BACKGROUND: Massangam health district (HD), in the West Region of Cameroon, has received ivermectin mass drug administration (MDA) for 20 years, however there is evidence of continued high transmission of Onchocerca volvulus. In order to better understand the transmission dynamics in the HD and inform intervention strategies there is a need to delineate the boundaries of the suspected area of high transmission within the wider transmission zone. METHODOLOGY/PRINCIPAL FINDINGS: Parasitological and entomological surveys were conducted to map out the breeding sites of Simulium damnosum and evaluate the prevalence of onchocerciasis in neighbouring communities, including Makouopsap sentinel community. Potential rapids were prospected for identification of S. damnosum larvae and black flies collected to determine infectivity rates. Adults were assessed for the presence of O. volvulus microfilariae through a skin snip biopsy and examined for the presence of nodules. Anti Ov-16 antibodies were tested for in children. Four perennial breeding sites were identified on the Rivers Mbam and Nja. Large number of flies were collected along the River Mbam, especially in the rainy season, with up to 955 flies per day, suggesting this river is a perennial source of black flies. A total of 0.8% of parous flies were infective across the study area. Parasitological studies provided evidence of high rates of infection in the sentinel community and three neighbouring communities, with 37.1% of adults microfilariae positive in Makouopsap. High Ov-16 seropositivity in children also provided evidence of recent on-going transmission. In comparison, communities sampled further away from the sentinel community and neighbouring breeding sites were much closer to reaching onchocerciasis elimination targets. CONCLUSIONS/SIGNIFICANCE: This study provides evidence of a particular geographic area of high transmission in an approximate 12 km range around the sentinel community of Makouopsap and the neighbouring breeding sites on the River Nja. To eliminate onchocerciasis by 2025, there is a need to explore alternative intervention strategies in this area of high transmission.