We report our experience in the treatment with benzoimidazole carbamates (mebendazole and albendazole) of 337 patients affected by hydatid cysts with different localizations. The treated cysts showed degenerative modifications in 50.6% of the cases after mebendazole treatment and in about 80%o after albendazole treatment. Relapses after therapy were observed in 30%o of the cases; about 95% of the recurring cysts showed good susceptibility to a further cycle of therapy with benzoimidazole carbamates. Side effects observed with either drug were not severe and always reversible, consisting mainly of abdominal pains and increased levels of transaminases in serum. Among the factors that may influence the therapeutic results are the drug employed, the age of the cysts, the age of the patient, and the localization of the cysts and their morphological characteristics. Moreover, it can be hypothesized that each hydatid cyst has an intrinsic sensitivity to benzoimidazole carbamates.

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.

Despite inducing a strong host cellular and humoral immune response, the helminth Echinococcus granulosus is a highly successful parasite that develops, progresses, and ultimately causes chronic disease. Although surgery remains the preferred therapeutic option, pharmacological research now envisages antihelminthic strategies. To understand the mechanisms that E. granulosus uses to escape host immunosurveillance and promote chronic infection, we investigated how two hydatid cyst components, purified antigen B (AgB) and sheep hydatid fluid (SHF), act on host dendritic cell (DC) differentiation from monocyte precursors and how they influence maturation of DC that have already differentiated. We evaluated the immunomodulatory potential of these antigens by performing immunochemical and cytofluorimetric analyses of monocyte-derived DCs from healthy human donors. During monocyte differentiation, AgB and SHF downmodulated CD1a expression and upregulated CD86 expression. Compared with immature DCs differentiated in medium alone (iDCs), AgB-and SHF-differentiated cells stimulated with lipopolysaccharide included a significantly lower percentage of CD83؉ cells (P < 10 ؊4 ) and had weaker costimulatory molecule expression. When stimulated with AgB and SHF, iDCs matured and primed lymphocytes towards the Th2 response typical of E. granulosus infection. SHF and particularly AgB reduced the production of interleukin-12p70 (IL-12p70) and tumor necrosis factor alpha in lipopolysaccharide-stimulated iDCs. Anti-IL-10 antibodies increased the levels of IL-12p70 secretion in AgB-and SHF-matured DCs. AgB and SHF induced interleukin-1 receptor-associated kinase phosphorylation and activated nuclear factor-B, suggesting that Toll-like receptors could participate in E. granulosus-stimulated DC maturation. These results suggest that E. granulosus escapes host immunosurveillance in two ways: by interfering with monocyte differentiation and by modulating DC maturation.

Four hundred forty-eight patients with 929 Echinococcus granulosus hydatid cysts received 3- to 6-month continuous cycles of mebendazole or albendazole treatment and underwent prolonged follow-up by clinical visits and imaging studies (range, 1-14 years) to assess the long-term outcome of treatment. Degenerative changes and relapse were assessed by imaging techniques. At the end of therapy, 74.1% of the hydatid cysts showed degenerative changes. These were more frequent in albendazole-treated than in mebendazole-treated cysts (82.2% vs. 56.1%; P < .001). During long-term follow-up, 104 cysts (22%) had degenerative changes that progressed, whereas 163 cysts (approximately 25%) relapsed. The percentages of relapses in the two drug-treated groups were almost the same. Relapses occurred more frequently in type II cysts of the liver. Cysts recurred most often (78.5%; P < .001) within the first 2 years after treatment ended. Further chemotherapy cycles induced degenerative changes in >90% of relapsed cysts without inducing more frequent or more severe side effects than those observed during the initial cycles.

). AgB skewed the Th1/Th2 cytokine ratios towards a preferentially immunopathology-associated Th2 polarization, predominantly in patients with progressive disease. AgB-stimulated patients' PBMC also proliferated less than SHF-stimulated PBMC (P ‫؍‬ 9 ؋ 10 ؊3 ). In vitro Th2 cytokine production was reflected in vivo by elevated specific immunoglobulin E (IgE) and IgG4 antibodies binding to AgB. These findings confirm that AgB plays a role in the escape from early immunity by inhibiting PMN chemotaxis. They also add new information on the host-parasite relationship, suggesting that AgB exploits the activation of T helper cells by eliciting a nonprotective Th2 cell response.Cystic echinococcosis (CE) is a widely endemic helminthic disease caused by infection with metacestodes (larval stage) of the tapeworm Echinococcus granulosus. It affects humans and a wide range of livestock species (28). The disease is characterized by the growth in the host internal organs, mostly liver and lungs, of steadily growing fluid-filled, unilocular cysts surrounded by a two-layered hydatid cyst wall. The main feature of the host-parasite relationship is the coexistence of the chronic infection with detectable humoral and cellular responses against the parasite. Parasite survival in vivo depends on efficient evasion mechanisms starting to operate as the parasite develops toward a hydatid cyst. A fibrotic host capsule of variable thickness usually develops, thus forming together with the parasite-derived acellular laminated layer a formidable cystic structure. As a consequence, the actively dividing germinal layer within the cyst along with its associated brood capsule and enclosed protoscoleces are effectively sequestered from the host immune responses. In addition to this physical barrier, the hydatid cyst has probably evolved other strategies for immune evasion. Although older models suggested a more passive role for parasites in immune evasion-for example sequestration, antigenic masking by host proteins, and global immunosuppression-later studies suggest in human parasitoses the active deployment of strategies that manipulate and exploit the host response (12, 30).

The larval stage of Echinococcus granulosus causes cystic echinococcosis, a neglected infectious disease that constitutes a major public health problem in developing countries. Despite being under constant barrage by the immune system, E. granulosus modulates antiparasite immune responses and persists in the human hosts with detectable humoral and cellular responses against the parasite. In vitro and in vivo immunological approaches, together with molecular biology and immunoproteomic technologies, provided us exciting insights into the mechanisms involved in the initiation of E. granulosus infection and the consequent induction and regulation of the immune response. Although the last decade has clarified many aspects of host-parasite relationship in human cystic echinococcosis, establishing the full mechanisms that cause the disease requires more studies. Here, we review some of the recent developments and discuss new avenues in this evolving story of E. granulosus infection in man.

Cystic echinococcosis (CE) is a widespread chronic endemic helminthic disease caused by infection with metacestodes of the tapeworm Echinococcus granulosus. CE affects humans and has a worldwide prevalence of approximately six million. In this review, we discuss current findings in diagnosis and clinical management of CE and new concepts relating to E. granulosus molecules that directly modulate the host immune responses favouring a strong anti-inflammatory response and perpetuating parasite survival in the host. New insights into the molecular biology of E. granulosus will improve considerably our knowledge of the disease and will provide new potential therapeutic applications to treat or prevent inflammatory immune-mediated disease.

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