Optimal virulence in ageing populations

Global populations are ageing at an unprecedented rate. For many diseases, age is a strong indicator of susceptibility, morbidity, or mortality. Principles of evolutionary biology can be leveraged to understand how pathogens may optimally exploit new populations, and the impact of this on the global burden of infectious-disease-induced mortality. We parameterised an age-specific R0 model with 2017 epidemiological data on Measles, Tuberculosis, Meningitis, and Ebola, and age-specific demographic estimates for 2017 and 2050, for the seven Global Burden of Disease super-regions. We explored the theoretical trade-offs between pathogen virulence & transmission, and virulence & host recovery, parameterising trade-off parameters using Latin Hypercube Sampling. Population ageing between 2017-2050 saw an increase in virulence induced mortality in four settings: 1) Ebola in sub-Saharan Africa, 2) Measles in central/eastern Europe & central Asia region, 3) Measles in North Africa & the Middle East and 4) Tuberculosis in the central/eastern Europe & central Asia region. The decrease in infection duration due to an increase of elderly people drives pathogen virulence down for diseases in the remaining settings. Understanding the mechanisms that shape pathogen dynamics and leveraging this to predict future challenges is key to endemic disease management in a rapidly changing world. Author SummaryKey aspects of disease transmission including susceptibility to infection, the severity of infection, and the probability of dying from that infection, are affected by host age. Global populations are rapidly ageing, so that the mean age of most populations is generally higher than it used to be and is set to continue on this trajectory. This suggests that the dynamics of infectious diseases are also likely to change, although infectious disease dynamics tend to be non-linear as these key parameters interact. We have developed a dynamic modelling framework to explore how changes in population age structure might impact the optimal level of pathogen virulence in a population. We have chosen four infectious diseases as case studies, that differentially impact certain age classes to illustrate these dynamics. We have parameterised this framework with open access data for each of the seven Global Burden of Disease super-regions and show that population ageing can increase virulence for several diseases in differing global regions, whilst increased background rates of mortality can drive virulence down in others.