Slide2: History of malaria and antimalarial treatment M. Lontie MCH, Leuven 2006


Mala aria (Roman fever) (It.)Agues and feavers (E.)Palus (L.) = marsh (E.)Paludisme (F.)Moeras-, polderkoorts (NL.): Mala aria (Roman fever) (It.) Agues and feavers (E.) Palus (L.) = marsh (E.) Paludisme (F.) Moeras-, polderkoorts (NL.) Malaria


Malaria in antiquity: Malaria in antiquity Region between Tigris and Euphrates was malarious (2000 BC). Nei Ching Canon of Medicine (1700 BC). Egyptian mummies with enlarged spleens (1000 BC).


Hippocrates (460-370 B.C.): Hippocrates (460-370 B.C.) Hippocrates, “father of medicine”: feavers with black bile. Clear discussion of quartan and tertian fevers in his Book of Epidemics. Noted relationship between enlarged spleens and marshes.


Alexander the Great (356 B.C. - 323 B.C.): Alexander the Great (356 B.C. - 323 B.C.)


Cinchona officinalis (Rubiaceae) : Cinchona officinalis (Rubiaceae) Eastern slopes of the Andes. 1638: Countess Anna del Cinchon, wife of the Viceroy of Peru. 1640: Jesuit’s powder. Allowed European conquest of the tropics.


1672: Robert Talbor’s remedy: an infusion of cinchona powder in white wine: 1672: Robert Talbor’s remedy: an infusion of cinchona powder in white wine


Chinine and the Dutch: Chinine and the Dutch 1865: the Dutch buy 450 grams seeds from Charles Ledger in London. Cinchona ledgeriana in Java (10 % chinine in the bark). Amsterdamsche Chinine Fabriek till WWII.


20 mg quinine / bottle of tonic: 20 mg quinine / bottle of tonic


Nobel Prize Winners and Malaria: Nobel Prize Winners and Malaria 1902: Sir Ronald Ross 1907: Charles, Louis, Alphonse Laveran 1927: Julius Wagner-Jauregg 1948: Paul Hermann Müller


Sir Ronald Ross (1857-1932): Sir Ronald Ross (1857-1932) 1897: role of the mosquito. Nobel prize: 1902


Alphonse Laveran (1845-1922): Alphonse Laveran (1845-1922) Physician of the French Army. 1880: Constantine, Algeria, The malaria parasite: Laveriana, Plasmodium. Nobel Prize: 1907


Malariatherapy for syphilis: Malariatherapy for syphilis


Julius Wagner-Jauregg (1857-1940)  : Julius Wagner-Jauregg (1857-1940) Austrian psychiatrist. Malariatherapy (1918) with Plasmodium vivax. Der progressiven Paralyse (Dementia paralytica), also der fortschreitenden Gehirnerweichung als Folge der Syphilis. Nobel prize: 1927 Ab 1953 zierte er den 500 Schilling-Schein. NS-sympathy. Malariatherapy for HIV?


Paul Hermann Müller (1899-1965): Paul Hermann Müller (1899-1965) 1939: Dichloro-diphenyl-trichloro-ethane (DDT). Nobel Prize: 1948


Exoerythrocytic stage (e.e.): Exoerythrocytic stage (e.e.) Shortt H., Garham P. et al. 1948. Ross Institute at the London School of Hygiene and Tropical Medicine. E.e. or liver stage of rhesus monkeys and later of human volunteers.


American Civil War (1861-1865): patients with mosquito nets, Washington D.C.: American Civil War (1861-1865): patients with mosquito nets, Washington D.C. 50% of the white soldiers got malaria annually


Germany in the interbellum: Germany in the interbellum Malaria of birds (W. Röhl). 1924: 8-aminoquinolines: plasmochine, primaquine. 1930: mepacrine, quinacrine, Atebrine. 1934: 4-aminoquinolines: chloroquine.


General Douglas MacArthur is quoted as saying (WWII): General Douglas MacArthur is quoted as saying (WWII) "This will be a very long war, if for every division I have fighting the enemy, I must count on a second division in the hospital with malaria and a third division convalescing from this debilitating disease.“ Five hundred thousand American troops alone would catch malaria.


Amino-alcohols: Amino-alcohols Wars in South-East Asia (Vietnam) WR 180409: enpiroline WR 171669: halofantrine WR 142490: mefloquine


Eradication of malaria: Eradication of malaria Belgium: 1938 The Netherlands: 1958 USA, Cuba, Australia, Israël ...


Slide23: M. Wéry, 1995.


Malaria: numbers in millions : Malaria: numbers in millions 300-500 annual cases 1-2 deaths (mainly children < 5y) Mandell et al., 2005 - WHO, 2001


In 1931 Mussolini began the 3-year project to drain and reclaim the Pontine Marshes for 3000 new farms. : In 1931 Mussolini began the 3-year project to drain and reclaim the Pontine Marshes for 3000 new farms.


Slide29: Eradication of malaria 1934: Hans Andersag at Bayer discovers chloroquine 1939: Paul Müller at Geigy discovers DDT 1951: Sardinia malaria free 1955: WHA (WHAssembly): goal of global eradication 1955-1969: WHO uses DDT and chloroquine 50’s: DDT-resistance 1962-1970: chloroquine-resistance 1955-1965: expenditure of $ 1.4 billion 1969: WHO back to malaria control 1975: Europe free of malaria for first time in history Courtesy of C.D.C


Parasitology: Parasitology orphan parasites orphan drugs the disaster of the ban of DDT The Lancet. 2000. 356: 265 and 1189 (orphan reimbursement, B)


Threats: Threats Global warming El Nino (little child in Spanish, arriving around Christmas). Dams Diama dam in Senegal and large outbreak of Schistosoma mansoni infections. 1996. Kongs et al. Trop Med Int Health. 191-8. The Lancet. 2001. 570-1.


SPF 66 malaria vaccine: SPF 66 malaria vaccine Manuel Patarroyo from Columbia donated the patent of the vaccine to the WHO. Lancet. 1993 Mar 20;341(8847):705-10. "It's not only the first malaria vaccine but the first against any parasitic disease of humans."


The Lancet, 364, Nr. 9443, October 16-22, 2004: The Lancet, 364, Nr. 9443, October 16-22, 2004 “The road toward a safe and efficient malaria vaccine being available and useable on a large scale, or even incorporated into an expanded programme of immunisation, will be long and chaotic.”


Slide36: Recent history of the World Bank's work on malaria The World Bank co-founded the Roll Back Malaria (RBM) Partnership in 1998. Since July 2000, the Bank has committed about US$100-150 million in funds earmarked for malaria control. This includes only health sector investment credits and grants, as well as commitments through broad programmatic operations such as Sector-Wide Approaches (SWAps). Total World Bank support for malaria control was higher, due to financing through debt relief, multisectoral operations such as Poverty Reduction Support Credits (PRSCs), Emergency Recovery Credits and Social Funds. However, it is difficult to quantify exactly how much of these programmatic operations went to malaria control, since such operations do not track details of inputs into specific disease control programs.


RBM is enabling countries to take effective, sustainable action against malaria by focusing on : RBM is enabling countries to take effective, sustainable action against malaria by focusing on Preventing and controlling malaria during pregancy. Promoting the use of insecticide-treated mosquito nets as a means of prevention. Dealing effectively with malaria in emergency and epidemic situations. Providing prompt access to effective treatment.