Onchocerca volvulus is not detected in the cerebrospinal fluid of persons with onchocerciasis-associated epilepsy

Abstract

Epidemiological evidence links onchocerciasis with the development of epilepsy. The aim of this study was to detect Onchocerca volvulus microfilariae or its bacterial endosymbiont, Wolbachia, in the cerebrospinal fluid (CSF) of persons with onchocerciasis-associated epilepsy (OAE). Methods: Thirteen persons with OAE and O. volvulus skin snip densities of >80 microfilariae were recruited in Maridi County (South Sudan) and their CSF obtained. Cytospin centrifuged preparations of CSF were examined by light microscopy for the presence of O. volvulus microfilariae. DNA was extracted from CSF to detect O. volvulus (O-150 repeat) by quantitative real-time PCR, and Wolbachia (FtsZ gene) by standard PCR.To further investigate whether CSF from onchocerciasis-infected participants could induce seizures, 3-and 7-day old zebrafish larvae were injected with the CSF intracardially and intraperitoneally, respectively. For other zebrafish larvae, CSF was added directly to the larval medium. Results: No microfilariae, parasite DNA, or Wolbachia DNA were detected in any of the CSF samples by light microscopy or PCR. All zebrafish survived the procedures and none developed seizures. Conclusions: The absence of O. volvulus in the CSF suggests that OAE is likely not caused by direct parasite invasion into the central nervous system, but by another phenomenon triggered by O. volvulus infection.

Onchocerca volvulus and epilepsy: A comprehensive review using the Bradford Hill criteria for causation

“…However, recent studies on cerebrospinal fluid of patients with NS and epilepsy in onchocerciasis-endemic regions have failed to identify O . volvulus microfilariae or DNA [ 35 , 76 , 101 , 102 ].…”

“…Before the introduction of CDTI, the presence of O. volvulus microfilariae in the cerebrospinal fluid was reported in heavily infected patients, particularly after treatment with diethylcarbamazine [6,7,100]. However, recent studies on cerebrospinal fluid of patients with NS and epilepsy in onchocerciasis-endemic regions have failed to identify O. volvulus microfilariae or DNA [35,76,101,102].…”

OV16 Seroprevalence among Persons with Epilepsy in Onchocerciasis Endemic Regions: A Multi-Country Study

“…The level O. volvulus microfilarial load in children was shown to be a predictor for developing OAE later in life [ 3 , 4 ]; however, the pathophysiological mechanism on how the O. volvulus parasite causes the seizures remains unknown. No parasites or O. volvulus DNA and no Wolbachia DNA (an O. volvulus endosymbiont) were found in cerebrospinal fluid [ 28 ] or in brain tissue of persons who had died of OAE [ 29 ]. An auto-immune mechanism induced by neurotoxic O. volvulus cross-reacting antibodies was proposed [ 30 ], but this hypothesis still needs to be confirmed.…”

Zoonotic Implications of Onchocerca Species on Human Health

“…The first theories published on the etiology of OAE suggested that direct infection of the CNS by O. volvulus microfilariae could be the cause of OAE onset [ 157 , 160 ]. However, microfilariae nor O. volvulus DNA were observed in recent studies in cerebrospinal fluid (CSF) nor brain of persons with OAE [ 161 ].…”