trans

HELMINTHS AND CHEMOTHERAPY 427
FIGURE 16.8 Structure of the main drugs used against worm infections. (A) Praziquantel; (B) ivermectin;
(C) pyrantel; (D) benzimidazole.
of praziquantel is not known precisely. It is
known, however, to cause muscle contraction
that is linked to calcium flux, although no targets
have yet been pinpointed. The description
of resistant isolates from the field has not
yet been unambiguously described, although
there is evidence that suggests resistance is
indeed a possibility. Notably, a lower praziquantel
cure rate was noted in Senegal and Egypt.
Several factors, such as the infection intensity
or immunological factors, could contribute
to this reduced efficacy but arguments in favor
of resistant parasites are available. For example,
both non-responding clinical isolates and
praziquantel-resistant worms selected under
laboratory conditions had a lower percent
reduction in worm burdens in mice than controls.
The mechanisms by which resistance
occurs is unknown, but randomly amplified
polymorphic markers were circumstantially
linked to sensitive and resistant worms isolated
from Egypt. A difference between the
morphology of sensitive and resistant worms
has been observed in response to praziquantel,
and this change has been suggested as
an in vitro test to monitor praziquantel resistance.
Hycanthone and oxamniquine have
been used in the treatment of schistosomes
but the use of the former has been discontinued.
The drugs are probably converted in the
schistosome to an active molecule capable of
alkylating DNA. Resistance seems to be linked
to the absence of the enzymatic activity, that
seems to be a sulfotransferase capable of activating
the precursors of the two drugs.
Resistance to macrocyclic lactones
The macrocyclic lactones, avermectins, are
broad spectrum anthelmintics with a wide margin
of safety in vertebrates. Ivermectin is the
drug of choice in the treatment of Onchocerca
volvolus, the organism responsible for onchocerciasis.
It is also widely used in veterinary
medicine and agriculture. Ivermectin opens the
worms’ chloride channels and paralyses the
MEDICAL APPLICATIONS