indiatoday.intoday.in/story/influenza-viruses-circulate-in-delhi-throughout-the-year/1/179252.html

IAP RECOMMENDATIONS 2011

INTERNATIONAL SURVEILLANCE NETWORK

VACCINE MANUFACTURER

M A M J J A S O N D J FF M

Choice of strains VACCINE on time

Process of Influenza Recommendations and Vaccine Availability

WHO(Northern hemisphere)

PRODUCTION

WHO(Southern hemisphere)

PRODUCTION

Chalumeau HP. Vaccine manufacture at the time of a pandemic influenza. European journal of epidemiology1994;10: 487-490

Exciting Future ahead ?

QUADRIVALENT LIVE INFLUENZA VACCINE

FDA NEWS RELEASEFor Immediate Release: Feb. 29, 2012FDA 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 of influenza B. Including a second influenza B strain improves the odds of protection against whichever B strain is circulating.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm294057.htm

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