Transcript Vaccine Investment Strategy - Rabies analysis

GAVI Vaccine Investment Strategy
Rabies Analysis
Final
October 27, 2008
Rabies
Rabies
CONTENTS
• Disease Overview
• Vaccine Landscape
• Vaccination Policy & Strategies
• Vaccine Need & Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources
2
Rabies
Disease Overview
DISEASE PATHOGEN, TRANSMISSION & TARGET POPULATION1*
•
Disease Pathogen
–
•
•
Transmission
–
Usually dog bites in developing countries; animal to person via saliva from a bite
–
Incubation periods have been as short as 5-6 days, in the majority of cases is 20-60 days
Geographic Distribution
–
•
Rabies Virus (lyssavirus)
Most human cases are in rural areas of Africa and Asia
Disease Target Population
–
All ages are susceptible, however, rabies is most common in ages 5-15 years old, the
majority of whom are male
3
Rabies
Disease Overview
DISEASE IMPACT2,3
•
•
•
Total Morbidity
–
>10 million suspected cases per year in developing countries
–
Rural poor and children are most at risk
Total Mortality
–
~55,000 cases reported annually and thought to be grossly underreported with the
majority of deaths occurring in Asia and Africa
–
Case fatality rate is 100% once clinical symptoms present (with exception of one known
survivor to date)
Epidemic Potential
–
•
Human outbreaks can occur as a result of epidemics in the animal population and/or
when a rabid animal bites multiple people
Disease Sequelae
–
Permanent neurological sequelae in the one survivor to date
4
Rabies
Disease Overview
DISEASE BURDEN – GEOGRAPHIC DISTRIBUTION4
Note: “This figure is an unrealistic representation of the true epidemiological situation as a result of problems with reporting biases, e.g.
dog rabies is endemic throughout Africa” - Partners for Rabies Prevention Informal Group (PRP)
5
Rabies
0
Disease Overview
=
=
None Reported
Data Not Available
or Non-Endemic
DISEASE BURDEN IN GAVI-ELIGIBLE COUNTRIES – MORBIDITY5
Country
Afghanistan
Angola
Armenia
Azerbaijan
Bangladesh
Benin
Bhutan
Bolivia
Burkina Faso
Burundi
Cambodia
Cameroon
Central African Republic
Chad
Comoros
Congo, Dem. Rep.
Congo, Rep.
Côte d'Ivoire
Cuba
Djibouti
Eritrea
Ethiopia
Gambia, The
Georgia
Ghana
Guinea
Guinea-Bissau
Guyana
Haiti
Honduras
India
Indonesia
Kenya
Kiribati
Korea, DPR
Kyrgyzstan
WHO
Region
EMRO
AFRO
EURO
EURO
SEARO
AFRO
SEARO
AMRO
AFRO
AFRO
WPRO
AFRO
AFRO
AFRO
AFRO
AFRO
AFRO
AFRO
AMRO
EMRO
AFRO
AFRO
AFRO
EURO
AFRO
AFRO
AFRO
AMRO
AMRO
AMRO
SEARO
SEARO
AFRO
WPRO
SEARO
EMRO
Morbidity
(Annual Cases)
Morbidity Rate
(Cases/100,000)
Country
Lao People's Dem. Rep.
Lesotho
Liberia
Madagascar
Malawi
Mali
Mauritania
Moldova, Rep. of
Mongolia
Mozambique
Myanmar
Nepal
Nicaragua
Niger
Nigeria
Pakistan
Papua New Guinea
Rwanda
São Tomé and Principe
Senegal
Sierra Leone
Solomon Islands
Somalia
Sri Lanka
Sudan
Tajikistan
Tanzania, United Rep. of
Timor-Leste
Togo
Uganda
Ukraine
Uzbekistan
4
Viet Nam
Yemen
6 Zambia
Zimbabwe
WHO
Region
WPRO
AFRO
AFRO
AFRO
AFRO
AFRO
AFRO
EURO
WPRO
AFRO
SEARO
SEARO
AMRO
AFRO
AFRO
EMRO
WPRO
AFRO
AFRO
AFRO
AFRO
WPRO
EMRO
SEARO
EMRO
EURO
AFRO
SEARO
AFRO
AFRO
EURO
EURO
WPRO
EMRO
AFRO
AFRO
Morbidity
(Annual Cases)
Morbidity Rate
(Cases/100,000)
Rabies
0
Disease Overview
=
=
None Reported
Data Not Available
or Non-Endemic
DISEASE BURDEN IN GAVI-ELIGIBLE COUNTRIES – MORTALITY6,7
WHO
Mortality
Region
(Annual Deaths)
India
SEARO
23,500
Pakistan
EMRO
2,490
Bangladesh
SEARO
1,475
Myanmar
SEARO
381
Viet Nam
WPRO
426
Sri Lanka
SEARO
85
Bhutan
SEARO
2
Ghana
AFRO
59
Georgia
EURO
10
Mozambique
AFRO
43
Lesotho
AFRO
4
Afghanistan
EMRO
35
Guyana
AMRO
1
Nepal
SEARO
35
Eritrea
AFRO
5
Uganda
AFRO
30
Mongolia
WPRO
2
Malawi
AFRO
8
Sudan
EMRO
20
Bolivia
AMRO
5
Haiti
AMRO
5
Angola
AFRO
7
Ethiopia
AFRO
33
Côte d'Ivoire
AFRO
8
Zimbabwe
AFRO
5
Senegal
AFRO
4
Indonesia
SEARO
71
Cambodia
WPRO
4
Central African Republic
AFRO
1
Madagascar
AFRO
4
Honduras
AMRO
1
Cuba
AMRO
1
Ukraine
EURO
2
Armenia
EURO
Azerbaijan GAVI Vaccine Investment
EURO Strategy
Vaccine LandscapeAFRO
Analysis_Cholera_Apr08
Benin
Country
Mortality Rate
(Deaths/1,000,000)
21
16
10
8
5
4
3
3
2
2
2
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
Country
Burkina Faso
Burundi
Cameroon
Chad
Comoros
Congo, Dem. Rep.
