DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Chemotherapy of Protozoal
Infections: Amebiasis, Giardiasis,
Trichomoniasis, Trypanosomiasis,
Leishmaniasis, and Other
Protozoal Infections
Margaret A. Phillips
and Samuel L. Stanley, Jr.
Humans host a wide variety of protozoal parasites that
can be transmitted by insect vectors, directly from other
mammalian reservoirs or from one person to another.
Because protozoa multiply rapidly in their hosts and
effective vaccines are unavailable, chemotherapy has
been the only practical way to both treat infected individuals
and reduce transmission. The immune system
plays a crucial role in protecting against the pathological
consequences of protozoal infections. Thus, opportunistic
infections with protozoa are prominent in
infants, individuals with cancer, transplant recipients,
those receiving immunosuppressive drugs or extensive
antibiotic therapy, and persons with advanced human
immunodeficiency virus (HIV) infection. Treatment of
protozoal infections in immunocompromised individuals
is especially difficult, and the outcome is often
unsatisfactory.
Most antiprotozoal drugs have been in use for
years despite major advances in bioscience relevant to
parasite biology, host defenses, and mechanisms of disease.
Satisfactory agents for treating important protozoal
infections such as African trypanosomiasis
(sleeping sickness) and chronic Chagas’ disease still are
lacking. Many effective antiprotozoal drugs are toxic at
therapeutic doses, a problem exacerbated by increasing
drug resistance. Development of drug resistance also
poses a serious threat to better tolerated antiprotozoal
agents in current use. Unfortunately, many of these diseases
afflict the poor in developing countries, and there
is little economic incentive for pharmaceutical companies
to develop new antiparasitic drugs. Scientists and physicians
working in this field must be creative and have
turned to drugs developed originally for other indications
(e.g., amphotericin and miltefosine for leishmaniasis),
to investigational drugs made available directly
from the Centers for Disease Control and Prevention
(CDC), or to agents developed for veterinary use to discover
new antiparasitic therapies.
This chapter describes important human protozoal
infections other than malaria and the drugs used to
treat them.
INTRODUCTION TO PROTOZOAL
INFECTIONS OF HUMANS
Amebiasis. Amebiasis affects ~10% of the world’s population,
causing invasive disease in ~50 million people
and death in ~100,000 of these annually (Stanley, 2003).
In the U.S., amebiasis is seen most commonly in the
states that border Mexico and among individuals living
in poverty, crowded conditions, and areas with poor
sanitation. Three morphologically identical but genetically
distinct species of Entamoeba (i.e., E. histolytica,
E. dispar, and E. moshkovskii) have been isolated from
infected persons. Although the proportions vary worldwide,
E. dispar and E. moshkovskii account for ~90%
of human infections, with E. histolytica responsible for
only 10%. However, only E. histolytica is capable of
causing disease and thus requires treatment.