Are all hosts created equal? Transmission dynamics in a natural multi-host parasite community

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

Many of the most pressing concerns about emerging infectious disease in humans (eg pandemic influenza, West Nile virus, Hantavirus) and wildlife (eg bovine TB in cattle and badgers, squirrel pox transmission from grey to red squirrels) arise from parasites moving from one host species to another. As such there is considerable interest in how the composition of possible hosts in a community affects whether a disease spreads or not. Each host species can differ in their susceptibility to the parasite, their social structure and/or behaviour, so that the composition of the host community plays a key role in determining why some parasites cause an epidemic (i.e HIV), while others don't (i.e. Ebola). To aid our understanding of these complex, real-world communities, several mathematical models have been developed which show that the contribution each host species makes to the parasite's ability to spread is fundamental in determining whether the disease persists, and the outcome of targeted control. To date, however, these theories have not been tested with actual data, meaning they largely remain abstract conceptual frameworks. In particular, it is not known whether the host species' contributions to disease spread can be determined solely from the number of infected individuals within each host species. This is important as most studies of parasites that infect multiple hosts are likely to be purely observational, because it is logistically or ethically unfeasible to conduct the necessary experiments. However, there may be general guidelines, based on fundamental aspects of host-parasite ecology that can be used to infer these host contributions to parasite transmission and persistence. For example, both the transmission biology of the parasite (ie how it moves from one host to another) and the way host species interact in the community (eg their movement patterns, habitat usage, resource competition etc) will determine how each host species contributes to parasite persistence. Clearly, there is a need to determine whether disease patterns that we see in nature, combined with a basic understanding of host-parasite biology, can be used to predict how parasites will respond to control efforts targeting one host species or another. We will use a highly novel combination of large-scale manipulation experiments and mathematical modelling to measure host species contributions to parasite transmission across a diverse, natural multi-host-multi-parasite community. Overall we will provide one of the most comprehensive views of how very different parasites, with different transmission modes, use multiple host species to persist, and the implications for how such parasites respond to targeted host treatment. Given the increasing concerns about emerging infectious diseases around the globe, it has never been more pressing to develop a genuine understanding of the factors affecting parasite invasion, transmission, persistence, and control. This project will be a major step in that direction.

Planned Impact

As described in the 'Academic beneficiaries' section of this form, our primary beneficiaries will be the broad international scientific community working on infectious diseases. These academics, and wider collaborators, will directly benefit from the unique insights gained from this project, guiding current studies, and encouraging future research efforts that embrace the complexity of natural host-parasite communities. Impact with our primary beneficiaries, the academic community, will be initially through routine channels (peer reviewed publications (open access where possible), conference presentations, visits to other institutions and visits to our field sites). We will also initiate a Wiki-style online discussion resource, hosted through Liverpool University, enabling researchers from across the globe the chance to discuss relevant issues. In addition we will organise a 3-day workshop to explore practical aspects in the study of complex multi-host-multi-parasite communities, through a combination of presentations on key methodological topics (data analysis methods, mathematical modelling, ecological experimentation), discussion groups, and practical workshops in which participants will work through analyses of data in groups.

Other beneficiaries are future scientists. Throughout our existing NERC grant we have hired many undergraduate field assistants to help with the demanding trapping schedule and lab work of the project. These students have benefitted enormously from this experience, gaining expertise in the technical aspects of the project (field work, small mammal handling, lab assays and parasite identification) and, possibly more importantly, the whole process of research. Many of these students commented that it was the best thing they did at University, and they felt genuinely inspired by the experience. These students are now applying for graduate degrees in areas such as computational biology, veterinary parasitology and conservation, and we believe that their experience with us is crucial for their development as young scientists. We will do the same with this project, employing a number of undergraduate assistants (18) throughout its 3 years, and providing them with the opportunity to play a fundamental role in biological research. Furthermore, we will expand these volunteer opportunities to allow science teachers, school students (for example through the Nuffield bursary scheme) and other members of the public, to gain first-hand experience in cutting edge science, research methods, and practical field skills.

Finally, this project will also have relevance for non-academic beneficiaries, including conservation policy makers interested in the role that infectious diseases can have on threatened species, and those in the medical and veterinary communities where transmission of a pathogen from wildlife is of vital concern. Given our tractable field system, we have the ability to do field large-scale field manipulations, which are difficult to impossible in other mammal and human systems. These results can therefore provide general insight into identifying what data are needed to measure the contribution of each host species to disease persistence. Thus, this project has the potential to provide clear guidelines to public health and agricultural bodies into how to collect and analyse the appropriate data necessary to develop truly effective disease management programmes.

