Latent coinfection and the maintenance of strain diversity

Abstract

Technologies for strain differentiation and typing have made it possible to detect genetic diversity of pathogens, both within individual hosts and within communities. Coinfection of a host by more than one pathogen strain may affect the relative frequency of these strains at the population level through complex within- and between-host interactions; in infectious diseases that have a long latent period, interstrain competition during latency is likely to play an important role in disease dynamics. We show that SEIR models that include a class of latently coinfected individuals can have markedly different long-term dynamics than models without coinfection, and that coinfection can greatly facilitate the stable coexistence of strains. We demonstrate these dynamics using a model relevant to tuberculosis in which people may experience latent coinfection with both drug sensitive and drug resistant strains. Using this model, we show that the existence of a latent coinfected state allows the possibility that disease control interventions that target latency may facilitate the emergence of drug resistance.

Fig. 1

Schematic diagram of the baseline model (model A) with superinfection (a) and model B with coinfection (b). Dashed arrows in (b) represent the possibility that coinfected individuals undergo “reverse” strain replacement upon subsequent re-infection (model C).

Fig. 2

Stability of E₂ in models A, B, and C. Parameters are k = 0.5, μ = 0.06, a_q = 0.15, k_m = 0.4, μ_d = 1, χ = 0, $\frac{1}{4}$ (lower and upper dashed blue lines, respectively) and β₁ and β₂ are independent (and related to R₁ and R₂). The stability region of E₂ is the area below the solid line (red) in the model without coinfection (model A) and below the curved dashed lines (blue) in model B, where the upper of these refers to the coinfection model with strain replacement (see Section 2.3). (Color figure online.)

Fig. 3

Stability of E₂ in the models for tuberculosis with and without latent coinfection. The stability region of E₂ is the area below the curved dashed lines (blue) in the coinfection model, and below the straight solid lines (red) in the model without coinfection. (Color figure online.)