Modelling the impact of One Health interventions against foodborne toxoplasmosis
Lead Research Organisation:
Royal Veterinary College
Department Name: Pathobiology and Population Sciences
Abstract
Toxoplasmosis is a foodborne disease caused by the globally ubiquitous parasite Toxoplasma gondii. Congenital transmission in humans causes a high burden of disease and, in livestock, infection causes abortions that exert substantial economic losses and threaten the livelihoods of subsistence farmers. Current interventions are limited in scope and do not exploit the synergies offered by integrated control in humans and livestock. This PhD will measure the current burden of toxoplasmosis in Senegal and the United Kingdom using serological and molecular diagnostic assays and will develop mathematical models to project the potential public health and economic benefits of One Health interventions.
Organisations
People |
ORCID iD |
| Martin Walker (Primary Supervisor) | |
| Gregory Milne (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M009513/1 | 01/10/2015 | 31/03/2024 | |||
| 2089230 | Studentship | BB/M009513/1 | 01/10/2018 | 30/09/2022 | Gregory Milne |
| Title | Aided in the design of several scientific drawings |
| Description | Collaborated with the BioRender team to design several cons representing the different life stages of the parasite Toxoplasma gondii. |
| Type Of Art | Artwork |
| Year Produced | 2020 |
| Impact | The drawings are now published on the BioRender site for use for all users. |
| URL | https://app.biorender.com/ |
| Description | Using a mathematical model that I developed in collaboration with my supervisors (in a computer programme called R), I discovered that an immune marker of Toxoplasma gondii oocysts (a stage of the parasite excreted by cats) lasts for considerably longer in blood than previously thought. This is important because it means diagnostic test that detect this immune marker may be useful for population-level screening to determine whether infections from oocysts predominate, versus infections from other modes of parasite transmission. In turn, these findings could be used to make decisions about parasite control strategies in different regions of the world. Toxoplasma is known to influence the behaviour of people and animals, probably because it travels to and forms 'cysts' in the brain of infected hosts. My other work has reviewed the scientific literature which studied the associations between Toxoplasma infection and various autoimmune, behavioural, and psychiatric conditions in people. This research revealed that people infected with Toxoplasma are at a higher risk of many different conditions, including - amongst many others - addiction, epilepsy, schizophrenia, and even traffic accidents. By examining the scientific literature, we hypothesised reasons for these associations. For example, infection with Toxoplasma changes the brain chemistry, through its influence on neurotransmitters. Changes in specific neurotransmitters (which Toxoplasma influences) are known to cause various mental health and other conditions. For other conditions, like traffic accidents, infected people are known to have delayed reaction times compared to uninfected people, which could explain this link. The published article can be found here: https://www.sciencedirect.com/science/article/pii/S147149222030221X. My research has also investigated the extent to which infections can cause strange behaviours in animals. In a study where several veterinary students from the Royal Veterinary College collected information on wild and captive foxes in the UK, we discovered that foxes who were infected with Toxoplasma were more likely to have an unusual behavioural syndrome known as Dopey Fox Syndrome. While the study only included a small number of foxes, we found other important things. For example, foxes who were infected with Toxoplasma were more likely to be attracted to the scent of cat urine. This same phenomenon has been found in rodents, and was aptly named "fatal feline attraction", since it probably means that infected rodents are more likely to be eaten by cats. This is important because cats play a central role in the transmission of Toxoplasma (so the parasite "wants" to infect cats). However, for foxes, this is unlikely to increase the transmission of the parasite (obviously, cats don't eat foxes!), so instead probably represents a "by-product" effect of the evolution of this parasite manipulation behaviour. The published scientific paper can be found here: https://www.frontiersin.org/articles/10.3389/fpsyt.2020.513536/full. More recently, I have developed a mathematical model to understand if the chance of being infected with Toxoplasma is changing over time. This research focused on the risk of infection in pregnant women, since this is a key group who are at risk of passing the infection to their foetus if they are infected for the first time in pregnancy. As a result, this can cause congenital toxoplasmosis (shortened to CT), a condition which, in its most severe form, can cause stillbirth and foetal loss. In CT pregnancies that are successfully carried to term, infants can still have developmental problems throughout life, including brain mis-development and eye problems which can lead to partial or full blindness. This study, using collected on 11 countries from the scientific literature, determined that the chance of being infected with Toxoplasma is decreasing over time in many countries (8 of the 11 studied). In many countries, this decline in risk translated into a parallel decline in the number of cases of CT. However, in a select few countries where transmission of the parasite was initially very intense, declines in risk actually led to a temporary increase in CT cases. While this seems counter-intuitive, it is because in these countries, most women become infected at a very young age (due to a high risk of infection). These women are therefore not at risk of first-time infection during pregnancy. However, as the rate of infection declines, women are - on average - more likely to be infected for the first time slightly later in life, including during pregnancy. This translates into an increased number of CT cases. This work has important implications for policies that can be used to limit the number of CT cases, including pregnancy screening programmes, which are currently only mandatory in a handful of countries worldwide. This work is under consideration for publication in The Lancet Infectious Diseases but not yet published. |
| Exploitation Route | We were successful in applying for a grant to further develop route-specific diagnostics (UK-Canada Doctoral Exchange Scheme funding from Mitacs and UKRI), in collaboration with partners at the University of Montreal. |
