Interactions between chronic diseases: asymmetric outcomes of co-infection at individual and population scales

Co-infecting parasites and pathogens remain a leading challenge for global public health due to their consequences for individual-level infection risk and disease progression. However, a clear understanding of the population-level consequences of co-infection is lacking. Here, we constructed a model that includes three individual-level effects of co-infection: mortality, fecundity, and transmission. We used the model to investigate how these individual-level consequences of co-infection scale up to produce population-level infection patterns. To parameterize this model, we conducted a four-year cohort study in African buffalo to estimate the individual-level effects of co-infection with two bacterial pathogens, bovine tuberculosis (BTB) and brucellosis, across a range of demographic and environmental contexts. At the individual-level, our empirical results identified BTB as a risk factor for acquiring brucellosis, but we found no association between brucellosis and the risk of acquiring BTB. Both infections were associated with reductions in survival and neither infection was associated with reductions in fecundity. Results of the model reproduce co-infection patterns in the data and predict opposite impacts of co-infection at individual and population scales: whereas BTB facilitated brucellosis infection at the individual-level, our model predicts the presence of brucellosis to have a strong negative impact on BTB at the population-level. In modeled populations where brucellosis is present, the endemic prevalence and basic reproduction number (Ro) of BTB were lower than in populations without brucellosis. Therefore, these results provide a data-driven example of competition between co-infecting pathogens that occurs when one pathogen facilitates secondary infections at the individual level. 1/30 ar X iv :1 71 2. 00 91 9v 1 [ qbi o. PE ] 4 D ec 2 01 7 Significance Statement Infection with multiple parasite species is common and the majority of co-infections involve at least one long-lasting infection. Our data-driven model of chronic co-infection dynamics shows that accurate prediction at the population-level requires quantifying both the individual-level transmission and mortality consequences of co-infection. The infections characterized in this study compete at the population-level. Competition occurs because one pathogen facilitates both the transmission and progression of the second pathogen. This mechanism of competition is unique compared to previously described mechanisms and occurs without of cross-immunity, resource competition within the host, or a period of convalescence. We recommend assessing the generality of this mechanism, which could have important consequences for other chronic, immunosuppressive pathogens such as HIV or TB.