Influenza vaccination in IndiaWhen, whom & how to vaccinate?

Dr Gaurav Gupta,Pediatrician,

Member AAP, IAP,Charak Clinics, Mohali

March 2013

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!!!

Impact of influenza on children

Annual attack rate in preschool age exceeds 40% and in school age more than 30% during outbreaks

Influenza contributes to:Up to 3 days of fever, 5 days school absenteeismUp to 35% increase in OPD visits and excess hospitalizationUp to 20-30% increase in AntibioticsComplications Absenteeism in parents, more with those nursing younger children

1. Neuzil KM et al. The effect of influenza on hospitalizations,outpatient visit and courses of antibiotics in children,NEJM 2000,342:225-312. Turner D et al, National Institute of Clinical Excellence.Systematic review and economic decision modelling for the prevention and treatment of influenza A & B 29th Apr 2002.

< 6 months

6-12 months

1-3 years 3-5 years 5-15 years0

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40

60

80

100

120

104

50

19

94

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os

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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**

9

*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.

Indian scenarioRegion Period Influenza positive Additional

Delhi (NCDC) May 09 – Sep 10

7943 / 33751 (23.5%)

11.1% (+) for seasonal influenza

Delhi (AIIMS-Ballabhgarh)

Jan - Dec 09 315 / 1071 (29% for all)

51% of these- pandemic, 49%- seasonal strains

Jan - Dec 10 116 / 661 (17% for all)

51% of these- pandemic, 49%- seasonal strains

Kolkata Jul – Aug 10 129 / 440 (29.3%) 47 pts (11%) comorbidities, 4 patients died

Rajasthan Nov 09 – Apr 10 533 / 1782 (29.9%) -

Sangli (Maharashtra)

Oct 09 – Sep 10 142 / 466 (30.47%) Maximum deaths in monsoon

Surat (Gujarat)

Jun 09 – Mar 10 154 / 824 (18.68%) 37.66% comorbidities (MC DM and HT)ARDS, need for ventilator and comorbidities – poor prognosis

Choudhry A. Indian J Med Res. 2012 Apr;135(4):534-7.Broor S et al. PLoS One. 2012;7(1):e29129Biswas DK. Indian J Med Res. 2012 Apr;135(4):529-33.Joshi V. Indian J Med Res. 2012 Mar;135:437-8.Rajderkar SS. IJHSR Vol.2; Issue: 2; May 2012 Bhatt KN. J Assoc Physicians India. 2012 May;60:15-9.

jan - mar 2008

apr-jun 2008

july-sept 2008

oct 2008-dec 2008

jan to march 2009

apr to june 2009

july to sept 2009

Oct 2009 to dec 2009

Jan to march 2010

Apr to june 2010

july to sept 2010

Oct 2010 to dec 2010

Jan to march 2011

Apr to June 2011

0

50

100

150

200

250

Incidence of ILI from our center

Private pediatric outpatient (clinical) setting

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

preventing ILI 1, 2

1. WSPID, Nov 2011, Melbourne, Poster Presentation.2. ISPOR Asia Conference, September 2010, Thailand, Poster Presentation.

Methodology

• Prospective Observational Cohort Study• Vaccinated cohort (n=170) vs. Unvaccinated

cohort (n=330)Study Design

• Healthy child, of either sex, above 6 months of

age up to 18 years of age

• No chronic illness except asthma

Inclusion criteria

• Standard Predefined Data Form used. • Parameters measured –

ILI, Absenteeism, ARI, Unscheduled Physician visits Data Collection

13

Methodology

• Private outpatient pediatric setting (Charak

Care Clinics, Mohali)Study site

• September, 2010 to May, 2011Study period

14

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.

Conclusion

• Flu vaccine is effective in reducing ILI & unscheduled visits to doctor. No effect of partial vaccination

• Vaccine effectiveness studies have found VE of 60-85% in children < 5 yrs age when vaccine strains match well with circulating strains

• Limited data indicate additional protection of unvaccinated household and community contacts by immunization of children

Sage working group: Background Paper on Influenza Vaccines and Immunization. April 2012

SAGE Data- Protection against influenza

WHOM TO VACCINATE???

Vaccine Recommendations

• Ideally, all

individuals

should have the

opportunity to be

vaccinated

against

influenza.

• Priority should

be given to high

risk population

• All those

aged over 6

months in a

clinical at-

risk group

• Only in all

high risk

children >6

months

• Universal

Vaccination

of all children

from the age

of 6 months.

• Special

attention for

children upto

60 months

• Routine

influenza

vaccination is

recommended

for all persons

aged ≥6 months

*CEVAG: Central European Advisory Grouphttp://www.who.int/docstore/wer/pdf/2002/wer7728.pdf http://www.cdc.gov/mmwr/preview/mmwrhtml/rr59e0729a1.htm?s_cid=rr59e0729a1_e http://www.sehd.scot.nhs.uk/cmo/CMO(2010)14.pdf http://www.biomedcentral.com/content/pdf/1471-2334-10-168.pdf

*

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?

Influenza Activity And Peaks

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)

WHO recommendations

• 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 strain of vaccine

WHO Influenza Vaccine Recommendations

2009July- August

2010July- August

India

India 2011

Influenza virus circulation peaks in June-August

J J A S

March- April August - October

IAP 2012 recommendations

• Data since 2004 suggests a clear peaking of circulation during the rainy season across the country- ‘June to August’ in north (Delhi), west (Pune) and east (Kolkata), and ‘October to December’ in south (Chennai)

• Influenza vaccines are given before the peak

season. Hence, the best time for offering vaccine for individuals residing in southern states would be just before the onset of rainy season, i.e. before October while for rest of the country, it should be before June

IAPCOI. Consensus Recommendations on Immunization and IAP Immunization Timetable 2012. Indian Pediatr. 2012 Jul 8;49(7):549-64.

INTERNATIONAL SURVEILLANCE NETWORK

VACCINE MANUFACTURER

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

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

NH vaccineRecommended composition of influenza virus vaccines for use in the 2012-2013 northern hemisphere influenza season

an A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; a B/Wisconsin/1/2010-like virus.

WHO recommendation for SH 2013 : 21 September 2012

Strains are same as those in NH 2012-13

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.