Background Nodding syndrome (NS) is a progressive neurological disease that has been described in several sub-Saharan African counties, but South Sudan is considered the most affected. However, knowledge about the exact burden and the epidemiological risk factors of NS in South Sudan is lacking. Objective To determine the prevalence, distribution and epidemiological risk factors of NS in the Greater Mundri area, the epicenter of NS in South Sudan. Methods A NS prevalence house-to-house survey was conducted in multiple villages between February 2018 and November 2019. Geographical distribution and clustering of NS cases was identified using spatial and binomial regression analysis. Epidemiological risk factors of NS were identified using univariate and multivariate models. Results Of the 22,411 persons surveyed in 92 villages, 607 (2.7%) persons with NS were identified, of which 114 (19%) were new-onset cases. The highest prevalence was found in Diko village with a prevalence of 13.7%. NS showed a significant spatial pattern with clustering of cases between adjacent households and along rivers. Risks factors for NS include all behaviors around rivers (drinking, cooking, handwashing and bathing) and exposure to poultry. On the other hand, ownership of mobile phone decreased the risk of NS. Many other factors, including prior ivermectin treatment and internal displacement were not associated with NS. Conclusion Our study demonstrates a very high burden of the NS disease in the Greater Mundri area, strengthens the association with rivers, and identified possible new clues for an underlying cause.

We conducted a house-to-house survey in the Mundri, Western Equatoria state of South Sudan to investigate the clinical characteristics, risk factors, access to treatment and perceptions about nodding syndrome (NS). In total, 224 NS cases with median age of seizure onset of 10 years were identified. Head nodding only was reported in 50 (22.3%) cases, and head nodding plus other types of seizures in 174 (77.7%) cases. Wasting, stunted growth, delayed sexual development and speech and behavioral abnormalities were observed in 17 (23.6%), 16 (22.2%), 9 (17.3%), 14 (19.4%) and 4 (5.6%) cases, respectively. The consumption of rat meat, but not other bushmeat was associated with an increased risk of NS (OR 9.31, 95% CI 1.27–406.51). Children with NS were more likely to have taken ivermectin in the last 5 years (OR 2.40, 95% CI 1.33–4.43). NS cases were less likely to share a bedroom with other children (OR 0.06, 95% CI 0.02–0.16) or adults (OR 0.27, 95% CI 0.13–0.56). In conclusion, rat meat consumption is an unlikely risk factor for NS, and ivermectin intake was more common among NS cases than controls. Importantly, we documented that children with NS are stigmatized because of the misconception that NS is transmitted through direct contact.