1. Malaria Global update, progress, priorities Steve Taylor GLHLTH310 Sept 6 2012

2. Overview Malaria – Microbiologically, – Epidemiologically – Historically – Clinically Malaria today Progress Future

3. What is malaria?

5. Homo sapiens and Plasmodia > 3000 yrs old – Chinese, Assyrian, Indian medical texts European wars European colonialisation Cinchona bark

6. Europe and malaria Cold sweats occurring with an acute fever, indicate death; and along with a milder one, a protracted disease. Hippocrates, Aphorisms Section IV, 500 BCE As one who has the shivering of the quartan so near, That he has his nails already pale And trembles all, still keeping the shade, Such as I became when those words were uttered Dante Alighieri, La Divina Commedia, 14 th c. You are so very choleric of complexion. Beware the mounting sun and all dejection, Nor get yourself with sudden humours hot; For if you do, I dare well lay a groat That you shall have the tertian fever’s pain, Or some ague that may well be your bane Geoffrey Chaucer, The Canterbury Tales, 14 th c.

7. H. sapiens and P. falciparum Hay Nat Comm 2010 Fairhurst NEJM 2004

8. Where was malaria? memory.loc.gov

9. How big of a problem is malaria? Malaria J 2011; 10: 378 P. falciparum P. vivax

10. How big of a problem is malaria? Nature 2004; 234: 214

11. How big of a problem is malaria? Lancet 2012; 379: 2151 U5 deaths Total: 7.6m Malaria: 564,000

12. Who gets malaria? Children Nat Immunol 2008; 9: 725 Asymptomatic infection Mild malaria Severe malaria ? ?

13. Who gets malaria? Pregnant women http://www.cdc.gov/malaria/malaria_worldwide/reduction/iptp.html PLoS Med 2010; 7(1): e1000221

14. Who gets malaria? Travelers MMWR 2012; 61

15. Malaria today

16. Who is working on malaria?

17. How is malaria treated? Artemisinin combination therapies: e.g. Coartem Bark of Cinchona tree: Quinine Chloroquine Mefloquine SP (Fansidar)

18. Artemisinin combination therapies

19. Drug resistance Antimalarial Drug Year IntroducedFirst Reported Resistance Difference (years) Quinine16321910278 Mepacrine1935194510 Chloroquine1945195712 Proguanil194819491 Fansidar1967 0 Mefloquine197719825 Atovaquone1996 0 Artemisinin19802009?

20. New malaria drugs? RegistrationPreclinical ResearchTranslationalDevelopment Lead OptPhase IIaPhase ILead GenPhase IVPhase IIb/III Novartis miniportfolio Novartis 2 Projects Artesunate for injection Guilin Coartem®-D Novartis GSK miniportfolio Broad/Genzyme miniportfolio Oxaboroles Anacor Other Projects 17 Projects Sanofi Orthologue screen Kinases Monash Antimalarials Ferrer-GSK GSK 2 Projects NITD609 Novartis OZ439 (Monash/UNMC/ STI) Azithromycin chloroquine Pfizer Pyramax Shin Poong /University of Iowa Aminopyridine UCT ELQ-300 (USF/ OHSU- VAMC ) 21A092 (DrexelMed/UW) AstraZeneca miniportfolio GNF156 Novartis DSM265 (UTSW/UW/ Monash) Aminoindole Broad/Genzyme Eurartesim® sigma tau Antimalarials St Jude/Rutgers/USF Tafenoquine GSK P218 DHFR ( Biotec/Monash/LSH TM) Antimalarials Dundee DHODH UTSW/UW/ Monash Pyramax Paediatric Shin Poong/University of iowa Eurartesim® Paediatric sigma tau Sanofi 1 Project Tetraoxanes LSTMH Included in MMV portfolio post registration SP-AQ Guilin ASAQ Winthrop sanofi /DNDi www.mmv.org

21. How do we prevent malaria? Vector insecticide resistance Parasite drug resistance Vector insecticide resistance

22. Prevention in pregnant women Lancet ID 2011; 11: 190

23. Progress? “Malaria mortality rates have fallen by more than 25% since 2000” “Off 99 countries with ongoing malaria transmission, 43 recorded decreases of more than 50%... Between 2000 and 2010” LLINs 88m  145m RDTs 45m  88m WHO, World Malaria Report 2011

24. Progress? Lancet 2008; 372: 1555

25. Progress? ZanzibarEthiopiaFajara Kilifi Limpopo, SA Sao Tome & Principe Bioko I. Lancet ID 2010; 10: 545

26. What about a vaccine? NEJM 2008; 359: 2521 NEJM 2011; 365: 1863

27. Malaria vaccines? www.malariavaccine.org

28. What’s next? Preventive measures Vector control New drugs – Combinations – Adjunctive Better diagnostics – Surveillance New vaccines – Antigens – Adjuvants Molecular pathogenesis

29. Parting words “Be sure to give the poor the aid they most need. There are a thousand hacking at the branches of evil to one who is striking at the root, and it may be that he who bestows the largest amount of time and money on the needy is doing the most by his mode of life to produce the misery which he strives in vain to relieve.” -- H.D. Thoreau

30. The DR Congo 128,881 annual U5 deaths in higher endemicity areas 26,488 associated with increased malaria endemicity PLoS ONE 2011; 6: e16420