1. Building blocks to success in malaria elimination

2. Proven Successes in Global Health – case studies
Eradicating smallpox
Preventing HIV/STDs in Thailand
Trachoma in Morocco
Health in Mexico
Infant diarrhea deaths in Egypt
Onchocerciasis in Africa
Polio in the Americas
TB in China
Safe motherhood in Sri Lanka
Guinea worm control in Africa and Asia
Tobacco use in Poland
Measles in Southern Africa
Hib in Chile and Gambia
Iodine deficiency in China
Flouridation in Jamaica
Chagas in Southern Cone through vector control
Fertility in Bangladesh
Source: Levine, R., Millions Saved: Proven Successes in Global Health, Center for Global Health, What Works Working Group, 2005

3. Proven Successes in Global Health – common elements
Technical consensus about the appropriate biomedical or public health approach
Technological innovation with an effective delivery system, at a sustainable price
Predictable, adequate funding from both international and local sources
Political leadership and champions
Good management on the ground
Effective use of information
This slide shows common themes that were identified in the analysis, Millions Saved by Ruth Levine of the Center for Global Development, which analyzed 17 successes in global health. From this analysis, six “Elements of Success” emerged – common features of most or all of the 17 case studies.
The MV TRM process was originated to develop the technical consensus described in the first bullet and stimulate technological innovations described in the second bullet. However, if we are successful as a community in developing an effective roadmap, the other four elements of success will also come.
The Malaria Vaccine TRM has the potential to cultivate these elements of success for malaria vaccines.
Source: Levine, R., Millions Saved: Proven Successes in Global Health, Center for Global Health, What Works Working Group,

4. Transformations: Control vs. Elimination/Eradication
Goal - Control
Goal – E/E
Prevent death – RTS,S
Case management
Risk groups such as malaria in pregnancy, severe malaria
Scale up existing interventions – LLINs, ACTs, IRS
Prevent transmission – TBVs, SERPAC, etc.
Simplify toolbox – single dose treatment, avoid and prevent resistance
Make tough decisions
Refocus R&D targets
MalERA

5. The inquiry agenda in support of malaria elimination
Complex systems – both biology and health systems
Fonts: Header: 28pt (black); sub-header 24 pt (blue); Lign up: Header or sub-header (if used) lined up with lower end of STI text
Font in bullet lists: 24, 21, 18 pt decreasing with each indent
Color codes:
Blue (sub-header): R 65; G 91; B 155
Blue (dark): R 51; G 51; B 153
Green (dark): R 0; G 115; B 71
Red: R 255; G 51; B 0
Red (dark): R 176; G 29; B 65
“Malaria systems” “Health systems”
25/04/2017 from Marcel Tanner

6. Summary of proposed key responses
PLoS Medicine 25 January 2011
Summary of proposed key responses
Control
Scalling for impact (SUFI)
Sustaining control (SC)
Prevention of reintroduction
Pre-elimination
Elimination
Single Encounter Radical Cure and Prophylaxis drug suitable for MDA
SERCaP / MDA
VIMT
Vaccine (s) that Interrupt Malaria Transmission
Diagnostics +
New Diagnostics (individual, community/MDA)
Surveillance as an intervention
Vector Control/TPP for outdoor populations
Surveillance as an Intervention
Modeling Intervention Mixes inc. CEA
Sustained Vectorial Capacity Reduction Tool
HSR
Predictive modeling allowing strategic and operational, including costing, assessment of combining different control and elimination strategies
Essential R&D backbone, enabling technologies and platforms
Continuous culture of P. vivax
Biology of liver stages
Genomic and proteomic platforms
Approaches and tools for measuring transmission
Framework and tool for effectiveness decay analysis and health system integration
Harmonization of data bases, model outputs, user interface
Training
Minimal Enabling Framework for Health Systems Readiness
25/04/2017

7. Synergy of connected system-level interventions
Decentralization,& local ownership
Household health surveillance
New communication tools
District Health Profiles
District Health Accounts
SWAp
Basket 1$
per capita
New planning & management skills
New mix of services; higher coverage, quality, & utilization
Community voice tool
25/04/2017
Source: MOHSW TEHIP Tanzania

