EXOGENOUS PATHOGENS AND TOXINS 585
c. Sporozoa
Plasmodium(causing malaria—high fever, sweating, headache, nausea)
d. Ciliophora
Balantidium(causing balantidiasis—diarrhea, dysentery, ulcers)
B. Helminths (worms)
a. Platyhelminths (flatworms)
Cestode (tapeworms)
Tenia (beef/pork tapeworm—5 m long worm in bowel)
Trematode (flukes)
Schistosoma (blood or bladder flukes—headache, gut symptoms)
b. Nematode
Ancylostoma(hookworm—intestinal ulcerations, lung lesions)
Enterobius (pinworm—perianal itching)
Ascaris(roundworm—30 cm long worm in small intestine)
Trichuris (whipworm—5 cm long worm in colon)
C. Arthropods (ectoparasitic infestations; insects)
Sarcoptes scariei (scabies—severe itching in skin fold areas)
Pediculus corporis (lice—itching of scalp and skin)
(This is only a partial list of the more common parasitic infestations.)
Parasitic infections affect (and sometimes kill) a huge number of people worldwide.
Conservative estimates suggest that more than one billion people have parasitic infections;
other epidemiologists suggest a figure of three billion—that is, almost one-half of this
planet’s human population. In some developing countries more than 80% of the popula-
tion has a parasitic infection. Parasitic infections constitute one of the most widespread
human health problems in the modern world. It is a sad comment on the “drug design
culture” that so little is done for so great a problem. Regrettably, the intellectual and tech-
nical might of modern drug design is seldom focussed on the issue of parasitic infection.
Designing drugs for parasitic infections presents some undeniable challenges.
Worms are surprisingly sophisticated and differentiating helminths from humans is not
always easy. As with the other microbes, the key to successful drug design is to iden-
tify druggable targets that permit selective parasite killing. This may be achieved using
three classes of druggable targets:
- Enzymes unique to the parasite and not found in humans (e.g., dihydropteroate syn-
thesis enzymes, trypanothione reductase) - Enzymes found in both parasites and humans, but essential to parasite life while
being nonessential or less essential to human life (e.g., purine nucleoside kinase,
ornithine decarboxylase) - Non-enzymatic proteins found in both parasites and humans, but exhibiting differ-
ent pharmacological profiles between the two species (e.g., thiamine transporter)
Using these strategies enables rational drug design of antiparasitic agents.
Because of the importance of malaria, antiparasitic drugs are sometimes divided into
two classes: antiparasitic agents for protozoans, especially malaria, and antiparasitic
agents for helminthic infestations. Each of these classes will be examined separately.