Influenza vaccination in children - rationale & opportunities
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Transcript of Influenza vaccination in children - rationale & opportunities
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
Nu
mb
er o
f S
amp
les
po
siti
ve f
or
Infl
ue
nza
/wee
k
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.