Pneumococcal Conjugated Pneumococcal Conjugated Vaccine (PCV) :Vaccine (PCV) :

Is the introduction to the Is the introduction to the National Immunization Program in National Immunization Program in

Sri Lanka justified ?Sri Lanka justified ?

Dr. Pushpa Ranjan Wijesinghe, MDConsultant Epidemiologist

Presentation at the Immunization Summit 2011

Is introduction of PCV a dilemma for Is introduction of PCV a dilemma for

National EPI managers ? 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 ?

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

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 ?

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

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

All cause PMS 2251 3759 39167

•Epidemiological and economic analysis of pneumococcal disease in Sri Lanka conducted by Dr. S.Kularatne for the Epidemiology Unit - 2009

Annual incidence rates of IPD/100000

in under 5 children Country Pneumococcal

meningitisPneumococcal 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

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)

IPD 83.3

(95% CI- 65-101)

139

(95% CI -108-169)

1449

(95% CI -1131-1757)

* Epidemiological and economic analysis of pneumococcal disease in Sri Lanka conducted by Dr. S.Kularatne for the Epidemiology Unit - 2009

Pneumococcal surveillance ( 2004-2009)

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%)

Antibiotic sensitivity of Pneumococcal isolates ( n=125)

Source : SAPNA

Is there an appropriate vaccine?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

Is there an appropriate vaccine?Is there an appropriate vaccine?

Type of vaccine

No. of

Serotypes contained

Serotypes Status

PCV 7

7 4, 6b,9v,14,18C, 19F, 23F licensed product

PCV 9 9 1 & 5 (additionally) unlicensed product

PCV 10 10 7(additionally) In production

PCV 13

13 3,6A,9A(additionally) In production

Pneumococcal surveillance ( 2004-2009)

Distribution of serotypes in Sri Lanka ( LRH & 5 sites) Coverage of PCV 7 = 62.2%Coverage of PCV 10=63.1%Coverage of PCV 13= 69.7%

1

4

1 1

22

1 1 10

21 1

4

1 1 1 1 1 1

29

0

5

8

1 1

4 4

11

1

5

7

0

5

10

15

20

25

30

35

1 3 4 13

14

15

16

20

23

38

11a

11c

15b

15c

16a

17f

18A

18F

19c

19f

22

23a

23f

33b

35,4

2

47f

6A

6B

9N

9V

NT

Type

Nu

mb

er

Coverage of PCV 7 = 62.2%Coverage of PCV 10=63.1%Coverage of PCV 13= 69.7%

Are the globally available Are the globally available safety and efficacy data safety and efficacy data

conclusive ?conclusive ?

Is there a need for local immunogenicity/efficacy and

safety data ?

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

54% (41-64%)

All cause acute otitis media

6%(4-9%) 6% ( -4-16%)

Source : WHO

SafetySafety –– key pointskey 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

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

Can the vaccine be incorporated in to the Can the vaccine be incorporated in to the current EPI schedule ?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

What are the costs involved ?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

11 06553 $

per year

Additional space due to increasing Cold chain requirements

Volume per dose

59.7cm3/dose *

(1130529 X 59.7) 67.5 m3

Is the suggested vaccine cost effective ?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

Where are we compared to the previous Where are we compared to the previous

summitsummit ??• 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)

Where are we compared to the previous Where are we compared to the previous

summitsummit ??• 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)

Points for the discussionPoints 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 ?

AcknowledgementAcknowledgement

• 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