Abstract
Trypanosoma brucei are extracellular kinetoplastid parasites transmitted by the blood-sucking tsetse fly. They are responsible for the fatal disease human African trypanosomiasis (HAT), also known as sleeping sickness. In late-stage infection, trypanosomes cross the blood–brain barrier (BBB) and invade the central nervous system (CNS) invariably leading to coma and death if untreated. There is no available vaccine and current late-stage HAT chemotherapy consists of either melarsoprol, which is highly toxic causing up to 8% of deaths, or nifurtimox–eflornithine combination therapy (NECT), which is costly and difficult to administer. There is therefore an urgent need to identify new late-stage HAT drug candidates. Here, we review how current imaging tools, ranging from fluorescent confocal microscopy of live immobilized cells in culture to whole-animal imaging, are providing insight into T. brucei biology, parasite-host interplay, trypanosome CNS invasion and disease progression. We also consider how imaging tools can be used for candidate drug screening purposes that could lead to new chemotherapies.
Highlights
Human African trypanosomiasis (HAT) is caused by infection with African trypanosomes (Trypanosoma brucei), which are transmitted by the haematophagous tsetse fly (Glossina spp.)
Human African trypanosomiasis is characterized by two stages, the early or haemolymphatic stage where trypanosomes proliferate at the bite site, travel to local lymph nodes and establish infection in the bloodstream, and the late or meningoencephalitic stage in which trypanosomes cross the blood–brain barrier (BBB) invading the central nervous system (CNS)
Preliminary analysis of brains isolated from mice at day 2 post-infection, labelled with rabbit anti-GFAP 594 to detect glial fibrillary acidic protein, the main intermediate filament protein expressed by astrocytes, revealed GVR35 eGFP parasites in the cerebellar parenchyma (Figure 2d), suggesting that trypanosome CNS invasion occurs before neurological signs are detected
Summary
Trypanosoma brucei are extracellular kinetoplastid parasites transmitted by the blood-sucking tsetse fly. They are responsible for the fatal disease human African trypanosomiasis (HAT), known as sleeping sickness. In late-stage infection, trypanosomes cross the blood–brain barrier (BBB) and invade the central nervous system (CNS) invariably leading to coma and death if untreated. There is an urgent need to identify new late-stage HAT drug candidates. We review how current imaging tools, ranging from fluorescent confocal microscopy of live immobilized cells in culture to wholeanimal imaging, are providing insight into T. brucei biology, parasite-host interplay, trypanosome CNS invasion and disease progression. We consider how imaging tools can be used for candidate drug screening purposes that could lead to new chemotherapies
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