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PARACORT Report Summary

Project ID: 661690
Funded under: H2020-EU.1.3.2.

Periodic Reporting for period 1 - PARACORT (The role of macroPARAsite COinfection in Rodent-borne microparasite Transmission)

Reporting period: 2015-05-22 to 2016-08-21

Summary of the context and overall objectives of the project

Summary and Objectives
Rodent-borne microparasitic diseases (e.g. Lymphochoriomeningitis virus and Hantavirus), are of increasing public health concern due to rising prevalences worldwide. Additionally, rodents are themselves a threat to food security because they damage agricultural crops and food stores. To effectively control rodent-borne emerging and re-emerging diseases, and the rodent hosts themselves, we need to fully understand the relationship between these rodent hosts and their parasites. Importantly, a high proportion of wild rodents carry endemic macroparasites (e.g. ticks, mites, intestinal worms) but little is known about how these infections change the spread and emergence of the important human transmissable diseases or the dynamics and demography of their rodent hosts. There are good reasons to believe that macroparasites could alter the transmission of microparasitic disease. Firstly, macroparasites alter the host immune response, generally stimulating what is known as a T-helper II response. This is important because a type II response down-regulates the T-helper I response, which is broadly responsible for control of microparasites. It is possible therefore, that rodents that are infected with macroparasites could have less resistance to infection with a range of microparasites. Secondly, a frequent characteristic of macroparasite species is that they can alter the demography and dynamics of host populations. As all parasite dynamics are integrally linked to the dynamics of their host populations, any change in rodent dynamics (e.g. by altering survival or fecundity) due to macroparasites may alter the dynamics of coinfecting microparasites. The key objective of this research was to determine the potential for macroparasites of wild rodents to control host demographics and to alter the transmission of important human transmissible diseases and to assess the implications of these findings for rodent and infection control.

Specifically the project had 5 objectives: 1) To determine whether there were any direct interspecific relationships between the macro- and macroparasites in the two most prevalent forest rodents in the Autonomous Province of Trentino, in Northern Italy. 2) To determine the role macroparasites and microparasites play in controlling host demographic parameters. 3) To determine the community dynamics (of both hosts and parasites) that result from the combination of these interspecific parasite interactions and host demographic influences. 4) To assess how changing host or parasite numbers (e.g. via rodent or parasite control strategies) would affect host demography and parasite transmission, given the interplay between the components of the system. 5) To provide advice on co-ordinated control of hosts and parasites, which complement the needs of key local stakeholders

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Stage 1 of the project was the collation and preliminary assessment of the project database and calculation of the demographic data for the rodent populations. The key resource used was data collected during a previous Marie-Curie Skłodowska fellowship (ROCOALPS) supplemented with additional data on viral presence or absence for Hantavirus and LCMv. In addition, new data was collected from rodents trapped on agricultural land to ensure that the ROCOALPS data was also representative of the agricultural environment. (Timeframe - 22nd May 2015 to 30th November 2015)

Following the basic preliminary analyses contacts were made with the SME Albatros srl. Through this interaction a scientific styled presentation describing the project was designed for Albatros to adapt for a lay audience. This presentation was then used throughout the remainder of the project to aid in discussion with stakeholders (Timeframe: June –August 2015).

In the next phase of the project the interactions between the parasites of both rodent hosts Apodemus flavicollis (mice) and Myodes glareolus (voles) were explored using a combination of Principal Component Analysis (PCA) generalised linear mixed modeling (GLMM) techniques. No direct interactions between the parasites were apparent from this data, suggesting that any suppression of T-helper type I immune response by macroparasites was not strong enough to result in a detectable alteration in viral dynamics. (Timeframe: September 2015-November 2015).

In the next stage of the project the analysis of the demographic data for the two key rodent hosts was undertaken (Apodemus flavicollis – mice and Myodes glareolus – voles). It was determined that macroparasites had significant effects on the survival of mice and the abundance of voles, indicating a demographic control exerted by macroparasites, particularly by ticks and the most abundant helminth Heligmosmoides polygyrus. Evidence from mice was strongest as this was the more common rodent and hence models gave greater explanatory power, however, the pattern of interaction was similar in both species. The key finding was that in both systems macroparasites were importance in changing host demography. Which macroparasite was the driver of population control was determined chiefly by abundance with ticks being of greatest importance at low altitudes and helminths at higher altitudes. Conversely, there was no significant affect of microparasites on host demography
(Timeframe 1st December 2015-25th January 2016).

In the final stage of data analysis, the potential affect of changes in host demography on parasite dynamics was assessed in a series of GLMMs. Mouse data was again the stronger dataset but with data from voles showing similar patterns. Host abundance was strongly and negatively correlated with the prevalence of both Hantavirus and LCMv, indicating a form of dilution effect for these two microparasites. Further analysis suggested that this effect was chiefly the result of increasing the proportion of subadult mice in the population. (Timeframe: February 2016 – March 2016).

