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The therapeutic effects of mebendazole and piperazine on certain helminth parasites of the garden lizard, Calotes versicolor
Inlernurronul Journalfor Prm1rd in Grea1 Brrraln
Purourlologr.
Vol.
22, No.
6.p~.
843-845,
1992 ‘01992
002Cb7519192 $5.00 + 0.00 Prrgomon Press Lid Ausrralinn .Smer.v for Parmirolog?,
RESEARCHNOTE THE THERAPEUTIC EFFECTS OF MEBENDAZOLE AND PIPERAZINE ON CERTAIN HELMINTH PARASITES OF THE GARDEN LIZARD, CALOTES VERSICOLOR MARY Department
of Zoology,
E. KONDA
Andhra
University,
Waltair
530 001, India
(Received 27 March 1992; accepred 2 June 1992)
Abstract-KoNoA M. E. 1992. The therapeutic effects of mebendazole and piperazine on certain helminth parasites of the garden lizard, Calotes versicolor. Infernational Journal for Parasitology 22: 843-845. The therapeutic efficacies of mebendazole and piperazine were assessed separately at various doses. Calotes versicolor naturally infected with Paradistomum orientalis, Thelandros thelandros and Oochoristica indica were orally administered with mebendazole (MBZ) or piperazine (PIP) at dose rates of 40, 80,200, and 400 mg kg-’ body weight and 400 mg kg-’ for 3 consecutive days (= 1200 mg kg-’ body weight). Both MBZ and PIP were 100% effective against T. thelandros at 400 mg kg- ’ but only expelled 85-90% of 0. indica and P. orienfalis infections, respectively at a 1200 mg kg~ ’ dosage. These results suggest that in the present hostparasite relationship the nematodes were more susceptible to the effects of these anthelmintics than were the cestodes and trematodes. INDEX KEY WORDS: Paradistomum orientalis. Thelandros rhelandros; Oochoristica indica; Calotes versicolor; mebendazole; piperazine; efficacy.
MEBENDAZOLE (MBZ) is one of the most widely used benzimidazole (BZ) compounds; BZs are considered as broad spectrum anthelmintics (Hennessy, Lacey, Steel & Prichard, 1987; Campbell, 1990; Diaz-Jidy, Ferniandez, Millian-Marcel0 & Ruiz, 1990), fungicides (Davidse & Flach, 1977) and antitumor agents (Dustin, 1984). These drugs exert their action by binding to the tubulin protein of helminths (Lubega & Prichard, 1991), thereby inhibiting the formation of microtubules or causing the depolymerization of microtubules, resulting in the simultaneous loss of microtubules (Enos & Coles, 1990) and degenerative changes in the absorptive cells of different helminth parasites (Borgers & DeNollin, 1975; Borgers, DeNollin, Verheyen, Vanparijs & Thienpont, 1975). PIP is an effective anthelmintic which by altering the electric charge of the nerve cells causes neuromuscular hyperpolarization and subsequent paralysis of helminth parasites (Abdulazizov, 1975; Campbell, 1977). The studies cited above were directed at human as well as animal hosts of economic and veterinary importance, which are all homoiotherms. My aim was to examine a potential model host among poikilotherms, namely the garden lizard, Calotes versicolor, as it is easily obtainable, of a manageable size and above all harbours a variety of helminth parasites.