Congo, Rep.
Djibouti
Gambia, The
Guinea
Guinea-Bissau
Kenya
Kiribati
Korea, DPR
Kyrgyzstan
Lao People's Dem. Rep.
Liberia
Mali
Mauritania
Moldova, Rep. of
Nicaragua
Niger
Nigeria
Papua New Guinea
Rwanda
São Tomé and Principe
Sierra Leone
Solomon Islands
Somalia
Tajikistan
Tanzania, United Rep. of
Timor-Leste
4 Togo
Uzbekistan
7 Yemen
Zambia
WHO
Region
AFRO
AFRO
AFRO
AFRO
AFRO
AFRO
AFRO
EMRO
AFRO
AFRO
AFRO
AFRO
WPRO
SEARO
EURO
WPRO
AFRO
AFRO
AFRO
EURO
AMRO
AFRO
AFRO
WPRO
AFRO
AFRO
AFRO
WPRO
EMRO
EURO
AFRO
SEARO
AFRO
EURO
EMRO
AFRO
Mortality
(Annual Deaths)
Mortality Rate
(Deaths/1000000)
Rabies
Disease Overview
NON-VACCINE PREVENTION & TREATMENT INTERVENTIONS8
•
Non-Vaccine Preventions
–
•
Control and vaccination of domestic dogs and wild carnivores
Treatment Interventions
–
Post-exposure prophylaxis rabies vaccination and passive immunoglobulin
administration around the wound (to neutralize the virus before it enters the CNS)
–
After symptoms ensue there is no recognized effective treatment
8
Rabies
Disease Overview
INEQUITIES8
•
Inequity of Poor
–
•
Poor access to post-exposure prophylaxis and increased inability to control and vaccinate
dogs exists in low socioeconomic areas
Gender Inequities
Gender Based Criteria
Applies
Rationale
Do men or women suffer from
the disease differently?
-
NA
Is disease prevalence greater
in men or women?
√
Does the disease adversely affect
women during pregnancy?
-
• 40% of cases found in children 5 to 14 years, with the
highest incidence rates in males living in rural areas
NA
9
Rabies
Rabies
CONTENTS
• Disease Overview
• Vaccine Landscape
• Vaccination Policy & Strategies
• Vaccine Need & Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources
10
Rabies
Vaccine Landscape
LICENSED VACCINES* (I)
Supplier (1° Partner)
Vaccine
Novartis (previously Chiron-Behring)9,10
Rabivac
Strain / Antigen
Adjuvant / Platform
Inactivated; human
diploid cell
Sanofi-Pasteur9,11,12
Verorab, TRC Verorab,
Rabies/Rage, Rabies
BP, Rabies vero, SMBV
RabAvert (US),
Rabipur (EU)
Imovax
Flury LEP strain
PM-1503-3M strain
Inactivated; primary
Chick Embryo Cell
Inactivated; human
diploid cell
Inactivated; purified
Vero cell
Administration Route
IM, ID
Formulation
Lyophilized
Presentation
1ml vial
1 ml vial
Zydus Cadila
(previously Berna)13
1 ml vial
Inactivated; purified
Duck Embryo
0.5ml vial
1ml vial
Dosing Schedule
IM: 4 doses (2,1,1); 3 visits (0, 7, 21d)
ID: 8 doses (2,2,2,2); 4 visits (0, 3, 7, 28d)
Target Population
for Licensure
Post-exposure prophylaxis &
high risk children, adolescents & adults for pre-exposure prophylaxis
Safety
No major safety concerns
Efficacy
Highly efficacious when all doses administered
Expected Duration of
Protection
Long
Licensure Date
(Location)
1978
(EU)
1984
(US, EU, ROW)
1984
(US, EU, ROW)
1985
(EU, ROW)
Prior to 2008
(Europe, ROW)
Estimated WHO
Prequalification Date
WHO PQ prior to
2008
(Discontinued)
2002
WHO PQ prior to 2008
WHO PQ prior to 2008
1Q09
*PEP dosing only
11
Rabies
Vaccine Landscape
LICENSED VACCINES* (II)
Vaccine China
Biol14,15
Supplier (1° Partner)
SII14,15
Bharat Biotech14,15
BioPort
Vaccine
Rabivax
INDIRAB/ Rabirix
BioRab
Strain / Antigen
Pitman-Moore strain
Pitman-Moore strain
Adjuvant / Platform
Inactivated; human
diploid cells
Inactivated; purified
Vero Cell
Inactivated; rhesus cell
Inactivated; primary
Hamster Kidney Cell
Administration Route
IM
IM
IM
IM
Formulation
Liquid
Lyophilized
Lyophilized
Presentation
1 ml vial
0.5 ml vial
Dosing Schedule*
Target Population
for Licensure
IM: 5 doses (1,1,1,1,1); 5 visits (0,3,7,14,28d)
Multiple Suppliers14,15
Semple &
Fuenzalida strain
IM: 5 doses (1,1,1,1,1);
5 visits (0,3,7,14,28d)
Inactivated, from animal
brain
≤17 doses PEP
Post-exposure prophylaxis & high risk children, adolescents & adults for pre-exposure prophylaxis
