Abstract
BackgroundThe possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.MethodsPubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome.ResultsOnchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes.ConclusionApplying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.
Highlights
The possibility that onchocerciasis may cause epilepsy has been suggested since the pioneering work of Casis-Sacre in 1938 [1,2,3,4,5]; an etiological link is still pending universal acceptance
On the basis of the findings presented in this paper, it appears that onchocerciasis control may be able to prevent onchocerciasis-associated epilepsy (OAE)
Onchocerca volvulus microfilariae, the small first-stage larval progeny produced by the adult female worms which are responsible for the disease manifestations of onchocerciasis, have not been found in the brain parenchyma
Summary
The possibility that onchocerciasis may cause epilepsy has been suggested since the pioneering work of Casis-Sacre in 1938 [1,2,3,4,5]; an etiological link is still pending universal acceptance. Onchocerca volvulus microfilariae, the small first-stage larval progeny produced by the adult female worms which are responsible for the disease manifestations of onchocerciasis (river blindness), have not been found in the brain parenchyma. No systematic review that considers all the available original research data concerning the association between epilepsy including NS and onchocerciasis has so far been performed. The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association
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