D. H. Taylor

Comparison of albendazole, mebendazole and praziquantel chemotherapy of Echinococcus multilocularis in a gerbil model.

The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to less than 2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes significantly more effective than mebendazole (p less than 0.05), praziquantel (p less than 0.01) or untreated controls (p less than 0.01).

Echinococcus granulosus: in vitro maintenance of whole cysts and the assessment of the effects of albendazole sulphoxide and praziquantel on the germinal layer

Small entire cysts of Echinococcus granulosus of human and animal origin were cultured in vitro in the presence or absence of albendazole sulphoxide (1000 micrograms/litre) or praziquantel (500 micrograms/litre) for 10 or 11 d, and subsequently passaged into the peritoneal cavity of gerbils to assess viability by continued cyst growth. Viability was reduced in the presence of albendazole sulphoxide, and disintegration of the germinal layer immediately after culture was demonstrated at the ultrastructural level. Praziquantel had no apparent effect on cyst growth.

Echinococcus multilocularis: in vivo results of therapy with albendazole and praziquantel

The effects of albendazole and praziquantel on the growth of Echinococcus multilocularis were studied in cotton rats. Albendazole (20 and 50 mg/kg) reduced parasite weight and increased the length of survival of infected animals but viable infection was present after treatment. In an in vitro system albendazole sulphoxide entered cysts of E. multilocularis passively. Praziquantel 100 mg/kg was ineffective but 500 mg/kg significantly inhibited growth. A combination of albendazole and praziquantel was no more effective than either agent alone.

Combination chemotherapy of Echinococcus granulosus — in vitro studies

Both benzimidazole carbamates and isoquinoline compounds have activity against protoscoleces of Echinococcus granulosus in culture in vitro; combinations of albendazole sulphoxide and praziquantel are more effective than either agent alone.

Comparison of Albendazole and Praziquantel therapy of Echinococcus granulosus in naturally infected sheep.

The effects of albendazole (10 mg kg-1 day-1) and praziquantel (50 mg kg-1 day-1) for 6 weeks on naturally infected sheep with pulmonary cysts of Echinococcus granulosus of proven viability were studied. Immediately following therapy, one of three sheep treated with praziquantel had viable cysts and 7 months later one of two sheep had viable cysts. One sheep died during albendazole therapy, but 7 months following therapy only one of five sheep had viable cysts. Electron microscopy demonstrated necrotic germinal layer tissue in most albendazole-treated cysts and praziquantel also had an effect on cyst ultrastructure. These data suggest that recurrence in humans treated with albendazole may be small. Whilst praziquantel was not particularly effective in this animal model, its clear effect on the ultrastructure suggests that an increased dose and combination therapy with albendazole may be more effective.

Echinococcus granulosus: development of resistance to albendazole in an animal model.

Gerbils with well developed peritoneal cysts of Echinococcus granulosus were randomized to albendazole 50 mg/kg/day or untreated control. Treated animals had less disease at post mortem after 3 months of treatment. Cysts were then taken from both albendazole-treated and control animals and cultured in vitro either with or without albendazole sulphoxide (Alb Sx) 500 micrograms/L for 14 days. Viability of cysts was then established by implantation of whole cysts into gerbils. Whilst naive cysts were affected by Alb Sx (only 2 cysts developed/gerbil) cysts from animals treated with albendazole were not sensitive to further therapy (6.4 cysts/gerbil).

Optimal timing of post-operative albendazole prophylaxis in E. granulosus

Recurrence is an important problem following operations for hydatid disease in man. Significant protection against an intraperitoneal injection of 5000 protoscoleces was achieved in gerbils by a one-month course of albendazole (10 mg kg-1 day-1). However, when prophylaxis was delayed for 15 days after peritoneal inoculation albendazole had no protective effect. Whilst higher serum concentrations probably allow treatment of older infections, these data suggest that protoscoleces are most easily killed by therapy immediately following spillage.

Rapid recovery of Echinococcus granulosus following successful albendazole therapy in a gerbil model

Peritoneal Echinococcus granulosus in gerbils was treated with albendazole. Both early and late infections were studied; response to albendazole therapy and the ability of the parasite to recover after treatment was found to depend on dose and length of therapy. Even after treatment at 50 mg/kg for 2 months late infections retained the ability to recover over 3 months.

Perioperative prophylactic chemotherapy of Echinococcus granulosus: determination of minimum effective length of albendazole therapy in in vitro protoscolex culture.

Protoscoleces of Echinococcus granulosus were cultured in vitro in 500, 250 or 100 μg/1 albendazole sulphoxide for 1, 3, 7, 10, 14d and then ‘recued’ (R) into drug-free medium for the remainder ofthe culture period. Successful minimum lengths of therapy were much longer than for praziquantel, and only at 500μg/1 was the 10dR treatment as effective as continuous therapy for 28d. Treatment with 100 μg/1 both in continuous culture and in the ‘R’ experiments was ineffective over a 35d period. The results are compared with those from similar experiments using praziquantel.

Albendazole is effective against established Echinococcus granulosus in gerbils: comparison of serum concentrations achieved by gavage and feed administration

Serum levels of albendazole sulphoxide in gerbils infected with Echinococcus granulosus and treated with albendazole (20 or 50 mg kg-1 day-1) by gavage were dose dependent, whereas albendazole administered in feed at a rate equivalent to 80 mg kg-1 day-1 achieved serum levels calculated to be equivalent to those produced by administration of 40 mg kg-1 day-1 by gavage. This regimen, over a three-month period, was effective and reduced parasite weight to 4.6% of that in control gerbils, and the treated parasite tissue showed ultrastructural changes ranging from severe accumulation of residual bodies to total disintegration of the germinal layer.