Human African trypanosomiasis, also known as sleeping sickness, is only endemic in South Sudan within the WHO Eastern Mediterranean Region. Foci of T.b. gambiense occur in the Equatoria region, a belt bordering the Central African Republic, Democratic Republic of Congo and Uganda. In South Sudan, Western Equatoria is the most affected state, followed by Central Equatoria and Eastern Equatoria states. Historically, cases of T.b. rhodesiense were anecdotally reported in Eastern Equatoria (Torit County) and Jonglei (Akobo County), but there is no recent evidence of cases being reported there.
Nine counties are endemic for the disease, namely Tambura, Ezo, Yambio, Maridi, Mundri, Juba, Yei, Kajo Keji and Magwi. The number of people at risk of human African trypanosomiasis is estimated at 1.8 million.
Large epidemics of human African trypanosomiasis have periodically occurred in South Sudan since the early 20th century. When outbreaks occur, large-scale control reduces the number of cases but when the programme scales down disease resurgence occurs. After the latest epidemic registered in the mid-1990s control programmes were re-initiated by a number of international nongovernmental organizations in several counties.