For the first time using a prospective design, a study confirms the results of previous retrospective studies, which found that strengthening onchocerciasis elimination efforts decreases the incidence of epilepsy, including nodding syndrome. Therefore, this study confirms the solid epidemiological link between onchocerciasis and epilepsy.

This study also shows that a community-based "Slash and Clear" vector control method can effectively decrease blackfly biting rates and potentially decrease onchocerciasis transmission.

Moreover, this study shows that epilepsy is a major cause of death in onchocerciasis endemic areas with high ongoing transmission.

Background High onchocerciasis transmission predisposes communities in endemic areas to a high epilepsy burden. The 4·4% (95%CI:4·1-4·7%) epilepsy prevalence documented in 2018 in Maridi, South Sudan, motivated the strengthening of onchocerciasis elimination measures. We evaluated the effect of these interventions on the incidence of epilepsy, including nodding syndrome (NS).

Methods Annual community-directed treatment with ivermectin (CDTi) was implemented in 2019, temporarily interrupted in 2020 and reimplemented biannually in 2021. Additionally, a community-based "Slash and Clear" vector control method was initiated in 2019 at the Maridi dam. A two-stage house-to-house survey was conducted before (2018) and after (2022) implementing the interventions, consisting of initial screening by community workers to detect suspected cases of epilepsy, followed by confirmation of the diagnosis by a trained clinician.

Finding Overall, 17,652 and 14,402 individuals participated in the pre- and post-intervention surveys, respectively. The epilepsy incidence decreased from 313·0 (95% confidence intervals (CI):273·7-357·7) to 34·7 (95%CI:17·6-66·1) per 100,000 person-years. Similarly, the incidence of NS decreased from 120·4 (95%CI:96·7-149·6) to 10·4 (95%CI:2·7-33·2) per 100,000 person-years. Despite biannual CDTi, only 56·6% of the population took ivermectin in 2021. Mortality of persons with epilepsy accounted for 17·1% (95%CI:14·0-20·7%) of the overall number of deaths in the population.

Interpretation In onchocerciasis-endemic areas with high prevalence of epilepsy, strengthening onchocerciasis elimination interventions can decrease the incidence of epilepsy, including NS. Additional efforts are needed in Maridi, where epilepsy is a major cause of mortality, to increase CDTi coverage and sustain blackfly control.

Inclusion Criteria:

• entire population of selected villages in Maridi County

Exclusion Criteria:

• No

The study was conducted in 44 villages from eight study areas in the central area of Maridi County: Hai-Gabat, Hai-Matara, Hai-Tarawa, Kazana-1, Kazana-2, Kwanga, Mudubai and Nagbaka.

After de-identification (text, tables, figures, and appendices), all individual participant data that underlie the results reported in this article will be made available immediately and indefinitely via the Zenodo repository following publication for anyone who wishes to access the data for any purpose.