To engage with non-academics, we will post a regular blog on an established blogpage hosted by the owners of one of our field sites (http://www.woodlands.co.uk/blog/). We will provide regular updates of host species abundance patterns throughout the year, allowing the public to appreciate the hidden biodiversity within these woodlands, and get a feel for the kind of research that we do.

Publications

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Clerc M (2018) Antibodies and coinfection drive variation in nematode burdens in wild mice. in International journal for parasitology

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Clerc M (2019) Age affects antibody levels and anthelmintic treatment efficacy in a wild rodent in International Journal for Parasitology: Parasites and Wildlife

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Johnson PT (2015) Why infectious disease research needs community ecology. in Science (New York, N.Y.)

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Lello J (2018) Correction to 'Lost in transmission?' in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

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Maurice CF (2015) Marked seasonal variation in the wild mouse gut microbiota. in The ISME journal

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McCallum H (2017) Breaking beta: deconstructing the parasite transmission function. in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

 
Description This project has recently finished, however the analysis is still underway. Here are several of our current findings, although we anticipate more in the future.:

1) We have created theoretical frameworks to identify the contributions of different host species to disease maintenance in host communities, as well as to predict the consequences of various control strategies. We used data from a wild mammal - multiple parasite system to test this framework (Streicker et al 2013; Fenton et al. 2015).

2) Through a combination of gene sequencing, analysis of observational data and large-scale experimental perturbations, we have shown that the is considerable 'covert specificity' among a community of co-circulating pathogen species within a natural mixed rodent host community. This means that pathogen species that appear to be generalists (able to infect multiple different host species) tend to comprise many host-specialist strains (Withenshaw et al, in prep). Furthermore we showed that the 'filter' preventing infection by the different pathogen species is more likely to occur due to pathogen-rodent incompatibility, rather than from a lack of exposure (Withenshaw 2016).
Exploitation Route Our theoretical frameworks provide a simple means for identifying host species' contributes to disease transmission and persistence, from readily available parasitological data. These methods are widely applicable to a broad range of host-parasite systems and provide a simple, intuitive means of identifying 'key hosts' for optimally targeting control within infectious disease reservoirs.
Sectors Environment,Healthcare

URL http://www.biology.ed.ac.uk/research/groups/apedersen/
 
Description A simple epigenetic clock for a wild mouse'
Amount £7,724 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom
Start 01/2019 
End 12/2019
 
Description National Science Foundation Postdoctoral Research Fellowship in Biology
Amount $170,000 (USD)
Organisation National Science Foundation (NSF) 
Sector Public
Country United States
Start 10/2013 
End 09/2015
 
Description Standard Discovery Grant
Amount £789,000 (GBP)
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 06/2018 
End 05/2021
 
Description The impact of resource availability on parasite transmission: insights from a natural multi-parasite community
Amount £641,701 (GBP)
Funding ID NE/R011397/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 06/2018 
End 06/2021
 
Description University of Edinburgh Moray Endowment Fund
Amount £1,992 (GBP)
Organisation University of Edinburgh 
Department Moray Endowment Fund
Sector Academic/University
Country United Kingdom
Start 01/2017 
End 12/2017
 
Description Wellcome Trust Institutional Strategic Support Fund (WT ISSF)
Amount £24,810 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom
Start 01/2014 
End 12/2014
 
Description Wellcome Trust Institutional Strategic Support Fund Grant
Amount £29,640 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom
Start 01/2015 
End 02/2017
 
Description Wellcome Trust Institutional Strategic Support Fund Grant
Amount £30,400 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2017 
End 06/2018
 
Title Wild derived parasite isolates 
Description We have collected wild isolates of several important murine pathogens and parasites that can then be used in laboratory experiments to test natural host - parasite combinations. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2019 
Provided To Others? Yes  
Impact These wild derived parasites have been a part of a recently published paper (Clerc et al. 2019), contributed to the preliminary data that was used in a successful NERC Standard Grant application (2018) and will be shared with other groups working on these systems. 
 