8. Decentralisation 25/04/2017 National Government MoH
NGOs
MoH
Regional Health Authorities
District Health System
Self-help Groups / Community Based Organisations (formal and informal)
Communities / Families / Citizens
Traditional Health System
National Government
Regional / Province Government
Local / District Government
Private Sector
25/04/2017

9. From Efficacy to Effectiveness Health System Factors / Partnership
The systems context
From Efficacy to Effectiveness
Efficacy
80%
X Access
x 80%
Health System Factors / Partnership
X Targeting Accuracy
x 80%
X Provider Compliance
x 75%
X Consumer Adherence
X 75%
= Effectiveness
= 29%

10. System effectiveness of ALU in Rufiji Tanzania
1000 simple malaria fevers
Sought care
Individual behaviour
Health system behaviour
Sought care within 24 h
Individual & drug behaviour
Accessed ACT provider within 24 h
Correctly diagnosed or prescribed
ACT stocked in
110 cases successfully treated
Adhered to treatment
Treatment effective
413 lost
12 lost
2 lost
50 lost
64 lost
101 lost
248 lost
890 failures to treat effectively
25/04/2017 10

11. Real time mHealth monitoring of ACT supply chains..
We have good drugs for malaria!
But a continuing challenge of global, national and local responses to antimalarial drug procurement and supply chain system realities.
Current situation in 5,126 public health facilities in Tanzania on Oct 5th, 2012
Red if a stock out this week
Green if in stock this week
Surveillance in place
Modern Approaches
M-Health with incentives
but
Action is lacking
Training
Understanding
Management…
Source: SMS for Life Tanzania

12. Source: NMCP-Tanzania
Malaria Prevalence: 2012
ACT-Stockouts: 2012
Source: NMCP-Tanzania
25/04/2017

13. Research Priorities: Surveillance - Response Systems (SRS)
Dynamic mapping of „pockets“ of transmission and/or reintroduction
Capturing population dynamics
Analyses of M&E data and modeling to optimize SRS
Parasite – Man – Vectors
Sampling in space and time
Design and validate with use of (i) evidence from programs and (ii) modeling (intervention mixes) effective response packages tailored to different transmission settings and levels
Use of new technologies (m/e-health, diagnostics)
Validation, validation, validation…alongside with programs

16. IPTc now Seasonal Mass Chemoprophylaxis
Field implementation Guide published (English and French)
3 workshops (2012, 2013) have been organized by WHO in collaboration with the UCAD / LSHTM, and RBM/WARN that provided countries with support and to guide SMC planning and implementation.
9 countries have adopted and added it in their strategy
Large scale implementation yet to start due to funding constraints, small scale implementation ongoing in a few countries (Mali, Senegal, Niger, Nigeria)
Challenges in sourcing pre-qualified medicines
Based on implementation plans developed by the WARN eligible countries (9 countries), 19 million children can potentially benefit from SMC during the next three malaria seasons (up to 2016).

17. Global changes in malaria incidence rate, 2000-2010
World Health Organization
25 April, 2017
Global changes in malaria incidence rate,
This slide and the next one are animated – all you have to do is click once and it will run through from 2000 to 2010
Incidence per 1000 population
Unfortunately, the legend is a bit hard to read, so:
Darkest green: 0
Light green: 0-1
Yellow: 1-10
Orange: 10-50
Red: >50
2010
2000

18. Global changes in malaria death rate, 2000-2010
World Health Organization
25 April, 2017
Global changes in malaria death rate,
2010
2000

24. Extent of malaria transmission: 1945
Select Topics
Hypothetical phasing scenario
Extent of malaria transmission: 1945
Malaria transmission
No Malaria transmission
Source: Malaria Elimination: Geography, finance, and economics, presentation by Prof. Sir Richard Feachem, at ASTMH 7 Dec 2008.

25. Extent of malaria transmission: 2008
Select Topics
Hypothetical phasing scenario
Extent of malaria transmission: 2008
Malaria transmission
No Malaria transmission
Planning for elimination or eliminating
Source: Malaria Elimination: Geography, finance, and economics, presentation by Prof. Sir Richard Feachem, at ASTMH 7 Dec 2008.

