Nodding syndrome—a new hypothesis and new direction for research

• Nodding syndrome (NS) caused an epilepsy epidemic in South Sudan and northern Uganda.
• NS is mainly affecting children between 5 and 15 years of age.
• In many onchocerciasis endemic areas there is a high prevalence of epilepsy.
• Blackflies infected with microfilariae may also transmit another pathogen causing NS.
• Treating rivers with larvicides may stop NS epidemics.

SummaryNodding syndrome (NS) is an unexplained neurological illness that mainly affects children aged between 5 and 15 years. NS has so far been reported from South Sudan, northern Uganda, and Tanzania, but in spite of extensive investigations, the aetiology remains unknown. We hypothesize that blackflies (Diptera: Simuliidae) infected with Onchocerca volvulus microfilariae may also transmit another pathogen. This may be a novel neurotropic virus or an endosymbiont of the microfilariae, which causes not only NS, but also epilepsy without nodding. This hypothesis addresses many of the questions about NS that researchers have previously been unable to answer. An argument in favour of the hypothesis is the fact that in Uganda, the number of new NS cases decreased (with no new cases reported since 2013) after ivermectin coverage was increased and with the implementation of a programme of aerial spraying and larviciding of the large rivers where blackflies were breeding. If confirmed, our hypothesis will enable new strategies to control NS outbreaks.