Therefore in this study the therapeutic efficacies of MBZ and PIP on Paradistomum orientalis (trematode), Thelandros thelandros(nematode) and Oochoristica indica (cestode), the helminth parasites of gall bladder, rectum and intestine, respectively of C. versicolor were explored. Naturally infected, adult calotes, weighing 40-50 g each, were obtained from the Rishikonda area of Visakhapatnam district, India. They were maintained in an animal house, at a rate of six calotes per grilled metal cage with food and water adlibitum. Mebex was obtained from Cipla, Bombay. Each 5 ml contained 100 mg mebendazole. Helmacid was from Burroughs Wellcome (India), Bombay. Each 5 ml contained 100 mg piperazine citrate. Five different doses of MBZ or PIP were orally administered to different groups of calotes with an 18 gauge needle. Each group (a, b, c, d, e and f) consisted of 18 calotes. The experimental groups b, c, d and e were treated with single doses of 40, 80, 200 and 400 mg kg,-’ respectively, of either MBZ or PIP. The control group (a) of calotes were not treated with any drug. Group f calotes were given 400 mg kg-’ of MBZ or PIP for 3 days (= 1200 mg kg-‘). Groups b, c, d and e calotes were autopsied 24 h post-treatment, together with the control animals. Group f calotes were 843
844
M. E. TABLE I
Group No.
Period of treatment
Dose rate
(wk
‘1
~ Tub EFFICACYor MEBENDALOLF
Total worm counts T
(h)
P
144 (X.0 + 0.05) 113 (6.3*0.06) 108 (6.0 + 0.09) 12 (4.0&0.06) 23 (1.3+0.03) 11 (0.6 + 0.02)
a
Control
24
b
40
24
c
80
24
d
200
24
e
400
24
f
1200
12
KONDA
12 (4.0* 0.05) 72 (4.0+0.02) 36 (2.0 ok0.03) IX (l.O* 0.006) 0
0 129 (7.2 zt 0.26) 54 (3.0*0.15) 72 (4.0*0.13) 54 (3.0*0.16) 54 (3.010.15) IX (1.0*0.03)
0
Efficacy T
P
(‘%I) 0
21.6
0*
5x.4
25.0
50.0
44.2
50.0
75.0
5x.4
84.
I
92.4
IOO.0
5x.4
100.0
86.
I
Each group contained I8 calotes. Figures in parentheses indicate mean f s P P, P. orient&; T, T. thelmdros; 0, 0. indicu * Statistically insign$can/. The rest were significant at P
Dose rate
Period of treatment
(mg kg ‘)
(h)
P
a
Control
24
b
40
24
C
80
24
d
200
24
e
400
24
f
1200
12
I67 (9.3*0.08) 173 (9.6 * 0.08) 144 (8.0 * 0.03) 90 (5.0+0.02) 54 (3.0* 0.026) 18 (l.o*o.o3)
Group No.
Total worm counts T 54 (3.3ztO.03) 47 (2.6f0.01) 24 (1.3&0.06) 24 (1.3~kO.l) 0 0
0
180 (10.0*0.03) II9 (6.6kOo.02) 83 (4.6f0.05) 54 (3.0 * 0.07) 41 (2.3 f 0.05) 23 (i.3*o.oI)
P
Efficacy T
Of
72 h after drug treatment. Then the calotes were given a mid-ventral incision and the entire guts were opened to recover Oochoristica and Thelandros. The gall bladder was opened and Paradistomum were recovered. The worms were identified under a microscope, counted and the % efficacies of these drugs at various dose rates were calculated in comparison with the control worms. For statistical analysis of the data the Student’s t-test was used. MBZ (Table I) was 21.6% effective against Paradistomum at a low dose of 40 mg kg- ‘, which increased gradually and reached a maximum of 92.4% at 1200 mg kg’ dosage. Thus MBZ significantly reduced
0
13.4*
33.9
14.0*
55.6
53.9
46.3
55.6
70.0
61.8
100.0
77.3
x9.3
100.0
X7.3
Each group contained I8 calotes. Figures in parentheses are values of mean * s L P, P. orient&; T, T. thrlundros; 0, 0. indica *Statistically insignificunr. The rest were signiticant at P ~0.0025, unless the P values are mentioned sacrificed
(%)
in the text.