26. Funding and investments
Global need: GMAP estimates Malaria implementation and R&D combined will require $5-7B per year through 2020
Millions US$
6,939
6,094
5,837
5,558
3,838
Implementation
R&D
2009
2010
2015
2020
2025
Source: Roll Back Malaria Global Malaria Action Plan (RBM GMAP) published September 2008

27. Globally, total malaria spend estimated to be ~$3b in 2010H
Funding and investments
Globally, total malaria spend estimated to be ~$3b in 2010
Millions US$
Does not include potential future commitments
Implementation: Global Fund
Implementation: World Bank
3,494
Implementation: PMI
3,296
Implementation: Other
3,102
R&D: BMGF
2,960
2,878
R&D: NIH
2,645
2,696
R&D: Other
2,215
1,604
1,496
1,117
888
370
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
Note: Implementation spend assumes all committed spend will be disbursed. Implementation includes World Bank, Global Fund, PMI and Other USAID, Other International Donors, Local Country Spend, and Private Household Spend. R&D spend includes BMGF, NIH and "Other R&D Spend" 1. BMGF implementation spend is assumed to be all captured in donation to Global Fund and is not listed out separately. Global Fund also includes Round Commitments, RCC Funding, and AMFm additional funding.2. Assumed that 2007 spend (sourced from GFinder report) will remain constant through Prior to 2007, estimates from 2007 Malaria Strategy work. Total of US$468m assumed to remain constant 2007 – Source: WHO Malaria Report 2008, Global Fund Pledges (website), GMAP report, USAID website ( PMI website, World Bank website, George Institute G-Finder Report for year 2007 and 2008

30. 2013 World Malaria Report
Impact from GFATM, PMI, national investments in malaria
Decrease in 45% mortality since 2000 – about 627K
Greatest impact in highest burden countries
50% access to LLINs
BUT:
Still have 200M +/- cases
Gains are fragile – documented resurgence
Resistance in Thai-Cambodia-Myanmar

31. WHO Malaria Situation Room – focus on meeting 2015 goals
Nigeria Democratic Republic of the Congo Tanzania Uganda Mozambique Côte d’Ivoire Ghana Burkina Faso Cameroon Niger

32. Malaria – the post 2015 agenda
Global transitions
World Bank – focus on extreme poverty
What comes after the MDGs – High Level UN Panel
Chronic Disease agenda –
Does health remain on the agenda?
Eradication framework
BMGF strategy – focus on transmission, Ho is based on strategic use of drugs at scale
MalERA research agenda

33. IVCC Progress To Date

34. New medicines for Malaria Eradication
Replacing three days ACT and 14 days primaquine with a simpler therapy
Overcoming concerns about resistance
Post treatment
Protection
Fast killing
Radical
cure
Transmission
blocking
SERCaP
single exposure
radical cure and prophylaxis
Alonso P et al.,(2011) A research agenda for malaria eradication: drugs PLoS Med. Jan 25;8

