Malaria
Building blocks to success in malaria
elimination
1
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
2
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
Source: Levine, R., Millions Saved: Proven Successes in Global Health, Center for Global
Health, What Works Working Group, 2005 . www.cgdev.org/globalhealth
3
Transformations: Control vs.
Elimination/Eradication
Goal - Control
 Prevent death – RTS,S
 Case management
 Risk groups such as
malaria in pregnancy,
severe malaria
 Scale up existing
interventions – LLINs,
ACTs, IRS
Goal – E/E
 Prevent transmission –
TBVs, SERPAC, etc.
 Simplify toolbox – single
dose treatment, avoid
and prevent resistance
 Make tough decisions
 Refocus R&D targets
» MalERA
4
The inquiry agenda
in support of malaria elimination
Complex systems – both biology and health systems
“Malaria systems”
09/04/2020 from Marcel Tanner
“Health systems”
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5
PLoS Medicine 25 January 2011
Summary of proposed key responses
Control
Scalling for impact (SUFI)
Sustaining control (SC)
Pre-elimination
Elimination
Prevention of
reintroduction
SERCaP / MDA
VIMT
Diagnostics +
Surveillance as an intervention
Vector Control/TPP for outdoor populations
Modeling Intervention Mixes inc. CEA
HSR
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
09/04/2020
• Framework and
tool for effectiveness decay
analysis and health system integration
• Harmonization of data bases, model outputs,
user interface
• Training
Single Encounter Radical
Cure and Prophylaxis drug
suitable for MDA
Vaccine (s) that Interrupt
Malaria Transmission
New Diagnostics (individual,
community/MDA)
Surveillance as an Intervention
Sustained Vectorial
Capacity Reduction Tool
Predictive modeling
allowing strategic and
operational, including
costing, assessment of
combining different control
and elimination strategies
Minimal Enabling
Framework for Health
Systems Readiness
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6
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
Community voice
tool
09/04/2020
New mix of
services; higher
coverage, quality,
& utilization
Source: MOHSW TEHIP Tanzania 7
7
Decentralisation
National Government
MoH
NGOs
Local / District
Government
Regional Health
Authorities
Private Sector
Regional / Province
Government
District Health System
Self-help Groups / Community Based Organisations (formal and informal)
Communities / Families / Citizens
Traditional Health System
09/04/2020
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The systems context
From Efficacy to Effectiveness
Efficacy
80%
X Access
x 80%
X Targeting Accuracy
x 80%
X Provider Compliance
x 75%
X Consumer Adherence
X 75%
= Effectiveness = 29%
9
System effectiveness of ALU in Rufiji Tanzania
1000
simple
malaria
fevers
Sought
care
Individual
behaviour
Health
system
behaviour
Sought
care
within
24 h
Accessed
ACT
provider
within
24 h
101 lost
Individual
& drug
behaviour
Correctly
diagnosed
or
prescribed
50 lost
ACT
stocked
in
Adhered to
treatment
110 cases
Treatment successfully
treated
effective
12 lost
2 lost
64 lost
413 lost
248 lost
890 failures to treat effectively
09/04/2020
10
Real time mHealth monitoring of ACT supply
chains..
We have good drugs for
malaria!
Surveillance in place
Modern Approaches
M-Health with incentives
but
Action is lacking
Training
Understanding
Management…
Source: SMS for Life Tanzania
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
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Malaria Prevalence: 2012
ACT-Stockouts: 2012
09/04/2020
Source: NMCP-Tanzania
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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
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).
Global changes in malaria incidence rate, 2000-2010
2010
2000
Global changes in malaria death rate, 2000-2010
2010
2000
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.
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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.
