1. Presentation at the Immunization Summit 2011
Pneumococcal Conjugated
Vaccine (PCV) :
Is the introduction to the
National Immunization Program in
Sri Lanka justified ?
Dr. Pushpa Ranjan Wijesinghe, MD
Consultant Epidemiologist

2. Is introduction of PCV a dilemma for
National EPI managers ?
• Need for achieving MDGs and role of immunization
• Opportunities for introduction of appropriate new
vaccines to the NPI
• Are we going to use these opportunities ?
• Inequity
• public sector responsibility
• If so, will there be a place for pneumococcal vaccines?
• Is scientific evidence available for such a decision ?
• If the decision is made, is it self- sustainable in the
longer run ?

3. Consensus statement
The immunization stake holder's meeting -2007
• Pneumococcal vaccines :
• Current disease burden (2007) is inadequate for
decision making
• Due to high pneumonia specific morbidity, mortality and
high AB resistance of S.pneumoniae, consideration of
the pneumococcal vaccine in future given the financial
feasibility and GAVI support
• Extension of surveillance activities to more sentinel sites
to represent different geographical regions, further
strengthening and revisit in 2008

4. Does the disease burden warrant health
intervention ?
• Consensus statement –The immunization stake
holder's meeting -2007
“Current disease burden (2007) is inadequate for decision making “
•
Is the situation different in 2010 ?
“ High AB resistance of S.pneumonia “
• Is
this real in the Sri Lankan context ?

5. Pneumococcal Surveillance 2004-2008)
•
Syndromic surveillance of PMS patients aged 2-60 months at the LRH
Type of testing
No. tested (n)
positivity rate for S.pneumoniae
Blood cultures
2275
0.68%
( range - 0.57%-0.69%)
CSF cultures
9495
0.65%
( range – 0.23% - 1.1%)
Latex agglutination tests
1861
1 .9%
( range – 0.88% - 2.5%)
Higher detection by latex antigen test from CSF than CSF cultures
*Diminished growth of S.pneumoniae in cultures due to probable prior use of
antibiotics
Source : SAPNA

6. Incidence rate /100000 and estimates of PMS for
Colombo district and Sri Lanka
Syndrome
Incidence rate *
(per 100000)
Estimate for
Colombo district *
Estimate for
Sri Lanka
All cause
pneumonia
1342
2227
23551
All cause
meningitis
519
866
9030
All cause
sepsis
390
651
6786
3759
39167
All cause PMS 2251
•Epidemiological and economic analysis of pneumococcal disease in
Sri Lanka conducted by Dr. S.Kularatne for the Epidemiology Unit - 2009

7. Annual incidence rates of IPD/100000
in under 5 children
Country
Pneumococcal
meningitis
Pneumococcal
sepsis
Pneumococcal
pneumonia
IPD
Sri Lanka
( Colombo)
31.1
(95% CI= 20-42)
18.0
(95% CI= 10-26)
34.2
(95% CI= 23-46)
83.3
(95% CI= 65-101)
Spain
90.0
Germany
14.0
USA
Gambia
250
(500 - < I yr)
Kenya
597

8. Annual incidence rate/100000 and estimates of
IPD for Colombo district and Sri Lanka
Syndrome
Incidence rate *
(per 100000)
Estimate for
Colombo *
Estimate for
Sri Lanka
Pneumococcal
pneumonia
34.2
(95% CI -23-46)
57
(95% CI- 38-76)
595
(95% CI- 400 -800)
Pneumococcal
meningitis
31.1
(95% CI -20-42)
51
(95% CI - 33-70)
539
(95% CI -348 – 730)
Pneumococcal
sepsis
18
(95% CI -10-26)
30
(95% CI-17-4)
313
(95% CI -174-452)
83.3
(95% CI- 65-101)
139
(95% CI -108-169)
1449
(95% CI -1131-1757)
IPD
* Epidemiological and economic analysis of pneumococcal disease in
Sri Lanka conducted by Dr. S.Kularatne for the Epidemiology Unit - 2009