the worm burden of Paradistomum from low to high dose rates as was assessed by the t-test (P < 0.0025). but this drug was not effective against Thelundros at a low dose rate (40 mg kg-‘). However, there was 50% increase in its efficacy against Thekzndros at 80 mg kg- ‘, which later gradually increased to a peak of 100% at the 400 mg kg- ’ dose level. These results differ from the results of Evans, Hollmann & Du Preezh (I 987) who found that single dose 500 mg MBZ treatment of children reduced the egg output of Ascari.7 lumhricoides (95%), hookworm (84%) and Trichuris trichiurrc. The reduction in total worm recovery following MBZ treatment in the present study correlates well with the
Research
results of Forrester, Scott, Bundy & Golden (1990) who observed correlation between the reduction in egg output and worm burden after MBZ treatment in two Mexican communities, infected with Ascuris lumbricoidrs and Trichuris trichiura. In the present investigation, MBZ expelled around 60% of Oochoristica from 40 to 400 mg kg-’ and its efficacy increased to 86% at a dose of 1200 mg kg-‘. These results were almost similar to those of Belicchi, Cartasegna, Montorsi, Peta, Spiropoulos, Torzilli & Constantino (1991) who found that low doses of MBZ (30-50 mg kg-‘) when given separately were effective against human hydatidosis. Similarly, the cure rates obtained by MBZ treatment were 50-59% against H. nuna infection in children (Khalil, el Shimi, Sarwat. Fawzy & el Sorougy. 1991). PIP (Table 2) was ineffective against Paradistomum at low doses such as 40 and 80 mg kg-‘. Later ins efficacy was significantly increased to 89% at high dose rates (P < 0.05 at 200 and 400 mg kg-’ and P < 0.0025 at 1200 mg kg-‘). This drug was not effective against Thelundros at a dose of 40 mg kg-‘, but its efficacy increased with increasing dose rates and reached 100% at a 400 mg kg-’ dose. These results suggest that PIP was more effective against Thrlundros than against Puradistomum at a low dose rate, i.e. at the 80 mg kg-’ level. Similarly a single dose of 100 mg kg-’ PIP was effective against A. lumbricoides infection (Abdulazizov, 1975). PIP could significantly expel 0. indica from calotes, even from low to high dose rates suggesting that this drug was more effective against 0. indica than against T. thelundros and P. orientalis infections at a dose of 40 mg kg-‘. These results indicate that both MBZ and PIP were 100% effective against T. thelundros at the 400 mg kg-’ dose rate but 85-90% effective against 0. indicu and P. orient& at 1200 mg kg-‘, suggesting that nematodes arc more susceptible to these drugs than trematodes and cestodes. A&no~/r&mc~~ -The
author is grateful to the Council of Scientific and Industrial Research (C.S.I.R.). New Delhi, India, for its financial assistance.
REFERENCES ARDI:LAZIZOV A. I. 1975. Histological changes in Asc~aris lumhricoides caused by some anthelmintics. Act&’ nye V0pro.s~~Sovrenennoi Parusitologii 84: 14417.