| Sectors | Agriculture, Food and Drink,Healthcare,Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology |
| URL | https://www.rvc.ac.uk/static/newsletter/eclipse/2020/index.html |
| Description | Funding helped to fund a placement at the Joint Biosecurity Centre (outlined in 'Influence on Policy, Practice, Patients and the Public' section) where I developed a mathematical model that can be used by the government to answer operational research questions related to COVID-19 restrictions in England. I also wrote a review of immunity to SARS-CoV-2 infection that has implications for COVID-19 policy going forwards. Finally, I co-authored a working paper on documenting and handling uncertainty in epidemiological models, which also has important implications for policy and decision makers. |
| First Year Of Impact | 2021 |
| Sector | Government, Democracy and Justice |
| Impact Types | Policy & public services |
| Description | Research Analyst internship at Joint Biosecurity Centre (contributing to policy-relevant analysis of COVID-19) |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Description | Improving diagnostics for toxoplasmosis to support public health interventions |
| Amount | £10,268 (GBP) |
| Funding ID | NE/V019309/1 |
| Organisation | Natural Environment Research Council |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2021 |
| End | 05/2022 |
| Description | Mathematical Models for Infectious Disease Dynamics: award to cover the cost of attending the 2-week course |
| Amount | £800 (GBP) |
| Organisation | Wellcome Genome Campus |
| Sector | Private |
| Country | United Kingdom |
| Start | 02/2020 |
| End | 02/2020 |
| Title | Mathematical model for estimating temporal changes in exposure to Toxoplasma gondii and congenital disease resulting from infection |
| Description | A model which estimates, using country-specific demographic data (i.e. age-specific population size, fertility distribution, and mortality rate) and anti-T. gondii IgG seroprevalence in pregnancy, the temporal change in exposure to T. gondii, and the impact of any changes on the incidence of congenital toxoplasmosis. |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2022 |
| Provided To Others? | No |
| Impact | The model will be detailed in a manuscript soon to be submitted for publication. The model and other associated code will be uploaded to a public repository on GitHub at the same time (on my page, found here: https://github.com/gcmilne). |
| Title | Model to infer the longevity of Toxoplasma gondii oocyst-specific antibodies |
| Description | The model was developed to estimate the longevity of Toxoplasma gondii oocyst-specific antibodies, work that has been published in Clinical Infectious Diseases (https://doi.org/10.1093/cid/ciaa428). |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | A paper published in Clinical Infectious Diseases (https://doi.org/10.1093/cid/ciaa428). The code is now publicly available on GitHub: https://github.com/gcmilne/oocyst-mod |
| URL | https://github.com/gcmilne/oocyst-mod |
| Description | Alumni magazine summary of research |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | I wrote an article summarising research from my first PhD publication, for the RVC alumni magazine: Milne, G., 2020. Improving Interventions against Toxoplasmosis. Royal Veterinary College Eclipse Alumni Magazine (Autumn Edition), p. 30. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.rvc.ac.uk/static/newsletter/eclipse/2020/index.html |
| Description | Article on LIDo website summarising my research |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | I wrote a summary piece describing some of my PhD research, for the LIDo-DTP website: Milne, G., 2020. Toxoplasma gondii: An Underestimated Threat? London Interdisciplinary Doctoral Programme PhD Student News. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.lido-dtp.ac.uk/news/gregory-milne-toxoplasma-gondii-underestimated-threat |
| Description | Article on LIDo website summarising my research |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | I wrote a summary piece for the LIDo-DTP website describing some of my published PhD research: Milne, G., 2020. Towards Improving Interventions against Toxoplasmosis by Identifying Routes of Transmission using Sporozoite-Specific Serological Tools. London Interdisciplinary Doctoral Programme PhD Student News. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.lido-dtp.ac.uk/news/gregory-milne-toward-improving-interventions-against-toxoplasmosis-i... |
| Description | Lead Editor for Science Innovation Union |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | As Lead Editor for the non-for-profit organisation Science Innovation Union, I write and edit digestible scientific material for our website and help to organise events on a variety of scientific topics. Of relevance to my PhD, I wrote an article about toxoplasmosis which was published on our website: Milne, G. (Jones, R.S., Ed.), 2020. Parasites and Behaviour: The Influence of Toxoplasma gondii on Human Populations. Science Innovation Union. |
| Year(s) Of Engagement Activity | 2020,2021 |
| URL | https://science-union.squarespace.com/articlelist/2020/6/7/parasites-and-behaviour-the-influence-of-... |
| Description | Published article press release |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Press release for one of my published articles: Milne, G. New RVC Research Highlights the Considerable Behavioural and Psychiatric Effects of a Mind-Altering Parasite. Royal Veterinary College. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.rvc.ac.uk/research/news/general/new-rvc-research-highlights-the-considerable-behavioural... |
| Description | Royal Institution Event |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | I attended a Royal Institution Veterinary Science event alongside some members of my research group, where we had a stall set up to talk to the public about toxoplasmosis, the topic of my PhD research. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.rigb.org/whats-on/events-2019/march/public-animal-csi-predator |
| Description | STEM for Britain 2020 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Was selected to attend the STEM for Britain poster competition, held in UK parliament, to present a poster detailing my work on estimating the longevity of Toxoplasma gondii oocyst-specific antibodies (https://doi.org/10.1093/cid/ciaa428). Here I explained my work to fellow contestants (all of whom were other early career researchers), members of parliament and other individuals (e.g. from societies and industry) sponsoring the event. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://stemforbritain.org.uk/ |