Safety
No major safety concerns
SAEs
(encephalitis & polyneuritis)
Efficacy
Highly efficacious when all doses administered
Not as efficacious as cellbased vaccines
Expected Duration of
Protection
Licensure Date
(Location)
Estimated WHO
Prequalification Date
Prior to 2008
(India)
2006
(India)
No longer producing
May be motivated to seek WHO PQ
*PEP dosing only
12
1980
(China, Russia)
Prior to 2008
Assume will
not seek WHO PQ
Not recommended
by WHO
Rabies
First NRA Licensure
Vaccine Landscape
WHO Pre-Qual Approval
ESTIMATED VACCINE AVAILABILITY
RabAvert/Rabipur (Novartis)
Rabivac (Novartis/Chiron-Behring)
Imovax Rabies (Sanofi-Pasteur)
Verorab (Sanofi-Pasteur)
PDEV* (Zyddus Cadila)
Emerging Supplier (Bharat, SII)
(if motivated)
BioRab (BioPort)
Rabies Vaccine (Vaccine China Biol)
Prior to
2009
2009
2010
13
2011
2012
2013
RABIES
Vaccine Landscape Analysis
COST EFFECTIVENESS LITERATURE SUMMARY
•
Post-exposure rabies prophylaxis is estimated to prevent 330,304 (90% CI: 141,844
- 563,515) deaths in Asia and Africa. Rabies is responsible for an estimated 1.74
million (90% CI: 0.25M – 4.57M) DALYs. Global expenditure for rabies prevention
is over $1 billion.16
•
A 1996 study demonstrated that pre-exposure rabies prophylaxis for the
international traveler was worth $275,000 per case averted.17
•
Cost comparison of rabies pre-exposure vaccination to post-exposure vaccination in
Thai children showed that pre-exposure vaccination was cost-effective when the
dog bite incidence is 2% to 30% of the population.18
14
Rabies
Rabies
CONTENTS
• Disease Overview
• Vaccine Landscape
• Vaccination Policy & Strategies
• Vaccine Need & Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources
15
Rabies
Vaccination Policy & Strategies
CURRENT POLICY
Policy Type
Source
Category
Vaccine
considerations
• Human RIG (HRIG) is preferred but purified equine RIG or F(ab’)2 products should be used where
HRIG is not available or affordable.
• It is imperative that production and use of nerve tissue-based vaccines (NTVs) be discontinued as
soon as possible and replaced by cell-culture vaccines (CCVs).
Target population
• Pre-exposure vaccination using any of the modern CCVs is recommended for anyone at increased
risk of exposure to rabies virus. Children living in rabies-enzootic regions of the developing world
are at greatest risk.
• Post-exposure prophylaxis is recommended for all category II (minor) and III (severe) contacts with
potentially infected animals.
Usage strategies
• Since 1991, WHO has recommended the intradermal (ID) route of administration for rabies pre- and
post-exposure prophylaxis.
• Following exposure to a suspected rabid animal, prevention of human rabies consists of prompt
wound cleansing and administration of a modern CCV and, in cases of category III exposure or
category II exposure in immunodeficient individuals, of rabies immunoglobulin (RIG).
Programmatic
recommendations
• Measures to increase the supply and accessibility of high-quality CCVs and RIG among poorer
segments of affected populations are strongly encouraged.
• WHO encourages carefully designed studies on the feasibility and impact of incorporating CCVs in
routine childhood immunization programs.
WHO Position Paper
• Weekly Epi. Record, No.
49/50, 2007, 82: 425-436
SAGE
Recommendation
• Weekly Epi. Record, No. 1,
2008, 83: 1-16
Vaccine
considerations
Other
• WHO State of the art of new
vaccines: R&D, p. 89, 2006.
Policy Statement
Usage strategies
• SAGE noted that studies have demonstrated the feasibility, safety, immunogenicity and costsavings of ID administration of CCVs.
• The ID route schedule reduces the number of vaccine vials and thereby the cost of PEP by up to
80% (US$5-10 for vaccine alone).
