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Biology and clinical staging of trypanosome neuroinvasion in sleeping sickness


The project, based on a joint effort of five African and three European partners, foresees a highly integrated investigation of sleeping sickness or human African trypanosomiasis (HAT). This is a neglected but re-emerging disease in sub-Saharan Africa. HAT develops into an early haemolymphatic and a subsequent encephalitic stage, during which the causative parasite Trypanosoma brucei and/or increased numbers of lymphocytes are found in the cerebrospinal fluid. Arsenic compounds are still the drugs of choice for treatment of the encephalitic stage, but they are associated with severe and often fatal side effects. Relapses after current treatments also pose a serious problem.

There are important gaps in knowledge concerning:
(i) mechanisms by which trypanosomes invade the brain,
(ii) when, post-infection, such invasion occurs, and
(iii) effects of drugs on trypanosomes that have invaded the brain parenchyma.

To discover mechanisms of parasite neuro-invasion and thereby devising candidates of diagnostic markers for an effective staging and new therapeutic management of HAT, the project plans to:
1. Unravel the mechanism/s by which African trypanosomes cross the BBB and invade the brain;
2. Identify candidate biomarkers for this event for diagnostic tools for therapeutic decisions and cure assessment;
3. Investigate the therapeutic potential of new low-toxicity drugs, already in use for other diseases, which can interfere with trypanosomes that are invading or have invaded the brain;
4. Determine clinical, immunological and neuro-physiological parameters that correlate to trypanosome neuro-invasion, as well as therapeutic windows for drugs to clear trypanosomes from the brain;
5. Strengthen the research capacity of African investigators by providing transfer of technology and training for junior investigators, especially African scientists, to develop expertise on HAT and other neuro-inflammatory diseases, which are a plague in the African continent.

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Nobels väg 5

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Participants (7)