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Nodding Syndrome: a trans-disciplinary approach to identify the cause and decrease the incidence of river epilepsy

Periodic Reporting for period 3 - NSETHIO (Nodding Syndrome: a trans-disciplinary approach to identify the cause and decrease the incidence of river epilepsy)

Reporting period: 2018-10-01 to 2020-03-31

Nodding syndrome (NS) is a devastating epileptic syndrome appearing in previously healthy children between the ages of 3 and 18 years. The syndrome is characterized by head-nodding, an atonic seizure, and is often associated with a declining cognitive function, psychiatric problems, stunting growth, and early death. Until recently the cause of the syndrome was unknown. Therefore, no strategy for prevention and cure was possible.
NS was initially reported to occur only in onchocerciasis-endemic regions in Tanzania, Uganda and South Sudan. Onchocerciasis (or river blindness) is a disease caused by a worm transmitted by blackflies. A high frequency of epilepsy has also been observed in onchocerciasis endemic regions in other African countries, such as in Cameroon where it was called “river epilepsy” or onchocerciasis associated epilepsy (OAE)

NS and OAE are catastrophic for the persons, families and villages affected. Most OAE-affected children are intellectually disabled and have psychiatric problems. Parents are left desperate and living in fear because some children simply wander off, disappear and die. Mentally retarded girls with OAE are at risk of being sexually abused. Children often fall in a fire or drown in the river. In most remote onchocerciasis endemic regions in Africa, people do not have continuous access to anti-epileptic treatment or basic care for burn wounds. Parents generally are not aware that with medical treatment the health condition of the children may improve. Therefore they may abandon their children with resultant malnourishment and early death. There is a belief in the affected communities that epilepsy-affected people are possessed by evil spirits and hence the entire family may be isolated from society.

As children form the social security of the family in these regions, having one or more affected children has a large impact on the family income and social status. Children with OAE with intellectual disability will not be able to provide income for the family nor take care of elderly family members. OAE affected children require constant care/supervision. As a consequence, a family member may not be able to go to work because he/she needs to watch the OAE affected children. Children with OAE also often die at a young age. Family income is decreasing because having to care for a sick child. This suggests that the economic cost of OAE is considerable.

The aim of the NSETHIO project is to identify the cause of NS and OAE and to detect ways to prevent OAE.
We discovered that NS is only one of the clinical presentations of “river epilepsy” or onchocerciasis associated epilepsy (OAE) and that this form of epilepsy is probably present in all onchocerciasis endemic regions where onchocerciasis is insufficiently controlled. We documented a prevalence of epilepsy between 2 and 6% in many villages near such rapid flowing rivers in the Bas Uele, Tshopo and Ituri province in the Democratic Republic of the Congo (DRC). This is a much higher than the prevalence of epilepsy (<1%) observed in African regions where there is no onchocerciasis. In case-control studies in the DRC we showed that the excess of epilepsy in villages in onchocerciasis endemic regions is likely to be explained by OAE. Based on our data we estimate that the number of excess cases of epilepsy due to onchocerciasis could reach as high as 100,000 people.
NSETHIO collected evidence that optimal coverage with ivermectin (the treatment of onchocerciasis) can stop an epidemic of NS and protect individuals in onchocerciasis endemic regions from developing epilepsy. We documented however that in many onchocerciasis endemic regions in South Sudan, the DRC, the Mahenge region in Tanzania and in certain villages in the Mbam valley in Cameroon, ivermectin coverage is sub-optimal. We also collected data suggesting that ivermectin given to patients with OAE may decrease the frequency of seizures but we aim to proof this in a clinical trial that will be performed in the Logo Health zone in Ituri in the DRC.
It is now clear that NS and OAE are triggered by the Onchocerca volvulus parasite but NSETHIO still needs to determine the exact pathophysiological mechanism. To determine the histopathological abnormalities associated with OAE a postmortem study is ongoing in Uganda.

Our research findings were picked up by several newspapers and disseminated through interviews: e.g. for BBC world and presentations at international conferences. We also organized the first international workshop on onchocerciasis associated epilepsy 12-14 October 2017 in Antwerp, Belgium.
"Based on NSETHIO research findings we obtained an ERC Poc proposal ""NS stop"" that will develop together with stake holders and interested partners an innovative comprehensive onchocerciasis associated epilepsy (OAE) policy plan that can prevent children from developing OAE, and reduce the negative consequences of OAE for the economy and society."
R Colebunders during epilepsy prevalence study in Bas Uele province, DRC
NSETHIO participants in Kick-off meeting
NSETHIO team investigating onchocerciasis associated epilepsy in Ituri, DRC