impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

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affected by malaria cannot be overstated or ignored.
The WHO even published its guidelines in December
of 2005, for the first time stating that artemisinins are
first line therapy for much of malaria. These recommendations
did not take long to catch on in most of the
world most severely affected by malaria. Table 1 shows
the governmentally accepted first line artemisinin therapy
recommendations as of 2007.
Team,” there was a momentous decision to be made,
and that was that quinidine must be replaced. To
understand the importance of this decision, one must
first understand a little about quinidine. While this
drug has saved the lives of people with severe malaria
in the United States over the time it has been available,
it has toxicities that require admission to an intensive
care unit to safely give the drug. Like its cousin quinine,
quinidine has several side effects associated with
its use. Quinidine happens to be “better” for the treatment
of malaria, as far as how rapidly it works, but it
is also much more toxic than its cousin quinine. Among
the numerous side effects common to both drugs is
prolongation of the “Q-T” interval. This action of the
drug is why quinidine was originally licensed in the
United States. It was a pro-arrhythmic drug used to
cause changes in the heart’s electrical impulses and correct
unstable electrical rhythms in cardiology patients.
The fact that quinidine was already licensed for cardiac
reasons in the U.S., and the fact that it was more effective
for treating malaria than even quinine, made it a
perfect candidate for being the drug of choice for
severe malaria. But this ease in licensing came at a
price, and this price was more difficult and costly treatment
of severe malaria in intensive care units.
P. J. Weina - History of Artemisinins
Table 1. Governmental Policy for 1 st Line Artemisinin Recommendations as of 2007
The U.S. military’s most recent saga in the development
of artemisinin compounds started in late 2000 when
the drug development group at the WRAIR decided
that it was time to replace the only currently licensed
drug to treat severe and complicated malaria in the
United States. In a committee first known as the
“Severe and Complicated Malaria Working Group” and
later as the “Intravenous Artesunate Integrated Product
AS + AQ AS + SP AS + MQ AL DHA/Pip
Africa Burundi, Cameroon,
Congo, Côte d’Ivoire,
Democratic Republic of Congo,
Equatorial Guinea, Gabon,
Ghana, Guinea, Liberia,
Madagascar, Malawi, Mauritania,
Senegal,
Sao Tomé & Principe,
Sierra Leone, Sudan (S),
Tanzania (Zanzibar)
Mozambique, Djibouti,
Somalia, South Africa
(Mpumalanga),
Sudan (N)
Asia Indonesia Afghanistan, India (5
Provinces), Iran,
Tajikistan, Yemen
South
America
Cambodia,
Malaysia,
Myanmar,
Thailand
Ecuador, Peru Bolivia,
Peru,
Venezuela
Angola, Benin, Burkina
Faso, Central African
Republic, Chad, Comoros,
Ethiopia, Gambia,
Guinea Bissau, Kenya, Mali,
Namibia, Niger, Nigeria,
Rwanda, Uganda, South
Africa (Kwa Zulu Natal),
Tanzania (Mainland), Togo,
Zambia, Zimbabwe
Bangladesh, Bhutan, Laos,
Saudi Arabia
Brazil, Guyana, Suriname
AS – artesunate; AQ – amodiaquine; SP – sulfadoxine/pryimethamine; MQ – mefloquine; AL – artemether/lumefantrine;
DHA/Pip – dihydroartemisinin/piperaquine
Viet Nam
The artemisinin compounds, especially the water soluble
forms, seemed the perfect possible replacement for
this potentially highly toxic drug. The WRAIR drug
development group began developing artesunic acid
(artesunate) and artelinic acid side-by-side to determine
which drug to carry forward into intensive
advanced clinical development. Artelinic acid was certainly
favored by the Experimental Therapeutic team in
this side-by-side comparison. Artelinic acid was developed
by chemists at the WRAIR, was much more stable
than artesunate, and most importantly for finding a
commercial partner, it was patentable. Much of the
development effort in the early days focused on artelinic
acid as the “odds on favorite” in this unusual race for
predominance in development to licensure. On
October 7, 2002, the entire WRAIR team gathered
together with a broad collection of scientists, medical
professionals, and advisors from the throughout the
Army’s drug development program. All eyes were on
artelinic acid as the most probable winner of the race
between these two compounds. Certainly a quick vote
of those entering the room that day would have resulted
in artelinic acid as the choice for further development.
Over the course of that day fifteen different presentations
were given that compared the pros and cons