ArticlesEfficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial
Introduction
Neurocysticercosis caused by Taenia solium is regarded as the most frequent cause of acquired epilepsy worldwide.1, 2 In the lifecycle of this parasite, human beings harbour the adult tapeworm in their intestines and are the only definitive host. Both human beings and pigs can act as intermediate hosts by harbouring the larvae or cysticerci in their tissues.3 The infection and resulting disease is highly endemic in all developing countries where pigs are raised as a food source.1 Neurocysticercosis is now also increasingly diagnosed in industralised countries because of migration and travel from endemic zones.4
Cyst death after antiparasitic treatment is a result of not only the direct action of the drug, but also of an attack by the host immune system in response to the release of antigens caused by treatment-associated damage, which is most pronounced during the initial days or weeks after the start of antiparasitic treatment.5 Antiparasitic treatment of patients with viable intraparenchymal brain cysts seems to improve the prognosis of their seizure disorders.6, 7, 8, 9 However, antiparasitic treatment has suboptimum efficacy, killing roughly 65% of parasites and obtaining complete cyst resolution (no viable parasites remaining) in less than 40% of patients after a course of praziquantel or albendazole.10, 11
Praziquantel is a pyrazinoisoquinoline derivative, of which the main pharmacological effects include muscle contractions, paralysis, and tegumentary damage, whereas albendazole is a benzimidazole, of which the main method of action is through selective degeneration of cytoplasmic microtubules resulting in energy depletion, disrupted cell division, and altered glucose intake.12, 13 We postulated that combinination of these two antiparasitic drugs would improve the destruction of brain cysts without affecting patient safety, and designed a clinical study to compare treatment with albendazole alone with combined albendazole plus praziquantel. An initial pharmacokinetic substudy showed increased serum albendazole concentrations in patients receiving combination treatment compared with concentrations in those receiving albendazole alone.14 This difference in concentrations was presumed to be due to a pharmacokinetic interaction between praziquantel and albendazole. Hence, the question arose whether any reported superiority of the albendazole–praziquantel combination in elimination of viable cysts would be due to an additional cysticidal effect of praziquantel or due to increased albendazole concentrations arising from an interaction with praziquantel. Therefore, in response to a suggestion by our data and safety monitoring board, we added an increased dose albendazole study group so that we could establish whether any recorded increase in efficacy was a result of increased albendazole concentrations or to the direct action of praziquantel. We also compared seizure rates during periods before and after complete cyst resolution, to assess whether complete cyst resolution resulted in a decrease in seizure frequency.
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Study design and participants
For this double-blind, placebo-controlled, randomised phase 3 clinical trial, we recruited patients from the Instituto Nacional de Ciencias Neurologicas, and the national hospitals Cayetano Heredia, Eduardo Rebagliati, and Guillermo Almenara, Lima, Peru. We did the study at the CNS Parasitic Diseases Research Unit, Universidad Peruana Cayetano Heredia, Lima, Peru.
Inclusion criteria were age between 16 and 65 years; one to 20 viable neurocysticercosis cysts; serological confirmation on western
Results
Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel, 43 standard albendazole, and 40 increased albendazole). Enrolment was halted by the study data and safety monitoring board after interim analyses showed parasiticidal superiority of one of the treatment groups. Up to this point, 167 patients (100 men, 67 women) had entered the screening phase in whom 43 patients were excluded (figure 1). Of 124
Discussion
Findings from this randomised controlled trial have shown the increased antiparasitic efficacy of an albendazole plus praziquantel regimen, and that further seizures are less frequent in individuals with complete cyst resolution after antiparasitic treatment (panel). Neurocysticercosis, particularly intraparenchymal brain cysticercosis, is associated with seizures and epilepsy in most of the world.1, 22 The parasitic larvae establish and survive in the brain for a variable period (often years
References (33)
- et al.
Neurocysticercosis: updated concepts about an old disease
Lancet Neurol
(2005) - et al.
Short course albendazole treatment for neurocysticercosis in Columbia
Trans R Soc Trop Med Hyg
(1993) The anthelmintic action of praziquantel
Parasitol Today
(1988)- et al.
Imaging of parasitic infections of the central nervous system
Handb Clin Neurol
(2013) - et al.
Epilepsy in poor regions of the world
Lancet
(2012) - et al.
Cysticercosis and neurocysticercosis as pathogens affecting the nervous system
Prog Neurobiol
(2010) Commission on Tropical Diseases of the International League Against Epilepsy. Relationship between epilepsy and tropical diseases. Commission on Tropical Diseases of the International League Against Epilepsy
Epilepsia
(1994)Taeniasis and cysticercosis due to T solium
- et al.
Neurocysticercosis: neglected but not forgotten
PLoS Negl Trop Dis
(2012) - et al.
Timeresponse curve of oxfendazole in the treatment of swine cysticercosis
Am J Trop Med Hyg
(1998)
A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis
N Engl J Med
Metaanalysis: cysticidal drugs for neurocysticercosis: albendazole and praziquantel
Ann Intern Med
A diagnostic and therapeutic scheme for a solitary cysticercus granuloma
Neurology
Drug therapy for solitary cysticercus granuloma: a systematic review and metaanalysis
Neurology
Comparison of therapeutic regimen of anticysticercal drugs for parenchymal brain cysticercosis
J Neurol
Albendazole
J Antimicrob Chemother
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