Nodding syndrome The puzzle of tropical diseases in sub-Saharan Africa

Nodding syndrome (NS) is a debilitating and stigmatizing neurological illness affecting thousands of individuals in multiple sub-Saharan African countries. It often presents with distinctive clinical features including repetitive head-nodding and other types of seizures, and growth, sexual and cognitive retardation. Although, multiple studies have been conducted, the etiology remains unknown and no curative treatment available. Public health interventions including community-directed treatment with ivermectin (CDTI) and larviciding of the rivers were implemented because of the multiple associations found between NS and Onchocerca volvulus (OV). However, the effectiveness of these interventions is yet to be proven.
We carried out several studies including a systematic scoping review to establish up-to-date available evidence of NS, a large epidemiological population-based study to evaluate the burden, distribution, clinical presentation and risk factors of NS in South Sudan and a case-control study to determine the possible etiology of NS.
NS is now prevalent in Tanzania, South Sudan, Uganda, DRC, Cameroon and the Central African Republic. Highest prevalence is found in the Mundri area, Western Equatoria State of South Sudan, where more than one in five households affected and newer cases continue to emerge. We found spatial clustering of NS cases within adjacent households, while living near the rivers and all behaviors around rivers increased the risk of NS; suggesting a possible link with pathogens such as OV, blackflies, neurotropic virus, or toxins like heavy metals. We documented a complex interplay between multiple pathogens and micronutrient levels may cause NS, in which we detected significant associations with Mansonella perstans, Necator americanus, higher vitamins A and E and lower vitamin B12, the consumption of rat-meat, and exposure to poultry within a household. Further studies are required to confirm our novel associations and determine the direction of causality. We also confirmed the misconception amongst the NS-affected communities that NS is transmitted from person-to-person resulting into isolation and stigmatization of the NS cases.
In conclusion, NS is a multifactorial syndrome of unknown definitive cause with no curative treatment options. The current public health interventions including CDTI and larviciding of the rivers need to be evaluated while being implemented. Control of seizures with antiepileptics, nutritional supplementation, rehabilitation programs, and psychosocial and economic support need to be adequately and urgently implemented.