Michel Ndahura Mandro’s research while affiliated with Ministry Health Care and other places

Background In October 2017, a community-based epilepsy treatment program (CBETP) was initiated in the Logo health zone (Ituri province, Democratic Republic of Congo), consisting mainly of community epilepsy education, provision of free antiepileptic drugs (AEDs), and monthly follow-up of persons with epilepsy (PWE). Prior to the implementation of the CBETP, qualitative research had revealed several misconceptions about the cause of epilepsy, major epilepsy-related stigma, and high economic cost for families of PWE mainly because of costly treatment by traditional healers. One year after the implementation of the CBETP, we assessed the perceived effect of this program on the community’s perceptions and attitudes regarding epilepsy and on disease costs. Methods Focus group discussions (FGD) and semi-structured in-depth interviews (SSI) were conducted with different target groups. Additionally, the cost associated with epilepsy was evaluated using questionnaires administered to 74 PWE and/or their families. Results Nine FGDs and 16 SSIs were conducted. There was a notable shift in perceptions and attitudes, as most community members no longer believed that epilepsy is contagious, while acknowledging that this condition can be treated in local health centers. Persons with epilepsy and their family experienced less epilepsy-related stigma and consulted less frequently traditional healers; the latter showed a growing willingness to collaborate with health professionals in the management of PWE. The direct and indirect costs for families caring for a PWE decreased by 95.2% and 95.7%, respectively. Conclusion The main perceived benefits of the CBETP were the decrease in misconceptions about epilepsy and epilepsy-related stigma. Families with PWE understood the benefit of seeking health care from trained health professionals rather than with traditional healers. The direct and indirect costs for families to take care of a PWE reduced considerably after the program. However, the cost-effectiveness and long-term sustainability of this approach remain to be assessed.

Nodding syndrome is a highly debilitating, generalized seizure disorder, affecting children in subregions of sub-Saharan Africa. Despite numerous efforts to uncover the etiology, the exact cause of this syndrome still remains obscure. Therefore, to date, patients only receive symptomatic care, including the administration of first-generation anti-epileptic drugs (AEDs) for seizure control. As data on the efficacy of drugs within this population are completely lacking, the aim of this study was to explore how therapeutic drug monitoring (TDM) could help to understand the differential response to therapy. Considering the challenging environment in which sampling had to be performed (remote areas, devoid of electricity, running water, etc.), dried blood matrices (i.e. dried blood spots, DBS) and volumetric absorptive microsampling (VAMS) were considered fit-for-purpose. Additionally, owing to the similarities between the syndrome and other forms of epilepsy, samples originating from patients suffering from (onchocerciasis-associated) epilepsy were included. In total, 68 patients with Nodding syndrome from Uganda, 58 Ugandan patients with epilepsy, and 137 patients with onchocerciasis-associated epilepsy from the Democratic Republic of the Congo (DRC) were included. VAMS samples and DBS were analyzed using validated methods, involving manual extraction or fully automated extraction, respectively, prior to quantification using liquid chromatography coupled with tandem mass spectrometry. Analysis revealed that serum concentrations (calculated from DBS) within the respective reference ranges were attained in only 52.9% of the 68 Nodding syndrome patients treated with valproic acid, in 21.4% of the 56 Ugandan epilepsy patients treated with carbamazepine, and in 65.7% of the 137 onchocerciasis-associated epilepsy patients from the DRC treated with phenobarbital. In all other instances, concentrations were subtherapeutic. Furthermore, on comparing DBS to VAMS concentrations, an inexplicable overestimation was observed in the latter. Finally, no obvious link could be observed between the obtained drug concentrations and the number of seizures experienced during the last month before sampling, elaborating the fact that the level of improvement in some patients cannot simply be linked to reaching therapeutic concentrations.

Background High epilepsy prevalence and incidence were observed in onchocerciasis-endemic villages in the Democratic Republic of Congo (DRC). We investigated the clinical characteristics of onchocerciasis-associated epilepsy (OAE), and the relationship between seizure severity and microfilarial density. Methods In October 2017, ivermectin-naive persons with epilepsy (PWE) were recruited from onchocerciasis-endemic areas in the Logo health zone in the DRC. Additional PWE were enrolled in the Aketi health zone, where ivermectin had been distributed annually for 14 years. Past medical history, clinical characteristics and skin snips for Onchocerca volvulus detection were obtained from participants. Bivariate and multivariable analyses were used to investigate associations with microfilarial density. Results Of the 420 PWE in the Logo health zone, 392 were skin snipped (36.5% positive). Generalized motor seizures were most frequent (392 PWE, 93.3%), and nodding seizures were reported in 32 (7.6%) participants. Twelve PWE (3.1%) presented Nakalanga features. Sixty-three (44.1%) skin snip-positive PWE had a family history of epilepsy, compared to only 82 (32.9%) skin snip-negative PWE (p = 0.027). Eighty-one onchocerciasis-infected PWE were recruited in the Aketi health zone. Positive correlations between seizure frequency and microfilarial density were observed in Logo (Spearman-rho = 0.175; p<0.001) and Aketi (Spearman-rho = 0.249; p = 0.029). In the multivariable model adjusted for age, gender, and previous treatment, high seizure frequency was associated with increasing microfilarial density in Aketi (p = 0.025) but not in Logo (p = 0.148). Conclusion In onchocerciasis-endemic regions in the DRC, a wide spectrum of seizures was observed. The occurrence of Nodding seizures and Nakalanga features, as well as an association between seizure severity and O. volvulus microfilarial density suggest a high OAE prevalence in the study villages. Trial registration ClinicalTrials.gov NCT03052998.

