1. Malaria Global update, progress, priorities
Steve Taylor
GLHLTH701
Sept

2. Overview Malaria Malaria today Progress Future
Microbiologically, epidemiologically
Historically, clinically
Malaria today
Progress
Burden
Vaccines
Future

3. What is malaria?

4. What is malaria?

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

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

7. Where was malaria?
memory.loc.gov

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

9. How big of a problem is malaria?
Plos Med 2010; 7: e

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

11. Who gets malaria? People in Africa and S. Asia
60%
Plos Med 2010; 7: e

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

13. Who gets malaria? Pregnant women
PLoS Med 2010; 7(1): e

14. Who gets malaria? Travelers
MMWR 2012; 61

15. Malaria today

16. Who is working on malaria?

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

18. Artemisinin combination therapies

19. First Reported Resistance
Drug resistance
Antimalarial Drug
Year Introduced
First Reported Resistance
Difference (years)
Quinine
1632
1910
278
Mepacrine
1935
1945 10
Chloroquine
1957 12
Proguanil
1948
1949 1
Fansidar
1967
Mefloquine
1977
1982 5
Atovaquone
1996
Artemisinin
1980
2009 ?

20. New malaria drugs? Sept 2012 www.mmv.org Research Translational
Development
Lead Gen
Lead Opt
Preclinical
Phase I
Phase IIa
Phase IIb/III
Registration
Phase IV
Novartis
miniportfolio
Novartis
2 Projects
DSM265
(UTSW/UW/
Monash)
GNF156
Novartis
OZ439
(Monash/UNMC/
STI)
Azithromycin chloroquine
Pfizer
Coartem®-D
Novartis
GSK
miniportfolio
GSK
2 Projects
Aminoindole
Broad/Genzyme
NITD609
Novartis
Tafenoquine
GSK
Artesunate for injection
Guilin
Broad/Genzyme
miniportfolio
Sanofi
1 Project
P218 DHFR
(Biotec/Monash/LSHTM)
Pyramax
Paediatric
Shin Poong/University of iowa
Eurartesim®
sigma tau
Antimalarials
Ferrer-GSK
Antimalarials
St Jude/Rutgers/USF
ELQ-300
(USF/ OHSU-VAMC)
Eurartesim®
Paediatric
sigma tau
Pyramax
Shin Poong /University of Iowa
Sanofi
Orthologue screen
Aminopyridine
UCT
21A092
(DrexelMed/UW)
ASAQ Winthrop
sanofi /DNDi
AstraZeneca
miniportfolio
Antimalarials
Dundee
SP-AQ
Guilin
Kinases
Monash
DHODH
UTSW/UW/
Monash
Other Projects
17 Projects
Oxaboroles
Anacor
Included in MMV portfolio post registration
Tetraoxanes
LSTMH

21. New malaria drugs? Sept 2013 Research Translational Development
Lead Gen
Lead Opt
Preclinical
Phase I
Phase IIa
Phase IIb/III
Registration
Phase IV
Miniportfolio
Novartis
1 Project
Novartis
P218 DHFR
(Biotec/Monash/ LSHTM)
DSM265
(UTSW/UW/
Monash)
OZ439
(Monash/UNMC/
STI)
Azithromycin chloroquine
Pfizer
Coartem®-D
Novartis
Miniportfolio
GSK
4 Projects
GSK
ELQ-300
(USF/ OHSU-VAMC)
KAE609
Novartis
Tafenoquine
GSK
Artesunate for injection
Guilin
Miniportfolio
Sanofi
Orthologue Leads
Sanofi
21A092
(DrexelMed/UW)
KAF156
Novartis
Pyramax
Paediatric
Shin Poong/ University of iowa
Eurartesim®
Sigma-Tau
Heterocycles
Celgene
Whole Cell Leads
AstraZeneca
MMV390048
(UCT)
Eurartesim®
Paediatric
Sigma-Tau
Pyramax
Shin Poong/ University of Iowa
Miniportfolio
AstraZeneca
Oxaboroles
Anacor
SJ557733
St Jude/Rutgers
Nauclea pobeguinii
DRC/Antwerp
ASAQ Winthrop
sanofi /DNDi
Other Projects
19 Projects
2 Projects
Liverpool STM/Liverpool Uni
Argemone mexicana
Mali/Geneva
SP-AQ
Guilin
DHODH
UTSW/UW
Aminopyridines
UCT
Included in MMV portfolio post registration
Heterocycles
Dundee

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

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

24. 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 6m  145m  66m
2010 – 2011: RDTs 88m  155m
: ACTs 11m  278m
WHO, World Malaria Report 2011

25. Progress?
Lancet 2008; 372: 1555

26. Progress? Zanzibar Ethiopia Fajara Kilifi Sao Tome & Principe
Limpopo, SA
Bioko I.
Lancet ID 2010; 10: 545

27. Progress: Rwanda
Malaria J 2012; 11: 236

28. What about a vaccine?
Annu Rev Med 2011; 63: 345

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

30. What about a vaccine?
Science 2013

31. Malaria vaccines?

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

33. 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