PCV 10 v/s PCV 13 – Indian Scenario

Dr Gaurav Gupta

18th March, 2012

Overview

Pneumococcal Disease Burden – Indian Context

Studies from India & abroad NTHi Recommendations & Comparison

Overview

Pneumococcal Disease Burden – Indian Context

Studies from India & abroad NTHi Recommendations & Comparison

4

Description of PCV vaccines

4, 6B, 9V, 14, 18C, 19F, 23F

PCV 13 (Prevenar13) 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F

CRM197 Diphtheria carrier protein

CRM197 Diphtheria carrier protein

PCV 7 (Prevenar)

3, 6A, 19A

NTHi protein D

4, 6B, 9V, 14, 23F, 18C, 19F 1, 5, 7F

NTHi protein DTT DT

PCV 10 (Synflorix)

Strep Pneumoniae in developing countries

Countries with the greatest number of pneumococcal deaths among children under 5

years

O,Brien K, et al. Lancet. 2009;374:893-902.

Pneumococcal Disease Burden

TOP TEN

Pneumonia & IndiaPneumonia & IndiaPneumonia remains the leading killer of children1

410,000 children < 5 die of pneumonia every year1,2

25% of all child deaths are due to pneumonia3

Meta-analysis of 4 CTs suggest 30-40% of all severe pneumonia in children is pneumococcal.

In Indian context, around 123,000 to 164,000 children <5 years die annually from pneumococcal pneumonia1

1. Levine OS et al Indian Pediatrics 2007; 44:491-4962. Pneumonia – The forgotten killer of children, WHO, UNICEF, 20063. Thacker N. IPD burden - An Indian Perspective. Pediatrics Today 2006; 9(4): 208-213

Strep Pneumoniae & Pneumonia – Indian Disease Burden Pneumonia is the single most important

cause of death among children in the postneonatal period, contributing as much as 27.5% of total under-five mortality

It appears that about 10-15% of childhood pneumonias are caused by H. influenzae and RSV each; and 12-35% by pneumococcus. *

* Mathew J et al. ARI & Pneumonia in India – A systematic review . Indian Pediatrics, March 2011

We are missing the target(Millennium Development Goal 4)

9

AAR =average annual rate of reduction MDG=millennium development goal

U5MR in 2015 at current AAR

MDG Target U5MR in 2015

85

38

Under-five mortality ratio (U5MR) projections 60 priority countries

Source: UN Population Division World Population Prospects, 2004.

Overview

Pneumococcal Disease Burden – Indian Context

Studies from India & abroad NTHi Recommendations & Comparison

Epidemiology of Pneumococcal Serotypes in India in Children under 5 yrs : An overview of available data

1999 : IBIS study (Invasive Bacterial Infection Surveillance) 2006-07 :SAPNA network (South Asia Pneumococcal

Alliance) 2008 : Asian Network for Surveillance Of Resistant

Pathogens ( ANSORP 2008 ) 1992-07 : S. Pneumoniae Surveillance for Serotype

distribution in Bangladesh: 2008 : KIMS Study (PneumoNET) 2009 :Pneumo ADIP (Pneumococcal vaccine Accelerated

Development and Introduction Plan ) 2011 : Alliance for Surveillance of Invasive Pneumococci

(ASIP)

11

Burden of Disease –Pneumonet Data*

Age group (months)

No. of cases

No. in group

Incidence rate per 1,00,000

population

1 to 6 3 8,186 36.35

6 to 12 6 13,040 46.01

12 to 24 3 22,777 13.17

24 to 36 4 22,470 17.80

36 to 60 1 46,010 2.17

Overall 17 112,483 15.10

2 year prospective study Based in 3 Bengaluru

hospitals Study of IPD (culture of

S. pneumoniae from a normally sterile site) and pneumonia as defined clinically and on X-ray

Interim data for 1 year Poster at ESPID- June

2011

* Study Funded by Wyeth, a division of Pfizer Inc.

Incidence of IPD in children < 2 years is15.91(pn) + 6.82(pyomen) + 5.55(bact) = 28.28/1,00,000 population

Burden of Disease –Pneumonet Data Age group (months)

Clinical Pneumonia No. of cases

Incidence rates per

1,00,000 pop.

X-ray Pneumonia No. of cases

Incidence rates per

1,00,000 pop.

1 to 6 393 4,800.88 145 1,771.32

6 to 12 499 3,826.69 214 1,641.10

12 to 24 627 2,752.78 318 1,396.15

24 to 36 384 1,708.95 175 778.82

36 to 60 468 1,017.17 254 552.05

Overall 2,371 2,107.87 1,106 983.26

These are total pneumonia cases. Incidence of Pneumococcal pneumonia has to be by extrapolation on possible fraction of S. pneumonae as a cause of pneumonia in this age groups