During door-to-door surveys in onchocerciasis-endemic regions in Africa, the age-specific ivermectin coverage in 29 722 individuals was assessed. Children 5-6 y of age had significantly lower coverage compared with older participants. Insufficient ivermectin intake among young children could prolong onchocerciasis elimination prospects, as they may serve as human reservoirs of Onchocerca volvulus; moreover, it increases the risk of developing onchocerciasis-associated epilepsy (OAE). The causes of the low ivermectin coverage observed among children 5-6 y of age need to be explored. Integrating ivermectin distribution into chemoprophylaxis strategies for other neglected diseases could increase coverage in a cost-effective manner.

Background: High epilepsy prevalence and incidence were observed in onchocerciasis-endemic villages in the Democratic Republic of Congo (DRC). We sought to investigate the clinical characteristics of onchocerciasis-associated epilepsy (OAE), and the relationship with microfilarial density. Methods: In October 2017, ivermectin-naive persons with epilepsy (PWE) were recruited from onchocerciasis-endemic areas in the Logo health zone in the DRC. Additional PWE were enrolled in the Aketi health zone, where ivermectin had been distributed annually for 14 years. Past medical history, clinical characteristics and skin snips for Onchocerca volvulus detection were obtained from participants. Bivariate and multivariable analyses were used to investigate associations with microfilarial density. Results: Of the 420 PWE in the Logo health zone, 392 were skin snipped (36.5% positive). Generalized motor seizures were most frequent (392 PWE, 93.3%), and nodding seizures were reported in 32 (7.6%) participants. Twelve PWE (3.1%) presented Nakalanga features. More skin snip-positive participants reported a family history of epilepsy (p=0.027). Eighty-one onchocerciasis-infected PWE were recruited in the Aketi health zone. Positive correlations between seizure frequency and microfilarial density were observed in Logo (Spearman-rho=0.181; p=0.0003) and Aketi (Spearman-rho=0.228; p=0.046). In the multivariable analysis which adjusted for age, gender and previous anti-epileptic drug use, factors associated with high seizure frequency included: high microfilarial density (RR=1.004, 95% CI: 1.002–1.007; p<0.001), history of nodding seizures (RR=3.852, 95% CI: 2.926–5.082; p<0.001) and shorter duration of epilepsy (RR=0.948, 95% CI: 0.928–0.968; p<0.001). In Aketi, previous ivermectin use was associated with reduced seizures (RR=0.69, 95% CI: 0.58–0.83; p<0.001). Conclusion: In onchocerciasis-endemic regions in the DRC, a wide spectrum of seizures was observed. Nodding seizures, Nakalanga features, and a positive association between microfilarial density and seizures suggest a high OAE prevalence in the study villages, requiring a double management strategy: treatment with anti-epileptic drugs and stronger onchocerciasis elimination programs.

Background Epilepsy is still very prevalent in Sub-Saharan Africa, particularly in remote, poverty-confronted onchocerciasis-endemic villages. It constitutes a significant burden for the families and communities. However, the financial costs of managing persons with epilepsy (PWE) have not been assessed in these settings. Proper cost analyses will facilitate future health interventions. Methods In November 2017, persons with epilepsy (PWE) and their caretakers were recruited at health centres of the Logo health zone in the Democratic Republic of Congo. A pre-tested questionnaire was administered to collect information on both direct and indirect costs of epilepsy, as well as household income of participants. Findings The weighted mean cost of epilepsy was 241.2 USD per PWE per year (50.2% direct cost, 49.8% indirect cost). Epilepsy-related expenses represented 46.5% of the mean household income. Traditional medicine accounted for 68.2% of the direct cost. An estimated cumulative cost of 1929.6 USD attributable to epilepsy had been incurred by the populations of the Logo health zone for each PWE in the community. Interpretation Almost half of the household revenue was spent on epilepsy care. Expenses on traditional medicine must be discouraged via education and regular provision of affordable anti-epileptic drugs. Prevention of onchocerciasis-associated epilepsy using optimal control measures will avert additional epilepsy-related costs on the community. Early diagnosis and proper management of epilepsy would be economically beneficial in the study villages.