PLOS Neglected Tropical Diseases, caused by the filarial parasitic nematode Onchocerca volvulus, remains a significant source of morbidity throughout sub-Saharan Africa and is a primary cause of infectious blindness. Research on this disease has been hindered by an absence of suitable small animal hosts. Here we describe the development of humanized mouse models that are susceptible to O. volvulus infection supporting both growth and maturation of the parasite. These novel mouse models have enabled the identification of a number of new O. volvulus biomarkers with potential to play a role in the development of specific and sensitive diagnostic tests for presence of viable parasites. Development of Onchocerca volvulus in NSG mice PLOS Neglected Tropical Diseases