The results of the range of analyses therefore demonstrate that macroparasites may potentially alter Hantavirus and LCMv dynamics indirectly by altering the demography of the rodent host populations i.e. reducing survival.

In the final stages of the project a mathematical model was produced of the mouse-macroparasite-microparasite system. The model was then initially parameterised with a estimates derived from the literature and then refined using model fitting to the ROCOALPS data. This model is a major step forward in two key respects. First, to our knowledge, the model is the only microparasite-macroparasite coinfection model fit to a real world system. Second, it is the first coinfection model to incorporate a dynamic aggregation term. Macroparasites in particular demonstrate an aggregated distribution in their host, this has normally been modeled with a fixed term (k) describing the shape of a negative binomial distribution. Our model allows the aggregation to vary dynamically in relation to parasite densities in the host, which is what happens in the real world. The distribution of a parasite within its host is integrally linked to the parasite capacity to control host demography. Therefore this represents an important theoretical step forward in coinfection modeling.

Additional activities undertaken during the project include dissemination of the projects aim to stakeholder groups (i.e. public health officials and agricultural groups – specifically apple growers). This dissemination took the form of both formal and informal meetings and support through rodent trapping activities on agricultural land. We utilized the Alabtros srl powerpoint presentation in most of these encounters. In so doing we have raised the importance of macroparasites to both of these groups and initiated discussions which could lead to joint initiatives in the future.

The fellow held two workshops (in association with the British Ecological Society and in her role as Chair of the Special Interest Group ‘Parasites and Pathogen Ecology and Evolution’) during the course of the project, the first in August 2015, in mid-Wales on the topic of Transmission. This workshop has led to the production of a special issue of Philosophical Transactions of the Royal Society Series B, “Opening the black box: re-examining the ecology and evolution of pathogen transmission” which will be published in early 2017 and which the fellow is co-editing. In addition to her editorial she is last author on a paper in the issue “Breaking beta: deconstructing the parasite transmission function.” The second workshop was a European Grant Writing Workshop (June 2016), bringing together disease ecologists from across Europe for training (provided through and to form collaborations or consortia to build toward future EU grant submissions. Both meetings were extremely successful and provided platforms to present the work of the fellowship to relevant audiences.

In July 2016 the fellow was invited to present her work to the heads of a large number of European Parasitology Societies, at the Annual General Meeting of the European Multicolloquium Of Parasitology in Turku, Finland. The presentation was well received and has provided contact for the fellow both with potential future collaborators and also with potential future grant assessors.

Throughout the project period the fellow provided statistical support and training on a one-to-one basis to a range of staff and students at host institute Fondazione Edmund Mach. This support has both raised the statistical capacity of staff and students at FEM and also provided opportunity for future collaborations within and outside of the research group in which the fellow was placed, thus expanding future grant and publication opportunities for the fellow.

During the project two meetings were held with MUSE to discuss potential opportunities to disseminate aspects of the work to the general public. During the final meeting held in July 2016 a plan was forged to develop a game which would highlight to children the similarities between predator-prey interactions in the 'macro' world and the relationship between parasites and host immunity in the 'micro' world. Children could choose to play as either predator or immune system or as prey or parasites respectively. This project development is ongoing.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project is the first to demonstrate that macroparasites can indirectly alter transmission of important human transmissible disease through host demographic effects. It is also the first to use a coinfection model incorporating variable parasite aggregation (mimicking the real world). As macroparasite infections are ubiquitous in natural and agricultural systems (and for humans in many parts of the world) these findings have far reaching implications for the development of future parasite control strategies.

The rodent-macroparasite-microparasite model is now at a stage where it can be used to make predictions about the consequence of perturbation to host and / or parasite dynamics, e.g. simulating rodent or parasite control strategies. In particular, it will be used to determine the consequence of changing macroparasite densities on the transmission potential of Hantavirus and LCMv and to assess the importance of subadults in transmission of these serious human transmissible diseases. Understanding which factors influence disease transmission and how strong these effects are is essential to successful disease control. We intend to use this model to provide guidelines for agriculture and public health regarding the likely consequences of a) rodent control strategies and b) climatic change – which will affect the dynamics of the macroparasite species with potential consequences for the spread and emergence of microparasitic infection. We will disseminate these findings in a series of reports and scientific papers. At least three scientific manuscripts are intended, the first two being a paired submission aimed at the journal ELife: 1) The role of macroparasites in the transmission of Hantavirus and LCMv, 2) Aggregation matters: the role of a variable aggregation parameter in coinfection modeling (planned joint submission Jan / Feb 2017). The third manuscript will explore the role of subadults in the spread of Hantavirus through an ongoing adaptation of the main model, incorporating age structure of the rodent hosts.

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