Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts

S Mahanty, A Paredes, M Marzal, E Gonzalez, S Rodriguez, P Dorny, C Guerra-Giraldez, HH Garcia, T Nash

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    Abstract

    Neurocysticercosis resulting from Taenia solium (Ts) infections is a major cause of adult acquired seizures worldwide. Disease is caused by larval cysts, and treatment consists of anthelmintics drugs, albendazole or praziquantel. There are no standard methods to assess drug activity to Ts cysts in vitro. Morphological, functional and biochemical changes that might reflect damaging (inhibiting, cytotoxic) drug effects were analyzed after exposure of cysts to albendazole sulfoxide (ABZ-SO), the major active metabolite of the drug in vivo, praziquantel (PZQ), or combinations of both. PZQ exposure led to a decrease in cyst size and inhibition of evagination while ABZ-SO exposure resulted in minimal changes. Alkaline phosphatase (AP) is normally secreted by cysts and both drugs inhibited AP secretion at concentrations of 5 ng/ml and 50 ng/ml for PZQ and ABZ-SO, respectively. Some combination of both drugs resulted in additive and/or synergistic activities. Parasite-specific antigen, detected in the cerebrospinal fluid and blood of infected patients, is also normally secreted by Ts cysts. Antigen secretion was similarly inhibited by ABZ-SO and PZQ and a combination of both drugs, suggesting that inhibition of secretion is a common downstream consequence of the activities of both drugs. These studies establish quantitative methods to measure in vitro anthelmintic activity and suggest combination therapy with ABZ-SO and PZQ may have clinical benefit.
    Original languageEnglish
    JournalAntimicrobial Agents and Chemotherapy
    Volume55
    Issue number1
    Pages (from-to)211-217
    Number of pages7
    ISSN0066-4804
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Helminthic diseases
    • Neurocysticercosis
    • Taenia solium
    • Cysts
    • Larvae
    • Treatment
    • Anthelmintics
    • Praziquantel
    • Albendazole
    • Drug activity
    • Assessment
    • In vitro
    • Morphology
    • Biochemistry
    • Drug combinations
    • Alkaline phosphatase
    • Antigen detection
    • Combination therapy

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