Dataset Information

Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials.

ABSTRACT:

Background

Neurocysticercosis, infection of the brain with larvae of Taenia solium (pork tapeworm), is one of several forms of human cysticercosis caused by this organism. We investigated the role of albendazole and praziquantel in the treatment of patients with parenchymal neurocysticercosis by performing a meta-analysis of comparative trials of their effectiveness and safety.

Methods and principal findings

We performed a search in the PubMed database, Cochrane Database of Controlled Trials, and in references of relevant articles. Six studies were included in the meta-analysis. Albendazole was associated with better control of seizures than praziquantel in the pooled data analysis, when the generic inverse variance method was used to combine the incidence of seizure control in the included trials (patients without seizures/[patients x years at risk]) (156 patients in 4 studies, point effect estimate [incidence rate ratio] = 4.94, 95% confidence interval 2.45-9.98). In addition, albendazole was associated with better effectiveness than praziquantel in the total disappearance of cysts (335 patients in 6 studies, random effects model, OR = 2.30, 95% CI 1.06-5.00). There was no difference between albendazole and praziquantel in reduction of cysts, proportion of patients with adverse events, and development of intracranial hypertension due to the administered therapy.

Conclusions

A critical review of the available data from comparative trials suggests that albendazole is more effective than praziquantel regarding clinically important outcomes in patients with neurocysticercosis. Nevertheless, given the relative scarcity of trials, more comparative interventional studies--especially randomized controlled trials--are required to draw a safe conclusion about the best regimen for the treatment of patients with parenchymal neurocysticercosis.

SUBMITTER: Matthaiou DK

PROVIDER: S-EPMC2265431 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Publications

Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials.

Matthaiou Dimitrios K DK Panos Georgios G Adamidi Eleni S ES Falagas Matthew E ME

PLoS neglected tropical diseases 20080312 3

<h4>Background</h4>Neurocysticercosis, infection of the brain with larvae of Taenia solium (pork tapeworm), is one of several forms of human cysticercosis caused by this organism. We investigated the role of albendazole and praziquantel in the treatment of patients with parenchymal neurocysticercosis by performing a meta-analysis of comparative trials of their effectiveness and safety.<h4>Methods and principal findings</h4>We performed a search in the PubMed database, Cochrane Database of Contro ...[more]

PMID: 18335068

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Project description:BackgroundThe onset of anthelmintic treatment of neurocysticercosis (NCC) provokes an acute immune response of the host, which in human cases is associated with exacerbation of neurological symptoms. This inflammation can occur at the first days of therapy. So, changes in the brain cysts appearance may be detected by medical imaging. We evaluated radiological changes in the appearance of brain cysts (enhancement and size) on days two and five after the onset of antiparasitic treatment using naturally infected pigs as a model for human NCC.Methods and resultsContrast T1-weighted magnetic resonance imaging with gadolinium was performed before and after antiparasitic treatment. Eight NCC-infected pigs were treated with praziquantel plus albendazole and euthanized two (n = 4) and five (n = 4) days after treatment; another group of four infected pigs served as untreated controls. For each lesion, gadolinium enhancement intensity (GEI) and cyst volume were measured at baseline and after antiparasitic treatment. Volume and GEI quantification ratios (post/pre-treatment measures) were used to appraise the effect of treatment. Cysts from untreated pigs showed little variations between their basal and post treatment measures. At days 2 and 5 there were significant increases in GEI ratio compared with the untreated group (1.32 and 1.47 vs 1.01, p = 0.021 and p = 0.021). Cyst volume ratios were significantly lower at days 2 and 5 compared with the untreated group (0.60 and 0.22 vs 0.95, p = 0.04 and p = 0.02). Cysts with lower cyst volume ratios showed more marked post-treatment inflammation, loss of vesicular fluid and cyst wall wrinkling.Conclusion/significanceA significant and drastic reduction of cyst size and increased pericystic enhancement occur in the initial days after antiparasitic treatment as an effect of acute perilesional immune response. These significant changes showed that early anthelmintic efficacy (day two) can be detected using magnetic resonance imaging.

Project description:BACKGROUND:Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. METHODS:In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. FINDINGS:Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10-2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87-2·38, p=0·151). No significant differences in adverse events were reported between treatment groups (18 in combined treatment group, 11 in standard albendazole group, and 19 in increased albendazole group). INTERPRETATION:Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects. A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health.

Project description:OBJECTIVE:To develop a causal model for the occurrence of neurocysticercosis (NC)-related seizures and test hypotheses generated from the model. METHODS:We used data from a randomized controlled trial comparing albendazole with placebo among patients newly diagnosed with NC. Based on our causal model, we explored the associations among albendazole treatment, NC cyst evolution, and seizure outcomes over 24 months of follow-up using generalized linear mixed effect models. RESULTS:We included 153 participants, of whom 51% received albendazole. The association between seizure outcomes and treatment over time demonstrated lack of linearity and heterogeneity, requiring the inclusion of time-treatment interaction terms for valid modeling. Participants in the albendazole group had fewer seizures overall and of partial onset at all time points compared with the placebo group, but the difference increased over the first few months following treatment, then decreased over time. Generalized seizures exhibited a more complex association; those in the albendazole group had fewer seizures compared with those in the placebo group for the first few months after treatment, and then the association reversed and those in the placebo arm had fewer seizures. Adjusting for the number of NC cysts in each phase resulted in an attenuation of the strength of association between albendazole and seizure outcomes, consistent with mediation. Among participants in whom all cysts had disappeared (n = 21), none continued to have seizures. SIGNIFICANCE:Albendazole treatment is associated with a possible reduction in focal seizures in the short term (3-6 months), perhaps by hastening the resolution of the cysts. However, the effect is not discernible over the long term, because most cysts either calcify or resolve completely, regardless of whether treated with albendazole. The stage of evolution of the cysticercus is an important consideration in the evaluation of albendazole effect on seizure outcome.

Dataset Information

Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials.

Background

Methods and principal findings

Conclusions

Publications

Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials.

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