- This paper describes the development and evaluation of an optical fiber immunosensor (OFIS) for the detection of IgG antibody to Rift Valley fever virus (RVFV) in humans. The OFIS was based on a sandwich enzyme-linked immunosorbent assay (S-ELISA) format, whereby gamma-irradiated RVFV and control antigens were immobilized on the optical fiber surface coated with a mouse anti-RVFV antibody. Data sets derived from field-collected sera in Africa (n = 242) were dichotomized according to the results of a virus neutralization test. Compared to standard colorimetric S-ELISA, the OFIS technique was more sensitive in detecting smaller quantity of specific IgG to RVFV in human sera. At cut-off value selected at a 95% accuracy level by the two-graph receiver operating characteristic analysis, the OFIS diagnostic sensitivity was 97.22% and diagnostic specificity 98.86%. Our results demonstrate that the OFIS technology reported here is highly accurate, simple to perform and has the potential to be used in a portable format.