Constrained minimization problems for the reproduction number in meta-population models

The basic reproduction number ( R 0 ) can be considerably higher in an SIR model with heterogeneous mixing compared to that from a corresponding model with homogeneous mixing. For example, in the case of measles, mumps and rubella in San Diego, CA, Glasser et al. (Lancet Infect Dis 16(5):599–605, 2016 . https://doi.org/10.1016/S1473-3099(16)00004-9 ), reported an increase of 70% in R 0 when heterogeneity was accounted for. Meta-population models with simple heterogeneous mixing functions, e.g., proportionate mixing, have been employed to identify optimal vaccination strategies using an approach based on the gradient of the effective reproduction number ( R v ), which consists of partial derivatives of R v with respect to the proportions immune p i in sub-groups i (Feng et al. in J Theor Biol 386:177–187, 2015 . https://doi.org/10.1016/j.jtbi.2015.09.006 ; Math Biosci 287:93–104, 2017 . https://doi.org/10.1016/j.mbs.2016.09.013 ). These papers consider cases in which an optimal vaccination strategy exists. However, in general, the optimal solution identified using the gradient may not be feasible for some parameter values (i.e., vaccination coverages outside the unit interval). In this paper, we derive the analytic conditions under which the optimal solution is feasible. Explicit expressions for the optimal solutions in the case of n = 2 sub-populations are obtained, and the bounds for optimal solutions are derived for n > 2 sub-populations. This is done for general mixing functions and examples of proportionate and preferential mixing are presented. Of special significance is the result that for general mixing schemes, both R 0 and R v are bounded below and above by their corresponding expressions when mixing is proportionate and isolated, respectively.