CystiHuman: A model of human neurocysticercosis
PLoS Computational Biology(2022)
Abstract
IntroductionThe Taenia solium tapeworm is responsible for cysticercosis, a neglected tropical disease presenting as larvae in the body of a host following taenia egg ingestion. Neurocysticercosis (NCC), the name of the disease when it affects the human central nervous system, is a major cause of epilepsy in developing countries, and can also cause intracranial hypertension, hydrocephalus and death. Simulation models can help identify the most cost-effective interventions before their implementation. Modelling NCC should enable the comparison of a broad range of interventions, from treatment of human taeniasis (presence of an adult taenia worm in the human intestine) to NCC mitigation. It also allows a focus on the actual impact of the disease, rather than using proxies as is the case for other models. MethodsThis agent-based model is the first model that simulates human NCC and associated pathologies. It uses the output of another model, CystiAgent, which simulates the evolution of pig cysticercosis and human taeniasis, adding human and cyst agents, including a model of cyst location and stage, human symptoms, and treatment. CystiHuman also accounts for delays in the appearance of NCC-related symptoms. It comprises three modules detailing cyst development, seizure probability and timing, and intracranial hypertension/hydrocephalus, respectively. It has been implemented in Java MASON and calibrated in three endemic villages in Peru, then applied to another village (Rica Playa) to compare simulation results with field data in that village. Results and discussionDespite limitations in available field data, parameter values found through calibration are plausible and simulated outcomes in Rica Playa are close to actual values for NCC prevalence and the way it increases with age and cases with single lesions. Initial simulations further suggest that short-term interventions followed by a rapid increase in taeniasis prevalence back to original levels may have limited impacts on NCC prevalence. Author summaryThis paper presents CystiHuman, the first model of human neurocysticercosis, a parasitic disease that is responsible for a large proportion of epilepsy cases in developing countries and also contributes to intracranial hypertension, hydrocephalus and death. Existing modelling efforts have focused so far on parasite transmission i.e., how the parasite responsible for neurocysticercosis, Taenia solium, persists through interactions between humans and pigs. Such models, however, generally do not simulate neurocysticercosis itself or associated symptoms. CystiHuman complements these efforts by proposing a model of neurocysticercosis, associated symptoms, and likelihood of treatment. Overall, initial model outcomes are coherent with field data regarding neurocysticercosis prevalence and age patterns. The model suggests that short-term interventions that successfully reduce parasite transmission to a small fraction of its original level, but are followed (as has often been the case so far) by a rapid recuperation in transmission levels, will likely fail to produce a substantial reduction in neurocysticercosis prevalence. We view the present model as a first iteration of CystiHuman. Future iterations should use new field data to refine aspects of the model and ensure its full validation. They should also include cost information to inform cost-effectiveness analyses of interventions to address the disease.
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