Human African trypanosomiasis, also known as “African sleeping sickness,” is an affliction endemic to sub-Saharan African (Stich, Abel, & Krishna, 2002). It is caused by trypanosomes, a type of parasite. The specific etiological agent that is responsible for most cases of African sleeping sickness is Trypanosoma brucei gambiense, although the disease can also be caused by Trypanosoma brucei rhodesiense. Trypanosoma brucei rhodesiense causes a rarer, acute form of the illness that kills over a few months. Trypanosoma brucei gambiense causes a chronic form of the illness that can take up to a few years to kill.
Trypanosomes have a complicated life cycle, part of which takes place within an insect called the tsetse fly (Stich, Abel, & Krishna, 2002). When an infected tsetse fly bites a human, the parasites are transmitted from the fly to the victim. A more detailed view of the tsetse fly life cycle can be seen in the image below.
The human immune system is naturally immune to attack from most trypanosomes (Vanhollebeke et al., 2008). During the first stage of disease, trypanosomes live in the bloodstream, where they reproduce and scavenge heme, a compound that is part of hemoglobin (the protein in red blood cells that transports oxygen between tissues) from red blood cells. Heme binds to a specific receptor on the trypanosome surface, and is then taken in by the parasite. The human immune system can usually kill trypanosomes by binding a compound called Hrp to heme (Pays et al., 2014). When this Hrp-heme complex is taken up by the trypanosome (which thinks that it is merely heme), Hrp enters the parasite and kills it from within.
If humans are usually naturally immune to trypanosomes, why do Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense cause disease? The answer lies in the trypanosome’s heme receptor. As previously mentioned, the immune system can bind a compound called Hrp to heme. This Hrp/heme complex binds to the trypanosome heme receptor, and Hrp can cause the death of the trypanosome. Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense have a single amino acid mutation in their heme receptors which prevents heme from binding when it is complexed with Hrp (Uzureau et al., 2013). Since it is the Hrp/heme complex that is deadly to trypanosomes, if its binding is blocked, the trypanosome can continue to thrive.
The stage of disease in which trypanosomes are multiplying in the circulatory system is known as the hemolymphatic stage (Lundkvist, 2004). When the trypanosomes have finished obtaining heme in the bloodstream, they cross over the blood-brain barrier and begin to attack the central nervous system (Mogk et al., 2014). This marks the beginning of the second stage of the disease, during which it is harder to treat. Potentially the most obvious effect of this infiltration is a significant disturbance of the sleep-wake cycle, caused by a release of tryptophol, a compound that is associated with proper circadian rhythms (Cornford et al., 1979). This sleep disturbance is where African sleeping sickness gets its name. The disease is eventually fatal if not treated. There are therapies available, but any treatment for second-stage African trypanosomiasis has a risk for severe side effects.
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Uzureau, P., Uzureau, S., Lecordier, L., Fontaine, F., Tebabi, P., Homblé, F., Grélard, A., Zhendre, V., Nolan, D.P., Lins, L., et al. (2013). Mechanism of Trypanosoma brucei gambiense resistance to human serum. Nature 501, 430–434.
Vanhollebeke, B., De Muylder, G., Nielsen, M.J., Pays, A., Tebabi, P., Dieu, M., Raes, M., Moestrup, S.K., and Pays, E. (2008). A Haptoglobin-Hemoglobin Receptor Conveys Innate Immunity to Trypanosoma brucei in Humans. Science 320, 677–681.