16
Rabies
Vaccination Policy & Strategies
VISP DECISION FRAMEWORK
GAVI VIS Rabies
Decision Framework
Offer Vaccine Financing
to GAVI-Eligible Countries
Support Strategies for
Financial Planning Purposes
PEP Only
Pilot Regional Bite Center
& District Hospital Studies to
Demonstrate Impact
of GAVI Support
Provide Alternative
Investment Support
Pilot Rabies
Education Programs to
Demonstrate Reduced
Disease Burden Impact
Fund RIG Capacity
Building in GAVI Countries
To Eliminate Shortages and
Reduce Treatment Costs
Don’t Support
in 2009 - 2013
17
• Develop & implement pilot programs in
2-3 countries
• Monitor & evaluate impact and develop
recommendations
• Develop educational programs aligned
with national rabies prevention control
strategies
• Implement pilot programs in 2-3 countries
• Monitor & evaluate impact and develop
recommendations
• Accelerate tech transfer of RIG to
emerging suppliers
• Motivate supplier capacity
development
Rabies
Rabies
CONTENTS
• Disease Overview
• Vaccine Landscape
• Vaccination Policy & Strategies
• Vaccine Need & Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources
18
Rabies
Vaccine Need & Adoption Forecast
GAVI-ELIGIBLE COUNTRY VACCINE NEED
Vaccine Need: 49
VISP Scope: 49
• The vast majority of deaths due to rabies occur in Asia and Africa (WHO position paper,
Dec07); the current countries in scope represent countries with high rabies incidence or
countries in need of rabies education and vaccination with safe rabies vaccines (F. Meslin,
WHO & D. Briggs, Alliance for Rabies Control)
GAVI-Eligible Country Vaccine Need
Category
(# out of 72)
AFRO
(23 of 36)
Least Poor
(9 of 12)
Cameroon
Intermediate
(13 of 16)
Ghana
Kenya
Nigeria
Zimbabwe
Poorest
(20 of 31)
Benin
Burkina Faso
Chad
Ethiopia
Madagascar
Malawi
Mali
Mozambique
Rwanda
Senegal
Fragile
(7 of 13)
Angola
CAR
Congo DR
Côte d'Ivoire
AMRO
(5 of 6)
EMRO
(3 of 6)
Bolivia
Honduras
Cuba
Nicaragua
Pakistan
Tanzania
Togo
Uganda
Zambia
Haiti
19
Afghanistan
Sudan
EURO
(7 of 8)
SEARO
(8 of 9)
WPRO
(3 of 7)
Armenia
Azerbaijan
Georgia
Ukraine
Indonesia
Sri Lanka
Kyrgyzstan
Tajikistan
Uzbekistan
India
Korea DPR
Viet Nam
Bangladesh
Bhutan
Myanmar
Nepal
Cambodia
Lao
Rabies
Vaccine Need & Adoption Forecast
INTEGRATED ADOPTION FORECAST
Vaccine Need: 49
VISP Scope: 49
Rabies
# of Countries Adopting Vaccine
25
20
Bolivia
Burkina Faso
Cameroon
Ethiopia
India
Tanzania
Togo
Sri Lanka
Viet Nam
15
10
Armenia
Benin
CAR
Lao
Mali
Nepal
Pakistan
Rwanda
Tajikistan
Uzbekistan
Bangladesh
Bolivia
Djibouti
Georgia
Haiti
Honduras
Korea
Nicaragua
Uganda
Cambodia
Cameroon
Chad
Cote d’Ivoire
Kenya
Malawi
Senegal
Sudan
Zimbabwe
Angola
Indonesia
Mozambique
Zambia
Azerbaijan
Kyrgyzstan
Ukraine
5
Madagascar
Nigeria
DR Congo
Ghana
Afghanistan
0
2009
2010
2011
2012
2013
2014
20
2015
2016
2017
2018
2019
2020
Rabies
Vaccine Need & Adoption Forecast
RABIES DEMAND METHODOLOGY
Total
Country
Population
Rural
Population
AFRO: 75%
AMRO: 50%
EMRO: 50%
EURO: 50%
SEARO: 100%
WPRO: 100%
%
%
%
%
Rural
at
Risk
Rural
Urban
Urban
at
Risk
At Risk
Rural
Population
75%
30% ID
Rural Bites
Presenting
At Risk
Urban
Population
(Based on UN data)
Rural
Suspect
Bites
%
Rural
Bites
Presen
-ting
Rural
Bites Tx
with ID
Urban
Population
Rural
Suspect
Bite
Rate
Urban
Suspect
Bites
Urban
Suspect
Bite
Rate
AFRO: 1000/M
AMRO: 500/M
EMRO: 500/M
EURO: 500/M
SEARO: 1000/M
WPRO: 1000/M
AFRO: 1000/M
AMRO: 500/M
EMRO: 500/M
EURO: 500/M
SEARO: 1200/M
WPRO: 1200/M
90%
Urban
Bites
Presenting
AFRO: 100%
AMRO: 50%
EMRO: 50%
EURO: 50%
SEARO: 100%
WPRO: 100%
%
Urban
Bites
Presen
-ting
90% ID
Urban
Bites Tx
with ID
10% IM
70% IM
Rural
Bites Tx
with IM
Rural
Bites
Requiring
RIG
66%
%
Rural
Bites
Req.
RIG
21
%
Urban
Bites
Req.
RIG
66%
Urban
Bites
Requiring
RIG
Urban
Bites Tx
with IM
Rabies
Vaccine Need & Adoption Forecast
CURRENT COUNTRY SUPPORT AS PERCENT OF TOTAL NEED
Country
Afghanistan
Angola
Armenia
Azerbaijan
Bangladesh
Benin
Bhutan
Bolivia
Burkina Faso
Burundi
Cambodia
Cameroon
CAR
Chad
Comoros
Congo, DR
Congo, Rep.
