Reducing the burden of onchocerciasis : a focus on onchocerciasis-associated epilepsy morbidity, mortality and prevention

Onchocerciasis, or river blindness, is a neglected tropical disease caused by 'Onchocerca volvulus' and transmitted by blackflies. Although classically associated with skin and eye disease, growing evidence links high-intensity 'O. volvulus' infection to neurological sequelae, termed onchocerciasis-associated epilepsy (OAE). OAE spans a spectrum of seizure disorders, including nodding and Nakalanga syndromes, yet remains insufficiently recognised in global disease burden estimates. This thesis investigates the burden, management and prevention of OAE and onchocerciasis across South Sudan, Tanzania and Togo, three countries at different stages of onchocerciasis control. It combines epidemiological studies, clinical follow-up data, programme evaluation and transmission modelling to examine how epilepsy clusters in highly endemic areas, how strengthened control may reduce epilepsy incidence, and how community-based care improves outcomes for those already affected by epilepsy. In Mahenge, Tanzania, a case-control study found no association between 'Mansonella perstans' and nodding syndrome, whereas 'O. volvulus' exposure markers were significantly more frequent among persons with epilepsy, including those with probable nodding syndrome. Frequent seizures predicted poorer quality of life, while schooling and access to alternative antiseizure medications predicted better outcomes. In South Sudan, surveys across five counties screened over 34,000 individuals and found a high epilepsy prevalence (4.1%) associated with markers of ongoing 'O. volvulus' transmission. Persons with epilepsy were seven times more likely to die than those without. Strengthened onchocerciasis control was followed by marked declines in epilepsy incidence (per 100,000 person-years): from 327 to 97 in Mvolo, South Sudan, with sustained annual ivermectin; from 178 to 46 in Mahenge after a shift from annual to biannual ivermectin treatment; and from 349 to 42 in Maridi, South Sudan, where biannual treatment was combined with community-led slash and clear vector control that reduced blackfly biting rates by 90%. Transmission modelling in Togo indicated that onchocerciasis elimination is likely in settings with moderate pre-control endemicity, whereas highly endemic areas may require intensified or alternative interventions. Finally, a community-based epilepsy care programme in Mahenge substantially reduced seizure frequency and improved treatment adherence. The thesis argues that OAE should be recognised in global burden estimates and integrated into onchocerciasis elimination planning. It also identifies broader priorities for the onchocerciasis elimination agenda, from diagnostics, surveillance and elimination verification to complementary vector control and alternative treatments for highly endemic foci. Overall, strengthened onchocerciasis control can be followed by marked declines in epilepsy incidence, while decentralised care can alleviate suffering and reduce premature mortality among those already affected.