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” 5 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 6 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 8 8 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 11 Malaria Prevalence: 2012 ACT-Stockouts: 2012 09/04/2020 Source: NMCP-Tanzania 12 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. 24 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 26 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 27 29 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 30 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 31 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 32 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 34 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 40 IT ALWAYS SEEMS IMPOSSIBLE… UNTIL IT IS DONE Nelson Mandela 41