11

Malaria

Building blocks to success in malaria elimination

22

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

33

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

44

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

5521/04/23 from Marcel Tanner 5

The inquiry agenda in support of malaria elimination

“Malaria systems” “Health systems”

Complex systems – both biology and health systems

6621/04/23 6

ControlScalling 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

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

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

Summary of proposed key responses

HSR

Minimal Enabling Framework for Health Systems Readiness

PLoS Medicine 25 January 2011

7721/04/23 7

Synergy of connected system-level interventions Decentralization,

& local ownership

Household health

surveillance

SWApBasket 1$ per capita

New mix of services; higher

coverage, quality, & utilization

District Health Profiles

New planning & management

skills

New communication

tools

Community voice tool

District Health Accounts

Source: MOHSW TEHIP Tanzania

8821/04/23 8

NG

Os

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 / ProvinceGovernment

Local / District Government

Priv

ate

Se

cto

r

Decentralisation

99

The systems context

Efficacy

X Access

X Targeting Accuracy

X Provider Compliance

X Consumer Adherence

= Effectiveness

80%

x 80%

x 75%

X 75%

= 29%

x 80%

From Efficacy to Effectiveness

Health System Factors / Partnership

21/04/23 10

System effectiveness of ALU in Rufiji Tanzania

Sought care

Sought care

within 24 h

Correctly diagnosed

or prescribed

ACT stocked

in Adhered to treatment

Treatment effective

110 cases successfully

treated

Individual behaviour Health

system behaviour

Individual & drug

behaviour

890 failures to treat effectively

2 lost12 lost

101 lost413 lost

Accessed ACT

provider within

24 h

1000 simple malaria fevers

50 lost 64 lost

248 lost

1111

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

Source: SMS for Life Tanzania

Surveillance in placeModern Approaches

M-Health with incentives

butAction is lacking

TrainingUnderstandingManagement…

21/04/23 12

Malaria Prevalence: 2012

ACT-Stockouts: 2012

Source: NMCP-Tanzania

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

20002010

Global changes in malaria death rate, 2000-2010

20002010

2424

Extent of malaria transmission: 1945

No Malaria transmissionMalaria transmission

Source: Malaria Elimination: Geography, finance, and economics, presentation by Prof. Sir Richard Feachem, at ASTMH 7 Dec 2008.

Hypothetical phasing scenarioSelect Topics

2525

Extent of malaria transmission: 2008

No Malaria transmissionMalaria transmission

Source: Malaria Elimination: Geography, finance, and economics, presentation by Prof. Sir Richard Feachem, at ASTMH 7 Dec 2008.

Planning for elimination or eliminating

Hypothetical phasing scenarioSelect Topics

2626

Global need: GMAP estimates Malaria implementation and R&D combined will require $5-7B per year through 2020

759 759 800 681 460

5,3356,180

5,0374,877

3,378

0

2,000

4,000

6,000

8,000

R&D

Implementation

6,094

2009

6,939

2010

3,838

2025

5,837

2015

5,558

2020

Millions US$

Source: Roll Back Malaria Global Malaria Action Plan (RBM GMAP) published September 2008

Funding and investments

2727

Globally, total malaria spend estimated to be ~$3b in 2010

0

1,000

2,000

3,000

4,000

370

2003

888

2004

1,117

2005

1,604

2006

2,215

2007 2009

3,1022,960

2010

3,296

2,645

2011

3,494

2012

2,878

2013

2,696

1,496

20152008 2014

R&D: BMGF

R&D: NIH

R&D: Other

Implementation: Global Fund

Implementation: Other

Implementation: PMI

Implementation: World Bank

Millions US$

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

Does not include potential future commitments

Funding and investments

2929

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

IVCC Progress To Date

New medicines for Malaria Eradication

Fast killingPost treatmentProtection

Radicalcure

Transmissionblocking

SERCaPsingle exposure

radical cure and prophylaxis

34 Alonso P et al.,(2011) A research agenda for malaria eradication: drugs PLoS Med. Jan 25;8

Replacing three days ACT and 14 days primaquine

with a simpler therapy

Overcoming concerns about

resistance

Global Portfolio of Antimalarial Medicines

Non MMV

Nauclea pobeguinii

DRC/Antwerp

Argemone mexicana

Mali/Geneva

RegistrationPreclinicalResearch Translational Development

Phase IIaPhase ILead Optimisation Phase IVPhase IIb/III

1 ProjectNovartis

Artesunate for injection

Guilin

Coartem®-DNovartis

AminopyridinesUCT

3 ProjectsGSK

KAE609Novartis

OZ439(Monash/UNMC/

STI)

