The lane to the brain: how African trypanosomes invade the CNS

•African trypanosomes settle in the pia mater and induce a chronic meningeal stage.•Long slender trypanosomes are formed during the meningeal stage.•African trypanosomes enter the choroid plexus and cross the blood–CSF barrier.•Bloodform trypanosomes do not survive in brain parenchyma after intrathecal application.

African trypanosomes induce sleeping sickness. Although it is clear that this parasite moves from the blood to the central nervous system (CNS) to induce the second stage of the disease, little is known about the molecular details of this process. Considering new findings of the trypanosome localization, this opinion paper will summarize the current knowledge about CNS infection, propose a different perception of the invasion process, and discuss possible consequences for drug development.