Influenza vaccination in IndiaA Pediatrician’s Perspective

Dr Gaurav Gupta,Pediatrician,

Member AAP, IAP,Charak Clinics, Mohali

21 May 2016

Conflict of Interest

• Received grants from various vaccine manufacturers including – - Sanofi Pasteur– - GSK– - Abbott(Manufacturers of different Influenza vaccines)

Overview

• Influenza – is it really that big a problem – Indian Children?

• Influenza vaccine – Indian Data• Whom, how & when to vaccinate ?

CASEAlisha 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)

Global Burden of Influenza in Children

05/01/2023 www.thelancet.com. Published online November 11, 20117

……concluded that, in 2008, 90 million cases of influenza occurred among children < 5

20 million cases of ALRI, one million cases of severe ALRI and

28,000-111,500 deaths

Influenza incidence in children < 5 year is ~ 3 times higher in developing as compared to developed countries

Incidence per 1,000 children/yr (95% CI)Mortality rate %

(95% CI)Influenza Influenza acute

LRIInfluenza severe

ALRI

Developing countries 154 (84-275) 35 (22-55) 1.7 (1.1-2.5) 2.96 (0.79-5.13)

Industrialised countries 55 (28-106) 12 (7.5-18) 1.2 (0.9-1.7) 0.17 (0.08-0.26)

28,000–111,500 deaths in 2008, 99% in developing countries.

Nair et al. The Lancet, Volume 378, Issue 9807, Pages 1917 - 1930, 3 December 2011

Influenza is a common cause of pediatric medical visits

• In Thailand in 2004, 23% of 1092 febrile outpatients were influenza positive by PCR1

• In Vietnam during 2006-07, national surveillance reported that 19% of 11,082 febrile outpatients had lab-confirmed influenza infection by PCR3

• In Cambodia during 2006-08, 4,233 febrile pediatric outpatients were screened by PCR and 27.7% were influenza positive4

• In China during 2008-10, 1,472 febrile pediatric outpatients were screened by PCR and 30.9% were positive (Type A 13.3%, Type B 6.8%, pH1N1 10.8%)5

1. Simmerman JM et al. The Cost of Influenza in Thailand. Vaccine 24 (2006) 4417–44262. Brooks, A et al. Influenza is a Major Contributor to Childhood Pneumonia in a Tropical Developing Country. PIDJ. Vol 29, Number 3, March 2009

3. Nguyen, HT et al. National influenza surveillance in Vietnam. Vaccine 28(2010) 398-402.4. Blair, PJ et al. Influenza epidemiology in patients with acute fever in Cambodia. Epidemiol. Infect 138 (2101) 199-209.

5. Pen, J et al. The Epidemiology and Etiology of Influenza-Like Illness in Chinese Children From 2008 to 2010. Journal of Medical Virology 84:672–678 (2012)

05/01/20239

Have we made any progress towards Prevention?

Multisite Influenza surveillance Network & Improved Influenza Detection

05/01/202310

Pune (NIV),Kasauli (CRI)Mumbai (Haffkins Institute)

WHO National Influenza Center s(as of April 2011)

10 cities data suggests 14% of the total samples sent were Influenza positive

05/01/202311

A(H1N1) in India, 2009-15*Time period

May 2009-Dec 2009

Jan 2010-Dec 2010

Jan 2011-Dec 2011

Jan 2012-Dec 2012

Jan 2013-Dec 2013

Jan 2014-Dec 2014

Jan 2015-Feb 2015*

Cases 27236 20604 603 5044 5253 937 18,105

Deaths 981 1763 75 405 699 238 1,005

Mortality ratio

3.60% 8.55% 12.44% 8.03% 13.31% 25.40% 5.75 %

• Data till February 27, 2015 (Source: Office of the Director, Emergency Medical Relief, Directorate General of Health Services, Government of India, New Delhi.)

https://flutrackers.com/forum/forum/india/seasonal-flu-2009-2014-including-h1n1-pandemic-2009-ai/721670-india-influenza-2015-2-868-media-reported-fatalities/page6

• http://www.japi.org/april_2015/08_ua_h1n1_revisited_after_six.html

ARE WE

SEEING TIP OF THE ICEBERG?

Not everyone that dies with an influenza-like illness is tested for influenza;

Influenza-associated deaths are often a result of complications secondary to underlying medical problems, which may be missed.

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

What do we understand?

With very limited data there’s enough reason to believe that the magnitude of the problem is much higher in developing countries including India as compared to the developed

countries

05/01/202314

15

Clinical effectiveness of Influenza Vaccine

Clinical effectiveness of

TIV (450 subjects)

Vaccinated cohortN=150

Followed upN=137

Fully vaccinatedN=106

Partially vaccinatedN=31

Unvaccinated cohortN=300

Followed upN=282

16

Fully vaccinated Vs UnvaccinatedOutcome Fully

Vaccinated cohort (%)

Unvaccinated cohort (%)

Relative Risk

p-value 95% CI

UV 2.8 38.7 0.0987 0.0001 0.032-0.304

ARI 8.5 16.7 0.5478 0.0832 0.277-1.082

ILI 0.9 35.5 0.0357 0.0009 0.005-0.253

Ab. 0.9 6.4 0.1558 0.0686 0.021-1.152

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

Evidence of effectiveness in children younger than 3 years

www.thelancet.com/infection Vol 11 January 2011

9 m- 3y: 66% VE against any influenza, 84% against influenza A < 2 years, VE 66% against any influenza, 79% against influenza A