25
Funding and investments
Global need: GMAP estimates Malaria implementation and
R&D combined will require $5-7B per year through 2020
Millions US$
8,000
6,939
6,094
5,837
6,000
4,000
5,558
3,838
6,180
5,335
5,037
4,877
3,378
2,000
759
759
800
681
460
2009
2010
2015
2020
2025
0
Implementation
R&D
Source: Roll Back Malaria Global Malaria Action Plan (RBM GMAP) published September 2008
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Funding and investments
Globally, total malaria spend estimated to be ~$3b in 2010
Millions US$
4,000
Implementation: Global Fund
Implementation: World Bank
3,494
Implementation: PMI
3,296
Implementation: Other
3,000
Does not include
potential future
commitments
3,102
R&D: BMGF
2,960
2,878
R&D: NIH
2,696
2,645
R&D: Other
2,215
2,000
1,604
1,496
1,117
1,000
888
370
0
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 2015. Prior to 2007, estimates from 2007 Malaria Strategy work. Total of US$468m assumed to remain constant 2007 –
2015. Source: WHO Malaria Report 2008, Global Fund Pledges (website), GMAP report, USAID website (www.usaid.gov/our_work/global_health/home/Funding/funding_rd.html), PMI
website, World Bank website, George Institute G-Finder Report for year 2007 and 2008
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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
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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
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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
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IVCC Progress To Date
New medicines for Malaria Eradication
Fast killing
Post treatment
Protection
Radical
cure
Transmission
blocking
Replacing three
days ACT and 14
days primaquine
with a simpler
therapy
Overcoming
concerns about
resistance
SERCaP
single exposure
radical cure and prophylaxis
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Alonso P et al.,(2011) A research agenda for malaria eradication: drugs PLoS Med. Jan 25;8
Global Portfolio of Antimalarial Medicines
Research
Translational
Lead Optimisation
Oxaboroles
Development
Preclinical
Phase I
Phase IIa
P218 DHFR
(Monash/UNMC/
STI)
Phase IIb/III
Registration
Phase IV
Tafenoquine
Mefloquine
Artesunate
Coartem®-D
Novartis
(Biotec/Monash/
LSHTM)
DSM265
(UTSW/UW/
Monash)
DHODH
3 Projects
ELQ-300
UTSW/UW/Monash
GSK
(USF/
OHSU-VAMC)
Antimalarial
KAE609
Actelion
Novartis
21A092
CDRI 97-78
(DrexelMed/UW)
Ipca
KAF156
Novartis
Eurartesim®
Paediatric
ArtiMist™
Anacor
1 Project
OSDD
Orthologue Leads
Univ Sydney
Sanofi
Heterocycles
Dundee
Long Duration
Leads
Merck Serono
HKMT
IC/ CNRS
dUTPase inhibitors
Medivir
Imidazolidinediones
WRAIR
Whole cell leads
AstraZeneca
DF02
Ferroquine
(UCT)
Dilafor
Sanofi
SJ557733
N-tert butyl isoquine
Fosmidomycin
Piperaquine
MMV390048
Tetraoxane
Liverpool
STM/Liverpool Uni
Aminopyridines
UCT
OZ439
St Jude/Rutgers
Liverpool STM/GSK
Pyramax
Paediatric
Shin Poong/
University of iowa
Sigma-Tau
Proto Pharma
Farmaguinhos/DNDi
Artesunate i.r.
WHO/TDR
Arterolane/PQP
Ranbaxy
NPC-1161-B
AQ13
University of
Mississippi
Immtech
SAR97276
Sanofi
DOS
SAR116242
Artemisone
Palumed
UHKST
Guilin
Eurartesim®
Sigma-Tau
Pyramax
Shin Poong/
University of Iowa
ASAQ Winthrop
sanofi /DNDi
SP-AQ
Guilin
Uni. Heidelberg
RKA182
Artesunate for
injection
ARCO
Methylene Blue
AQ
Liverpool STM
Novartis
Naphthoquine/
Artemisinin
Jomaa Pharma GmbH
NDH2
Liverpool
STM/Liverpool Uni
Broad Institute
GSK
Included in MMV portfolio post
registration
Non MMV
Nauclea
pobeguinii
DRC/Antwerp
Argemone
mexicana
Mali/Geneva
MVI’s current portfolio
FEASIBILITY STUDIES
Antigen
Delivery
Antigen discovery
(Seattle BioMed)
pDNA
(Inovio/UPenn)
Antigen discovery
(NMRC)
Pfs25
(NIAID, Fraunhofer
CMB)
CSP RI conjugates
(NYU/Merck)
TRANSLATIONAL PROJECTS
Preclinical
Phase 1/2a
Translational research
Multivalent
Multivalent pDNA/
ChAd63/MVA
adenovirus
(Oxford U)
(NMRC/Oxford U)
PvDBPII
(ICGEB/MVDP)
RTS,S-AS01/
ChAd63/MVA-TRAP
(Oxford U/GSK)
Translational development
RTS,S-AS01 delayed
fractional dose
(GSK/WRAIR)
B cell targets
(Seattle BioMed, JHU,
NIAID, WRAIR, NMRC)
Pfs25-EPAAlhydrogel®
(NIAID)
Antigen discovery
(NIAID)
Pfs25-VLPAlhydrogel®
(Fraunhofer CMB)
EBA-Rh
(WEHI/Gennova)
PvDBP3-5
(WEHI)
AnAPN1
(JHU)
P. falciparum vaccines: Pre-erythrocytic
P. vivax vaccines:
Pre-erythrocytic
Blood-stage
Transmission-blocking
Blood-stage
Transmission-blocking
VACCINE CANDIDATES
Phase 2b
Phase 3
RTS,S-AS01
(GSK)
Estimated declines in malaria mortality
rates from 2000-2012:
45% globally
49% in WHO African Region
Estimated 3.3 million lives saved
(69% in 10 countries with highest burden
in 2000)
Estimated declines in malaria mortality
rates among children <5 years of age from
2000-2012:
51% globally
54% in WHO African Region
90% of lives saved (3 million) among
children <5 years of age
Estimated declines in malaria case
incidence rates, 2000-2012:
29% globally
31% in WHO African Region
Funding and investments
A range of players in Malaria
Multilaterals
Foundations
Research and
Academia
Clinton
Foundation
Private sector
Donor Countries
NGOs
Malaria-Endemic Countries
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IT ALWAYS
SEEMS
IMPOSSIBLE…
UNTIL IT IS
DONE
Nelson Mandela
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