Onchocerciasis-associated epilepsy an unrecognised important preventable public health problem

Abstract

Background: 5 years ago we started the NSETHIO project to investigate whether nodding syndrome (NS) could be caused by onchocerciasis. Methods & Materials: Epidemiological, clinical, and entomological studies were performed in onchocerciasis-endemic areas in DRC, Uganda, Tanzania, Cameroon, Nigeria and South Sudan. Results: NS was found to be only one of the clinical manifestations of OAE. OAE is clustered in certain families and villages close to blackfly breeding sites in rapid flowing rivers. A high OAE prevalence was observed in onchocerciasis-endemic areas with sub-optimal elimination measures. OAE is characterised by seizures starting between the ages of 3 and 18 years in previously healthy children, without another obvious cause of epilepsy. In a case-control study in the DRC, in an area without previous ivermectin exposure, persons with epilepsy were twice likely to present skin microfilariae (mf) and with a 10 times higher mf density than controls. A biological gradient and temporality between mf load and the risk of developing epilepsy were demonstrated in a cohort study in Cameroon. NS is the most severe form of OAE and presents with higher mf skin densities than other forms of OAE. Mathematic modelling showed that there may be more than 300,000 persons with OAE in Africa. In a clinical trial in the DRC among persons with OAE, ivermectin was shown to decrease the frequency of seizures. A study in northern Uganda showed that the NS epidemic stopped and that the incidence of other forms of epilepsy also drastically decreased after implementing bi-annual ivermectin treatment and vector control. In Kabarole, western Uganda, since the vector transmitting onchocerciasis was eradicated, new cases of OAE including NS stopped to appear. Examination of CSF of persons with OAE from S Sudan did not reveal mf nor Onchocerca volvulus DNA. A post-mortem study in Uganda of persons who died of NS/OAE showed signs of neuro-inflammation. Conclusion: OAE is a preventable condition by strengthening onchocerciasis elimination programs. Given the absence of parasites in CSF and brain, the most likely pathophysiological mechanism is an auto-immune phenomenon caused by cross-reacting antibodies or by the secretion of a neurotoxic substances by the parasite.