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Human African trypanosomiasis (HAT) has been a major public health problem in South Sudan for the last century. Recurrent outbreaks with a repetitive pattern of responding-scaling down activities have been observed. Control measures for outbreak response were reduced when the prevalence decreased and/or socio-political crisis erupted, leading to a new increase in the number of cases. This paper aims to raise international awareness of the threat of another outbreak of sleeping sickness in South Sudan. It is a review of the available data, interventions over time, and current reports on the status of HAT in South Sudan. Since 2006, control interventions and treatments providing services for sleeping sickness have been reduced. Access to HAT diagnosis and treatment has been considerably diminished. The current status of control activities for HAT in South Sudan could lead to a new outbreak of the disease unless 1) the remaining competent personnel are used to train younger staff to resume surveillance and treatment in the centers where HAT activities have stopped, and 2) control of HAT continues to be given priority even when the number of cases has been substantially reduced. Failure to implement an effective and sustainable system for HAT control and surveillance will increase the risk of a new epidemic. That would cause considerable suffering for the affected population and would be an impediment to the socioeconomic development of South Sudan. [ABSTRACT FROM AUTHOR]