These strong long-lasting peripheral serological responses suggest that these persons are asymptomatic carriers who are able to control parasitaemia at levels that are undetectable by microscopy and PCR . instances . The disease evolves from an early Netupitant haemolymphatic phase (1st stage, P1) to a meningoencephalitic phase (second stage, P2) when the parasites invade the central nervous system leading to neurological disorders . Whereas some individuals develop a chronic disease (i.e. remaining in stage 1 for several years), others progress more rapidly to stage 2 within several months . In the absence of treatment, HAT is definitely widely assumed to be 100% fatal. Indeed, HAT probably killed more than one million people on the three major epidemics that ravaged the African continent during the twentieth century , . Little is known about illness end result in the absence of treatment, because usually HAT individuals are systematically treated as soon as possible after analysis, actually in the absence of medical symptoms, since the disease is definitely potentially fatal and tsetse flies can be infected by feeding on these individuals . Although reports on asymptomatic service providers and spontaneous treatment have been published, questions within the living of human being trypanotolerance still remain , , , . Among the few recently published studies is the example of 53 HAT individuals diagnosed in the Sinfra focus (western central part of the Ivory Coast) in 1995C1996 but refusing treatment. These individuals were re-examined several times between 1997 and 1999 in order to convince them to accept treatment . Twenty-nine individuals accepted treatment, mainly because of the progressive appearance of neurological disorders. Two individuals still refused treatment despite the onset of neurological indications and eventually died. Such courses can be considered as the classic fatal progression of HAT. In 1999, among 15 individuals who remained untreated, six were still parasitologically positive with only one showing neurological indications. Interestingly, in nine individuals, an apparent parasitological clearance was observed, among whom six still experienced positive results within the cards agglutination test for trypanosomiasis Netupitant (CATT)  and three experienced bad CATT results. Of these individuals refusing treatment, three of the six individuals who have been Netupitant still parasitologically positive and three of the six still CATT-positive but parasitologically bad in 1999 were re-examined in 2002. All were parasite-negative by microscopy, but PCR-positive , suggesting that these individuals carried latent infections. During surveillance activities in 2004 and 2009, the above-mentioned untreated individuals as well as treated HAT individuals from your same Sinfra focus who have been diagnosed within the same period (1995C1996) were re-visited to assess their parasitological and serological status. In addition, we included additional HAT instances diagnosed between 2000 and 2007 in the nearby Bonon focus Prox1 , , as we had learnt from the local health government bodies that they had not yet been treated. We statement here on the data acquired throughout this long-term follow-up period. Our results, based on medical, serological, molecular, and parasitological investigations, combining field diagnostic tools and highly specific and sensitive laboratory checks, constitute probably the most comprehensive study within the natural evolution of illness in its human being sponsor. At least two alternate natural progressions of HAT to the classic fatal one were observed. Materials and Methods Ethics statement All samples were collected within the platform of medical studies and epidemiological monitoring activities supervised from the national HAT control system (NCP). No samples other than those collected for routine testing and diagnostic methods were collected. All participants were informed about the objective of the study in their personal language and authorized an informed consent form. This study is definitely part of a larger project aiming at improving HAT diagnosis for which approval was from the WHO (Study Ethics Review Committee) and Institut de Recherche pour le Dveloppement (Comit Consultatif de Dontologie et d’Ethique) honest committees. Study subjects Within the platform of monitoring activities carried out in February 2004 and May 2009 in.