Assessment of effectiveness

of influenza vaccination by comparing the

proportions of laboratory-confirmed

influenza A and B infections in fully vaccinated and

unvaccinated children a prospective cohort study

Impact of Vaccination In Pre-school And School-going Children

05/01/2023

1.Neuzil KM et al Pediatr Infect Dis J, 2001: 20:733-40. Heikkinen T et al.Influenza vaccination in the prevention of acute otitis media in children: Am J Dis Child 1991;45:445-8 Pediatric Infect Disease J 2006:25;5;401-404 New England J Med 2000; 342:225-31 Principi N et al. socioeconomic impact of influenza on healthy children and their families Pediatr Infect Dis J 2003; 22:S2007-10.20

Studies confirm effectiveness of Influenza vaccination in Pre-School

Children

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

• Not only effective in reducing the sufferings

• But also a Cost Saving proposition

Reduction in Influenza related morbidity

Direct & Indirect benefits of Vaccination

WHOM TO VACCINATE???

Vaccine recommendations by authorities

Ideally, all

individuals

should have the

opportunity to be

vaccinated

Priority should

be given to high

risk population

including

children between

6-23 months

• 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 Accessed on 2/08/2010

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr59e0729a1.htm?s_cid=rr59e0729a1_e Accessed on 2/08/2010http://www.sehd.scot.nhs.uk/cmo/CMO(2010)14.pdf Accessed on 2/08/2010

http://www.biomedcentral.com/content/pdf/1471-2334-10-168.pdf. Accessed on 2/08/2010

*

Annual influenza vaccine is widely recommended for children above 6 months globally, including WHO

IAP Position Paper (2013) Points Out :

Amongst pediatric population, apart from children with chronic medical conditions , children below 2 years of age

should be considered a target group for influenza immunization because of a high burden of severe disease in

this group.

05/01/2023VM VASHISHTHA, A KALRA AND P CHOUDHURY; INDIAN

PEDIATRICS VOLUME 50__SEPTEMBER 15, 201323

Recent Ministry of Health Recommendation:

http://mohfw.gov.in/showfile.php?lid=3069

When to vaccinate?

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

WHO recommendations

• 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

Influenza Activity And Peaks

05/01/2023

Data source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN) 29

Trends in influenza circulation in India

Influenza virus circulation

peaks in June-August

IAP recommendations 2013

05/01/2023

INDIAN PEDIATRICS VOLUME 50__SEPTEMBER 15, 201330

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

IAP recommendation

Vaccine type Composition Immunogen

icityReactogen

icityWhole-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.

Good Immunogenicity and tolerability

01/05/2023 Split Vs Subunit Dr SS | 33

http://www.ifpma.org/resources/influenza-vaccines/influenza-vaccines/about-influenza-vaccine.html

Types of Inactivated Influenza Vaccines

01/05/2023 Split Vs Subunit Dr SS | 34

• The vaccine effectiveness for the split virion influenza vaccine was 77.8% (CI 58.5%-90.3%) for subunit vaccine was 44.3% (CI -11%-70.9%)

Findings

01/05/2023 Split Vs Subunit Dr SS Kim YK et al. 2013

• The proportion of subjects with HI titers ≥40 for H1N1; H3N2 and B viruses were higher in children receiving split virus vaccine.

• The proportions of seroconversion for H1N1, H3N2 and B viruses were also higher in subjects receiving the split virus vaccine.

• The overall local reactions were similar in both vaccine types. 35

Exciting Future ahead ?

QUADRIVALENT LIVE INFLUENZA VACCINE

FDA NEWS RELEASEFor Immediate Release: Feb. 29, 2012FDA approves first quadrivalent vaccine to prevent seasonal influenzaThe 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

Scientists made the vaccine by fusing key proteins of the flu virus, made synthetically by genetic engineering technology, with a bacterial protein called ferritin that can automatically assemble itself into “nanoparticles” smaller than the virus. The flu proteins, which stick out from the ferritin like the spikes on a sea mine, stimulate immunity against the virus.

Nature (2013) doi:10.1038/nature12202Received 28 August 2012 Accepted 18 April 2013 Published online 22 May 2013

Newer VaccinesDriven by Science or Commerce?

1st J & K State Medical Science Congress. 21st May 2016

ASCOM, Sidhra

• US and Europe- Health of people is State's responsibility.- Include (almost) every vaccine in NIP – Hepatitis A, Varicella, Rota, PCV, HPV etc.

• India– People's health is Personal responsibility.– Health & disease prevention is not in human

control, it is God/ Fate

Summary: Reasons for Expanded Pediatric Influenza Vaccination

High disease burden exists in India

Children are at increased risk for serious complications

Children play an important role in transmission in the community

The long-term experience with influenza vaccine, confirms its effectiveness and excellent tolerability

IAP points out that children below 2 years of age should be considered a target group for influenza immunization

Recent MOH guidelines highlight that vaccination is desirable in children between 6m -8years of age

05/01/2023

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