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Malaria Global update, progress,
priorities Steve Taylor GLHLTH310 Sept 6 2012
Overview
• Malaria – Microbiologically, – Epidemiologically – Historically – Clinically
• Malaria today • Progress • Future
What is malaria?
What is malaria?
Homo sapiens and Plasmodia
• > 3000 yrs old – Chinese, Assyrian, Indian medical texts
• European wars • European colonialisation • Cinchona bark
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, 14th 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, 14th c.
H. sapiens and P. falciparum
Hay Nat Comm 2010 Fairhurst NEJM 2004
Where was malaria?
memory.loc.gov
How big of a problem is malaria?
Malaria J 2011; 10: 378
P. falciparum
P. vivax
How big of a problem is malaria?
Nature 2004; 234: 214
How big of a problem is malaria?
Lancet 2012; 379: 2151
U5 deaths Total: 7.6m Malaria: 564,000
Who gets malaria? Children
Nat Immunol 2008; 9: 725
Asymptomatic infection
Mild malaria
Severe malaria
? ?
Who gets malaria? Pregnant women
http://www.cdc.gov/malaria/malaria_worldwide/reduction/iptp.html PLoS Med 2010; 7(1): e1000221
Who gets malaria? Travelers
MMWR 2012; 61
Malaria today
Who is working on malaria?
How is malaria treated?
Artemisinin combination therapies: e.g. Coartem
Bark of Cinchona tree: Quinine
Chloroquine Mefloquine
SP (Fansidar)
Artemisinin combination therapies
Drug resistance Antimalarial
Drug Year Introduced First Reported
Resistance Difference
(years) Quinine 1632 1910 278
Mepacrine 1935 1945 10
Chloroquine 1945 1957 12
Proguanil 1948 1949 1
Fansidar 1967 1967 0
Mefloquine 1977 1982 5
Atovaquone 1996 1996 0
Artemisinin 1980 2009 ?
New malaria drugs? Registration Preclinical
Research Translational Development Lead Opt Phase IIa Phase I Lead Gen Phase IV Phase 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/
LSHTM)
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
How do we prevent malaria?
Vector insecticide resistance
Parasite drug resistance
Parasite drug resistance
Vector insecticide resistance
Prevention in pregnant women
Lancet ID 2011; 11: 190
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
Progress?
Lancet 2008; 372: 1555
Progress? Zanzibar Ethiopia Fajara
Kilifi
Limpopo, SA Sao Tome & Principe
Bioko I.
Lancet ID 2010; 10: 545
What about a vaccine?
NEJM 2008; 359: 2521 NEJM 2011; 365: 1863
Malaria vaccines?
www.malariavaccine.org
What’s next? • Preventive measures • Vector control • New drugs
– Combinations – Adjunctive
• Better diagnostics – Surveillance
• New vaccines – Antigens – Adjuvants
• Molecular pathogenesis
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
The DR Congo
128,881 annual U5 deaths in higher endemicity areas 26,488 associated with increased malaria endemicity
PLoS ONE 2011; 6: e16420
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