Untreated human infections by Trypanosoma brucei gambiense are not 100% fatal.

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.

Diversity and spatial distribution of vectors and hosts of T. brucei gambiense in forest zones of, Southern Cameroon: epidemiological implications.

Host and vector distribution of Trypanosoma brucei gambiense was studied in relation to habitat types and seasons. Six (19.35%) of the 31 mammal species recorded in Bipindi were reservoir hosts. Cercopithecus nictitans was confined to the undisturbed forest and the low intensive shifting cultivation zones, while Cephalophus monticola, Cephalophus dorsalis, Cricetomys gambianus, Atherurus africanus and Nandinia binotata occurred in all the habitat types. As for vectors of human African trypanosomiasis (HAT), Glossina palpalis palpalis, was the most abundant (99.13%) among tsetse fly species. It occurs in all biotopes with its highest density recorded in the village-adjacent forest. The village-adjacent forest is therefore the most risky transmission zone for HAT mainly during the short rainy season when G. palpalis palpalis' density is highest (2.91); while, the high and low intensive shifting cultivation zones are the most important contact zones between humans, G. palpalis palpalis and wild mammals in all seasons.

Influence of habitat and seasonal variation on wild mammal diversity and distribution with special reference to the Trypanosoma brucei gambiense host-reservoir in Bipindi (Cameroon).

To evaluate the role of wildlife in the resurgence and perenisation of human African trypanosomiasis (HAT), we investigated the influence of habitat and seasonal variations on the diversity and spatial distribution of wild mammals, with special reference to those recognised as potential host-reservoirs of Trypanosoma brucei gambiense in Bipindi (southwestern Cameroon). To achieve this, we carried out transect surveys in four habitat types over two years. A total of 31 mammal species were recorded, of which 14 occurred in the undisturbed forest, 9 in cocoa plantations, 11 in farmlands and 11 in village-adjacent gallery forests. Among them, six species (Cephalophus monticola, Cephalophus dorsalis, Atherurus africanus, Cricetomys emini, Nandinia binotata and Cercopithecus nictitans), known as reservoir hosts of T. b. gambiense, occurred in all kinds of habitats suitable or unsuited to Glossina palpalis palpalis and in all seasons. These species are the most involved in the transmission cycle (human being/tsetse flies/wild animals). Cercopithecus cephus, Miopithecus talapoin and Heliosciurus rufobrachium host Trypanosoma brucei spp.; however, only C. cephus does not occur permanently in the suitable habitat of G. palpalis palpalis. In general, some species (C. monticola, Tragelaphus spekei and C. emini) showed a slight density increase from the long dry to the heavy rainy season within the undisturbed and farmland habitats, and a slight decrease within cocoa plantations and village-adjacent forests in the same period. The density of A. africanus increased greatly from the long dry season to the heavy rainy season in the undisturbed forest while, the density of primates in this habitat decreased slightly from the long dry season to the heavy rainy season. These variations indicate a permanent movement of wild mammal reservoir or feeding hosts from one biotope to another over the seasons. Thryonomys swinderianus needs to be investigated because it occurs permanently in the suitable habitat of G. palpalis palpalis and Potamochoerus porcus for its genetic similarities to domestic pigs, favourable feeding hosts of G. palpalis palpalis.

Interest of tumor necrosis factor-alpha -308 G/A and interleukin-10 -592 C/A polymorphisms in human African trypanosomiasis.

This study aimed to determine whether single nucleotide polymorphisms (SNPs) within tumour necrosis factor-alpha (TNF) and interleukin-10 (IL10) promoters and genes are associated with human African trypanosomiasis (HAT). The polymorphisms used in the analysis were TNF(-308G/A), TNF(-238G/A), TNF(-1031T/C), TNF(+488G/A), IL10(-1082G/A) and IL10(-592C/A). A familial case-control sample of 277 individuals (102 cases and 175 parents) and a matched case-control group of 225 subjects (88 cases and 137 unrelated controls) were gathered together in this study. A conditional logistic regression was used to test for association. We carried out this analysis in the overall population and after stratification by time of exposure, age and ethnic group. Our results show that in the overall population, and after stratification by time of exposure, the IL10(-592A) allele is associated with a lower risk of disease, suggesting the possibility of a protective effect. After stratification by time of exposure, individuals homozygous for the SNP located in the TNF(-308) promoter were shown to present a higher risk of developing the disease early after exposure. Our study shows that TNF(-308G/A) and IL10(-592C/A) SNPs are polymorphisms of interest in the investigation of the genetic susceptibility to human African trypanosomiasis. Larger studies are currently underway to confirm these results.