9. Pneumococcal surveillance ( 2004-2009)
Antibiotic sensitivity of Pneumococcal isolates ( n=125)
Antibiotic
Sensitive
Intermediate
resistant
Resistant
Penicillin
53 (42%)
41(33%)
31(25%)
Co-trimaxazole
33 (26%)
21(17%)
71(57%)
Chlorampenicol
99(79%)
00
26 (21%)
Erythromycin
42(33%)
01(1%)
82(66%)
Cefotaxime
94(75%)
25(20%)
06(5%)
Source : SAPNA

10. Is there an appropriate vaccine?
• PCV 7
– contains 7 sero -types
– 4, 6b,9v,14,18C, 19F, 23F
– a licensed product
• PCV 9
– Contains additional serotypes – 1 & 5
– unlicensed product
• PCV 10
– contains additional serotype - 7
• PCV 13
– contains additional serotypes- 3,6A,9A

11. Is there an appropriate vaccine?
Type of
vaccine
No. of
Serotypes
contained
Serotypes
PCV 7
7
PCV 9
9
1 & 5 (additionally)
PCV 10
10
7(additionally)
In production
PCV 13
13
3,6A,9A(additionally)
In production
4, 6b,9v,14,18C, 19F, 23F
Status
licensed
product
unlicensed
product

12. Pneumococcal surveillance ( 2004-2009)
Distribution of serotypes in Sri Lanka ( LRH & 5 sites)
35
30
Coverage of PCV 7 = 62.2%
Coverage of PCV 7 = 62.2%
Coverage of PCV 10=63.1%
Coverage of PCV 10=63.1%
Coverage of PCV 13= 69.7%
Coverage of PCV 13= 69.7%
29
25
20
15
11
8
9V
9N
19c
6B
18F
1
6A
18A
5
4
1
47f
17f
Type
1
0
35,42
1
33b
1
4
23f
1
23a
1
22
1
19f
1
16a
1
15c
20
1
15b
16
0
11c
15
2
11a
1
38
1
23
1
14
1
13
0
1
3
1
5
4
4
4
5
7
NT
10
1
Number
22

13. Are the globally available
safety and efficacy data
conclusive ?
Is there a need for
local immunogenicity/efficacy and
safety data ?

14. End points
evaluated
Individual
randomized
(direct effect)
Cluster
randomized ( +
herd immunity)
Individually RCT
Individual
Efficacy (95% CI)
Efficacy (95% CI)
Efficacy (95% CI)
Efficacy (95% CI)
IPD –vaccine
sero types
94% (80-99%)
83% (21-96%)
71%(46-86%)
IPD-all pneumococal
types
89% ( 74-96%)
52 % (-7-79%)
45%(19-62%)
Radiologically
confirmed
pneumonia
26% ( 7-41%)
-21% ( -62-9%)
35%(26-43%)
Well defined clinical
pneumonia
6% ( 1-11%)
Severe clinical
pneumonia
-
Hospital admissions
13% (6-19%)
Mortality (all cause)
14%(2-24%)
Vaccine type acute
Otitis media
All cause acute otitis
media
54% (41-64%)
6%(4-9%)
6% ( -4-16%)
Source : WHO

15. Safety – key points
• Generally safe and well tolerated
• even among children infected with HIV
• Post marketing surveillance
• No significant serious AE among 30 million users in USA
• Most common reported adverse events
• Injection site reactions (slight soreness and swelling)
• Transient fever above 38.5 C
• Rare adverse events
• Febrile seizures
• Hypotonic-Hypo responsive Episodes (HHE)
• Very rare adverse events
• Urticarea, angioneurotic oedema, erythema multiforme and
hypersensitivity including anaphylaxis

16. Preventable number of cases by PCV 7
in Sri Lanka
Non
vaccinated
scenario
Vaccinated –
vaccine
recipients
(90%)
Vaccinated –
vaccine non
recipients
(10%)
Total cases
prevented by
vaccine
IPD
1444
120
25
1299
Non Pnc
PMS
38280
25417
5206
7657
Efficacy – 83% for IPD

