Epidemiology and Treatment of Epilepsy in Sub-Saharan Countries 2007-2008

We used a three-stage screening process to identify cases of active convulsive epilepsy. In the first stage, two screening questions were asked during a routine, door-to-door census organised by each HDSS centre. Heads of households were interviewed about whether any residents had had convulsions. In the second stage, trained lay fieldworkers administered a detailed questionnaire to individuals identified as having a history of convulsions in stage one. Individuals whose responses to the questionnaire suggested they might have epilepsy were examined during stage three by clinicians who made a final diagnosis.

To enable comparison between our three-stage method and the two-stage surveys used in other population-based studies in Africa, we selected a random population sample from each centre’s census database with the RAND() command in MySQL (Oracle, Redwood Shores, CA, USA). The questionnaire used in the second stage of the study was administered to this randomly sampled population; individuals identified as possibly having epilepsy after the questionnaire results were assessed clinically in stage three.

For each epilepsy case, an age-matched control individual was randomly selected from the relevant centre’s census database with the RAND() command. The control individuals were frequency matched by age groups: 0–5 years, 6–12 years, 13–18 years, 19–28 years, 29–49 years, and 50 years or older. In the case-control study, two or three control individuals were selected to compensate for non-response and ensure balance in the number of cases and control individuals at each centre. All control individuals were assessed by a clinician to confirm that they did not have epilepsy. Fieldworkers then administered questionnaires based on those used in previous studies to individuals identifi ed as having epilepsy and control individuals. Fieldworkers, who were masked to the status (case or control) of the person they were interviewing, gathered data on sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Clinical history was also obtained by masked, trained clinicians (the same clinicians who made initial diagnoses) and they made a diagnosis of active convulsive epilepsy. When the study participants were younger than 18 years or had cognitive impairment, the mother or caregiver was interviewed. The questionnaires administered to mothers or caregivers included questions about antenatal (eg, severe abdominal pain, vaginal bleeding, or infection during pregnancy) and perinatal events (difficulties breathing, feeding, or crying after birth, as recalled by the mother or caregiver). Questions about consumption of alcohol and use of recreational drugs were administered to adult participants only.

Blood samples were taken from a subgroup of 300 participants with epilepsy and 300 control individuals from each centre who were randomly selected with the RAND() command. This sample size would allow detection of an odds ratio (OR) greater than 2.4, with 80% power and the assumption that 5% of control individuals had epilepsy. The samples were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. Exposure was established by detection of IgG antibodies to the parasitic antigens. IgG antibodies against T canis were detected with a commercial kit (Toxocara IgG-ELISA, Cypress Diagnostics, Belgium; sensitivity 97%; specificity 78%). Anti-Toxocara IgG4 antibodies with an optical density greater than the cutoff (mean plus three standard deviations of 30 IgG-negative serum samples) were interpreted as positive. IgG antibodies against T gondii were detected with a commercial kit (Toxoplasma IgGELISA, Genesis Diagnostics, Ely, UK; 100% agreement with test samples) and were judged positive when optical density was greater than that of the positive 8 IU/mL sample in the kit. Exposure to O volvulus was established with a modification of an ELISA that detects IgG4 to the recombinant antigen Ov-16GST (sensitivity 90%; specificity 98%). A sample with an optical density greater than the cutoff (mean plus three standard deviations of 30 serum samples from the Agincourt HDSS, where onchocerciasis is not prevalent) were interpreted as positive. Exposure to malaria was established with an in-house ELISA30 that tests for IgG antibodies to crude schizont extract from a P falciparum A4 clone line, which is derived from a laboratory strain. Exposure to the larval stage (cysticercosis) and adult stage (taeniasis) of the parasite T solium was established with a Western blot (sensitivity 97%; specifi city 99%; detection of cases with two or more viable cysts in the brain) and antibodies to taeniasis (RES33 antigen; sensitivity 99%; specifi city 93%). IgG antibodies to HIV type 1 or type 2, or both, were detected with the fourth generation screening test Vironostika HIV Uniform II Ag/Ab (BioMerieux, France) according to the manufacturer’s instructions.