Malaria, a World Public Health Problem. New challenges for its control. Pierre AMBROISE-THOMAS Académie de Médecine de France

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1 Malaria, a World Public Health Problem. New challenges for its control. Pierre AMBROISE-THOMAS Académie de Médecine de France

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3 million P.falciparum cases / year (?)

4 ~1.5 M deaths/year (?)

5 Other human species: Plasmodium malariae Plasmodium ovale (P.knowlesi)

6 Plasmodium vivax

7 Malaria (MalariaS?) is a group of four separate diseases with different epidemiology, public health importance and areas of distribution, hence with different eradicability.

8 ERADICATION a dream? a political slogan? a realistic though difficult future possibility?

9 Malaria versus Smallpox

10 The Global Malaria Action Plan Launch Secretary-General Ban Ki-moon addresses the high-level interactive panel on malaria to launch the Global Malaria Action Plan. New York, USA; 25 September 2008

11 .Roll Back Malaria (RBM) initiative.roll Back Malaria (RBM) initiative. Global Fund for HIV, Tuberculosis & Malaria.G8 summits.un Secretary General.Millennium Development Goal (MDG). Bill & Melinda Gates Foundation (BMGF). Malaria conference 2007 : Call for the eradication of malaria.

12 Plasmodiumgenomics: Genomics and proteomics gave the way for controlling malaria

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14 Tools for malaria control - (Long lasting) Insecticide Treated Bednets -Antimalarial Drugs: Artemisinin-based Combination Therapies (ACTs) - Future Antimalarial Vaccines

15 (Long lasting) Impregnated Bednets Antimalarial Drugs Antimalarial Vaccines

16 INSECTICIDE TREATED BEDNETS / CURTAINS TRIALS IN AFRICA THE GAMBIA 2 THE GAMBIA 1 KENYA GHANA BURKINA FASO Reduction in child mortality (%) Cochrane Meta-analysis

17 (Long lasting) Impregnated Bednets Antimalarial Drugs Antimalarial Vaccines

18 Antimalarial R&D throughput AM/LF AS+AQ blister AS+MQ blister AS+SP DHA/PPQ AS/MQ AS/AQ CDA AS/ PRN Primaquine Chloroquine Quinine Amodiaquine Pyrimethamine/ Mefloquine sulfas Artemisinin (China) Halofantrine Atovaquone/ proguanil CPG/ DPS

19 Global antimalarial drug portfolio Predevelopment Preclinical OZ277 & other trioxanes 4(1H) Pyridone Choline inhibitors Isoquine Trioxaquine Ferroquine Azithomycin +CQ Tafenoquine Development PhI-II PhIII Trioxane Rbx1116 Artemisone Fosmidomycin+ clindamycin Short-chain CQ (AQ-13) i.v. AS AS/PRD DHA/PPQ Eurartesim Registration Coartem paediatric i.r. AS AS/MQ fixed AS/AQ fixed Deployment CPG/DDS Lapdap AM/LF Coartem AS+MQ Co-blist AS+AQ Co-blist DHA/PPQ Artekin i.v. AS (Guilin) AS rectocaps

20 Me-too's products NOVELTY?

21 Needs for real innovation New chemical classes with new mechanisms of action needed in the pipeline New companion drugs - to replace drugs compromised by resistance - to provide mutual protection against resistance Discovery...but - Higher attrition rates -Long time to registration

22 (Long lasting) Impregnated Bednets Antimalarial Drugs Antimalarial Vaccines

23 Candidate vaccines in clinical phases Stage Target Antigen Vaccine/adjuvant Phase Developer RTS,S/ASO1-2 I-IIb GSK/MVI Preerythrocytic Sporozoite Hepatocyte PfCSP Af35 CS (adeonovirus vector) I-IIa WRAIR/Crucell/GSK PhCSP DNA/MVA-CS I NIAID ME-TRAP FP9/MVA, ME-TRAP I-IIb Un.Oxford/MVI/W-T LSA-1 LSA-1/ASO1-2 I-IIa WRAIR/GSK/MVI LSA-2 LSA-2/Montanide-Alum I-IIa Inst.Pasteur/EMVI FMP1/ASO1-2 I-IIb WRAIR/GSK MSP1(42) MSP+(42)_C1-Alum+/-CPG7909 biallelic I-IIa MVDB Blood stage Sexual stage Multistage Merozoite Gametocyte Sporozoite+ Merozoite MSP2 MSP2_C1/Montanide biallelic Ia QIMR MSP3 MSP3 LSP Alum/Montanide Ia AMA-1 AMA-1 FMP2.1/ASO2 I-IIb WRAIR/GSK AMA1_C1-Alum+/-CPG7909 biallelic Ib MVDB Inst.Pasteur/EMVI/AMA NET AMA1_FVO_Alum-Montanide-ASO2 Ib MVDB/EMVI/GSK EBA-175 EBA175 RII-NG Ia NIAID AMA+MSP1 Chimeric 2.9 AMA1+MSP1/ISA720 Ia GLURP+MSP3 Recombinant hybrid GMZ 2 Alum I WanxingBio/MVI/WHO SSI/EMVI/AMANET Pf25+Pv25 PpPfs25/ISA51 + ScPvs25/ISA51 Ia NIAID AMA40_C1 + UK39 I Pevion/STI CSP+AMA1 NMRC-M3V-Ad_PfCA I USNavy

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25 Challenges with malaria vaccines Plasmodium has: Complex biology Extensive antigenic diversity Immune evasion Immunity is: Species- / strainspecific Short-lived

26 Eradication Permanent reduction to zero of the worldwide incidence of infection. Intervention measures are no longer needed once eradication has been achieved. Elimination Reduction to zero of the incidence of infection in a defined geographical area without necessarily elimination of the vectors capable of transmitting the parasite. Continued measures to prevent re-establishment of transmission are required

27 What are the main challenges/obstacles to eradicate malaria? More/better tools? More money? More political support? Better operation/organization? More malariologists and entomologists?

28 With better tools, organization, political will, Malaria control elimination eradication Looks simple But isn't: Slow progress

29 ELIMINATION VERSUS ERADICATION of malaria transmission

30 ERADICATION of malaria mortality

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32 MUITO OBRIGADO