Note
845
BELICCHI M., CARTASEGNA S., MON~ORSI M., PETA M., SPIROPOULOSJ., TORZILLI G. & CONSTANTINO D. 1991. Mebendazole in the therapy of hydatidosis. Recenti Progressi in Medicina 82: 2 19-224. BORGERSM. & DENOLLIN S. 1975. Ultrastructural changes in Ascaris ,suum intestine after mebendazole treatment in viva. Journalqf Parusitology 61: 110-122. BORGERS M.. DENOLLIN S., VERHEYENA., VANPARIJSD. & THIENPONTD. 1975. Morphological changes in cysticerci of Tuenia taeniaeformis after mebendazole treatment. Journal of’Parasitolo,yy 61: 830-843. CAMPBELLW. C. 1977. The control of parasites: the role of drugs. Proceedings of the Helmintholo~ical Society of Washington 44: 7-28. CAMPBELL W. C. 1990. Benzimidazoles: veterinary uses. Puravitology Todq 6: 130-l 33. DAVIDSE L. C. & FLACH W. 1977. Differential binding of methyl benzimidazole-2-yl carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans. Journal qf Cell Biology 12: 174-193. DIAZ-JIDY M.. FFRNIANDEZA. H., MILLIAN-MARCELOJ. C. & RUIZ P. A. 1990. Levamisole, mebendazole, thiabendazole. Their effectiveness as helminthicides in African patients recently arrived in Cuba. From 1987 to 1988. Revisra Cuhana De Medicina Tropiul42: 240-246. DUSTIN P. 1984. Microtubules. Springer, Berlin. ENOS A. & COLES G. 1990. Effect of benzimidazole drugs on tubulin in benzimidazole resistant and susceptible strains of Cuenorhahditis r1egan.v. International Journul for Parasitology 20: 161-167. EVANS A. C., HOLLMAN A. W. & DUPREEZH L. 1987. Mebendazole 500 mg for single dose treatment of nematode infestation. South .4frican Medical Journal 12: 665-667. FORRESTERJ. E., SCOTTM. E., BUNDYD. A. &GOLDEN M. H. 1990. Predisposition of individuals and families in Mexico to heavy infection with Ascaris lumbricoides and Trichuris trirhiura. Transuciions of the Rqlrtl Sociei?’ .for Tropical Medicine and Hygiene 84: 722-726. HENNESSY D. R.. LACEYE.. STEELJ. W. & PRICHARDR. K. 1987. The kinetics of triclabendazole disposition in sheep. Journul of Veterinary Pharmacology and Therapeutics 10: 6472. KHALIL H. M., EL SHIMI S., SARWATM. A., FAWLYA. F. &EL SOROUGYA. 0. 1991. Recent study of Hymenolepis ncma infection in Egyptian children. Journa/ of the Egyptian Society ofParasitology 21:293-300. LL.REGAG. W. & PRICHARDR. K. 1991. Specific interaction of benzimidazole anthelmintics with tubulin. Comparison of developing stages of thiabendazole-susceptible and thiabendazole-resistant strains of Haemonchus c’ontorfus. Bioc~hemicalPharmacology 41: 93-10 I.
Purourlologr.
Vol.
22, No.
6.p~.
843-845,
1992 ‘01992
002Cb7519192 $5.00 + 0.00 Prrgomon Press Lid Ausrralinn .Smer.v for Parmirolog?,
RESEARCHNOTE THE THERAPEUTIC EFFECTS OF MEBENDAZOLE AND PIPERAZINE ON CERTAIN HELMINTH PARASITES OF THE GARDEN LIZARD, CALOTES VERSICOLOR MARY Department
of Zoology,
E. KONDA
Andhra
University,
Waltair
530 001, India
(Received 27 March 1992; accepred 2 June 1992)
Abstract-KoNoA M. E. 1992. The therapeutic effects of mebendazole and piperazine on certain helminth parasites of the garden lizard, Calotes versicolor. Infernational Journal for Parasitology 22: 843-845. The therapeutic efficacies of mebendazole and piperazine were assessed separately at various doses. Calotes versicolor naturally infected with Paradistomum orientalis, Thelandros thelandros and Oochoristica indica were orally administered with mebendazole (MBZ) or piperazine (PIP) at dose rates of 40, 80,200, and 400 mg kg-’ body weight and 400 mg kg-’ for 3 consecutive days (= 1200 mg kg-’ body weight). Both MBZ and PIP were 100% effective against T. thelandros at 400 mg kg- ’ but only expelled 85-90% of 0. indica and P. orienfalis infections, respectively at a 1200 mg kg~ ’ dosage. These results suggest that in the present hostparasite relationship the nematodes were more susceptible to the effects of these anthelmintics than were the cestodes and trematodes. INDEX KEY WORDS: Paradistomum orientalis. Thelandros rhelandros; Oochoristica indica; Calotes versicolor; mebendazole; piperazine; efficacy.
