Structured treatment interruption in patients with alveolar echinococcosis

Abstract

In human alveolar echinococcosis (AE), benzimidazoles are given throughout life because they are only parasitostatic. It has been a longstanding goal to limit treatment, and recent reports suggest that, in selected cases, benzimidazoles may be parasitocidal. Previously, we showed that positron -emission tomography (PET) using [ 18 F]fluoro-deoxyglucose discriminates active from inactive lesions in AE. We have now performed a 3-year prospective study in 23 patients and conducted a structured treatment interruption in those without signs of PET activity. Disease progression was further assessed by ultrasound, computerized tomography, laboratory parameters, and clinical examination.We found PET-negative lesions in 15 of 23 patients and benzimidazoles were discontinued in these patients. After 18 months, patients were reevaluated, and, of the 15 initially PET-negative patients, 8 showed either new activity on PET (n ‫؍‬ 6) or signs of clinical progression (n ‫؍‬ 2). Reinitiation of benzimidazoles halted parasite growth again. No further progression was detected after 36 months. PET had a sensitivity of 91% for the detection of active lesions. In conclusion, despite successful suppression of metabolic activity, in most cases benzimidazoles do not kill the parasite. PET is a reliable tool for assessing metabolic activity and for timely detection of relapses. Neither duration of treatment, kind of treatment, lesion size, calcifications, or regressive changes reliably indicate parasite death. We discourage the discontinuation of benzimidazoles in inoperable AE even after many years of treatment. However, patients with a poor compliance of benzimidazole intake or patients suffering from side effects to benzimidazoles might be assessed for PET negativity. If permanent discontinuation of benzimidazoles is attempted, the course of disease should be followed by PET. (HEPATOLOGY 2004;39: 509 -517.)

Multimodality imaging in diagnosis and management of alveolar echinococcosis: an update

“…PET/CT cannot explain the viability of the parasite directly and a negative study does not mean the death of the parasites completely. However, it can reliably evaluate the inflammatory response and can show the parasitic activity indirectly (40). Therefore, it is the most accepted imaging modality in adjusting the primary therapy, the longterm benzimidazole therapy in inoperable patients, and in follow-up of the patients (12, 13, 40).…”

“…Benzimidazoles (mebendazole and albendazole) are parasitostatic drugs that can be used against parasitic metacestodes (2,12,16). Although benzimidazoles are widely regarded as parasitostatic, it has been reported that they may, in some cases, exert parasiticidal effect and thus the treatment may be safely terminated after some time (37,40). On the other hand, these drugs have some side effects and are potentially teratogenic.…”

In Vitro and In Vivo Treatments of Echinococcus Protoscoleces and Metacestodes with Artemisinin and Artemisinin Derivatives

“…For alveolar echinococcosis, these compounds were shown to act parasitostatically rather than parasitocidally, with high recurrence rates after interruption of therapy. Improved drug treatments are needed (8,24).Most countries to which malaria is endemic have now adopted artemisinin-based combination therapy as a first-line treatment for Plasmodium falciparum infection (34), and activities of artemisinins against other protozoans have been reported (1, 12). Trematodes, including schistosomes (31) and others, have proven susceptible to artemisinins and semisynthetic derivatives (13)(14)(15)(16)26), and antitumor activities of artemisinins have been reported (11,18,35).…”

In Vitro Activities of Itraconazole, Methiazole, and Nitazoxanide versus Echinococcus multilocularis Larvae

“…Severe side effects may be observed, and the parasitostatic effect of these drugs implies that E. multilocularis is not depleted and may resume growth after discontinuation of treatment (3,18). The overall success rate of benzimidazole treatment ranges between 55 and 97% (4,9,19).…”