Encephalitic Arboviruses of Africa: Emergence, Clinical Presentation and Neuropathogenesis

Abstract

Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the Flaviviridae and Togaviridae families that cause neurologic infections, their neuropathogenesis and host neuroimmunological responses in Africa. We also discuss the potential for neuroimmune responses to aide in the development of new diagnostics and therapeutics, and current knowledge gaps to be addressed by arbovirus research.

Keywords: Africa; CNS; Flavivirus; alphavirus biology; neuroimmunology.

Figure 1

Distribution of flaviviruses and alphaviruses in Africa. The distribution of Culex- and Aedes-transmitted flaviviruses WNV, ZIKV, and DENV, and Aedes- and Culex-transmitted alphaviruses CHIKV and SINV, respectively, throughout Africa are shown (17).

Figure 2

Mechanisms of arbovirus entry into the CNS. Arboviruses enter the CNS via three routes: (A, B) Retrograde transport of virus along axon microtubules (MT) of peripheral neurons allows entry into the spinal cord. (C) Infection of olfactory sensory neurons (OSNs) in the olfactory neuroepithelium (ONE) following infection from fenestrated capillaries (FC) allows viral intra-axonal migration through the cribiform plate (CP), followed by transynaptic infection of mitral cells (MC) at the glomeruli (G) of the olfactory bulb (OB). (D) Virus entry through the blood brain barrier (BBB) occurs via transcellular transport of virions, paracellular migration of virions following disruption of tight junctions (TJs), or via transmigration of infected leukocytes.