Clemons Karl V, Sobel Raymond A, Martinez Marife, Correa-Oliveira Rodrigo, Stevens David A
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California.
California Institute for Medical Research, San Jose, California.
Am J Trop Med Hyg. 2017 Oct;97(4):1141-1146. doi: 10.4269/ajtmh.16-0975. Epub 2017 Aug 18.
Acute and chronic infection with affects millions of people. The current therapeutic options are highly toxic and often not effective. Liposomal amphotericin B (LAMB) has been demonstrated previously to have some activity in murine models. In our studies, higher dosages given multiple times were tested for activity against acute or chronic disease, exploring whether intermittent and brief regimens could be effective, as might then prove useful in human, particularly outpatient, therapy. For acute infection, LAMB 25 mg/kg intravenously (i.v.) given one to three times prolonged survival and caused a rapid disappearance of Y strain trypomastigotes from the blood. However, even four or six doses of LAMB 30 mg/kg i.v., did not result in the cure of Y strain infection, with all mice relapsing after being immunosuppressed with cyclophosphamide. Similarly, chronic infection due to the CL strain was found to be unaltered by 1-3 treatments with LAMB 25 mg/kg. All surviving mice had histopathological evidence of infection in one or more tissues and equivalent antibody titers regardless of treatment regimen. Overall, LAMB at doses up to 30 mg/kg i.v. prolonged survival, but these doses were not curative in the regimens studied.
急性和慢性感染影响着数百万人。目前的治疗选择毒性很大，而且往往无效。此前已证明脂质体两性霉素B（LAMB）在小鼠模型中具有一定活性。在我们的研究中，测试了多次给予更高剂量对急性或慢性疾病的活性，探讨间歇性和短期给药方案是否有效，因为这可能对人类治疗，尤其是门诊治疗有用。对于急性感染，静脉注射（i.v.）25mg/kg的LAMB一至三次可延长生存期，并使血液中的Y株锥鞭毛体迅速消失。然而，即使静脉注射四剂或六剂30mg/kg的LAMB，也未能治愈Y株感染，在用环磷酰胺免疫抑制后，所有小鼠均复发。同样，发现用25mg/kg的LAMB进行1-3次治疗对CL株引起的慢性感染没有影响。所有存活小鼠在一个或多个组织中都有感染的组织病理学证据，且无论治疗方案如何，抗体滴度相当。总体而言，静脉注射剂量高达30mg/kg的LAMB可延长生存期，但在所研究的给药方案中，这些剂量并不能治愈疾病。
