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