PARASITOLOGY
n BOX 6.5
Hildreth et al. (1997) showed that the drug tunicamycin at a dose of 10 mg/ml significantly
inhibited the uptake of tritiated galactose into the worm.
Tunicamycin inhibits the synthesis of glycoproteins, procollagen and peptidoglycans
and the secretion of lgA and lgE by plasma cells. In addition the compound also affects
the fibroblast interferon cell system. The level of inhibitory effect of TM appears to be at
the level of protein glycosylation rather than carbohydrate (galactose) transport.
McCracken and Lipkowitz (1990) investigated the effect of tioxidazole (TIOX) on
H. diminutainfected rats. The following observations were made:nThere were alterations to the weight of the worms as well as their chemical composition.
The worms were found to be significantly smaller and contained less glycogen.
nThe protein concentrations increased to offset the drop in glycogen.
nGlycogen/protein ratio was less than in controls.
nThere were differences in absolute amounts of protein and glycogen compared to controls.During in vitro studies using TIOX treated worms, the worms absorbed less exogenous
glucose and the ability to absorb against a concentration gradient was significantly depressed.n 6.5 ANTIPARASITIC CHEMOTHERAPY
The structure of the drug molecules influences the affect they have on tapeworms.
For example the molecular configurations of benzothiazole and benzimidazole are
structurally related and both are active in causing irreversible damage to the tegument
of tapeworms.
Many parasites, especially the malaria parasites, have been shown to have developed
resistance to some of the more commonly used drugs. Among the parasitic helminths
the mechanism of resistance includes parasite-specific enzymes that are able to protect
against oxygen radicals and develop resistance against drugs acting via an oxidative
burst.
In many of the helminths, especially the nematodes, the microtubules and nervous
system appear to be the main chemotherapeutic targets in helminths. They differ
from those of the host because of the evolutionary distance separating mammals from
helminths. However one of the more recent discoveries has been that the microtubules
of free-living nematodes, eg Caenorhabditis elegansare just as susceptible to benzimidazole
anthelmintics as parasitic nematodes. The motoneural map for C. elegansis the same as
that for Ascaris lumbricoides. Both are immobilised by levamisole, piperazine, avermectins
etc. This interesting finding could possibly lead to many more free-living nematodes
being used for testing new drugs.
Problems with the drugs used against parasitic protozoa give a high potential for
mutation, which many of these parasites undergo. A rapidly forming new generation of
parasites provides the conditions for the possibility of drug resistance to develop. The
parasite causing cerebral malaria, Plasmodium falciparum, is known to have developed
resistance to some of the anti-malarials now available.
Phosphofructokinase (PFK) extracted from schistosomes is sensitive to antimonial
compounds which may due to the PFK from parasites being an isoenzyme of mammalian
PFK.