Jamonneau Vincent auteur aut IRD Ilboudo H. auteur aut IRD Kabore J. auteur aut IRD Kaba D. auteur aut IRD Koffi M. auteur aut IRD Solano Philippe auteur aut IRD Garcia André auteur aut IRD Courtin David auteur aut IRD Laveissière Claude auteur aut IRD Lingue K. auteur aut IRD Buscher P. auteur aut IRD Bucheton Bruno auteur aut IRD text journalArticle eng text/pdf reformatted digital access The final outcome of infection by Trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. While scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. Here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years) of a cohort of 50 human African trypanosomiasis (HAT) patients from the Ivory Coast among whom 11 refused treatment after their initial diagnosis. In 10 out of 11 subjects who continued to refuse treatment despite repeated visits, parasite clearance was observed using both microscopy and polymerase chain reaction (PCR). Most of these subjects (7/10) also displayed decreasing serological responses, becoming progressively negative to trypanosome variable antigens (LiTat 1.3, 1.5 and 1.6). Hence, in addition to the "classic" lethal outcome of HAT, we show that alternative natural progressions of HAT may occur: progression to an apparently aparasitaemic and asymptomatic infection associated with strong long-lasting serological responses and progression to an apparently spontaneous resolution of infection (with negative results in parasitological tests and PCR) associated with a progressive drop in antibody titres as observed in treated cases. While this study does not precisely estimate the frequency of the alternative courses for this infection, it is noteworthy that in the field national control programs encounter a significant proportion of subjects displaying positive serologic test results but negative results in parasitological testing. These findings demonstrate that a number of these subjects display such infection courses. From our point of view, recognising that trypanotolerance exists in humans, as is now widely accepted for animals, is a major step forward for future research in the field of HAT. specialized 052 6 6 e1691 2012 1935-2735 https://www.documentation.ird.fr/hor/fdi:010057088 10.1371/journal.pntd.0001691 1935-2735 [F B010057088] https://www.documentation.ird.fr/hor/fdi:010057088 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers15-10/010057088.pdf IRD - Base Horizon / Pleins textes 2012-09-03 2017-08-23 fdi:010057088 fre