Under- or misdiagnosed cases of disease caused by especially dangerous pathogens present public health and proliferation risks. Numerous studies have demonstrated that in low-resource settings, and particularly where malaria is endemic, patients presenting to healthcare facilities with febrile illness may not receive an accurate diagnosis due to, among other reasons, shortcomings in differential protocols and lack of available diagnostic tests. In Guinea, when patients present at the community or prefectural level with febrile illness, weaknesses in clinical differential protocols usually result in the patient being diagnosed with a common infection, notably malaria and occasionally typhoid, with no further testing performed. As such, acute febrile illness presents an unquantified and undifferentiated burden to the Guinean healthcare system. The specific challenge for public health authorities is that pathogens causing febrile episodes in the population, and the zoonotic transmission pathways that may drive them, have not been systematically nor comprehensively identified. Fever Project is a three-year research project with the objective to build capacity for threat reduction in Guinea and improve health security through an integrated approach to human and animal health for the identification of high-consequence aetiologies of acute febrile illness in humans. The project’s goals are to: I) identify the causative agents of acute febrile illness in humans in Guinea; II) uncover evidence for transmission of high-consequence zoonotic pathogens associated with acute febrile illness; III) investigate risk factors for acute febrile illness in humans, including exposure to domestic and peri-domestic animals; and IV) improve capacities for the detection of high-consequence pathogens associated with acute febrile illness.