Attributing Toxoplasma gondii infections to sources: current knowledge and addressing data gaps

Introduction

Toxoplasmosis is an important foodborne disease worldwide. Its public health importance has been largely under-recognized, but recent evidence has shown that Toxoplasma gondii leads to a high burden of disease at global, regional and national level. The World Health Organization ranked toxoplasmosis as number 13th among 31 foodborne diseases globally, also demonstrating regional differences, with for example a relative higher importance of toxoplasmosis in the Americas than in Europe (WHO, 2015). Several other studies have estimated a high public health impact in several regions (Torgerson et al., 2015) and specific countries (see. e.g. (Havelaar et al., 2007; Nissen et al., 2017; SCALLAN et al., 2015; Van Lier et al., 2016)).

Humans can be infected by T. gondii post-natal (i.e. acquired toxoplasmosis) or vertically (i.e. congenital toxoplasmosis). Because congenital toxoplasmosis is considered particularly problematic due to the severe health effects it can cause in children since birth and the possibility of fetal death, its public health impact has been more extensively studied than acquired toxoplasmosis, which is usually associated with mild flu-like symptoms. However, several newer studies suggest that in some cases ocular disease and severe syndromes such as psychiatric disorders, as well as suicide attempts and traffic accidents, may develop as a result of infection (Burgdorf et al., 2019; Flegr et al., 2014). Furthermore, infections acquired post-natal can cause ocular disease, and atypical strains, which are common in areas outside of Europe, have caused severe toxoplasmosis even in immunocompetent individuals.

Cats and wild felids are the only definite hosts of the parasite, but virtually all warm-blooded animals can act as intermediate hosts, and most species can be carriers of tissue cysts of T. gondii. T. gondii has been isolated from most livestock species such as pigs, cattle, sheep, poultry, as well as wildlife and game. Like many other foodborne hazards, T. gondii can be transmitted to humans through consumption of contaminated foods but also by other routes: through water, soil, or air; by direct contact between people, or by contact between people and animals. The relative importance of exposure from a contaminated environment versus consumption of meat or other foods is still unclear.

To identify and prioritize interventions for reducing the burden of foodborne diseases, evidence on the relative contribution of different sources and routes of transmission of T. gondii at regional and national levels is needed.

Source attribution of foodborne diseases

The process of partitioning the human disease burden of a foodborne infection to specific sources is known as source attribution, where the term source includes reservoirs (e.g. animal reservoirs like pigs, cattle, pets) and vehicles (e.g. food products like pork or beef) (Pires et al., 2009). Source attribution studies may also be able to distinguish between the contribution of different transmission routes from one or more sources for infection. A variety of methods to attribute foodborne diseases to sources are available, including approaches based on analysis of data of occurrence of the pathogen in sources and humans, epidemiological studies, intervention studies, and expert elicitations. Each of these methods presents advantages and limitations, and the usefulness of each depends on the public health questions being addressed and on the characteristics and distribution of the hazard (Pires, 2013).

Source attribution methods have been extensively used to investigate the contribution of food and animal sources for several infectious diseases, e.g. salmonellosis, campylobacteriosis, and listeriosis. Measuring the proportion of foodborne infections that is attributable to different sources has proven useful in several countries and regions, contributing to One Health efforts to guide food-safety interventions based on scientific evidence. However, application of source attribution methods for several zoonotic pathogens is often more challenging, which can be due to the characteristics of the pathogen or due to lack of data. To a large extent, this has been the case of T. gondii, for which robust, data-driven source attribution studies in most countries are still lacking.

Overview of studies attributing T. gondii infections to sources

Source attribution of toxoplasmosis is particularly challenging due to lack of data, and few studies have been conducted so far. To overcome this challenge, WHO’s Initiative to estimate the global burden of foodborne diseases included a large expert elicitation study to assess the contribution of sources for several diseases, including toxoplasmosis. This study estimated that between 42 and 61% of acquired toxoplasmosis cases globally are due to foodborne transmission, with other important routes being water (11-27%) and soil (18-38%) (Hald et al., 2016). The next step of the source attribution process is to measure the contribution of specific sources within these major transmission routes, which would ideally be based on data on prevalence, contamination and exposure of/to each source.

Opsteegh et al. measured the relative contribution of three meat types for infection with T. gondii in the Netherlands (Opsteegh et al., 2011). The authors used a comparative risk assessment approach and concluded that 70% of meat-related infections were due to consumption of beef products, 14% due to sheep meat, and that 11% were attributable to pork products. A more recent study from the same group has improved the model to include the effect of salting on parasite viability, as well as lower concentrations of bradyzoites in cattle, more specific heating profiles, and more recent consumption data (Deng et al., 2020). Results showed that beef remains the most important source of T. gondii in the Netherlands, contributing to 84% of the total number of predicted infections in the Dutch population, followed by pork (12%), mutton (3.7%), lamb (0.2%) pork/beef mixed products (0.1%), and veal (0.01%) (Deng et al., 2020). Quantitative risk assessment studies of T. gondii in meat products have also been conducted in the UK, Italy, the United States (Condoleo et al., 2018; Crotta et al., 2017; Guo et al., 2017). Guo et al. (2015) performed a qualitative risk assessment of meatborne toxoplasmosis in the United States, and estimated that exposure associated with meats from free-range chickens, and non-confinement-raised pigs, goats, and lamb were higher than those from caged chickens and confinement-raised pigs and cattle (Guo et al., 2015). Belluco et al. (2018) compared the relative risk of T. gondii exposure through bovine meat vs pork in Italy, and found that bovine meat was found to be a more likely route of transmission to consumers than pork (Belluco et al., 2018). Condoleo et al. (2018) estimated the risk associated with consumption of different pork products in Italy, and concluded that almost all infections are associated with the consumption of fresh meat cuts and preparations, and only a small percentage is due to fermented sausages/salami (Condoleo et al., 2018). Remaining risk assessment studies developed models that will be useful to inform source attribution models, but looked only into one type of food/ transmission route, and thus do not provide evidence on the relative contribution of sources for infections.

