Human host determinants influencing the outcome of Trypanosoma brucei gambiense infections

Abstract

Since first identified, human African trypanosomiasis (HAT) or sleeping sickness has been described as invariably fatal. Increasing data however argue that infection by Trypanosoma brucei gambiense, the causative agent of HAT, results in a wide range of outcomes in its human host and importantly that a number of subjects in endemic areas are apparently able to control infection to low levels, undetectable by the classical parasitological tests used in the field. Thus, trypanotolerance seems to occur in humans as has already been described in cattle or in the rodent experimental models of infection. This review focuses on the description of the diversity of outcomes resulting from T. b. gambiense in humans and on the host factors involved. The consequences/impacts on HAT epidemiology resulting from this diversity are also discussed with regard to implementing sustainable HAT control strategies.

Figure 1

Follow-up of patients and serological suspects in Guinea. Trypanolysis positive serological suspects (b) remained with high CATT titers during their follow-up and parasite DNA was detected by PCR in half of them. All together, the presence of parasite DNA and the high and long lasting CATT reactivity observed in these subjects, in contrast to what is observed in treated patients (a), strongly suggests that these individuals are asymptomatic carriers of T. b. gambiense with low blood parasitemia. Follow-up visits were made at six month intervals.

Figure 2

Diversity of Trypanosoma brucei gambiense infection outcomes in HAT endemic areas. The accepted view of trypanosome infections is that the disease progresses from stage 1 to stage 2 disease over time. However long-term seropositive have been identified and recently we have identified that some of these seropositive individuals have self-cured. Seropositive individuals are asymptomatic and can be considered tolerant whereas those that self-cured may be considered resistant.