Côte d'Ivoire
Cuba
Djibouti
Eritrea
Ethiopia
Gambia
Georgia
Ghana
Guinea
Guinea-Bissau
Guyana
Haiti
Honduras
India
Indonesia
Kenya
Kiribati
Korea, DPR
Kyrgyzstan
Current Estimated
Rabies Vaccine Use
20%
10%
10%
10%
35%
20%
20%
30%
30%
40%
30%
10%
10%
10%
20%
70%
10%
70%
30%
20%
50%
50%
30%
30%
10%
Country
Lao PDR
Lesotho
Liberia
Madagascar
Malawi
Mali
Mauritania
Moldova, Rep. of
Mongolia
Mozambique
Myanmar
Nepal
Nicaragua
Niger
Nigeria
Pakistan
Papua New Guinea
Rwanda
São Tomé & Principe
Senegal
Sierra Leone
Solomon Islands
Somalia
Sri Lanka
Sudan
Tajikistan
Tanzania
Timor-Leste
Togo
Uganda
Ukraine
Uzbekistan
Viet Nam
Yemen
Zambia
Zimbabwe
Current Estimated
Rabies Vaccine Use
30%
• Rabies experts provided estimate of
current country-by-county vaccine
usage as percent of total need*
40%
10%
10%
10%
30%
60%
40%
• Approximately 35% of total GAVIeligible country vaccine requirements
are currently being supported by
countries themselves
20%
30%
20%
20%
60%
10%
10%
30%
10%
30%
30%
10%
30%
10%
10%
22
*
F. Meslin, WHO & D. Briggs, Alliance for Rabies Control
Rabies
Vaccine Need & Adoption Forecast
GAVI VACCINE FINANCING POLICY
•
As a matter of policy, GAVI does not replace country funds already allocated to
rabies vaccines
•
However, most countries are under resourcing rabies vaccination due to:
–
–
High cost of vaccine and rabies immunoglobulin
Vaccine and immunoglobulin supply shortages
•
Therefore, GAVI would only plan to financially support the difference between actual
vaccine need and percent of need currently covered by country
•
This incremental need assessment will be complicated given a country’s level of
funding in any given year is influenced by many factors and may differ year on year
•
This analysis is focused on GAVI-eligible countries’ total need
23
Rabies
Vaccine Need & Adoption Forecast
VACCINE DEMAND GIVEN INTEGRATED FORECAST
Vaccine Demand including Wastage
60
Doses (M)
50
40
30
20
10
0
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025
Routine Vaccination
Catch-up Campaign
Periodic Campaign
Boost Vaccination
Buffer Stock
Stock Pile
Vaccine Demand including Wastage
Routine Vaccination
Catch-up Campaign
Periodic Campaign
Boost Vaccination
Buffer Stock
Stock Pile
Total
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
0
0
0
0
0
0
0
24
0
0
0
0
0
24
26
0
0
0
0
0
26
27
0
0
0
0
0
27
31
0
0
0
0
0
31
34
0
0
0
0
0
34
39
0
0
0
0
0
39
41
0
0
0
0
0
41
42
0
0
0
0
0
42
44
0
0
0
0
0
44
45
0
0
0
0
0
45
45
0
0
0
0
0
45
24
Rabies
Rabies
CONTENTS
• Disease Overview
• Vaccine Landscape
• Vaccination Policy & Strategies
• Vaccine Need & Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources
25
Rabies
Vaccine Cost Analysis
ANALYSIS INPUT SUMMARY – GENERAL
VARIABLE
Country Vaccine Need
(Number of GAVI countries)
Earliest WHO PQ Date
Equipment Needs
($/dose)
Wastage Rate
INPUT
Countries with high endemic areas of canine
rabies - defined by WHO Rabies expert
49
Available
Auto-Disable Syringe

Reconst. Syringe

Safety Box

RATIONALE/SOURCE
4 products already WHO prequalified
Lyophilized formulation
Lower than WHO guidelines because 20%
waste already accounted for in the ID doses
5%
26
Rabies
Vaccine Cost Analysis
ANALYSIS INPUT SUMMARY – STRATEGY-SPECIFIC
VACCINATION
STRATEGY
VARIABLE
RATIONALE/SOURCE
PEP
ID
8
8 (2,2,2,2) doses ID (0,3,7,28d)
IM
4
4 (2,1,1) doses IM (0,7,21d)
Vaccine
90/30
Urban/Rural bites treated with ID dosing regimen
F. Meslin (WHO) and D. Briggs (Alliance for Rabies Control)
RIG
66%
Percent Suspect Bites treated with RIG
F. Meslin (WHO) and D. Briggs (Alliance for Rabies Control)
Doses per Treatment
Proxy Coverage Rate
Time to Peak Coverage
Deaths Averted (per 1000 vaccinated)
1
41.25
Years to Deaths Averted
0
% Deaths Averted < 5yo
0%
Most countries already using rabies vaccine
Cleaveland et al, Bull of the WHO 2002;80(4)
Assumes only bites suspected of rabies are vaccinated
Immunoprotection after 2nd dose
Most bites occur in 5-15yo
Cases Averted (per 1000 vaccinated)
-
Post-bite treatment
Years to Cases Averted
-
Post-bite treatment
% Cases Averted < 5yo
-
Post-bite treatment\
Average Cost per Case
$207
Assumes 4 IM doses of vaccine at $9.20/dose plus $170 for Equine RIG
(UNICEF price for vaccine; WHO price for RIG)
27
Rabies
Rabies
CONTENTS
•
Disease Overview
•
Vaccine Landscape
•
Vaccination Policy & Strategies
•
Vaccine Need & Adoption Forecast
•
Vaccine Cost Analysis
–
Post-Exposure Prophylaxis (PEP)
–
Additional Investment Alternatives
•
Implementation-Associated Cost Analysis
•
Analysis Summary
•
Key Resources
28
Rabies
PEP
KEY OUTPUT SUMMARY
Integrated Demand Forecast
2009-2020
Cost Component
Cost
