Research Joseph Nelson Siewe Fodjo

Abstract

Epilepsy is a common neurological disorder, affecting about 50 million people worldwide with more than 80% of them living in developing countries. Besides the perinatal, traumatic, and metabolic causes of epilepsy, epidemiological associations have been established between epilepsy and several parasitic infections (malaria, neurocysticercosis, onchocerciasis, mansonellosis, etc.). The specific type of epilepsy caused by O. volvulus (known as onchocerciasis-associated epilepsy or OAE) is characterised by sudden seizure onset in previously healthy children between the ages of 3 and 18 years. However, the pathophysiological mechanisms by which O. volvulus can trigger epilepsy are still unclear. We recently discovered a virus inside the O. volvulus parasite, called OVRV1. OVRV1 is closely related to the family of lyssaviruses (e.g.: the rabies virus) and could be involved in the pathogenesis of OAE. So far, few cases of OAE have been reported from West Africa since O. volvulus transmission had been controlled in most of its onchocerciasis foci. However, a persisting hyper-endemic hotspot was identified in the Adansi South District of Ghana, with anecdotal reports of frequent epilepsy in that area. In this pilot project, we seek to determine the epilepsy prevalence in this hyper-endemic Ghanaian area and investigate whether OVRV1 constitutes a risk factor for developing OAE. Another filarial parasite that will be investigated as a potential risk factor for epilepsy is Mansonella perstans, which is also endemic in the target communities. Lastly, we will investigate why onchocerciasis persists in this area despite many years of mass treatment with ivermectin to break the transmission cycle. To achieve this, we will conduct door-to-door epilepsy surveys in the study villages. Epilepsy cases will be identified via questionnaires and clinical examination by trained physicians. All village residents will be questioned about ivermectin intake and reasons for ivermectin refusal documented. Children aged 5-9 years will be tested for onchocerciasis antibodies using a rapid diagnosis test as a measure of ongoing O. volvulus transmission. A nested case-control study will enrol all persons with epilepsy who will be age-and sex-matched with non-epileptic controls, and tested for O. volvulus, M. perstans, and OVRV1 infection. Our findings will be important to make informed decisions for onchocerciasis elimination interventions and epilepsy prevention/management in the study villages. This study also promises to significantly advance research on OAE pathophysiology and disease mechanisms of filarial parasites.

Researcher(s)

• Promoter: Siewe Fodjo Joseph Nelson

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

Onchocerciasis, caused by the parasite Onchocerca volvulus, is still endemic in Cameroon despite long-term annual community-directed treatment with ivermectin (CDTI). Low CDTI coverage and frequency (once a year) resulted in a high prevalence of onchocerciasis-associated morbidity (skin, eye, and neurological disease). Children infected with O. volvulus between the ages of 5-12 years are at risk of developing onchocerciasis-associated epilepsy. Moreover, O. volvulus infection during pregnancy induces "parasite tolerance" in the neonate and an increased risk to become infected with high parasitic loads, predisposing the child to develop onchocerciasis-associated morbidities. We hypothesize that maternal onchocerciasis has a negative impact on the neuro-cognitive development of the child. This will be investigated by recruiting nursing mothers with different exposures to onchocerciasis during pregnancy, and by monitoring the neurocognitive evolution of their children at 12 and 24 months of age.

Researcher(s)

• Promoter: Siewe Fodjo Joseph Nelson

Research team(s)

• Global Health Institute (GHI)

Project website

Project type(s)

• Research Project

Abstract

Onchocerciasis, caused by the parasite Onchocerca volvulus, is still endemic in Cameroon despite long-term annual community-directed treatment with ivermectin (CDTI). Low CDTI coverage and frequency (once a year) resulted in a high prevalence of onchocerciasis-associated morbidity (skin, eye, and neurological disease). Children infected with O. volvulus between the ages of 5-12 years are at risk of developing onchocerciasis-associated epilepsy. Moreover, O. volvulus infection during pregnancy induces "parasite tolerance" in the neonate and an increased risk to become infected with high parasitic loads, predisposing the child to develop onchocerciasis-associated morbidities. We hypothesize that maternal onchocerciasis has a negative impact on the neuro-cognitive development of the child. This will be investigated by recruiting nursing mothers with different exposures to onchocerciasis during pregnancy, and by monitoring the neurocognitive evolution of their children at 12 and 24 months of age. We also will evaluate a school-based ivermectin distribution strategy (adding to annual CDTI) to obtain six monthly intake of ivermectin by 5-12 year old children to prevent infection and ensuing morbidity. Understanding the impact of onchocerciasis on neurocognitive development during infancy and the possible benefits of an additional ivermectin dose in older children is expected to lead to interventions to preserve the intellectual capital of children in onchocerciasis-endemic regions.

Researcher(s)

• Promoter: Van geertruyden Jean-Pierre
• Co-promoter: Colebunders Robert
• Co-promoter: Weckhuysen Sarah
• Fellow: Siewe Fodjo Joseph Nelson

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project

Abstract

Background Epidemiological evidence suggests a strong association between onchocerciasis and epilepsy. A recent cohort study investigating the temporality of this association reported an increased risk to develop epilepsy following childhood infection with Onchocerca volvulus, with a strong dependence on the initial parasite load. Communities with high transmission of onchocerciasis are often confronted with a high burden of debilitating seizure disorders mainly affecting children and adolescents aged 3–18 years. These clinical conditions fit into the spectrum of onchocerciasis-associated epilepsy (OAE), which regroups generalized/focal epilepsy, nodding syndrome (NS), and Nakalanga features. The natural history of OAE is still poorly understood. However, follow-up data of persons with NS in Uganda suggests that the disease begins with an initial debilitating phase, which evolves towards the more conspicuous convulsive manifestations. This is confirmed by surveys in Cameroon where several persons with epilepsy (PWE) often showed signs of cognitive impairment reported to have started during their childhood or early adolescence. While seizure-related mechanisms can lead to cognitive deficits in PWE, it remains unclear if in the case of OAE, cognitive decline precedes the onset of seizures or is rather a consequence of the enduring epileptogenic state. A plausible hypothesis could be that an insidious deterioration of the cognitive function may occur before the onset of full-blown motor seizures observed in persons with OAE. Objectives and Methods The general objective of the proposed research is to identify early neurocognitive symptoms of OAE which could prompt rapid treatment, thus optimising patient prognosis. Specific objectives and methods include: • Neurocognitive assessment in children without epilepsy aged 5–15 years in onchocerciasis-endemic settings using validated tools • Investigating exposure to O. volvulus in these children by testing for Ov16 IgG antibodies testing by ELISA (as recommended by the World Health Organisation) • Case-control study comparing neurocognitive outcomes in onchocerciasis-exposed children (cases) and unexposed children (controls) • Community follow-up of all enrolled children to monitor signs of epilepsy onset Relevance Our findings would improve our understanding of the natural history of OAE, and thus inform policy makers regarding required interventions in affected communities. Our study addresses a real global health problem as it focuses on a neglected disease of poverty (onchocerciasis) and its interaction with a non-communicable condition (epilepsy). This project could result in strategies for early detection and management of OAE, but could also motivate stakeholders to strengthen onchocerciasis elimination efforts in epilepsy hotspots which are hyper-endemic for onchocerciasis.

Researcher(s)

• Promoter: Siewe Fodjo Joseph Nelson

Research team(s)

• Global Health Institute (GHI)

Project type(s)

• Research Project