The liver fluke Fasciola nyanzae infects the bile ducts of the enigmatic hippo (Hippopotamus amphibius) and can grow up to 9 cm in length. Its main intermediate host is the freshwater snail Radix natalensis, but invasive exotic species like Pseudosuccinea columella, and to a lesser extent Radix aff. plicatula, can also act as hosts. Historical studies describe notable liver damage, and a high infection prevalence in hippo populations. However, recent data on distribution and morbidity are lacking due to the vulnerable status of hippos, hindering postmortem investigations. Optimized molecular tools to monitor infections in snails and hippo dung present noninvasive alternatives to collect epidemiological data on F. nyanzae. The combined effect of invasive exotic snail species, climate change and increased use of agrochemicals can amplify disease transmission and thereby impact hippo populations throughout Africa.