trans

TREATMENT OF PARASITIC DISEASES 439
contributions of molecular parasitology are discussed
below in reference to each group of parasites.
The mechanisms of action and major
untoward effects of selected drugs are reviewed.
Specific therapeutic regimens, less common
side-effects, and the nuances of treatment are
summarized in The Medical Letter on Drugs and
Therapeutics and major textbooks on infectious
diseases and travel and tropical medicine.
TREATMENT OF PARASITIC
DISEASES
Chemotherapy of malaria
History
Malaria is considered by many to be the most
important human parasitic disease. It is a major
cause of morbidity and mortality, particularly
among children in the tropics. It is responsible
for more than a million deaths each year in
Africa alone. Malaria also poses a substantial
threat to non-immune travelers, workers, immigrants,
military personnel and diplomats in
endemic areas.
The first written reference to the treatment
of malaria in the Western literature referred to
the bark of the cinchona tree, which is indigenous
to South America. The Augustinian monk,
Calancha of Lima, Peru, wrote in 1633: ‘A tree
grows which they call “the fever tree” in the
country of Loxa, whose bark, the color of cinnamon,
is made into powder and given as a
beverage, cures the fevers and tertians; it has
produced miraculous results in Lima’. For the
next two centuries, an extract of cinchona bark
was administered in Europe as well as Latin
America for the treatment of presumed malaria.
In 1820 Pelletier and Caventou isolated the
active agent, quinine.
Similarly, the Chinese for centuries used
the herbal medication, qinghaosu, which is
an extract of the wormwood plant, Artemisia
annua, for the treatment of febrile illnesses,
many of which were likely due to malaria. Only
in the past decades have artemisinin, a sesquiterpene,
and its derivatives been systematically
studied. Artemisinin derivatives are now
extensively used in Thailand for the treatment
of multi-drug resistant Plasmodium falciparum
and are being increasingly used elsewhere
although the US Food and Drug Administration
has not yet approved them.
Quinine remained the treatment of choice for
malaria for approximately 300 years. While the
description of the life cycle, biology and epidemiology
of Plasmodium species by Ross and
others constituted a major scientific advance
and resulted in improved strategies for disease
prevention through vector control, they did
not dramatically alter therapy. The next major
therapeutic advance came from an extensive
research program in Germany that started when
supplies of quinine were interrupted during
World War I. Guttman and Ehrlich had reported
in 1891 that methylene blue dye (Figure 17.1)
had anti-malarial effects. The subsequent evaluation
of a series of related organic compounds
led to the identification of pamaquine and then
quinacrine following the war.
Chloroquine, one of a large series of 4-
aminoquinolines, was first produced in 1934,
but its value was not immediately recognized.
The toxicity associated with quinacrine eventually
fueled the quest for less toxic alternatives.
During WWII, chloroquine was re-evaluated in
the United States. It quickly proved to be highly
effective with minimal toxicity, and became the
drug of choice for the treatment and prophylaxis
of malaria by the end of the war.
Unfortunately, chloroquine resistance
emerged, first among isolates of P. falciparum
around the world and more recently in some
MEDICAL APPLICATIONS