Presentation at Ambala & Patiala CME organized by GSK

1. Dr Gaurav Gupta,
Pediatrician,
Member AAP, IAP,
Charak Clinics, Mohali
7th April 2012

2. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Design, Recommendations & Faqs

3. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Design, Recommendations & Faqs

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
1000 X
AOM
100 X
Non Invasive
pneumoneia
10 X
Bacteremia
Meningitis

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
 Design, Recommendations & Faqs

11. 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

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

13. PCV 10 - Coverage

14. PCV 13 - Coverage

15. Pneumococcal Polysaccharide and Non- Typable Haemophilus influenza
(NTHi)
Protein D conjugate vaccine, adsorbed
Europe Asia
North America
Africa
Latin America
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

16. 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) : (Jan – Nov )
16

17. PNEUMONET KIMS study… (1 year data)
•Study done at 3 hospitals in
Table 3: Serotype Distribution
Bangalore South Zone
(Kempegowda Institute of Medical Serotype N
Sciences Hospital, Vanivilas 6A 5
Hospital, and Indira Gandhi 5 3
Institute of Child Health) 1 2
3 2
•Limited no. of serotype and only
from part of a city of a region 14 2
hence can not represent a Sub 9V 1
continent like India 19F 1
18C 1
• No indication of high prevalence
of serotype 19 A 19A 1
a – In 1 subject 2 different serotypes were obtained from blood and CSF (6A in CSF and 3 in blood)
17

18. 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

19. CMC CNBC Inclusion
Study Centres Criteria
Ludhian Delhi
a • PAN India
• Age:
Safdar <5 years Network
•
JungClinically suspected case of pneumonia, meningitis
Delhior bacteremia (as per modified WHO case Institutes
• 12
definition)
KEM • Without previous antibiotic therapy
Mumba KEM • After informed consent by parent • 48 Sentinel
i Pune • Microbiology protocol as per modified WHO/CDC
Pediatricians
surveillance manual
BVP SRMC
Pune Chenn • 7 Sentinel
MGIM ai local labs
S Pushpag
Wardh iri
a Tiruvalla
LTMM
C
Mumba Central
i Monitoring
Lab CMC,
St. AIMS
Vellore
Johns Kochi
Bengalu
19

20. ASIP: Distribution of Serogroup/type
Preliminary Results (n=35), 2011
Serogroup / No. of
Serotype isolates
1 01
4 01 19 A % : 1/35 ( 2.85 %)
19F % : 3/35 ( 8.57%)
5 02
------------------------------------
10 04 19 % : 4/35 (11.4%)
7F -
• In line with previous studies and
9V - PneumoADIP- Asia: 2009
14 (F) 01
18C - • Others: includes serogroups with 1 isolates
19F 03
23F 02 No case of ST 3 in India,
3 - results in line with
6 03 Previous large
multicentric trials
19A 01
Others 17 20

21. 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

23. 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 by June 2012

24. 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

25. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Design, Recommendations & Faqs

26. Spectrum of disease caused by 2
bacteria
H. influenzae S. pneumoniae
Meningitis
Sepsis
Incidence of invasive H. influenzae
disease drastically reduced—but
not eliminated--where Hib
vaccination introduced
Pneumonia
Non-invasive diseases
+ NTHi (Otitis media)
(non-invasive &
invasive diseases)
26
26

27. NTHi is one of the leading pathogen in Otitis Media
40.0%
36.7%
35.0%
31.7%
30.0%
25.0%
20.0% 18.7%
15.0%
10.0%
5.0%
0.0%
S. NTHi M.
Pneumoniae Catarrhalis
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

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

29. Review of contribution of NTHi (non typable Haemophilus influenzae) and
S pneumonia in children Acute otitis media
Study Journal Year Place Sample Age group S. Non typable
pneumoniae H. influenzae
Alexandr BMC 2011 Colombia 99 3-60 months 30/99 (30%) 31/99 (31%)
a Sierra Infect.
et al. Dis
Parra M Vaccine 2011 Mexico 121 3-59 months 35/121 41/121 (34%)
Bacterial (29%)
et al.
Shiping AJ of 2011 Taiwan 225 1-94months --------------- 189/225 (84%)
He. et al med.
Res.
Barkai G. Ped. 200 Israel 8145 < 60months 4339/8145 4928/8145
et al Infect. 9 (53%) (60%)
Dis J
Ref: Alexandra Sierra et al.,BMC infectious diesease,2011
Parra M Bacterial et al., Vaccine. 2011 (29) 5544– 5549
Shiping He. African Journal of Microbiology Research Vol. 5(17), pp. 2407-2412
Barkai G. Pediatr Infect Dis J.2009 Jun;28(6):466-71

30. Conclusion:
 NTHi (Non Typable Haemophilus influenzae) and S.
pneumonia and are the major causative organism for
AOM among under 5 children worldwide.
 NTHi and S. pneumoniae mixed episodes are more
likely to occur in AOM, & interaction between these two
pathogens contribute to chronicity and complexity of AOM.

31. Synflorix Only new generation PCV offer dual
Pathogen Protection against S. Pneumoniae and
NTHi in AOM

32. Overview
 Pneumococcal Disease Burden – Indian
Context
 Studies from India & abroad
 NTHi
 Design, Recommendations & Faqs

33. Design of Synflorix
Why use a carrier protein derived from H. influenzae?
Synflorix designed to potentially:
• protect against most prevelent 10 pneumococcal serotypes
• minimize risk of interference with co-administered vaccines
• provide protection against NTHi disease
S.pneumoniae Non-Typeable
H. influenzae
protein D
[carrier protein]
Polysaccharides
(10 serotypes*)
* 2 polysaccharides conjugated on tetanus and diphtheria toxoid respectively 33

34. Summary : What about Serotype 3, 6A and 19A?
Is there any difference between these 2 Vaccines
? Serotype 3 (not a common pediatric serotype)

 is an atypical serotype and non boostable
 In large muticentric clinical studies, Serotype 3 has not been isolated in
children < 5 years of age in India ( IBIS 1999 TO ASIP 2011)
 Serotype 6A (globally accepted 6B-6A cross-protection)
 PCV 7 which included only ST 6B, reduced 90% of serotype 6A IPD cases
as per CDC surveillance data
 Serotype 19A (not rising in India)
 Data from pan India studies confirms that, there is no rise / upward trend
observed in serotype 19 A IPD cases
 Both the vaccine in India will offer > 70% IPD coverage

35. 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

36. 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

37. Q 1. Why should I use Synflorix when prophylactic use
of Paracetamol is not recommended as the immune
response may be lowered?

39. Q 2. Synflorix co-administration with IPV caused a
reduced immune response to IPV 2. Can I still use
Synflorix with IPV?
Answer: Synflorix can safely be co-administered
with IPV and will not cause a reduced antibody
response to the poliovirus antigens

40. Conclusion
 Pneumococcal disease is the #1
vaccine-preventable cause of death
worldwide in children aged <5 years1
 High Pneumococcal disease burden in
India, excellent safety and improved
efficacy profile, pneumococcal vaccine
should be offered to all affording children.
 PCV 10 offers good protection at better
price, with additional significant benefit of
protecting against AOM due to NTHi.