chem asked in Science & MathematicsMedicine · 4 weeks ago

bio question?

if researchers developed a drug that could prevent t brucei from undergoing antigenic variation do you think it could be successful in eradicating African sleeping sickness? would the drug be administered at a certain point before or after infection in order to be helpful?

1 Answer

  • Anonymous
    4 weeks ago

    Vaccination against trypanosomiasis should remain the ultimate goal in the fight against this disease, both in case of animal trypanosomiasis and HAT. This assumption is based on two main observation: first, taken that it is an impossible task to eradicate the entire parasite reservoir of endemic areas, only vaccination will provide a long lasting economically viable option to prevent human casualties and vast economic losses due to livestock infections. Second, taken that trypanotolerance occurs in many mammals endemic to regions where trypanosomiasis occurs, and that even in human infections immunological control of the infection has been reported, it appears that immune intervention to prevent the deadly outcome of trypanosomiasis should be somehow a feasible target.

    To date, not a single experimental anti-trypanosome vaccination protocol has made it to a stage where preliminary promising results have been reported in a field setting. One of the problems of experimental trypanosomiasis research might be the general use of murine models for basic research. While these models do serve their purpose in a certain context, it has become clear that with respect to B-cell function and memory maintenance during infection, mice suffer from trypanosomiasis-associated defects that might be specific for the model, and do not necessarily reflect the immunological situation of the natural host. Indeed, the fact that mice can be re-infected with previously encountered trypanosome variants suggest that antigenic variation only has a limited importance in the defense of the parasite against the destruction by the host (mouse) immune system. In contrast, the fact that trypanosomes very efficiently destroy vaccine induced immunological memory in a mouse setting, might be an exaggeration of what is observed in natural hosts, associated to the distorted parasite/immune cell ratio in mouse, that exhibit abnormally high circulating parasite numbers throughout infection. This last issue raises a very important question with respect to vaccine development and experimental vaccine trials: could it be that the murine model for trypanosomiasis is prone to failure when it comes to testing the effect of B-cell immunity and B-cell memory? If so, it could be that many of the ‘failed’ murine vaccine studies using various conserved trypanosome surface molecules are actually negatively biased by the intrinsic immune deficiency occurring during trypanosome infections in mice. Possibly, using other, more relevant models for infection, could lead to other outcomes in vaccine trials. While there is no ‘easily accessible’ alternative for initial murine experiments, maybe such alternatives have to be considered in order to increase the success of finding a future anti-trypanosome vaccination approach, taken the very specific features of host-parasite interactions.

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