35. Global Portfolio of Antimalarial Medicines
Registration
Preclinical
Research
Translational
Development
Phase IIa
Phase I
Lead Optimisation
Phase IV
Phase IIb/III
1 Project
Novartis
Artesunate for injection
Guilin
Coartem®-D
Aminopyridines
UCT
3 Projects
GSK
KAE609
OZ439
(Monash/UNMC/
STI)
Pyramax
Shin Poong/ University of Iowa
ELQ-300
(USF/ OHSU-VAMC)
21A092
(DrexelMed/UW)
KAF156
DSM265
(UTSW/UW/
Monash)
Eurartesim®
Sigma-Tau
Whole cell leads
AstraZeneca
Tafenoquine
P218 DHFR
(Biotec/Monash/ LSHTM)
Tetraoxane
Liverpool STM/Liverpool Uni
Paediatric
Shin Poong/ University of iowa
Orthologue Leads
Sanofi
Heterocycles
Dundee
Included in MMV portfolio post registration
SP-AQ
ASAQ Winthrop
sanofi /DNDi
MMV390048
(UCT)
dUTPase inhibitors
Medivir
DOS
Broad Institute
Imidazolidinediones
WRAIR
RKA182
Liverpool STM
NPC-1161-B
University of Mississippi
SAR116242
Palumed
Mefloquine
Artesunate
Farmaguinhos/DNDi
SAR97276
Ferroquine
Fosmidomycin
Piperaquine
Jomaa Pharma GmbH
Methylene Blue AQ
Uni. Heidelberg
AQ13
Immtech
Artesunate i.r.
WHO/TDR
Artemisone
UHKST
Antimalarial
Actelion
DF02
Dilafor
CDRI 97-78
Ipca
N-tert butyl isoquine
Liverpool STM/GSK
ARCO
Naphthoquine/ Artemisinin
Arterolane/PQP
Ranbaxy
ArtiMist™
Proto Pharma
OSDD
Univ Sydney
DHODH
UTSW/UW/Monash
Oxaboroles
Anacor
SJ557733
St Jude/Rutgers
NDH2
Long Duration Leads
Merck Serono
HKMT
IC/ CNRS
Non MMV
Nauclea pobeguinii
DRC/Antwerp
Argemone mexicana
Mali/Geneva

36. MVI’s current portfolio
feasibility studies
translational projects
vaccine candidates
Antigen
Delivery
Preclinical
Phase 1/2a
Phase 2b
Phase 3
Antigen discovery
(Seattle BioMed)
pDNA
(Inovio/UPenn)
Translational research
RTS,S-AS01 (GSK)
Multivalent pDNA/ adenovirus (NMRC/Oxford U)
Multivalent ChAd63/MVA (Oxford U)
Antigen discovery
(NMRC)
Pfs25
(NIAID, Fraunhofer CMB)
PvDBPII
(ICGEB/MVDP)
RTS,S-AS01/
ChAd63/MVA-TRAP (Oxford U/GSK)
CSP RI conjugates (NYU/Merck)
Translational development
RTS,S-AS01 delayed fractional dose (GSK/WRAIR)
B cell targets
(Seattle BioMed, JHU, NIAID, WRAIR, NMRC)
Pfs25-EPA-Alhydrogel® (NIAID)
Antigen discovery
(NIAID)
Pfs25-VLP-Alhydrogel®
(Fraunhofer CMB)
EBA-Rh
(WEHI/Gennova)
MVI identifies potentially promising malaria vaccine candidates and approaches, then…
MVI systematically move candidates and approaches through the development process.
This is MVI’s portfolio of vaccine projects today. As the products move from the left to the right, they become closer to reality.
[For the world as whole, there are about 40 malaria vaccine projects in either the preclinical or clinical phase.]
Since 2003, MVI has moved more than three dozen projects through the pipeline, including 12 into human testing.
One of them has made it to the last stages of development before licensure: RTS,S.
Phase 3 trial is designed to confirm and safety and efficacy of a vaccine, to confirm the results of previous, but much smaller studies.
This is a major achievement and a testament to the power of the product development partnership model.
RTS,S, which is under development through a partnership between the MVI program and GSK Vaccines, is the only vaccine candidate to advance so far in the development pipeline.
PvDBP3-5
(WEHI)
AnAPN1
(JHU)
Pre-erythrocytic
Blood-stage
Transmission-blocking
P. falciparum vaccines:
P. vivax vaccines:

37. Estimated declines in malaria mortality rates from : 45% globally 49% in WHO African Region Estimated 3.3 million lives saved (69% in 10 countries with highest burden in 2000)

38. Estimated declines in malaria mortality rates among children <5 years of age from : 51% globally 54% in WHO African Region 90% of lives saved (3 million) among children <5 years of age

39. Estimated declines in malaria case incidence rates, : 29% globally 31% in WHO African Region

40. A range of players in Malaria
Funding and investments
A range of players in Malaria
Multilaterals
Foundations
Research and Academia
Clinton Foundation
Private sector
Donor Countries
NGOs
Malaria-Endemic Countries

41. IT ALWAYS SEEMS IMPOSSIBLE…
UNTIL IT IS DONE
Nelson Mandela