trans

TREATMENT OF PARASITIC DISEASES 455
neonates can develop hemolytic anemia due
to glutathione instability.
Future considerations
Treatment of cryptosporidiosis in immunocompromised
individuals is the most urgent
need related to intestinal protozoal infections.
Infection with Cryptosporidium parvum in a
normal host results in days to occasionally several
weeks of non-bloody diarrhea, which is
self-limited. In persons with AIDS, cryptosporidium
infection may be persistent and
require therapy. The most effective approach in
patients with AIDS is to reverse the immunodeficiency
state with highly active antiretroviral
treatment (HAART) of HIV, which has led
to a 90% decrease in the incidence of cryptosporidiosis
in those treated in the United
States. In patients with severe AIDS who are not
responding to, or are intolerant of HAART, there
is little to offer in the way of treatment for cryptosporidiosis.
The one drug thought to be effective
was paromomycin, which was recently
shown to be no more active than placebo.
An attractive approach for new chemotherapeutic
agents would be to interfere with the
intracellular replication of the parasite. Upon
invasion of epithelial cells, cryptosporidia
undergo both the sexual and asexual stages of
the life cycle. It has long been appreciated that
the parasite resides within a unique intracellular,
yet extracytoplasmic compartment that
bulges into the lumen of the small bowel. This
parasite compartment is separated from the
host cytoplasm by an electron-dense material.
The nature of this material has recently been
shown by immunofluorescence to be filamentous
actin. This filamentous actin appears
to be intimately associated with the epithelialcell
plasma membrane, and contains the
actin-binding protein alpha-actinin. Understanding
the mechanism by which the
parasite induces host cell actin polymerization,
and delineating its importance in intracellular
replication of the parasite, are
important applications of basic cell biology
towards the search for effective therapies for
cyptosporidiosis.
Intestinal helminths
The intestinal helminths, or roundworms,
are the most prevalent of the human parasites.
In areas of the world where sanitation is poor,
the majority of residents harbor one or more
species. The major intestinal roundworms are
Ascaris lumbricoides, which is the only roundworm
that looks like an earthworm, the hookworms
Ancylostoma duodenale and Necator
americanus, and the whipworm, Trichuris
trichiura. All are susceptible to albendazole
and mebendazole.
Of the intestinal worms, Ascaris is the most
prevalent, with more than 1.5 billion people
infected worldwide. Heavy infections can
result in intestinal obstruction due to masses
of worms in the intestine. On occasion, adult
Ascaris migrate into the biliary tract, resulting
in ascending cholangitis or pancreatitis. The
hookworms are the next most prevalent and
are a major cause of iron deficiency anemia.
Trichuris trichiura causes gastrointestinal
symptoms including diarrhea, anemia and in
heavy infection, rectal prolapse. Recent evidence
suggests that pediatric infections with
intestinal helminths contribute to growth
retardation and adversely effect performance
at school and work.
Strongyloides stercoralis is the fourth major
intestinal helminth. It is important because of
its capacity for autoinfection. Strongyloides
stercoralis can persist indefinitely and progress
to disseminated hyperinfection in persons
who are taking corticosteroids and/or become
immunocompromised. The treatment of choice
MEDICAL APPLICATIONS