Effect of Amphotericin B on Larval Growth of
            <i>Echinococcus multilocularis</i>

Reuter, Stefan; Merkle, Marion; Brehm, Klaus; Kern, Peter; Manfras, Burkhard

doi:10.1128/aac.47.2.620-625.2003

Cited by 58 publications

(52 citation statements)

References 31 publications

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“…Amphotericin B (AMB) is the most effective drug for the treatment of visceral leishmaniasis (Murray, 2005) and it also acts against Trypanosoma (Yardley and Croft, 1999). Reuter et al (2003a) demonstrated that AMB is highly effective against E. multilocularis metacestodes in vitro, but only with a parasitostatic effect. The mode of AMB action is attributed to the selective and irreversible binding to sterols in cell membranes (Abu-Salah, 1996).…”

Section: Discussionmentioning

confidence: 99%

Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion

Porubcová

Ševčíková

2007

Helminthologia

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47 SummaryThe effect of amphotericin B colloidal dispersion (ABCD) on selected immunological parameters and growth of the larval cysts in mice infected intraperitoneally with Echinococcus multilocularis protoscoleces was observed. ABCD was administered at a dose 10 mg/kg body weight twice a week from week 5 to 10 post infection (p.i.). The Echinococcus infection suppressed the proliferative response of splenic T lymphocytes to nonspecific mitogen concanavalin A throughout almost the whole course of the experiment and ABCD administration did not affect this inhibittion. The increase in the proliferative response of B lymphocytes to lipopolysaccharide was found in infected mice with ABCD treatment from week 6 to 10 p.i. ABCD induced a significant rise of the splenic CD4 T cell subpopulation in infected mice only on week 6 p.i. The CD8 T subpopulation was not influenced by the therapy. The level of serum Th1 cytokine IFN-γ in infected and ABCD treated mice was elevated only at week 8 p.i., while the level of serum Th2 cytokine IL-5 was not influenced by the therapy. The ABCD treatment inhibited the IFN-γ production by splenocytes in vitro from week 6 to 10 p.i. On the contrary, the IL-5 production in vitro was stimulated at weeks 8 and 12 p.i. None antiparasitic effect of ABCD on larval growth was determined. Results suggest that amphotericin B colloidal dispersion did not affect the inhibited Th1 immune response after parasite infection. On the contrary, ABCD advanced the Th2 immune response development, which allows the progressive growth of the parasite.

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Section: Discussionmentioning

confidence: 99%

Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion

Porubcová

Ševčíková

2007

Helminthologia

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“…Therefore, alternatives to benzimidazoles are urgently needed. A novel potential chemotherapeutic option was recently discovered by demonstrating that AMB suppresses larval growth of E. multilocularis in vitro (26).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, AMB (20,32) has an effect on membrane-bound enzymes (2) and binds to sterols, thereby forming transmembrane channels (1,8,9,31). It was clear from the beginning that AMB would have to be given permanently due to its parasitostatic effect on E. multilocularis larvae in vitro (26). In those experiments AMB was effective at concentrations between 0.625 and 2.5 g/ml, and benzimidazoles were used at 1 g/ml.…”

Section: Vol 47 2003 Amphotericin B In Human Alveolar Echinococcosimentioning

confidence: 99%

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Salvage Treatment with Amphotericin B in Progressive Human Alveolar Echinococcosis

Reuter

Buck²,

Grebe³

et al. 2003

Antimicrob Agents Chemother

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Most patients with alveolar echinococcosis are diagnosed at a late stage when the disease has advanced to unresectable hepatic lesions. These patients require lifelong therapy with benzimidazoles, the only medical treatment currently available. To date, no treatment option remains for patients with benzimidazole intolerance or treatment failure. Amphotericin B was recently shown to exert antiparasitic activity in vitro. Here, we report the efficacy of amphotericin B in human alveolar echinococcosis. In three patients with extensive disease and without further treatment options, disease progression had been documented over several months. They were treated with amphotericin B intravenously at a dose of 0.5 mg/kg of body weight three times per week. Follow-up parameters were physical examination, laboratory parameters, and imaging techniques. Amphotericin B treatment effectively halted parasite growth in all three patients. The antiparasitic effect was most evident by spontaneous closure of cutaneous fistulae in two patients and by constant size of parasitic lesions during treatment, as assessed radiologically. Metabolic activity in parasitic areas was visualized by positron emission tomography and significantly decreased during treatment. However, progressive affection of the heart in one patient could not be stopped. All patients currently continue on amphotericin B and have been treated for 25, 17, and 14 months, respectively. We introduce amphotericin B as salvage treatment for alveolar echinococcosis patients with intolerance or resistance to benzimidazoles, as it effectively suppresses parasite growth. Amphotericin B is not parasitocidal; therefore long-term treatment has to be anticipated.The larval stage of Echinococcus multilocularis causes alveolar echinococcosis (AE). Surgical resection of hepatic lesions is often incomplete due to the diffuse infiltration into nonresectable structures or insufficient safety margins (7).Benzimidazoles (i.e., mebendazole and albendazole) are the only drugs licensed for the treatment of unresectable AE (6). These drugs have a parasitostatic effect on E. multilocularis metacestodes. Adverse reactions lead to treatment interruptions in up to 10% of cases (3,25), and treatment failure has been reported in 16% of patients (4). The overall success rate ranges somewhere between 55 and 97% (19, 25). In cases with treatment failure the disease will ultimately progress to death.New chemotherapeutic strategies against AE are needed, because alternative treatments have been tested with very limited success (11,14,21,30). Recently, suppression of parasite growth with amphotericin B (AMB) was demonstrated in an in vitro tissue culture model (26). We now report on the first three AE patients treated long-term with AMB. MATERIALS AND METHODSAMB deoxycholate treatment. After a loading dose of 0.5 mg/kg of body weight daily for the first 2 weeks, patients were treated as outpatients and were given AMB three times per week intravenously. For better tolerance of the drug 1 liter of isotonic...

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“…In a formulation as desoxycholate, it was shown to inhibit E. multilocularis larval growth in vitro and in human patients in vivo (Reuter et al, 2003a, b). Major drawbacks of AMB are its intravenous application mode and its nephrotoxic side-effects.…”

Section: Novel Chemotherapeutical Treatment Optionsmentioning

confidence: 99%

Alveolar and cystic echinococcosis: towards novel chemotherapeutical treatment options

Hemphill

Müller

2009

J. Helminthol.

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Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the neglected diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. The benzimidazoles albendazole and mebendazole are presently used for the chemotherapeutical treatment, alone or prior to and after surgery. However, in AE these benzimidazoles do not appear to be parasiticidal in vivo. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported, leading to discontinuation of treatment or to progressive disease. Therefore, new drugs are needed to cure AE and CE. Strategies that are currently employed in order to identify novel chemotherapeutical treatment options include in vitro and in vivo testing of broad-spectrum anti-infective drugs or drugs that interfere with unlimited proliferation of cancer cells. The fact that the genome of E. multilocularis has recently been sequenced has opened other avenues, such as the selection of novel drugs that interfere with the parasite signalling machinery, and the application of in silico approaches by employing the Echinococcus genome information to search for suitable targets for compounds of known mode of action.

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Effect of Amphotericin B on Larval Growth of Echinococcus multilocularis

Cited by 58 publications

References 31 publications

Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion

Immune response of mice to Echinococcus multilocularis infection after therapy with amphotericin B colloidal dispersion

Salvage Treatment with Amphotericin B in Progressive Human Alveolar Echinococcosis

Alveolar and cystic echinococcosis: towards novel chemotherapeutical treatment options

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