Browsing by Author "Kelvin, Elizabeth A."

Now showing 1 - 7 of 7

A longitudinal analysis of albendazole treatment effect on neurocysticercosis cyst evolution using multistate models
(2019) Hauser, Allen
© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. BACKGROUND: In neurocysticercosis, the larval form of the pork tapeworm Taenia solium appears to evolve through three phases-active, degenerative and sometimes calcification-before disappearance. The antihelmintic drug, albendazole, has been shown to hasten the resolution of active cysts in neurocysticercosis. Little is known about the time cysts take to progress through each phase, with or without treatment. METHODS: We reconfigured brain imaging data from patient level to cyst level for 117 patients in a randomized clinical trial of albendazole in which images were taken at baseline, 1, 6, 12 and 24 mo. Applying a multistate model, we modelled the hazard of a cyst evolving to subsequent cyst phases before the next imaging (vs no change). We examined the impact of albendazole treatment overall and by patient and cyst characteristics on the hazard. RESULTS: Albendazole accelerated the evolution from the active to degenerative phase (HR=2.7, 95% CI 1.3 to 6.5) and from the degenerative phase to disappearance (HR=1.9, 95% CI 1.1 to 3.9). Albendazole's impact was stronger for patients who were male, did not have calcified cysts at baseline and who had multiple cysts in different locations. CONCLUSIONS: This research provides a better understanding of where in the cyst trajectory albendazole has the greatest impact.
Effects of albendazole treatment on neurocysticercosis: A randomised controlled trial
(2008-06) Kelvin, Elizabeth A.; Carpio, Arturo; Bagiella, Emilia; Leslie, Denise; León, Pedro; Howard, Andrews; Hauser, W. Allen; Lisanti, Noemí; Aguirre, R.; Serrano, M.; Pesántes, J.; Moncayo, J.; Roman, M.
AIM: The aim of this trial was to evaluate the effects of albendazole (ALB) on cyst disappearance, reduction of the number of cysts and seizure recurrence. METHODS: 178 patients with new onset symptoms due to active or transitional neurocysticercosis were randomly assigned to receive either 800 mg of ALB daily or placebo for 8 days. All patients also received prednisone. Imaging studies were done at baseline and at months 1, 6 and 12 of follow-up. RESULTS: Active cysts were identified in 59 of 88 people randomised to ALB and 57 of the 90 in the placebo arm. By 1 month, 31% were free of active cysts in the treatment group compared with 7% in the placebo group (p = 0.001). In addition, the ALB group had a greater reduction in the number of active cysts compared with the placebo group (p = 0.001). After 1 month following treatment there was no additional gain by treatment group in the disappearance or reduction in the number of active cysts. ALB treatment had little effect on cysts in the transitional or calcification stage. We found no difference between the ALB and placebo groups in symptoms during treatment or in seizure recurrence during the 12 months after treatment. CONCLUSION: Albendazole plus symptomatic treatment leads to the disappearance of active cysts in 31% of patients compared with 7% of those with symptomatic treatment alone. This treatment effect occurs within the first 30 days after treatment.
Exploring the complex associations over time among albendazole treatment, cyst evolution, and seizure outcomes in neurocysticercosis
(2019) Zhang, Hongbin
Wiley Periodicals, Inc. © 2019 International League Against Epilepsy 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.
Investigation of familial aggregation of seizures in neurocysticercosis patients
(2009-03) Kelvin, Elizabeth A.; Carpio, Arturo; Bagiella, Emilia; Leslie, Denise; León, Pedro; Howard, Andrews; Hauser, W. Allen; Hesdorffer, Dale C.
Regional differences in the clinical manifestations of human neurocysticercosis (NCC) may indicate a role of host genetics. We examined whether there is familial aggregation of seizures in first-degree relatives of NCC patients with seizure versus NCC patients without seizure as presenting symptom in a group of patients in Ecuador. The results of our analyses were null, and there was no trend toward familial aggregation of seizures in NCC patients.
Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel?
(2014-04) Romo, Matthew L.; Carpio, Arturo; Kelvin, Elizabeth A.
Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co-administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized.
Seizure in people with newly diagnosed active or transitional neurocysticercosis
(2011-03) Kelvin, Elizabeth A.; Carpio, Arturo; Bagiella, Emilia; Leslie, Denise; León, Pedro; Howard, Andrews; Hauser, W. Allen
Purpose: The aim of this study is to describe seizure as a presenting symptom in individuals with recently diagnosed neurocysticercosis (NCC). Methods: Using logistic regression, we examined the probability of having seizures as a presenting symptom among those with active or transitional NCC by host age and gender, and by number of cysts, location of the cysts in the brain, and phase of evolution of the encysted parasite. Results: We found that the odds of having seizures as presenting symptom for those in the youngest age group (3–24 years old) were 12.9 times that of the oldest participants (age 55–82 years) (p = 0.006). People with cysts in parenchymal locations had a significantly higher odds of seizures compared to those with all their cysts elsewhere (ventricles or subarachnoid) (OR = 6.2, p = 0.028); and the number of cysts was significantly associated with having seizures (OR = 1.1, p = 0.026). Host gender and cyst phase were not significantly associated with having seizures after adjusting for confounders and covariates. Conclusion: Children, those with cysts in parenchymal locations, and those with a higher number of cysts appear to be more likely to experience seizure when they have NCC cysts in the active or transitional stage.
The association of host age and gender with inflammation around neurocysticercosis cysts
(2009-09-01) Kelvin, Elizabeth A.; Carpio, Arturo; Bagiella, Emilia; Leslie, Denise; León, Pedro; Howard, Andrews; Hauser, W. Allen; Lisanti, Noemí; Aguirre, R.; Serrano, M.; Pesántes, J.; Moncayo, J.; Roman, M.
The results of previous investigations indicate that age and gender may influence the strength of the human host's immune response to infection of the central nervous system with the larvae of Taenia solium. Most of the relevant research on such neurocysticercosis (NCC) has, however, been conducted on hospital-based samples in developing countries, where differential access to healthcare may bias the study results. Using data from 171 NCC patients participating in a treatment trial, the associations of patient age and gender with the presence of inflammation around NCC cysts (i.e. cysts in the transitional phase) have recently been explored, after controlling for measures of economic and geographical access to healthcare. Data on cysts were collected from computed-tomography or magnetic-resonance images taken at four time-points, from baseline to 12-months post-treatment. The odds of having transitional cysts were evaluated by logistic regression whereas Poisson regression was used to explore the numbers of transitional cysts, with generalised estimating equations (GEE) used to account for the multiple observations over time. After controlling for healthcare access, the odds of having transitional cysts were found to be 1.5-fold higher for the female patients than for the male, although this association was not statistically significant (P = 0.136). In the Poisson model, however, the number of transitional cysts was found to be 1.8-fold higher in the female patients than in the male, and this gender effect was not only statistically significant (P = 0.002) but also constant over time. The association of host age with transitional cysts was more complicated, with significant interaction between age and time. It therefore appears that there are significant gender and age differences in the local immune response to NCC, even after adjusting for differences in healthcare access.