Development of a dose-response model for porcine cysticercosis

Abstract

Taenia solium is an important cause of acquired epilepsy worldwide and remains endemic in Asia, Africa, and Latin America. Transmission of this parasite is still poorly understood despite the design of infection experiments to improve our knowledge of the disease, with estimates for critical epidemiological parameters, such as the probability of human-to-pig infection after exposure to eggs, still lacking. In this paper, a systematic review was carried out and eight pig infection experiments were analyzed to describe the probability of developing cysts. These experiments included different pathways of inoculation: with ingestion of proglottids, eggs, and beetles that ingested eggs, and direct injection of activated oncospheres into the carotid artery. In these experiments, different infective doses were used, and the numbers of viable and degenerated cysts in the body and brain of each pig were registered. Five alternative dose-response models (exponential, logistic, log-logistic, and exact and approximate beta-Poisson) were assessed for their accuracy in describing the observed probabilities of cyst development as a function of the inoculation dose. Dose-response models were developed separately for the presence of three types of cysts (any, viable only, and cysts in the brain) and considered for each of the four inoculation methods ("Proglottids", "Eggs", "Beetles" and "Carotid"). The exact beta-Poisson model best fit the data for the three types of cysts and all relevant exposure pathways. However, observations for some exposure pathways were too scarce to reliably define a dose-response curve with any model. A wide enough range of doses and sufficient sample sizes was only found for the "Eggs" pathway and a merged "Oral" pathway combining the "Proglottids", "Eggs" and "Beetles" pathways. Estimated parameter values from this model suggest that a low infective dose is sufficient to result in a 50% probability for the development of any cyst or for viable cyst infections. Although this is a preliminary model reliant on a limited dataset, the parameters described in this manuscript should contribute to the design of future experimental infections related to T. solium transmission, as well as the parameterization of simulation models of transmission aimed at informing control.

Fig 1. PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources.

*Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools. From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71. For more information, visit: http://www.prisma-statement.org/.

Fig 2. Exact beta-Poisson dose-response relationship for the “Oral” pathway by type of cyst.

Each graph shows the median (solid black curve) and 95% range (dashed black curves) of the probability of infection as a function of dose, median ID50 infectious dose (dashed black vertical line), and the available data point with its standard deviation (“Proglottids” and “Beetles” pathways only). (A) Development of any (viable or degenerated) cyst. (B) Development of viable cysts. (C) Development of brain cysts.

Fig 3. Exact beta-Poisson dose-response relationship for the “Eggs” pathway by type of cyst.

Each graph shows the median (solid black curve) and 95% range (dashed black curves) of the probability of infection as a function of dose, median ID50 infectious dose (dashed black vertical line), and the available data point. (A) Development of any (viable or degenerated) cyst. (B) Development of viable cysts. (C) Development of brain cysts.