MEBENDAZOLE (MBZ) is one of the most widely used benzimidazole (BZ) compounds; BZs are considered as broad spectrum anthelmintics (Hennessy, Lacey, Steel & Prichard, 1987; Campbell, 1990; Diaz-Jidy, Ferniandez, Millian-Marcel0 & Ruiz, 1990), fungicides (Davidse & Flach, 1977) and antitumor agents (Dustin, 1984). These drugs exert their action by binding to the tubulin protein of helminths (Lubega & Prichard, 1991), thereby inhibiting the formation of microtubules or causing the depolymerization of microtubules, resulting in the simultaneous loss of microtubules (Enos & Coles, 1990) and degenerative changes in the absorptive cells of different helminth parasites (Borgers & DeNollin, 1975; Borgers, DeNollin, Verheyen, Vanparijs & Thienpont, 1975). PIP is an effective anthelmintic which by altering the electric charge of the nerve cells causes neuromuscular hyperpolarization and subsequent paralysis of helminth parasites (Abdulazizov, 1975; Campbell, 1977). The studies cited above were directed at human as well as animal hosts of economic and veterinary importance, which are all homoiotherms. My aim was to examine a potential model host among poikilotherms, namely the garden lizard, Calotes versicolor, as it is easily obtainable, of a manageable size and above all harbours a variety of helminth parasites.
Therefore in this study the therapeutic efficacies of MBZ and PIP on Paradistomum orientalis (trematode), Thelandros thelandros(nematode) and Oochoristica indica (cestode), the helminth parasites of gall bladder, rectum and intestine, respectively of C. versicolor were explored. Naturally infected, adult calotes, weighing 40-50 g each, were obtained from the Rishikonda area of Visakhapatnam district, India. They were maintained in an animal house, at a rate of six calotes per grilled metal cage with food and water adlibitum. Mebex was obtained from Cipla, Bombay. Each 5 ml contained 100 mg mebendazole. Helmacid was from Burroughs Wellcome (India), Bombay. Each 5 ml contained 100 mg piperazine citrate. Five different doses of MBZ or PIP were orally administered to different groups of calotes with an 18 gauge needle. Each group (a, b, c, d, e and f) consisted of 18 calotes. The experimental groups b, c, d and e were treated with single doses of 40, 80, 200 and 400 mg kg,-’ respectively, of either MBZ or PIP. The control group (a) of calotes were not treated with any drug. Group f calotes were given 400 mg kg-’ of MBZ or PIP for 3 days (= 1200 mg kg-‘). Groups b, c, d and e calotes were autopsied 24 h post-treatment, together with the control animals. Group f calotes were 843
844
M. E. TABLE I
Group No.
Period of treatment
Dose rate
(wk
‘1
~ Tub EFFICACYor MEBENDALOLF
Total worm counts T
(h)
P
144 (X.0 + 0.05) 113 (6.3*0.06) 108 (6.0 + 0.09) 12 (4.0&0.06) 23 (1.3+0.03) 11 (0.6 + 0.02)
a
Control
24
b
40
24
c
80
24
d
200
24
e
400
24
f
1200
12
KONDA
12 (4.0* 0.05) 72 (4.0+0.02) 36 (2.0 ok0.03) IX (l.O* 0.006) 0
0 129 (7.2 zt 0.26) 54 (3.0*0.15) 72 (4.0*0.13) 54 (3.0*0.16) 54 (3.010.15) IX (1.0*0.03)
0
Efficacy T
P
(‘%I) 0
21.6
0*
5x.4
25.0
50.0
44.2
50.0
75.0
5x.4
84.
I
92.4
IOO.0
5x.4
100.0
86.
I
Each group contained I8 calotes. Figures in parentheses indicate mean f s P P, P. orient&; T, T. thelmdros; 0, 0. indicu * Statistically insign$can/. The rest were significant at P
Dose rate
Period of treatment
(mg kg ‘)
(h)
P
a
Control
24
b
40
24
C
80
24
d
200
24
e
400
24
f
1200
12
I67 (9.3*0.08) 173 (9.6 * 0.08) 144 (8.0 * 0.03) 90 (5.0+0.02) 54 (3.0* 0.026) 18 (l.o*o.o3)
Group No.
