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TREATMENT OF PARASITIC DISEASES 459
the pork tapeworm, Taenia saginata, the
beef tapeworm, Diphyllobothrium latum,
the fish tape worm, Dipylidium caninum, the
dog tape worm, and Hymenolepis nana, the
dwarf tapeworm, are susceptible to a single
dose of praziquantel. A higher dose is needed
for H. nana. Praziquantel is not effective in
the treatment of echinococcosis. Albendazole
(see Intestinal Helminths) is the drug with
the greatest activity against E. granulosus and
E. multilocularis, but high doses are needed for
prolonged periods of time, and it is variably
effective.
The treatment of neurocysticercosis, which
is caused by the larval form of T. solium, is controversial.
Both praziquantel and albendazole
can kill cysticerci in the central nervous system.
Corticosteroids are usually administered
with them to reduce inflammatory reactions
in the brain. The penetration of praziquantel
into the central nervous system is decreased
by corticosteroids while that of albendazole is
increased. Most physicians prefer albendazole
for that reason. It is also administered for a
shorter period of time than praziquantel. Both
drugs are contraindicated in persons with cysticerci
in the eye or spinal cord.
Praziquantel
The precise mechanism of action of praziquantel
is uncertain. The drug is rapidly taken
up by flukes and tapeworms. In adult schistosomes
the tegument of the worm is damaged,
resulting in intense vacuole formation and
calcium influx (Figure 17.2). Tetanic contraction
of the worm’s musculature and paralysis
follow. Damaged worms are often swept
back to the liver. A number of surface antigens,
including actin, are exposed. The damaged
surface is rendered susceptible to immune
attack.
In the case of Hymenolepis spp., praziquantel
causes calcium release from endogenous
stores, leading to massive contraction of the
worm. This is followed by expulsion from the
gastrointestinal tract. The tegument of the neck
region of the adult tapeworm develops vacuoles,
while the scolex and proglottids appear
to be unaffected.
Praziquantel is well absorbed orally. It is generally
administered in three doses daily for 1 or
2 days. Mild abdominal discomfort, diarrhea,
malaise, headache and dizziness are common,
but seldom require the termination of therapy.
Some recipients manifest allergic symptoms
with fever, rash, pruritus and eosinophilia in
response to released worm antigens.
Future considerations
For now, praziquantel provides excellent
efficacy with acceptable toxicity and pharmacodynamics
for the treatment of all but a few
trematode and cestode infections. The only
important human fluke that does not respond
to praziquantel is F. hepatica. The veterinary
drug, trichlabendazole, was effective, but it is
no longer in production. The only drug now
available is bithionol, which is associated with
nausea, vomiting, abdominal pain, diarrhea,
leukopenia, hepatitis and photosensitivity
reactions. Improved chemotherapy is needed
for F. hepatica.
In respect to cestodes, praziquantel is excellent
when administered as a single dose for the
treatment of adult tapeworms in the gastrointestinal
tract. The treatment of neurocysticercosis
remains controversial. Both praziquantel
and albendazole can kill cysticerci in the central
nervous system. The role of chemotherapy
may vary depending on the number and site of
the lesions. Neither drug works well against
cysts in the ventricles or subarachnoid space.
Studies of the natural history of cysticercosis
MEDICAL APPLICATIONS