Persistent febrile illness (PFI), defined as fever lasting over 7 days, is a neglected field of clinical research in low- and middle-income countries (LMICs). Determining the differential diagnosis of PFI in the rural tropics, including Nepal, is difficult due to the lack of available diagnostic tools and laboratory resources. This leads to failure to establish a confirmatory diagnosis, resulting in inadequate clinical management of patients including the improper use of antibiotics. In this thesis, which was carried out as a nested study within the framework of the Neglected Infectious Diseases DIAGnosis (NIDIAG) study, we present a systematic review of the literature on the causes of PFI in Nepal, then report the results of the NIDIAG study arm conducted in eastern Nepal with a focus on potentially severe and treatable conditions and the extent and risk factors of antibiotic use pre- and post-hospital admission in Nepal, Congo, Sudan and Cambodia.