Total worm counts T 54 (3.3ztO.03) 47 (2.6f0.01) 24 (1.3&0.06) 24 (1.3~kO.l) 0 0
0
180 (10.0*0.03) II9 (6.6kOo.02) 83 (4.6f0.05) 54 (3.0 * 0.07) 41 (2.3 f 0.05) 23 (i.3*o.oI)
P
Efficacy T
Of
72 h after drug treatment. Then the calotes were given a mid-ventral incision and the entire guts were opened to recover Oochoristica and Thelandros. The gall bladder was opened and Paradistomum were recovered. The worms were identified under a microscope, counted and the % efficacies of these drugs at various dose rates were calculated in comparison with the control worms. For statistical analysis of the data the Student’s t-test was used. MBZ (Table I) was 21.6% effective against Paradistomum at a low dose of 40 mg kg- ‘, which increased gradually and reached a maximum of 92.4% at 1200 mg kg’ dosage. Thus MBZ significantly reduced
0
13.4*
33.9
14.0*
55.6
53.9
46.3
55.6
70.0
61.8
100.0
77.3
x9.3
100.0
X7.3
Each group contained I8 calotes. Figures in parentheses are values of mean * s L P, P. orient&; T, T. thrlundros; 0, 0. indica *Statistically insignificunr. The rest were signiticant at P ~0.0025, unless the P values are mentioned sacrificed
(%)
in the text.
the worm burden of Paradistomum from low to high dose rates as was assessed by the t-test (P < 0.0025). but this drug was not effective against Thelundros at a low dose rate (40 mg kg-‘). However, there was 50% increase in its efficacy against Thekzndros at 80 mg kg- ‘, which later gradually increased to a peak of 100% at the 400 mg kg- ’ dose level. These results differ from the results of Evans, Hollmann & Du Preezh (I 987) who found that single dose 500 mg MBZ treatment of children reduced the egg output of Ascari.7 lumhricoides (95%), hookworm (84%) and Trichuris trichiurrc. The reduction in total worm recovery following MBZ treatment in the present study correlates well with the
Research
results of Forrester, Scott, Bundy & Golden (1990) who observed correlation between the reduction in egg output and worm burden after MBZ treatment in two Mexican communities, infected with Ascuris lumbricoidrs and Trichuris trichiura. In the present investigation, MBZ expelled around 60% of Oochoristica from 40 to 400 mg kg-’ and its efficacy increased to 86% at a dose of 1200 mg kg-‘. These results were almost similar to those of Belicchi, Cartasegna, Montorsi, Peta, Spiropoulos, Torzilli & Constantino (1991) who found that low doses of MBZ (30-50 mg kg-‘) when given separately were effective against human hydatidosis. Similarly, the cure rates obtained by MBZ treatment were 50-59% against H. nuna infection in children (Khalil, el Shimi, Sarwat. Fawzy & el Sorougy. 1991). PIP (Table 2) was ineffective against Paradistomum at low doses such as 40 and 80 mg kg-‘. Later ins efficacy was significantly increased to 89% at high dose rates (P < 0.05 at 200 and 400 mg kg-’ and P < 0.0025 at 1200 mg kg-‘). This drug was not effective against Thelundros at a dose of 40 mg kg-‘, but its efficacy increased with increasing dose rates and reached 100% at a 400 mg kg-’ dose. These results suggest that PIP was more effective against Thrlundros than against Puradistomum at a low dose rate, i.e. at the 80 mg kg-’ level. Similarly a single dose of 100 mg kg-’ PIP was effective against A. lumbricoides infection (Abdulazizov, 1975). PIP could significantly expel 0. indica from calotes, even from low to high dose rates suggesting that this drug was more effective against 0. indica than against T. thelundros and P. orientalis infections at a dose of 40 mg kg-‘. These results indicate that both MBZ and PIP were 100% effective against T. thelundros at the 400 mg kg-’ dose rate but 85-90% effective against 0. indicu and P. orient& at 1200 mg kg-‘, suggesting that nematodes arc more susceptible to these drugs than trematodes and cestodes. A&no~/r&mc~~ -The
author is grateful to the Council of Scientific and Industrial Research (C.S.I.R.). New Delhi, India, for its financial assistance.
