Proliferative kidney disease (PKD) is an emerging disease of salmonids caused by the myxozoan parasite Tetracapsuloides bryosalmonae, which plays a major role in the decrease of wild brown trout (Salmo trutta) populations in Switzerland. Strong evidence demonstrated that water temperature modulates parasite infection. However, less knowledge exists on how seasonal water temperature fluctuations influence PKD manifestation under field conditions, how further environmental factors such as water quality may modulate the disease, and whether these factors coalesce with temperatures role possibly giving rise to cumulative effects on PKD. The aims of this study were to (1) determine the correlation between seasonal course of water temperature and PKD prevalence and intensity in wild brown trout populations, (2) assess if other factors such as water quality or ecomorphology correlate with the infection, and (3) quantitatively predict the implication of these factors on PKD prevalence with a statistical model. Young-of-the-year brown trout were sampled in 45 sites through the Canton of Vaud (Switzerland). For each site, longitudinal time series of water temperature, water quality (macroinvertebrate community index, presence of wastewater treatment plant effluent) and ecomorphological data were collected and correlated with PKD prevalence and intensity. 251 T. bryosalmonae-infected trout of 1,118 were found (overall prevalence 22.5%) at 19 of 45 study sites (42.2%). Relation between PKD infection and seasonal water temperature underlined that the mean water temperature for June and the number of days with mean temperature ≥15°C were the most significantly correlated parameters with parasite prevalence and intensity. The presence of a wastewater treatment plant effluent was significantly correlated with the prevalence and infection intensity. In contrast, macroinvertebrate diversity and river ecomorphology were shown to have little impact on disease parameters. Linear and logistic regressions highlighted quantitatively the prediction of PKD prevalence depending on environmental parameters at a given site and its possible increase due to rising temperatures. The model developed within this study could serve as a useful tool for identifying and predicting disease hot spots. These results support the importance of temperature for PKD in salmonids and provides evidence for a modulating influence of additional environmental stress factors.