GAVI Vaccine Cost ($M)
$2,882
Country Vaccine Co-Pay Cost ($M)
$63
Total Vaccine Cost ($M)
$2,945
Deaths
Averted
(x1000)
<5 Deaths
Averted
(x1000)
Cases
Averted
(x1000)
Cost
Savings
($M)
GAVI Cost ($)/
Death Averted
GAVI Cost ($)/
Case Averted
GAVI Cost ($)/
$ Saved
483
24
n/a
$100
$5,970
n/a
$28.84
29
Rabies
PEP
ANNUAL ANALYSIS RESULTS
Integrated Demand Forecast
2009-2020
Vaccine Impact
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
Total1 Cost - High ($M)
0
233
255
256
263
285
291
297
293
294
284
288
Low ($M)
0
219
240
241
246
265
272
278
274
276
267
271
Total2 Cost to GAVI - High ($M)
0
230
251
252
259
280
285
291
287
287
277
280
Low ($M)
0
216
236
237
241
260
266
271
268
269
260
263
Total3 Cost to Countries - High ($M)
0
4
4
4
5
5
6
6
7
7
7
8
Low ($M)
0
4
4
4
5
5
6
6
7
7
7
8
Vaccine Cost to GAVI - High ($M)
0
124
135
133
121
127
107
98
91
82
69
69
Low ($M)
0
110
120
118
103
108
88
79
72
63
51
52
Vaccine Cost to Countries - High ($M)
0
4
4
4
5
5
6
6
7
7
7
8
Low ($M)
0
4
4
4
5
5
6
6
7
7
7
8
Vaccination Equipment Cost ($M)
Shipping & Insurance Cost ($M)
0
0
81
25
88
28
91
28
105
33
116
36
136
42
147
46
149
47
157
49
159
50
161
50
Projected Deaths Averted (x1000)
0
28
31
31
37
40
47
51
52
54
55
56
Projected Deaths Averted of < 5yo (X1000)
0
1
2
2
2
2
2
3
3
3
3
3
Cases Averted (x1000)
Costs Savings from Cases Averted ($M)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Total Doses Demanded (M)
Doses Demand without Wastage (M)
Total Potential Vaccinations (M)
0
0
0
24
23
1
26
25
1
27
25
1
31
29
1
34
32
1
39
37
1
41
39
1
42
40
1
44
42
1
45
42
1
45
43
1
M = millions
1
Vaccine cost + Equipment cost + S&I cost
2
3
GAVI pays Equipment and S&I costs
Country pays equipment and S&I costs
when GAVI support ends
30
Rabies
Rabies
CONTENTS
•
Disease Overview
•
Vaccine Landscape
•
Vaccination Policy & Strategies
•
Vaccine Need & Adoption Forecast
•
Vaccine Cost Analysis
–
Post-Exposure Prophylaxis
–
Additional Investment Alternatives
•
Implementation-Associated Cost Analysis
•
Analysis Summary
•
Key Resources
31
Rabies
Additional Investment Opportunities
BACKGROUND OF UNDERSTANDING
•
Although rabies has the highest case fatality rate of any disease known to mankind,
preventing human rabies in reality is not a complicated issue as it is one of the
easiest diseases to prevent
•
There are three basic steps to preventing human rabies:
1. Increase educational awareness activities to reduce exposures, increase professional
expertise and improve diagnoses and surveillance
2. Administer prompt and appropriate post-exposure prophylaxis (PEP) when exposures do
occur
3. Conduct preventative immunization (PreP) to protect the relatively few numbers of the
populace that are living in high-risk, remote geographic locations with no access to PEP
•
It has been proven in many countries that if and when these three steps are
instituted the number of human rabies deaths quickly and dramatically decreases
32
Rabies
Additional Investment Opportunities
OPTION A*
•
Pilot PEP in Select Countries
To Demonstrate GAVI Impact
Experience over two decades has proven that reduced dose regimens for PEP are both
efficacious and cost-effective
– Updated Thai Red Cross (TRC) intradermal (ID) regimen or “2-2-2-0-2” is most cost effective PEP
regimen recommended by WHO
– TRC has increased access to vaccines in poor countries and has reduced the PEP cost per patient
from 40 to 80%
• Awareness as to the utilization and benefit of reduced dose regimens is lacking in most
poor countries where it could be of great value
• By piloting ID PEP in 4 select countries (2 in Asia & 2 in Africa), GAVI can demonstrate the
health impact and cost reduction potential of this approach
– With pilot PEP data, GAVI can then decide whether to extend support to all relevant GAVI-eligible
countries
• Estimated Total 5-Year Budget: $6M ($300K/year/country)
– Vaccine + RIG: $2 million
– Service Delivery: $400,000 annually
– Social Mobilization/Education: $400,000 annually
* Potentially eligible for GAVI Operations
Research funding, if available
33
Rabies
Additional Investment Opportunities
OPTION B
Support Rabies Education Programs
to Reduce Disease Burden
• Rabies is one of few diseases that can be dramatically reduced through increased education
• Activities to improve educational awareness is inadequate in most poor developing countries
• Educational initiatives specifically targeted for national governments, professional public
health staff and the general public are clearly the least expensive of investments that would
result in the highest return in lives saved within the shortest amount of time.
