Nodding syndrome research re-visited

Abstract Nodding syndrome is one of several forms of onchocerciasis-associated epilepsy (OAE) occurring among children in areas formerly hyperendemic for Onchocerca volvulus transmission. These forms of epilepsy are highly prevalent and clustered in certain villages located close to blackfly (Diptera: Simuliidae) breeding sites. OAE presents with a wide spectrum of seizures, including generalized tonic-clonic and head nodding seizures, impaired cognitive function, growth stunting, and delayed puberty. We published a perspective paper in this journal in 2014, in which we hypothesized that nodding syndrome may be caused either by a neurotropic virus transmitted by blackflies or an endosymbiont present within the O. volvulus parasite. Seven years later, we present a critical review of nodding syndrome research progress and assess whether it is still plausible that a neurotropic virus or endosymbiont could be the cause of disease.