Density matters: How population dynamics of house mice (Mus musculus) inform the epidemiology of Leptospira

Rodents are maintenance hosts of numerous pathogens, and both their density and the pathogen prevalence determine the risk they pose to other animals or humans. However, density is often overlooked. We investigated a capture-mark-recapture-sampling strategy to study introduced mice (Mus musculus) and Leptospira as a model and demonstrate the advantages of a combined approach. We estimated population density and Leptospira prevalence in mice in a replicated longitudinal survey conducted between 2016 and 2018. Capture-mark-recapture sessions were undertaken at two sites in Spring and Autumn and blood and kidney samples were collected at the end of each session. Mouse density and areas of activity were estimated using spatially explicit capture-recapture (SECR) models and both were compared between Leptospira positive and negative mice. Leptospira exposure and shedding status were estimated using Microscopic Agglutination Test, and a combination of culture and lipL32 PCR on kidneys. Leptospira prevalence was higher in spring (83% to 86%) than in autumn (31% to 37%) and mouse densities simultaneously varied from 3.6 to 55.9/ha. However, despite these variations in prevalence and density, the density of infected animals remained relatively constant over time (3 to 8/ha). Shedding or being seropositive was also associated with the activity of mice. Shedding or seropositive mice had a larger activity area, and seropositive mice were trapped on average one day earlier than seronegative mice. 

Synthesis and applications. Our results show how understanding the population dynamics of pathogen-carrying rodents is critical in epidemiology. The wider movement patterns and easier encounters of positive mice highlight the possibility of biases in classical prevalence surveys and have implications for disease transmission within and between species. Importantly, and quite counter-intuitively, Leptospira prevalence was negatively associated with mouse density, resulting in a constant density of shedders that contradicts the conventional view of higher exposure risk at high rodent density. More broadly, such hybrid sampling designs can improve animal and disease control policies and better inform modelling studies by providing more parameter estimates than classical prevalence surveys.

Methods
This data was obtained using capture-mark recapture and bacteriology methods. Between Spring 2016 and Autumn 2018, four live-trapping sessions were conducted using two grids of 36 Longworth small mammal live-traps, and each session contained two phases. During the Capture-Mark Recapture (CMR) phase (first five nights), mice (Mus musculus) were captured, ear-tagged, sexed, weighed, and released. In the subsequent Removal phase, mice were also blood-sampled, euthanized, and their kidneys tested for Leptospira infection. Antibodies against Leptospira spp. and in particular L. borgpetersenii serovar Ballum were tested using the Microscopic Agglutination Test (MAT), and the presence of Leptospira spp. in the kidneys was determined via culture and real-time PCR.