Insights into persistence mechanisms of a zoonotic virus in bat colonies using a multispecies metapopulation model

Abstract

Rabies is a worldwide zoonosis resulting from Lyssavirus infection. In Europe, Eptesicus serotinus is the most frequently reported bat species infected with Lyssavirus, and thus considered to be the reservoir of European bat Lyssavirus type 1 (EBLV-1). To date, the role of other bat species in EBLV-1 epidemiology and persistence remains unknown. Here, we built an EBLV-1-transmission model based on local observations of a three-cave and four-bat species (Myotis capaccinii, Myotis myotis, Miniopterus schreibersii, Rhinolophus ferrumequinum) system in the Balearic Islands, for which a 1995-2011 serological dataset indicated the continuous presence of EBLV-1. Eptesicus serotinus was never observed in the system during the 16-year follow-up and therefore was not included in the model. We used the model to explore virus persistence mechanisms and to assess the importance of each bat species in the transmission dynamics. We found that EBLV-1 could not be sustained if transmission between M. schreibersii and other bat species was eliminated, suggesting that this species serves as a regional reservoir. Global sensitivity analysis using Sobol's method revealed that following the rate of autumn-winter infectious contacts, M. schreibersii's incubation- and immune-period durations, but not the infectious period length, were the most relevant factors driving virus persistence.

Figure 1. Map of Mallorca and Menorca.

Map of Mallorca and Menorca (in the Balearic Islands) and the locations of the caves (CA, CB and CC) considered in the system studied.

Figure 2. EBLV-1 seroprevalence by subpopulation.

Observed EBLV-1 seroprevalences with 95% CI in two Myotis myotis colonies (A, B) and one Rhinolophus ferrumequinum colony (C). Null rates of seroprevalence at some times might not be indicative of local virus extinctions, but just virus extinctions in that subpopulation or a consequence of under-reporting.

Figure 3. Model description.

(A) January to December occupation of the caves by each species (black). The number of individuals of each subpopulation at the beginning of the simulations is indicated on the left. Gray periods represent only one-third of the colony remaining in the cave. Gray arrows indicate the seasonal interisland exchanges of individuals at certain times. Bat species names are abbreviated: MC, Myotis capaccinii; MM, Myotis myotis; MS, Miniopterus schreibersii and RF, Rhinolophus ferrumequinum. (B) Schematic representation of the metapopulation model, with three patches corresponding to the caves (CA, CB and CC) considered. Black arrows represent exchanges between caves. Each subpopulation is compartmentalized according to its infectious status: S (Susceptible), E (Exposed), I (Infectious) and R (Recovered). (C) SEIRS-model structure for EBLV-1−infection dynamics in each subpopulation.

Figure 4. Virus persistence quantification.

Fluctuations due to stochasticity cause virus extinction over long times. In order to study virus persistence, we defined the persistence index, a. For a given parameter set, we run the model 100 times and estimate a by fitting the function f(t) = a ^(0.01t) to the decreasing proportion of simulations over time with virus persistence. (A, B) The decreasing proportion of simulations with EBLV-1 over time (circles) for two different parameter sets, and the corresponding fit of the function f(t) = a ^(0.01) (black line). The persistence index a quantifies the probability of EBLV-1 persistence over time. A value of a = 0.8 indicates that, after 100 years, EBLV-1 probability of persisting is 0.8. The parameter values used to generate the decreasing curves of simulations with virus persistence (corresponding to those in Mallorca) are the default values reported in Table 2, and for (A), R ₀ = 3, r = 0.6 and interisland exchange  = 15 individuals, and for (B), R ₀ = 3, r = 0.5 and interisland exchange  = 3 individuals. (C) f(t) over 200 years for ten reference values of the persistence index.

Figure 5. One model simulation run.

Gray lines correspond to anti-EBLV-1 antibody seroprevalence in each subpopulation over 50 years. Black lines correspond to seroprevalence measured at the end of May. The parameter values used are: R ₀ = 3, r = 0.6, interisland exchange  = 3 individuals, immune-period duration  = 6 months, and the default values reported in Table 2 for the incubation- and immune-period durations. Abbreviations are as given in the legend to Figure 3.

Figure 6. Ecological factors effect in EBLV-1 persistence on both islands.

The persistence index is represented as a function of the seasonal interisland exchanges (Y-axes) and reduction of contacts during low-transmission periods (X-axes), for three different intraspecies R ₀ values (2, 4 and 6). Persistence index shades of gray from white to black correspond, respectively, to low and high probabilities of virus persistence.

Figure 7. Individual bat species effect in EBLV-1 persistence.

The persistence index is represented as in Figure 6. The first column corresponds to the reference scenario (Ref), in which none of the species is removed from the transmission process. The remaining columns correspond to the tested scenarios in which one after the other the indicated species is excluded from the transmission process. Abbreviations are as given in the legend to Figure 3.

Figure 8. Estimated sensitivities of EBLV-1 persistence-index to the parameters in the model.

The persistence index is highly sensitive to the reduction of contacts in the low-transmission period, and three M. schreibersii and M. capaccinii related parameters (R ₀, and incubation- and immune-period durations). Virus persistence is also slightly sensitive to the R. ferrumequinum R ₀ and the infectious period duration. The remaining parameters have total-order Sobol' indexes <0.1. Abbreviations are as given in the legend to Figure 3.