Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts.
Neurocysticercosis resulting from Taenia solium infections is a major cause of adult-acquired seizures worldwide. Disease is caused by larval cysts, and treatment consists of the anthelmintic drugs albendazole or praziquantel. There are no standard methods to assess drug activity to T. solium 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, whereas 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 and 50 ng/ml for PZQ and ABZ-SO, respectively. Some combinations 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 T. solium 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.
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. smahanty@niaid.nih.gov
S
S
Mahanty
A
A
Paredes
M
M
Marzal
E
E
Gonzalez
S
S
Rodriguez
P
P
Dorny
C
C
Guerra-Giraldez
H H
HH
Garcia
T
T
Nash
D015766:Albendazole / Q000494:pharmacology*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D011223:Praziquantel / Q000494:pharmacology*; D041201:Taenia solium / Q000187:drug effects* / Q000378:metabolism
D000871:Anthelmintics; D011223:Praziquantel; D015766:Albendazole