Reservoir interactions and disease emergence

Abstract

Animal populations act as reservoirs for emerging diseases. In order for transmission to be self-sustaining, a pathogen must have a basic reproduction number R0>1. Following a founding transmission event from an animal reservoir to humans, a pathogen has not yet adapted to its new environment and is likely to have an R0<1. However, subsequent evolution may rescue the pathogen from extinction in its new host. Recent applications of branching process theory investigate how the emergence of a novel pathogen is influenced by the number and rates of intermediate evolutionary steps. In addition, repeated contacts between human and reservoir populations may promote pathogen emergence. This article extends a stepping-stone model of pathogen evolution to include reservoir interactions. We demonstrate that the probability of a founding event culminating in an emerged pathogen can be significantly influenced by ongoing reservoir interactions. While infrequent reservoir interactions do not change the probability of disease emergence, moderately frequent interactions can promote emergence by facilitating adaptation to humans. Frequent reservoir interactions promote emergence even with minimal adaptation to humans. Thus, these results warn against perpetuated interaction between humans and animal reservoirs, as occurs when there are ecological or environmental changes that bring humans into more frequent contact with animal reservoirs.

Figure 1

Digraph of a stepping-stone model of pathogen evolution with a reservoir. Types 1, 3, and 5 represent pathogen strains in humans while types 2, 4, and 6 represent strains in an animal reservoir. Types 1 and 2 are the same pathogen strain, types 3 and 4 are the same strain, and types 5 and 6 are the same strain. Type 1 is the strain of the founding event that has evolved from the wildtype pathogen. An epidemic emerges if an infinite number of cases occur. Frequent reservoir interactions can facilitate the process by slowing extinction at each evolutionary step. Pre-emergent strains each have a transmission intensity of 0.5 in humans, while the emergent strain has a transmission intensity of 2. The process is reducible because there is no path from type 5 to type 1 (see Section 3). The model parameters are the pre-emergence direct transmission R₁ = R₃, the emergent direct transmission R₅, the mutation probability m, homonotic transmission ρ, reservoir transmission κ, and zoonotic transmission σ.

Figure 2

Contour plots of the emergence probability, p = ϕ₁₅ as a function of the homonotic transmission intensity ρ and the zoonotic transmission intensity σ, for (A) κ = 0.99, and (B) κ = 0.79. Circles mark the locations of the elasticities shown in Table 1 (See Section 3.3). In the absence of any reservoir interactions, the pathogen has a low probability of emergence (p = ϕ₁₅ = 7.75 × 10⁻⁵). The probability for emergence increases significantly if the intensity of zoonotic transmission (σ) is sufficient for the human-adapted strain to become established. Reduced reservoir transmission intensity (ρ) significantly diminishes emergence when zoonotic transmission is slow. The parameter values are m = 0.01, R₁ = R₃ = 0.5, and R₅ = 2.

Figure 3

A. The emergence probability of type 3 given that type 5 emerges (Eq. (7)). B. How many times more likely type 5 is to emerge while type 3 becomes extinct, compared to the emergence probability of type 5 in the absence of reservoir effects (calculated from Eq. (9)). For large zoonotic transmission and homonotic transmission intensities, type 5 is unlikely to emerge without type 3 also emerging. For small homonotic transmission and zoonotic transmission intensities, the probability of emergence is about the same as it would be in the absence of a reservoir. Reservoir effects are most important when homonotic transmission is common but zoonotic transmission is rare. This is the parameter region of highest public health risk, since there will have been little opportunity for development of control measures based on partially-adapted strains prior to emergence. For example, if ρ = 1 and σ = 0.01, the probability of emergence of type 5 without the emergence of type 3 is more than 4 times as great as it would have been without reservoir interactions. Parameter values were κ = 0.99, and m = 0.01.