Reuter Stefan, Merkle Marion, Brehm Klaus, Kern Peter, Manfras Burkhard
Section of Infectious Diseases, Department of Internal Medicine, University Hospital of Ulm, 89081 Ulm, Germany.
Antimicrob Agents Chemother. 2003 Feb;47(2):620-5. doi: 10.1128/AAC.47.2.620-625.2003.
Alveolar echinococcosis is caused by the parasitic cestode Echinococcus multilocularis. Benzimidazoles, namely, mebendazole and albendazole, are the only drugs available for the treatment of inoperable alveolar echinococcosis. At present, no therapeutic alternative is available for patients with progressive disease under treatment or for patients who are unable to tolerate the side effects of the benzimidazoles. In addition, benzimidazoles are only parasitostatic for E. multilocularis. Thus, new therapeutic options are of paramount importance. In the present study we examined the in vitro effect of amphotericin B on E. multilocularis larvae. E. multilocularis metacestodes grown in the peritoneal cavities of Mongolian gerbils were transferred into a culture system. Vesicles budded from the tissue blocks and increased in number and size during the first 5 weeks. After 6 weeks drugs were added and deleterious effects on the vesicles were observed macroscopically and microscopically. By use of this in vitro tissue culture model we demonstrated that amphotericin B effectively inhibits the growth of E. multilocularis metacestodes. This destructive effect was significantly more rapid with amphotericin B than with the benzimidazoles. Cyclic treatment was effective in suppressing parasite growth. However, amphotericin B appears to be parasitostatic for E. multilocularis larvae, and regrowth occurs even after extended periods. In summary, amphotericin B constitutes the first promising alternative for the treatment of alveolar echinococcosis in cases of intolerance or resistance to benzimidazoles. It holds promise as an effective treatment option for otherwise fatal courses of disease.
泡型包虫病由多房棘球绦虫这种寄生性绦虫引起。苯并咪唑类药物,即甲苯达唑和阿苯达唑,是目前仅有的可用于治疗无法手术的泡型包虫病的药物。目前,对于正在接受治疗的病情进展患者或无法耐受苯并咪唑类药物副作用的患者,尚无其他治疗选择。此外,苯并咪唑类药物对多房棘球绦虫仅具有抑制寄生虫生长的作用。因此,新的治疗选择至关重要。在本研究中,我们检测了两性霉素B对多房棘球绦虫幼虫的体外作用。将在蒙古沙鼠腹腔中生长的多房棘球绦虫的原头蚴转移至培养系统中。在最初的5周内,从组织块上芽生出的囊泡数量和大小均增加。6周后加入药物,并从宏观和微观层面观察其对囊泡的有害作用。通过使用这种体外组织培养模型,我们证明两性霉素B可有效抑制多房棘球绦虫原头蚴的生长。两性霉素B产生的这种破坏作用比苯并咪唑类药物显著更快。循环治疗可有效抑制寄生虫生长。然而,两性霉素B对多房棘球绦虫幼虫似乎仅具有抑制寄生虫生长的作用,即使在延长治疗期后仍会出现再生长。总之,对于不耐受或对苯并咪唑类药物耐药的泡型包虫病患者,两性霉素B是首个有前景的替代治疗药物。它有望成为治疗其他致命病程疾病的有效治疗选择。