Follow up of Medically Treated Patients :

Most follow up measures especially clinical judgment are relatively insensitive for detection of cyst changes during medical treatment. Serologic tests are also not suitable for this purpose because of relative initial insensitivity and slow, delayed and unpredictable response even after successful treatment. (10,22) Therefore, imaging studies and in particular ultrasonography have the most important role in follow up of hydatid cysts. The relation between sonographic changes and cyst viability is clearly demonstrated in the excellent work by Gill- Grande et al (20) in which the viability was assessed by surgical removal, pathologic examination and inoculation to mice after albendazole treatment. They confirmed that size reduction of > 20%, membrane disruption and increased echogenicity of the cyst matrix are specific for non-viability (only one of 20 cysts showing these changes was viable but lacks specificity (only 41% of nonviable cysts show above sonographic changes. (20)

Efficacy and Outcome of Chemotherapy of Cystic Echinococcosis :

Chemotherapy with benzimidazole carbamates results in complete cure in about 30% (9-43% in different trials), degenerative changes and/or significant decrease in size (improvement) in 30-50% and no morphological change in about 20-40% of patients in different studies. (1) In long term follow up of cases of cystic echinococcosis treated with benzimidazole carbamates, it is noted that some cysts which had no or minimal initial response may respond later even in the third post-treatment year with morphologic changes in sonography. (9) The differentiation of above late-appearing responses form spontaneous degeneration is difficult because of absence of control group in majority of trials.

Relapses :

Relapses occur in 3-25% of cases in various studies and time of relapse varies from 1 to 100 months after end of the treatment, although majority of them occur during the first 2 years. (4,12,16,22). This relapse rate compares favorably with relapse rate of 11-30% reported with surgical treatment, especially with more conservative methods. (16) Signs of relapse on sonography include: reappearance of new daughter cysts or increase in the size. (22) There is no difference in relapse rate between treatment with mebendazole or albendazole but less recurrent cases are seen in younger patients and with extra hepatic cysts. (12) Further benzimidazole treatment of recurrent cysts results in high response rate of 75 to 90%, which is significantly higher than primary response. (4,12). This may be evidence against development of acquired albendazole resistance during treatment of cystic echinococcosis.

Measures to improve the efficacy of albendazole :

Because of unpredictable and relatively low response rate with albendazole, attempts are made to increase its efficacy. Continuous albendazole therapy may be superior to current method of intermittent therapy. Combination of praziquantel, an isoquinoline scolicide and albendazole used as both preoperative adjunct chemotherapy and sole treatment of cystic echinococcosis may be beneficial. Al karawi et al (1998) reported result of comparison between albendazole alone and albendazole plus praziquantel in a prospective, open label study. The complete response rate was 36.4% and 47.4% in albendazole and combination therapy groups respectively. It is of great importance that from total of 7 patients who did not respond to albendazole alone in a previous trial, 5 responded to combination therapy. (23) This combination also used as preoperative adjunct therapy resulted in significant decrease in percentage of viable protoscolices compared even with relatively high (20mg/kg/day) doses of albendazole alone. (24) Praziquantel was used in these studies in a daily dose of 20mg/kg -50mg/kg. (23,24). Praziquantel alone causes ultrastructural damage in parasite membranes but is not successful in treatment of hydatid cysts in animal studies (25) and its effect in improving the efficacy of albendazole is attributed to increased level of albendazole sulfoxide (24) which remains to be proven. Prescription of albendazole in a liposome-encapsulated form used as a method to increase bioavailability resulted in significant elevation of serum, hepatic tissue and cyst tissue concentrations of the parent drug and its active metabolite in experimental studies done on mice infected with E.Multilocularis. (9)