Study Centres

19

KEM Mumbai

KEM Mumbai

LTMMC MumbaiLTMMC Mumbai

BVP PuneBVP Pune

KEMPuneKEMPune

MGIMS WardhaMGIMS Wardha

St. JohnsBengaluruSt. JohnsBengaluru

PushpagiriTiruvalla

PushpagiriTiruvalla

SRMCChennaiSRMC

Chennai

Safdar Jung Delhi

Safdar Jung Delhi

CNBCDelhi

CNBCDelhi

CMCLudhiana

CMCLudhiana

• PAN India Network

• 12 Institutes

• 48 Sentinel Pediatricians

• 7 Sentinel local labs

Central Monitoring Lab CMC,

VelloreAIMSKochiAIMSKochi

Indian Data – A brief SynopsisStudy Total number

of IsolatesTop 3 Isolates

IBIS – 1999 307 6, 1, 19

SAPNA 4 1, 6 B

Pneumonet * 17 6 A, 5, 1/ 3/ 14

ASIP * 35 10, 19 F/ 6, 23F/ 5

A limited number of serotypes cause IPD in young Children

Johnson et al PLOS Medicine 2010

~ 10 Serotypes causes 75% of IPD in children under 5 years of age

PCV 7 - Coverage

References: 1. Johnson et al. Plos Medicine 2010

PCV 10 - Coverage

References: 1. Johnson et al. Plos Medicine 2010

PCV 13 - Coverage

References: 1. Johnson et al. Plos Medicine 2010

North America

Latin America

oceania

Africa

AsiaEurope

PCV7:<50%1PCV10:>70%1PCV13: 75%1

PCV7:<60%1PCV10:<80%1PCV13:~80%1PCV7:<70%1PCV10:~75%1PCV13:~80%1

PCV7:~70%1PCV10:~80%1PCV13:<90%1

PCV7:>80%1PCV10:~85%1PCV13:~90%1

PCV7:<50%2PCV10: 75%2PCV13: 75%2

PCV7:<50%1PCV10:>70%1PCV13: 75%1

References: 1. Johnson et al. Plos Medicine 2010 2.Nitin k. shah et al. summary of invasive pneumococcal disease burden among

children in Asia-Pacific region. Vaccine 28(2010) 7589-7605

Ongoing clinical trials

COMPAS study Being conducted in 24,000 children in 3 Latin

American Countries; 4 year follow-up Aim is to study the efficacy in preventing clinical and

radiological pneumonia in study group PCV10 (with NTHi D protein) in study arm with control

(Hep. B and Hep. A) Interim data – vaccine efficacy rate of 22% (clinical

pneumonia i.e. features of LRTI with CRP > 40 mg/L) and 25.7% (Consolidation on X-ray Chest)

Likely to be officially published in June 2012

PCV 10 IPD Effectiveness II:Pneumococcal Meningitis in Brazil, in <2 yr olds 1998-2011

PCV 10 introduction March-June 2010. UMV, 3+1 schedule

~48% reduction any Pn.

meningitis Jun11 vs Jun10

Cumulative number of Pneumococcal meningitis cases in children <2 years of age by month of occurrence, Brazil, 2007-10

Brazil National Pneumococcal menigitis reporting. MoH - SAUDE : http://portal.saude.gov.br/portal/saude/profissional/visualizar_texto.cfm?idtxt=37811 accessed 21Nov2011

2011

2010

2009

Acute Bacterial Core surveillance data (US)*

Rates of IPD with all serotypes per 1,00,000 pop. In children < 2 years of age (Total 15980 cases)

Effect of switch to PCV13 in Feb 2010

All serotypes

Vaccine serotypes

Quarter/Year Baseline 2006-2008

2010 Baseline 2006-2008

2010

Jan-Mar 43.4 48.4 27.0 31.8

Apr-Jun 37.1 27.8 22.9 18.4

Jul-Sept 22.0 17.5 10.7 11.2

Oct-Dec 40.3 18.8* 24.1 8.5* * P < 0.0001

Conclusion: These preliminary findings are consistent with early effects of PCV13 on IPD among young children

*Presented at ICAAC of ASM at Chicago Sept. 2011

Overview

Pneumococcal Disease Burden – Indian Context

Studies from India & abroad NTHi Recommendations & Comparison

NTHi is one of the leading pathogen in Otitis Media

The 3 predominant pathogens in otitis media: S. pneumoniae, NTHi and M. catarrhalis (from 8 different studies involving tympanocentesis and culture of middle ear fluid from 1990–2007).9–16Murphy et al The Pediatric Infectious Disease Journal • Volume 28, Number 10, October 2009

Indian data on NP carriage of NTHi in children under 2yrs of

age

Overview

Pneumococcal Disease Burden – Indian Context

Studies from India & abroad NTHi Recommendations & Comparison

New recommendations for PCV 10 Iceland – PCV10 April 20111

EMA(CMPH) – PCV10 June 20112

(extension of use for 2 to 5 year age group)

Brazil, Chile, Mexico, Colombia Finland, Sweden, Netherlands Albania, Bulgaria, Austria, Cyprus Kenya

1. EPI-ICE 7:2 Apr-Jun 2011 2. NELM News Service June 2011

New recommendations – PCV10 vs PCV13 Switch from PCV 10 to PCV 13

Hong Kong Nov 20111

Australia Aug 20112

Canada Sep 20103

Simultaneous use of PCV10 and PCV 13 Korea Apr 20114

No comment of superiority or otherwise of either vaccine No special recommendation for use of either vaccine in any

specific group New Zealand May 20115

Use of PCV10 routinely and PCV13 for “high-risk” group

1. Press Release: Health Dept. HK. Nov 29, 2011. 2. Dept. Memo dated 30th Aug, 20113. CCDR: Nov 2010. 4. Korean J Pediatr 2011;54(4):146-151 5. IAC – Univ. of Auckland

PCV 10 v/s PCV 13

Criteria Comment Winner

Effectiveness – IPD 2 - 8 % difference likely PCV 13

Effectiveness – AOM 6 % v/s 34 % PCV 10

Cost Almost 50 % difference PCV 10

Convenience & Support No difference Tie

Safety No serious concerns Tie

Conclusion

High Pneumococcal disease burden in India, excellent safety and improved efficacy profile, pneumococcal vaccine should be offered to all affording children.

PCV 13 is better in protecting against IPD, the main raison d'être for pneumococcal vaccination. 19 – A coverage may offer potential benefits.

PCV 10 offers good protection at better price, with additional significant benefit of protecting against AOM due to NTHi.