• Education for professionals in poor developing countries would include:
–
–
–
–
Use of intradermal (ID) administration for PEP
Dissemination of latest WHO recommendations
Increased awareness of source of rabies
Training on modern diagnostic tools currently available for rabies confirmation
• Estimated 5-Year Budget per Country: $1.2M
– Education materials development: $200,000
– Education and training: $200,000 annually
34
Rabies
Additional Investment Opportunities
OPTION C
Fund RIG Capacity Building
To Eliminate Shortages
and Reduce costs
•
Rabies immunoglobulin (RIG) is the most expensive component of rabies
treatment needed for approximately 66% of all suspect bites
•
Strengthening the production of equine RIG and supporting the development of
alternative technologies to replace equine RIG is critical for ensuring adequate
supplies and lowering the current price
•
Estimated 5-Year Budget: $4M
– Equine RIG: $3M
– Monoclonal antibody preclinical and clinical testing: $1M
35
Rabies
Rabies
CONTENTS
•
Disease Overview
•
Vaccine Landscape
•
Vaccination Policy & Strategies
•
Vaccine Need & Adoption Forecast
•
Vaccine Cost Analysis
•
Implementation-Associated Cost Analysis
•
Analysis Summary
•
Key Resources
36
Rabies
Implementation Associated Cost Analysis
TYPICAL IMPLEMENTATION CHALLENGES
Challenge
Category
Disease Burden
Training of
Personnel
Typical Implementation Challenges
• Establishing rabies as a reportable disease
• Training of personnel to administer ID injections
− Overcoming the anxiety of learning a new method
• Increase educational awareness about best practices to prevent rabies
Communication,
Education, Social
Mobilization
Supply &
Capacity
Waste
Management
− Education on preventing bites has the greatest impact on disease
• Continued advocacy required to eliminate nerve tissue based vaccines to eliminate
severe side effects associated with these older vaccines
• Building cold chain capacity
− Cold chain capacity can be significantly reduced with ID delivery
• Wastage associated with multi-dose vials
37
Rabies
Implementation Associated Cost Analysis
UNIQUE IMPLEMENTATION CHALLENGES
Challenge Category
Unique Implementation Challenges
• Non-EPI vaccination – animal (mostly dog) bite driven vaccination strategy
• Potential need to integrate vaccination strategy with other rabies control programs
• Vaccination strategy needs to include patient access via rabies ‘dog bite treatment
centers at central as well as district hospitals
Vaccination
Strategy
• Continued advocacy required to support promotion of:
− The use of economical and safe multisite ID post exposure prophylaxis
− Discontinuation of production and use of nerve tissue based vaccines
• Major vaccine shortage for safe cell culture based vaccines
• Severe bite cases require vaccination and rabies immunoglobulin (RIG)
– Major RIG shortage
Vaccination
Access Via Rabies
Bite Centers
• Significant facility and staff training upgrades required (e.g. wound wash stations)
• Need to promote and train medics overcome resistance to ID vs. IM vaccine
administration
38
Rabies
Implementation Associated Cost Analysis
POTENTIAL IMPLEMENTATION SYNERGIES
Traditional
HepB
Hib
YF
Pneumo
Rota
MenA
Cholera
HPV
JE
Rubella Typhoid
Rabies
Traditional = Routine EPI vaccines includes Baccillus Calmette-Guérin (BCG), Diphtheria-tetanus-pertussis (DTP) ,
measles containing vaccines (MCV), oral polio (OPV), Tetanus toxoid (TT)
Vaccine-Specific Synergies
• No vaccine-specific synergies were identified
Other Synergies
• No other synergies were identified
39
Rabies
Implementation Associated Cost Analysis
RELATIVE COST ASSESSMENT
Incremental Vaccine Implementation Cost Relative to Traditional EPI Costs
Implementation Cost
Categories
Cold Chain
Post-Exposure Prophylaxis
• Potentially significant impact where supply prior to GAVI support was insufficient to
meet demand, especially in newly established regional rabies dog bite treatment
centers
− Need for vaccine & RIG vial management and usage, particularly in small
decentralized dog bite treatment centers
Waste Management
Transport
Training of Personnel
Communication, Education,
Social Mobilization
Monitoring & Evaluation,
Surveillance
Service Delivery
• Less than typical given animal bite-driven demand
• Less than typical given regional rabies bite centers usually serving large populations
where animal bites are more common
• More than typical given IM to ID route of administration transition in rabies dog bite
treatment centers and potential increased use of RIG
• More than typical given significant impact on disease burden with educational
awareness on bite prevention
• Typical, given the need to strengthen systems for monitoring and evaluation given
