Nodding syndrome since 2012: recent progress, challenges and recommendations for future research.

Area of Science:

• Neurology
• Infectious Diseases
• Epidemiology

Background:

• Nodding syndrome (NS) and epilepsy of unknown etiology co-occur in onchocerciasis-endemic areas, suggesting a potential shared etiology.
• Difficulty in obtaining adequate brain tissue samples from deceased patients in remote villages hinders research.
• Previous research indicates a possible link between NS and onchocerciasis endemicity.

Purpose of the Study:

• To review the current epidemiology of nodding syndrome (NS).
• To identify research gaps in understanding NS.
• To propose a novel pathogen transmission hypothesis for NS and epilepsy.

Main Methods:

• Review of current epidemiological data on nodding syndrome.
• Proposal for immediate post-mortem transsphenoidal brain biopsies for tissue analysis.
• Recommendation for metagenomic studies of human samples, blackflies, and microfilariae.
• Proposal for a clinical trial on the impact of larviciding.

Main Results:

• Nodding syndrome and epilepsy cases are clustered in the same villages and families within onchocerciasis-endemic areas.
• A recent decrease in new NS cases in northern Uganda correlates with blackfly vector control activities.
• The findings support the hypothesis of a novel pathogen transmitted by blackflies.

Conclusions:

• Nodding syndrome and epilepsy may be distinct clinical manifestations of the same disease, potentially caused by a novel pathogen.
• Immediate post-mortem biopsies are crucial for neuropathological examination.
• Metagenomic studies and vector control trials are essential next steps to confirm the pathogen hypothesis and evaluate interventions.