Title Wild-caught wood mouse colony 
Description The development and maintenance of a formerly wild-caught, laboratory wood mouse (Apodemus sylvaticus) colony. To further test the findings and results that were emerging from our wild infection and immunity experiments, I acquired and maintain a now lab-reared colony of wood mice, and their naturally occurring parasites, in order to test how parasites and the immune response interact, but in a controlled environment. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2011 
Provided To Others? Yes  
Impact Mice, and samples from this colony, from this colony have been used in order to (i) measure the oral microbiome and test for associated bone disease and loss (that are not found in the standard lab mouse model (grant in review), (ii) understand the vast diversity seen in gut microbiomes compared to lab mice (published in ESME J), (iii) measure microbiome - immune response interactions and how that may be different than seen in lab mice (paper in review) and several other collaborations that are in progress. 
 
Title Wild small rodent parasite and pathogen database 
Description We have accumulated a spatially explicitly database from two consecutive NERC grants, totally 6-years of captures of individually marked individuals caught throughout their life, were at each capture significant demographic, physiological and infection histories are recorded. We monitor >30 species of parasites and pathogens. This data base currently involves wood mice and bank voles, captured 1- 20 times, and totally >8000 individually-tagged mice captured >12,000 times. We have spatially-explicit information of reach capture location on our sampling grids (rangingin size from 50x50m-70mx70m; with 6x6 -8x8 trap locations at 10m intervals with 2 traps/location,spanning 4 different woodlands, 2-8 grids/woodland, each grid replicated across 2-4 years). In addition to this data, we also have extracted DNA samples for the vast majority of captures, and immune gene polymorphism data for around 1000 mice. 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact We are just building these external collaboration now. 
 
Description During a Centre for Immunity, infection & evolution & ASCUS Art & Science Collaboration called 'Transmission' (2015), I engaged with artists working on an installation piece called 'Art, design and antimicrobial resistance' which focused on how contemporary society is challenged by microscopic organisms, and I was interviewed by film director Ann Milne as part of a piece aiming to put scientists themselves under the microscope to better understand their motivations. 
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 During a Centre for Immunity, infection & evolution & ASCUS Art & Science Collaboration called 'Transmission' (2015), I engaged with artists working on an installation piece called 'Art, design and antimicrobial resistance' which focused on how contemporary society is challenged by microscopic organisms, and I was interviewed by film director Ann Milne as part of a piece aiming to put scientists themselves under the microscope to better understand their motivations.
Year(s) Of Engagement Activity 2015
URL http://www.ascus.org.uk/ciie-micro-residency-2/
 
Description Edinburgh International Science Festival 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We created a stall for the Edinburgh International Science Festival which was held at the Scottish Natural History Museum in April highlighting our research and having several interactive activities for the general public. Hundreds of adults and children visited our stall.
Year(s) Of Engagement Activity 2015
 
Description Edinburgh Open Days 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Public were engaged in the presentation, leading to enthusiastic discussions.

There was general interest in the wild rodent research, specifically the community of parasites and pathogens that infect wild rodents.
Year(s) Of Engagement Activity 2012,2013,2014
 
Description Popular Press and science communication: I actively engage in communicating science to the public and my career and research have featured in the following: Bioscience, Nature, Lab Times, The Daily Telegraph, The Santa Barbara Independent, The Metro, Google News, Herald Scotland, Science Daily, Science, Newsline, News about Planet Earth, and Forth Radio and the South African Broadcast Company Radio. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Popular Press and science communication: I actively engage in communicating science to the public and my career and research have featured in the following: Bioscience, Nature, Lab Times, The Daily Telegraph, The Santa Barbara Independent, The Metro, Google News, Herald Scotland, Science Daily, Science, Newsline, News about Planet Earth, and Forth Radio and the South African Broadcast Company Radio.
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
 
Description Popular science lecture at the Edinburgh International Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Edinburgh International Science Festival (2018): I presented and participated in a panel discussion that was aimed at the general public, titled 'Bad Ways to Die'; where I was introducing the audience to the diversity and biology of human animal parasites.
Year(s) Of Engagement Activity 2018
URL https://www.ed.ac.uk/events/festivals/highlights/all-events/2018/science-festival-interview-with-dr-...
 
Description Soapbox Science Edinburgh 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Soapbox Science Edinburgh 2018. As part of a women in science & public engagement initiative I stood on a soapbox in city centre Edinburgh for 1 hour to openly discuss my research with passerby (estimate of 600 people came to the event).
Year(s) Of Engagement Activity 2018
URL http://soapboxscience.org/soapbox-science-2017-edinburgh/