Treatment Response of Cystic Echinococcosis to Benzimidazoles: A Systematic Review

Abstract

Over the past 30 years, benzimidazoles have increasingly been used to treat cystic echinococcosis (CE). The efficacy of benzimidazoles, however, remains unclear. We systematically searched MEDLINE, EMBASE, SIGLE, and CCTR to identify studies on benzimidazole treatment outcome. A large heterogeneity of methods in 23 reports precluded a meta-analysis of published results. Specialist centres were contacted to provide individual patient data. We conducted survival analyses for cyst response defined as inactive (CE4 or CE5 by the ultrasound-based World Health Organisation [WHO] classification scheme) or as disappeared. We collected data from 711 treated patients with 1,308 cysts from six centres (five countries). Analysis was restricted to 1,159 liver and peritoneal cysts. Overall, 1–2 y after initiation of benzimidazole treatment 50%–75% of active C1 cysts were classified as inactive/disappeared compared to 30%–55% of CE2 and CE3 cysts. Further in analyzing the rate of inactivation/disappearance with regard to cyst size, 50%–60% of cysts <6 cm responded to treatment after 1–2 y compared to 25%–50% of cysts >6 cm. However, 25% of cysts reverted to active status within 1.5 to 2 y after having initially responded and multiple relapses were observed; after the second and third treatment 60% of cysts relapsed within 2 y. We estimated that 2 y after treatment initiation 40% of cysts are still active or become active again. The overall efficacy of benzimidazoles has been overstated in the past. There is an urgent need for a pragmatic randomised controlled trial that compares standardized benzimidazole therapy on responsive cyst stages with the other treatment modalities.

Historical Aspects of Echinococcosis

“…Results for over 2000 well-controlled cases treated with benzimidazoles and evaluated for up to 12 months have shown that 10% to 30% of the cysts die (cure), 50% to 70% respond (degeneration or size reduction of cysts), and 20% to 30% do not exhibit morphological changes (Horton, 1997;Todorov et al, 1992;Pawlowski et al, 2001;Horton, 2003;Junghanss et al, 2008). Based on a meta-analysis, including 711 patients, it was estimated that even 2 years after initiation of treatment, 40% of the cysts are still active or become active again (Stojkovic et al, 2009).…”

The Italian registry of cystic echinococcosis (RIEC): the first prospective registry with a European future

“…However, comparison of notified cases with hospital records indicates a clear discrepancy, with consistent underestimation of the burden of CE [17,18] and imported cases and between new and re-admitted cases, and lack of collection of important epidemiological data such as occupation and other risk factors. Given the chronicity and frequent relapses in CE [24,25], patients often access different health centres over time, which could lead to potential duplication of data, which would also contribute to inaccurate statistics. In addition, aspects such as cyst stage and therapy outcome, which have a profound impact on the clinical management of patients and in turn on public health resource allocation, are generally not collected in notification forms.…”

Safety of the Combined Use of Praziquantel and Albendazole in the Treatment of Human Hydatid Disease

“…To date, the medical treatment of hydatidosis has relied on compounds belonging to the benzimidazoles family (albendazole or mebendazole); in particular, albendazole currently represents the best pharmacological option for the treatment of hydatidosis. [19][20][21][22] Over the past few decades, other anthelmintic chemotherapies such as praziquantel and nitazoxanide have also been tested against Echinococcus spp., but their efficacies are inferior to those of benzimidazoles. 16,23,24 Despite this, the combination of albendazole with praziquantel has shown synergistic activity against Echinococcus spp.…”