T. b. rhodesiense causes acute infection in eastern Africa and is responsible for less than 10% of reported cases [3] and [11]. The two forms of parasite are geographically separated by a line across Uganda [12]. Historically, disease prevalence followed in waves of epidemics mainly linked

to the socio-political instability of the affected countries. The resolutions adopted by the WHO and NGOs during the 1990s led to a consistent reduction in the number of reported cases, quantified by decreases of 69% for the gambiense form and 21% for the rhodesiense form, during the period 1997–2006 [3]. Currently, disease transmission is considered to be under control, with 19 of the 36 endemic countries registering no new cases in 2009 [11]. Sleeping sickness progresses through two stages. The Obeticholic Acid ic50 first stage (stage 1, S1), or haemolymphatic stage, occurs after an incubation period that can vary from 1 to 3 weeks after the bite of the tsetse fly. This stage is characterized by the proliferation of parasites in the bloodstream and the lymphatic system. If S1 patients are not properly treated, the disease progresses find more to the second stage (stage 2, S2) or meningo-encephalitic

stage, when parasites invade the CNS [13]. The disease is considered to be fatal if untreated [14]. The speed of progression from S1 to S2 varies according to the infecting parasite: for T. b. gambiense, S1 can last for months or years before evolving into S2, while the evolution of T. b. rhodesiense HAT from S1 to S2 occurs within a few weeks of infection [14]. In both forms of HAT, early stage patients present unspecific clinical symptoms and signs [15]. Stage 1 disease can often mimic other illnesses endemic in the same regions, such as malaria and HIV, which can even coexist in patients affected by sleeping sickness [16]. As the disease evolves into S2, the clinical symptoms and signs become more specific,

with the appearance of neurological disorders of different types as a consequence of meningo-encephalitis, including impaired Oxalosuccinic acid motor functions, tremors, psychiatric changes and coma [14]. The clinical manifestations of the two forms of HAT are different and, generally, T. b. gambiense patients present more evident neurological disorders [15]. A characteristic neurological complication of sleeping sickness, which gives the disease its name, is a dysfunction of the sleep-wake cycle, with daytime sleepiness and alterations of the normal sleep patterns with the appearance of sleep onset REM periods (SOREMPs) [17]. The diagnostic workflow for HAT patients consists of three phases. The first phase, the serological screening, consists in mass population examination using the Card Agglutination Test for Trypanosomiasis (CATT) to identify patients potentially affected by T. b. gambiense.