17. Can the vaccine be incorporated in to the
current EPI schedule ?
• Currently 2 recommended schedules of 3
doses
– 6 weeks, 10 weeks and 14 weeks
– 2 months, 4 months and 6 months
• Compatible with pentavalent 3 doses
• No need for an additional clinic visit

18. What are the costs involved ?
Approximate cost for
vaccines
5$
per a dose
(376843 X 5 $ X 3)
56 52645 $
per year
Treatment cost in a
non vaccinated
scenario
Per Pnc PMS
&
other PMS
cases
(25714 RS X1444)
+
(12495 Rs X 38280)
45 56221 $
per year
Treatment cost in a
vaccinated scenario
Per Pnc PMS
&
other PMS
cases
(25714 Rs X 145)
+
(12495 Rs X 30623)
34 49668 $
per year
Treatment cost
saved from
vaccination
Additional space due Volume per
to increasing Cold
dose
chain requirements
59.7cm3/dose *
11 06553 $
per year
(1130529 X 59.7)
67.5 m3

19. Is the suggested vaccine cost effective ?
GAVI’s economic
analysis
GAVI’s estimated
Cost effectiveness ratio
for
Sri Lanka
Estimated
Cost effectiveness ratio
based on
Sri Lankan study
Cost effective in
71/72
GAVI eligible
countries
( including Sri
Lanka )
4211 $ per
DALY averted
7397 Rs per
DALY averted
Benchmark – WHO CHOICE

20. Where are we compared to the previous
summit ?
• Availability of an estimate of the disease burden for the
Colombo district as a model for decision making
• Availability of an estimate of treatment cost
• More comprehensive collection of sero types from
LRH and 5 other hospitals
• Wide representativeness
• Antibiotic resistance data
• Circulating serotypes ( n=125)

21. Where are we compared to the previous
summit ?
•
Availability of a vaccine ( 7,10,13 valent) with a high coverage for
available serotypes
•
Comprehensive data on safety and immunogenicity of the intended
vaccine
•
Availability of results of an economic analysis as a guiding tool for
decision making
•
Established infra structure ,expertise on and experience in post
introduction surveillance of new vaccines
•
Availability and delivery of the intended vaccine in the private sector
•
WHO support for continued surveillance ( disease and laboratory)

22. Points for the discussion
•
•
•
•
•
Is
–
–
–
introduction of pneumococcal vaccine justifiable ?
Disease burden, economic burden
Competing priorities (MMR, typhoid)
Financial sustainability
• SL- no longer being GAVI eligible
• Self financing potential
Can a tentative timeline be determined ?
– consideration of the pneumococcal vaccine in future given the financial
feasibility and GAVI support – immunization stake holder's meeting 2007
What are the other constraints ?
How can we overcome them?
Any concerns of participants ?

23. Acknowledgement
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Dr. Nihal Abeysinghe for vision and guidance
Dr. Paba Palihawadana and Dr T.S.R.Pieris for continued vision & support
Dr.Ranjit Batuwanthdawe for the pioneering work
Dr. Malka Dissanayake & Dr.Kumudu Karunaratne for enabling
information generation
Dr.Sanjeewa Kuaratne for initiating epidemiological and economic analysis
All microbiologists at the SPnSN for their contributions
MLTs at the LRH microbiology lab for the excellent work
All pediatricians at the LRH for their precious contributions
Dr. Mark Stein Hoff, Prof. Kurian Thomas, Professor Lalitha Kesewan
Microbiology team @ the Christian Medical College , Vellore, Tamil Nadu
GAVI’s Pneumo ADIP, John Hopkins University, USA
International Clinical Epidemiological Network (INCLEN)
All research assistants of the SAPNA ( Sri Lanka) for the hard work
Iresha, Roshan, Priyangika for coordinating all the work