The neurological manifestations of Zika and chikungunya viruses

During 2015-16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (a disorder of the peripheral nervous system) in adults but other neurological associations are uncertain. I designed and performed a retrospective clinical study in Rio de Janeiro, Brazil, investigating patients presenting with an acute neurological disorder and suspected recent Zika virus infection. I found a wider spectrum of neurological disease associated with Zika than reported previously, including that of the central nervous system. This has implications for clinical diagnostic pathways and public health measures. The study also highlighted some of the diagnostic challenges associated with arbovirus-associated neurological disease, and showed an unexpected role of chikungunya virus, another arbovirus that has spread rapidly through the Americas since 2013 and continues to affect millions in explosive outbreaks throughout the tropics. This led me to perform a systematic review of neurological disease associated with chikungunya virus; I summarise all described neurological manifestations, highlighting the wide spectrum of disease in adults and children, its importance in vertical transmission in neonates, comparison with Zika and dengue viruses and recent insights into disease mechanisms. The review will be a useful reference tool for clinicians, researchers and public health officials involved in managing complications of this emerging pathogen. Looking forward, this thesis also discusses the important unanswered questions relating to arbovirus-associated neurological disease, including establishing causality, defining the burden of disease and considerations for vaccines, and how we might approach these challenges