current under reporting of rabies cases
• Less than typical given regional rabies dog bite treatment centers
40
Rabies
Implementation Associated Cost Analysis
QUANTITATIVE COST ASSESSMENT – PEP
Metric
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
Total
PEP Imp Costs ($M)
0
4
5
5
6
6
7
8
8
8
9
9
75
RIG Imp Costs ($M)
0
0.9
1.0
1.0
1.1
1.3
1.5
1.6
1.6
1.7
1.7
1.8
15
5.4
5.7
5.9
6.8
7.5
8.8
9.5
9.7
10
10
10
90
Total ImplementationAssociated Costs ($M)
0
WHO GIVS Study: Wolfson LJ, Gasse F, et.al., WHO, Estimating the costs of achieving the WHO-UNICEF Global Immunization Vision and Strategy, 2006-2015, BLT (2008) 86(1)
GIVS Assumptions
Proxy GIVS Vaccination Strategy
• Weighted average Rubella cost per dose leveraged for ID cost
• Weighted average Rota cost per dose leveraged for ID cost
Adjustments to Proxy
• Proxy costs applied to cold chain capacity and transportation cost
components only
• Applied average 10 min health visit cost estimate (across GAVI
countries) for all doses outside of traditional EPI schedule
41
Rabies
Rabies
CONTENTS
• Disease Overview
• Vaccine Landscape
• Vaccination Policy & Strategies
• Vaccine Need & Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources
42
Rabies
Analysis Summary
KEY METRIC SUMMARY
Cost Component
Post-Exposure Prophylaxis
GAVI Vaccine Cost ($M)
$2,882
Country Vaccine Co-Pay Cost ($M)
$63
Total Vaccine Cost ($M)
$2,945
Vaccination
Strategy
Deaths
Averted
(x1000)
<5 Deaths
Averted
(x1000)
Cases
Averted
(x1000)
Cost
Savings
($M)
GAVI Cost/
Death
Averted
GAVI Cost/
Case
Averted
GAVI Cost/
$ Saved
Country
Imp Costs
($M)
PostExposure
Prophylaxis
483
24
n/a
$100
$5,970
n/a
$28.84
90
43
Rabies
Rabies
CONTENTS
• Disease Overview
• Vaccine Landscape
• Vaccination Policy & Strategies
• Vaccine Need & Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources
44
Rabies
Key Resources
EXPERT CONSULTATION
• Vaccine Experts
– Francois Meslin, Head of Zoonotic Disease, WHO
– Deborah Briggs, Board of Directors, Alliance for Rabies Control
– Sarah Cleaveland, Board of Directors, Alliance for Rabies Control
– Charles Rupprecht, Chief of the CDC Rabies Program, CDC
– Herve Bourhy, Director of the WHO Collaborating Center for Rabies, Institute Pasteur
• Suppliers
– Michael Attlan, Marketing Director, Sanofi
– Shawn Gilchrist, Sanofi
– Ferdinando Borgese, Global Brand Manager, Novartis Vaccine
– John-Kenneth Billingsley, Executive Director, Novartis
– Olga Popova, Director Government Affairs, Crucell
45
RABIES
Appendix
REFERENCES (I)
1. Plotkin et al, Vaccines, 5th Edition, Chap. 27, 2008.
2. Weekly Epi Record, No. 49/50, 2007, 82, 425-436, 7Dec07.
3. WHO, Disease Outbreak News, Rabies,
www.who.int/csr/don/archive/disease/Rabies_disease/en/, Mar 2008.
4. WHO, Essential rabies maps, www.who.int/rabies/rabies_maps/en/index.html.
5. WHO, RabNet, “Human rabies, number of people bitten by suspected dogs per 100,000
population,” www.who.int/globalatlas/default.asp, Mar08 (data is incomplete or not
reported).
6. WHO, RabNet, Human rabies deaths, www.who.int/globalatlas/default.asp, Mar08
[Mortality = Average of reported deaths between 2000-2007].
7. UN Population Division, World Population Prospects: The 2006 revision population
database, esa.un.org/unpp/index.asp?panel=2
[Mortality Rate = Mortality/(Population) x 1,000,000].
8. Plotkin et al, Vaccines, 5th Edition, Chap. 27, 2008.
46
RABIES
Appendix
REFERENCES (II)
9. WHO Prequalified Vaccines,
www.who.int/immunization_standards/vaccine_quality/pq_suppliers/en/index.html.
10. RabAvert Package Insert, www.novartis-vaccines.com/products/Rabavert_PI_0404.pdf;
www.novartisvaccines.com/products/travel.shtml.
11. Imovax Product Insert,
www.vaccineshoppe.com/image.cfm?doc_id=5983&image_type=product_pdf.
12. Travel Med Infect Dis. 2007 Nov;5(6):327-48. Epub 2007 Sep 17;
www.ncbi.nlm.nih.gov/pubmed/17983973.
13. Berna Biotech recently transferred to Cadila Health Ltd, an Indian manufacturer;
Zyddus Cadila is currently seeking WHO prequalification according to Partners for
Rabies Prevention Informal Group; RIG = rabies immunoglobulin; TRC Verorab (Thai
Red Cross)
14. Plotkin et al, Vaccines, 5th Edition, Chap. 27, 2008.
15. Correspondence with WHO and Partners for Rabies Prevention Informal Group (PRP),
June-August 2008.
47
RABIES
Appendix
REFERENCES (III)
16. WHO, Weekly Epidemiology Record, No. 49/50, 2007, 82, 425-436, 7Dec07.
17. LeGuerrier P, et al, Pre-exposure rabies prophylaxis for the international traveler: a
decision analysis; Vaccine, 14(2):167-176, 1996.
18. Chulasugandha P, et al, Cost comparison of rabies pre-exposure vaccination with postexposure treatment in Thai children, Vaccine, 24(9): 1478-1482, 2006.
48