IAP Annual meet Chandigarh, PGI presentation

1. PCV 10 v/s PCV 13 – Indian
Scenario
Dr Gaurav Gupta
18th March, 2012

2. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Recommendations & Comparison

3. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Recommendations & Comparison

4. Description of PCV vaccines
PCV 7 (Prevenar) 4, 6B, 9V, 14, 18C, 19F, 23F
CRM197 Diphtheria carrier protein
PCV 10 (Synflorix) 4, 6B, 9V, 14, 23F, 18C, 19F 1, 5, 7F
NTHi protein D TT DT NTHi protein D
PCV 13 (Prevenar13) 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F 3, 6A, 19A
CRM197 Diphtheria carrier protein
4

5. Strep Pneumoniae in developing countries

6. Pneumococcal Disease Burden
Countries with the greatest number of pneumococcal deaths
among children under 5 years
TOP TEN
O,Brien K, et al. Lancet. 2009;374:893-902.

7. Pneumonia & India
Pneumonia 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; 44:491-496
2. Pneumonia – The forgotten killer of children, WHO, UNICEF, 2006
3. Thacker N. IPD burden - An Indian Perspective. Pediatrics Today 2006; 9(4): 208-213

8. 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

9. We are missing the target
(Millennium Development Goal 4)
Under-five mortality ratio (U5MR) projections
60 priority countries
U5MR in 2015
85
at current
AAR
38 MDG Target
U5MR in 2015
AAR =average annual rate of reduction
MDG=millennium development goal
Source: UN Population Division World Population Prospects, 2004. 9

10. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Recommendations & Comparison

11. 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

12. Burden of Disease –Pneumonet Data*
 2 year prospective study Age No. of No. in Incidence
 Based in 3 Bengaluru group cases group rate per
(months) 1,00,000
hospitals population
 Study of IPD (culture of 1 to 6 3 8,186 36.35
S. pneumoniae from a 6 to 12 6 13,040 46.01
normally sterile site) and 12 to 24 3 22,777 13.17
pneumonia as defined 24 to 36 4 22,470 17.80
clinically and on X-ray 36 to 60 1 46,010 2.17
 Interim data for 1 year Overall 17 112,483 15.10
 Poster at ESPID- June
Incidence of IPD in children < 2 years is
2011 15.91(pn) + 6.82(pyomen) + 5.55(bact)
= 28.28/1,00,000 population
* Study Funded by Wyeth, a division of Pfizer Inc.

13. Burden of Disease –Pneumonet Data
Age Clinical Incidence X-ray Incidence
group Pneumonia rates per Pneumonia rates per
(months) No. of cases 1,00,000 pop. No. of cases 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

14. CMC CNBC Study Centres
Ludhiana Delhi
• PAN India
Safdar Network
Jung
Delhi
• 12 Institutes
KEM KEM • 48 Sentinel
Mumbai Pune Pediatricians
BVP
SRMC • 7 Sentinel
Pune
Chennai
local labs
MGIMS
Wardha Pushpagiri
Tiruvalla
LTMMC
Mumbai Central
Monitoring
Lab CMC,
AIMS
Kochi Vellore
St. Johns
Bengaluru
19

15. Indian Data – A brief Synopsis
Study Total number Top 3 Isolates
of 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

17. A limited number of serotypes cause IPD
in young Children
~ 10 Serotypes causes
75% of IPD in children
under 5 years of age
Johnson et al PLOS Medicine 2010

18. PCV 7 - Coverage
References: 1. Johnson et al. Plos Medicine 2010

19. PCV 10 - Coverage
References: 1. Johnson et al. Plos Medicine 2010

20. PCV 13 - Coverage
References: 1. Johnson et al. Plos Medicine 2010

21. PCV7:
PCV7: <5
>8 PC V7 : PCV10 0% 1
PCV10 0% 1 ~7 :>70% 1
:~85% 1 PCV10 0% 1 PC V1 3
PC V1 3 :~ : 75% 1
:~90% 1 PCV13 80% 1
:<90% 1
Europe Asia
North America
PCV7:
<5
PCV10 0% 2
:7
PCV13 5% 2
: 75% 2
PCV7: Africa
<6
PC V1 0 0 % 1
:<80% 1
PCV13 PCV7:
:~80% 1 <5
PCV10 0% 1 PC V7 :
<7
:>7
PCV13 0% 1 PCV10 0% 1
: 75% 1 :~75% 1
PCV13
Latin America :~80% 1
oceania
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

22. 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

23. PCV 10 IPD Effectiveness II:
Pneumococcal Meningitis in Brazil, in <2 yr olds 1998-2011
Cumulative number of Pneumococcal meningitis cases in children <2 years of age by month of occurrence, Brazil,
2007-10
PCV 10 introduction March-June 2010. 2009
UMV, 3+1 schedule
2010
~48% reduction
any Pn.
meningitis
2011 Jun11 vs Jun10
Brazil National Pneumococcal menigitis reporting. MoH - SAUDE :
http://portal.saude.gov.br/portal/saude/profissional/visualizar_texto.cfm?idtxt=37811 accessed 21Nov2011

24. 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 Vaccine
serotypes serotypes
Quarter/Year Baseline 2010 Baseline 2010
2006-2008 2006-2008
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

25. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Recommendations & Comparison

26. 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).9–16
Murphy et al The Pediatric Infectious Disease Journal • Volume 28, Number 10, October 2009

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

29. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Recommendations & Comparison

30. 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

31. 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, 2011
3. CCDR: Nov 2010. 4. Korean J Pediatr 2011;54(4):146-151 5. IAC – Univ. of Auckland

32. 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

33. 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.