A case-control study in the United States found that the leading foodborne risks associated with toxoplasmosis were eating raw ground beef, rare lamb or processed meats produced and consumed without heat treatment (Jones et al., 2009). More recently, a systematic review and meta-analysis of case-control studies supported these estimates by identifying three risk factors of toxoplasmosis: consumption of raw/ undercooked meat, consumption of raw/undercooked beef, and consumption of raw/undercooked sheep meat (Belluco et al., 2018).

In the absence of data for the application of data-driven methods as described above for a regional and global study, the expert elicitation conducted by the WHO described above also measured the proportion of foodborne T. gondii infections attributable to specific foods (Hoffmann et al., 2017). In this study, red meats (i.e. beef, small ruminants’ meat and pork) were estimated to cause 50% to 64% of foodborne cases in all regions, but the specific source of that exposure was estimated to vary markedly across sub-regions. Small ruminants’ meat was estimated to cause over 40% of foodborne toxoplasmosis in the Eastern Mediterranean Regions, while beef was estimated to cause 30% to 40% in Africa and several sub-regions of the Americas, Europe and Western Pacific. Pork was estimated to account for roughly 20% of foodborne toxoplasmosis in less developed regions of the Americas, and in developed countries within Europe. Vegetables were estimated to play a slightly larger role (21% to 23%) in Europe and South-East Asia than in other sub-regions (14% to 19%). Eggs and dairy are not believed to contribute to foodborne toxoplasmosis.

To our knowledge, these are the published studies on source attribution of toxoplasmosis. Because the geographical differences in the epidemiology of T. gondii as well as in consumption habits affect the relative importance of different sources, results from few local studies cannot be extrapolated to other countries.

Main challenges and data gaps

Even though several studies investigated the sero-prevalence of T. gondii in different sources, including animals and foods, representative data from all potential sources of the parasite are still lacking globally. Such data are essential for estimating the relative contribution of each source. Furthermore, the variety routes of transmission of the parasite, which include consumption of contaminated meat products, but also other foods, contact with live animals and environmental exposure, make the data requirements and modelling exercises particularly demanding.

The comparative exposure assessment appears to be the best approach to perform source attribution. However, this is a data-hungry method, relying on representative data on source contamination, exposure and effect of different processing steps in the survival of the parasite through the transmission chain. The risk assessment studies that have been developed to estimate the risk of disease through consumption of one specific food type can be used as a baseline for further method development. Still to address are substantial data gaps.

What are we doing to address knowledge gaps?

A recently launched pan-European project – “TOXOSOURCES: Toxoplasma gondii sources quantified” - will collect and analyse data to identify and rank the most important sources of T. gondii in the region¹. In this regional initiative, raw data and published data will be collected for countries across Europe, enabling an estimation of the relative contribution of the different sources for infection. To inform source attribution in the region, TOXOSURCES will estimate the relative contribution of food and environmental transmission routes, provide an overview of the prevalence in food animals and cats, quantify human exposure to possible sources of infection, provide an overview of the processing parameters for relevant meat products, and provide an overview of prevalence and risk factors of human infection. The project will develop a methodological framework and deliver evidence for risk management, including prioritization of food safety strategies. We expect that this approach will be useful derive national and regional source attribution estimates for toxoplasmosis, identify differences between countries, and help understanding the reasons for such differences. Furthermore, the framework may be useful to apply similar studies in other countries and regions.

Conclusions

Conducting source attribution of toxoplasmosis has been challenging globally due to substantial data gaps. This is true even for countries with extensive and well-established surveillance and monitoring of foodborne diseases in foods, animals and humans. The evidence compiled so far points to a high contribution of beef and ruminant meat for foodborne infections globally. Lower attribution proportions have been estimated for pork products by some studies, and raw or undercooked vegetables may also be relevant sources of toxoplasmosis. However, substantial data gaps remain. Importantly, estimating the relative contribution of non-foodborne transmission routes, such as contact with animals or environmental transmission, is crucial to inform public health policies. Secondly, developing and applying more robust data-driven methods, such as comparative exposure assessments and national or regional level, requires collecting representative and comparative data from multiple sources, including source contamination, exposure, survival and dose-response data. We expect that recently launched large scale projects will provide a unique opportunity to address these knowledge gaps, and anticipate that upcoming research will focus on toxoplasmosis and further expand these efforts.

Acknowledgements

The author thanks Marieke Opsteegh, Pikka Jokelainen, the Nordic Toxoplasma Working Group and the TOXOSOURCES consortium for input to input for this article.

1 https://onehealthejp.eu/jrp-toxosources/

Published in the proceedings of the International Pig Veterinary Society Congress – IPVS2020. For information on the event, past and future editions, check out https://ipvs2022.com/en.