Characterization Of Infection-Associated Epilepsy In Sub-Saharan Africa

Abstract

Epilepsy affects 70M people worldwide, 80% of whom are in low-and-middle income countries. Infections of the central nervous system (CNS) cause a considerable burden of epilepsy in low and middle-income countries, but the nature of damages and consequences of these infections is not fully understood in people with epilepsy. The main aim of this study was to determine the association between exposure to CNS infections and occurrence of clinical features in epilepsy, including decision to seek biomedical treatment. This was a cross-sectional case comparison analysis where the study population comprised patients with epilepsy. Associations of infections with features of epilepsy were done using modified mixed effects Poisson regression model, with site as a random effect. Interactions were done on multiplicative scale and additive scale (RERI) to determine the effect of co-infections on epilepsy features. Population attributable fractions (PAF) were calculated to determine proportion of severe clinical and electroencephalographic features of epilepsy attributed to CNS infections. Seizures began in early childhood (Median age=6.7 years, IQR: 1.6-16.8), a period before which susceptibility to childhood infections is high. However, there was a significant difference in distribution of this age at onset across sites. Frequent seizures (daily/weekly) was significantly associated with any CNS infections in adult epilepsy (RR = 2.62, C.I. =1.64 - 4.18). In children, convulsive status epilepticus (RR=4.61, C.I: 3.82-5.56), cognitive difficulties (RR=1.99, C.I: 1.29-3.08), neurological deficits (RR=1.47, C.I: 1.16-1.87) and not using anti-epileptic drugs (AEDs) (RR=1.33, C.I: 1.05-1.67) were associated with any CNS infections. In particular, P. falciparum, O. volvulus, T. solium and T. caniswere positively associated with at least one feature of epilepsy in adults while in children, these features were associated with P. falciparum, T. gondii, T. solium, T. canis and HIV. Toxoplasma gondii and Toxocara canis interacted synergistically to increase the risk of status epilepticus (RERI=0.93, C.I:0.46-1.41) in the pooled data. Nervous system infections were responsible for up to 26% of severe features of epilepsy as shown by PAF. In conclusion, nervous system infections may determine features of epilepsy. Convulsive status epilepticus, cognitive difficulties, neurological deficits and AED use was significantly associated with infections in children. In adults, frequent seizures were associated with infections. Toxoplasma gondii and Toxocara canis interacted synergistically to increase the risk of convulsive status epilepticus. xii The presence of infections was responsible for up to 26% of severe clinical features of epilepsy as shown by PAF