PyramaxShin Poong/

University of Iowa

ELQ-300(USF/

OHSU-VAMC)

21A092(DrexelMed/UW)

KAF156Novartis

DSM265(UTSW/UW/

Monash)

Eurartesim® Sigma-Tau

Whole cell leadsAstraZeneca

TafenoquineGSK

P218 DHFR(Biotec/Monash/

LSHTM)

TetraoxaneLiverpool

STM/Liverpool Uni

PyramaxPaediatricShin Poong/

University of iowa

Eurartesim® PaediatricSigma-Tau

Orthologue LeadsSanofi

HeterocyclesDundee

Included in MMV portfolio post registration

SP-AQGuilin

ASAQ Winthropsanofi /DNDi

MMV390048(UCT)

dUTPase inhibitorsMedivir

DOSBroad Institute

ImidazolidinedionesWRAIR

RKA182Liverpool STM

NPC-1161-BUniversity of Mississippi

SAR116242Palumed

MefloquineArtesunate

Farmaguinhos/DNDi

SAR97276Sanofi

FerroquineSanofi

FosmidomycinPiperaquine

Jomaa Pharma GmbH

Methylene Blue AQ

Uni. Heidelberg

AQ13Immtech

Artesunate i.r.WHO/TDR

ArtemisoneUHKST

AntimalarialActelion

DF02Dilafor

CDRI 97-78Ipca

N-tert butyl isoquineLiverpool STM/GSK

ARCONaphthoquine/

Artemisinin

Arterolane/PQPRanbaxy

ArtiMist™Proto Pharma

OSDDUniv Sydney

DHODHUTSW/UW/Monash

OxaborolesAnacor

SJ557733St Jude/Rutgers

NDH2Liverpool

STM/Liverpool Uni

Long Duration Leads

Merck Serono

HKMTIC/ CNRS

MVI’s current portfolio

Antigen

FEASIBILITY STUDIES

Delivery Preclinical

TRANSLATIONAL PROJECTS

Phase 2b Phase 3

VACCINE CANDIDATES

Phase 1/2a

Pre-erythrocytic Blood-stage Transmission-blockingP. falciparum vaccines:

Pre-erythrocytic Blood-stage Transmission-blockingP. vivax vaccines:

Antigen discovery(Seattle BioMed)

Antigen discovery(NMRC)

EBA-Rh(WEHI/Gennova)

CSP RI conjugates (NYU/Merck)

PvDBPII(ICGEB/MVDP)

pDNA(Inovio/UPenn)

RTS,S-AS01 (GSK)

AnAPN1(JHU)

Pfs25-EPA-Alhydrogel®

(NIAID)

Multivalent ChAd63/MVA

(Oxford U)

PvDBP3-5 (WEHI)

B cell targets (Seattle BioMed,

JHU, NIAID, WRAIR, NMRC)

RTS,S-AS01 delayed fractional dose(GSK/WRAIR)

RTS,S-AS01/ChAd63/MVA-TRAP

(Oxford U/GSK)

Translational research

Translational development

Antigen discovery(NIAID)

Pfs25(NIAID, Fraunhofer

CMB)

Multivalent pDNA/ adenovirus

(NMRC/Oxford U)

Pfs25-VLP-Alhydrogel®

(Fraunhofer CMB)

Estimated declines in malaria mortality rates from 2000-2012:

45% globally49% 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% globally54% 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% globally31% in WHO African Region

4040

A range of players in Malaria

NGOs

Multilaterals Foundations

Clinton Foundation

Donor Countries

Research and Academia

Private sector

Malaria-Endemic Countries

Funding and investments

4141

IT ALWAYS SEEMS

IMPOSSIBLE…UNTIL IT IS

DONE Nelson Mandela