Stopping the burden of disease caused by onchocerciasis- associated epilepsy

There is growing epidemiological evidence that onchocerciasis (river blindness) can cause epilepsy (onchocerciasis-associated epilepsy, OAE), a major unrecognized public health problem in sub-Saharan Africa. However, the pathophysiological mechanism remains unknown. Neither the Onchocerca volvulus, nor its endosymbiont Wolbachia, appear to be able to pass the blood brain barrier (BBB). Annual community-directed treatment with ivermectin (CDTI), has limited efficacy in reducing OAE incidence. Therefore, we will 1] Investigate in onchocerciasis-endemic areas, in Cameroon, whether a community based vector control method “slash & clear” combined with CDTI is superior to CDTI alone to decrease the incidence of OAE; 2] Explore whether O. volvulus excretory/secretory products can cross the BBB and possibly trigger OAE, by comparing proteomic profiles of cerebro-spinal fluid of children with OAE with those of different stages of the parasite; 3] Explore whether O. volvulus infected blackflies may transmit a neutrotropic virus causing OAE, by testing blackflies and sera from OAE cases with Q-PCR targeting potential OAE specific viral sequences identified during a metagenomic case-control study in South Sudan. Our findings will provide context-specific evidence about a complementary strategy to accelerate onchocerciasis elimination and new insights into the underlying mechanisms of OAE, and as such contribute to reducing the burden and stigma of ‘river epilepsy’.

There is growing epidemiological evidence that onchocerciasis (river blindness) can cause epilepsy (onchocerciasis-associated epilepsy, OAE), a major unrecognized public health problem in sub-Saharan Africa. However, the pathophysiological mechanism remains unknown. Neither the Onchocerca volvulus, nor its endosymbiont Wolbachia, appear to be able to pass the blood brain barrier (BBB). Annual community-directed treatment with ivermectin (CDTI), has limited efficacy in reducing OAE incidence. Therefore, we will 1] Investigate in onchocerciasis-endemic areas, in Cameroon, whether a community based vector control method “slash & clear” combined with CDTI is superior to CDTI alone to decrease the incidence of OAE; 2] Explore whether O. volvulus excretory/secretory products can cross the BBB and possibly trigger OAE, by comparing proteomic profiles of cerebro-spinal fluid of children with OAE with those of different stages of the parasite; 3] Explore whether O. volvulus infected blackflies may transmit a neutrotropic virus causing OAE, by testing blackflies and sera from OAE cases with Q-PCR targeting potential OAE specific viral sequences identified during a metagenomic case-control study in South Sudan. Our findings will provide context-specific evidence about a complementary strategy to accelerate onchocerciasis elimination and new insights into the underlying mechanisms of OAE, and as such contribute to reducing the burden and stigma of ‘river epilepsy’.