Analysing global Taenia solium transmission dynamics to refine transmission modelling and support identification of optimal strategies for its control and elimination in low and middle-income countries

Abstract

Taenia solium taeniasis/cysticercosis is a neglected zoonotic disease caused by the Taenia solium pork tapeworm, responsible for a significant global public health and economic burden. Infection of the central nervous system with T. solium cysts, leading to neurocysticercosis, is the single most important risk factor for acquired (infectious) epilepsy worldwide. Economic consequences pertain not only to the human health sector, by also to the animal sector, resulting from pig infection in the food-value chain. The 2012 World Health Organization (WHO), first, roadmap and the London Declaration on Neglected Tropical Diseases (NTDs) called for a validated strategy towards T. solium control and elimination by 2015, and for interventions to be scaled up in selected countries by 2020. These targets have not yet been met. More recently, the second, post-2020 NTD WHO roadmap (published in April, 2020) reformulated the milestones for T. solium, as hyperendemic settings/countries having adopted intensified control by 2030. Mathematical transmission models can support efforts aimed to setting, achieving, and evaluating the proposed 2030 goals. Although a number of transmission dynamics and control frameworks for T. solium taeniasis/cysticercosis already exist, refinement of some of these will be required for the purposes of increasing their usefulness to inform public health policy and practice. Taenia solium has a complex multi-host transmission cycle, including the adult tapeworm stage in the human definitive host, larval stages in the intermediate porcine host (with humans also acting as accidental intermediate hosts), and contamination of the environment with eggs/proglottids. Various T. solium models have been published, capturing the transmission cycle to varying degrees of complexity. Therefore, this thesis first reviews the current state of the T. solium transmission modelling field, including assessing models for the wider Taeniidae family of tapeworms to identify important gaps and understand how these may be addressed. Characterising incidence patterns, using Force-of-infection (FoI) catalytic models fitted to age-(sero)prevalence data for porcine cysticercosis, human taeniasis and human cysticercosis, was identified as an important gap and, therefore, comprises a central component of this thesis. FoI estimates thus produced are applicable to parameterise T. solium transmission models, while reviewing age-(sero)prevalence profiles globally enables exploration of whether immunity-driven age-resistance, or exposure heterogeneity mechanisms operate in the human and porcine hosts. Putative T. solium taeniasis/cysticercosis endemicity levels are also presented, with the FoI estimates obtained being placed within the different proposed levels to investigate patterns between incidence parameters and (sero)prevalence. A deterministic, compartmental T. solium transmission model (EPICYST) is refined (by including, among other features, age structure in human and pig populations) with the aim of assessing the impact of the minimum pig slaughter age, an important setting-specific variable, on the outcome of simulated pig- and human-directed, age-targeted interventions. The resulting model outputs are presented in the context of the post-2020 WHO NTD goals (“intensified control in hyperendemic settings/countries”), by reporting, for a generalised hyperendemic setting, the number of years required, and the levels of intervention coverage necessary to achieve three distinct porcine cysticercosis operational prevalence thresholds proposed (ranging from lenient (<10%) to stringent (<1%)) over a 10-year (2020–2030) time-horizon. Finally, efforts to constitute a coalition of epidemiologists and modellers, CystiTeam, are described, highlighting the aim of the group as that of bringing together modelling, epidemiological, clinical, and programmatic expertise, to improve collaboratively T. solium transmission models and their use in guiding survey and intervention design and evaluation to support the post-2020 NTD WHO roadmap process for T. solium during the next decade.