REFERENCES ARDI:LAZIZOV A. I. 1975. Histological changes in Asc~aris lumhricoides caused by some anthelmintics. Act&’ nye V0pro.s~~Sovrenennoi Parusitologii 84: 14417.
Note
845
BELICCHI M., CARTASEGNA S., MON~ORSI M., PETA M., SPIROPOULOSJ., TORZILLI G. & CONSTANTINO D. 1991. Mebendazole in the therapy of hydatidosis. Recenti Progressi in Medicina 82: 2 19-224. BORGERSM. & DENOLLIN S. 1975. Ultrastructural changes in Ascaris ,suum intestine after mebendazole treatment in viva. Journalqf Parusitology 61: 110-122. BORGERS M.. DENOLLIN S., VERHEYENA., VANPARIJSD. & THIENPONTD. 1975. Morphological changes in cysticerci of Tuenia taeniaeformis after mebendazole treatment. Journal of’Parasitolo,yy 61: 830-843. CAMPBELLW. C. 1977. The control of parasites: the role of drugs. Proceedings of the Helmintholo~ical Society of Washington 44: 7-28. CAMPBELL W. C. 1990. Benzimidazoles: veterinary uses. Puravitology Todq 6: 130-l 33. DAVIDSE L. C. & FLACH W. 1977. Differential binding of methyl benzimidazole-2-yl carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans. Journal qf Cell Biology 12: 174-193. DIAZ-JIDY M.. FFRNIANDEZA. H., MILLIAN-MARCELOJ. C. & RUIZ P. A. 1990. Levamisole, mebendazole, thiabendazole. Their effectiveness as helminthicides in African patients recently arrived in Cuba. From 1987 to 1988. Revisra Cuhana De Medicina Tropiul42: 240-246. DUSTIN P. 1984. Microtubules. Springer, Berlin. ENOS A. & COLES G. 1990. Effect of benzimidazole drugs on tubulin in benzimidazole resistant and susceptible strains of Cuenorhahditis r1egan.v. International Journul for Parasitology 20: 161-167. EVANS A. C., HOLLMAN A. W. & DUPREEZH L. 1987. Mebendazole 500 mg for single dose treatment of nematode infestation. South .4frican Medical Journal 12: 665-667. FORRESTERJ. E., SCOTTM. E., BUNDYD. A. &GOLDEN M. H. 1990. Predisposition of individuals and families in Mexico to heavy infection with Ascaris lumbricoides and Trichuris trirhiura. Transuciions of the Rqlrtl Sociei?’ .for Tropical Medicine and Hygiene 84: 722-726. HENNESSY D. R.. LACEYE.. STEELJ. W. & PRICHARDR. K. 1987. The kinetics of triclabendazole disposition in sheep. Journul of Veterinary Pharmacology and Therapeutics 10: 6472. KHALIL H. M., EL SHIMI S., SARWATM. A., FAWLYA. F. &EL SOROUGYA. 0. 1991. Recent study of Hymenolepis ncma infection in Egyptian children. Journa/ of the Egyptian Society ofParasitology 21:293-300. LL.REGAG. W. & PRICHARDR. K. 1991. Specific interaction of benzimidazole anthelmintics with tubulin. Comparison of developing stages of thiabendazole-susceptible and thiabendazole-resistant strains of Haemonchus c’ontorfus. Bioc~hemicalPharmacology 41: 93-10 I.