Onchocerca volvulus as a risk factor for developing epilepsy in onchocerciasis endemic regions in the Democratic Republic of Congo: a case control study

Mandro, Michel; Suykerbuyk, Patrick; Tepage, Floribert; Rossy, Degratias; Ngave, Francoise; Hasan, Mirza Nazmul; Hotterbeekx, An; Mambandu, Germain; Kashama, Jean Marie; Laudisoit, Anne; Colebunders, Robert

doi:10.1186/s40249-018-0465-9

Cited by 24 publications

(32 citation statements)

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“…A generalized linear model fitted with a Poisson distribution was used to investigate the factors associated with seizure frequency in the study participants. Selected variables including age, sex, burn scars, and mf density [4], as well as covariates with a p-value less than 0.2 during bivariate analysis with seizure frequency [18], were included in the final model. Any p-value less than 0.05 was considered to be statistically significant.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis has reported a 0.4% increase in epilepsy prevalence, for every 10% increase in onchocerciasis prevalence [2]. Today, there is increasing evidence that onchocerciasis is a risk factor for epilepsy [3][4][5][6] and that proper onchocerciasis elimination strategies can reduce the incidence of onchocerciasis-associated epilepsy (OAE) [7]. However, the physiopathology explaining how Onchocerca volvulus (the parasite responsible for the clinical manifestations of onchocerciasis) may cause seizures remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Onchocerciasis-associated epilepsy in the Democratic Republic of Congo: Clinical description and relationship with microfilarial density

Fodjo

Mandro²,

Mukendi³

et al. 2019

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Onchocerciasis-associated epilepsy in the Democratic Republic of Congo: Clinical description and relationship with microfilarial density

Fodjo

Mandro²,

Mukendi³

et al. 2019

Preprint

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“…Case-control studies NSETHIO performed four case-control studies in the DRC (Colebunders et al 2016b;Levick et al 2017;Mandro et al 2018;Mukendi et al 2019). The lesson learned from these case-control studies is that in order to determine whether onchocerciasis is a risk factor for developing epilepsy, we need to take into account previous ivermectin use as a confounder.…”

Section: Studies Performed By the Nsethio Consortium Includedmentioning

confidence: 99%

Nodding syndrome research, lessons learned from the NSETHIO project

et al. 2019

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Background.Until recently, nodding syndrome (NS) was considered as a mysterious disease of unknown etiology. A link between onchocerciasis and epilepsy was suspected for a long time. However, onchocerciasis was not considered as the cause of NS because NS was believed to occur only in onchocerciasis-endemic regions in Uganda, South Sudan, and Tanzania. In October 2015, with funding from the European Research Council, the NSETHIO group launched a trans-disciplinary, multi-country research project to identify the cause of NS and to study the link between onchocerciasis and epilepsy.Methods.We reviewed NSETHIO activities as well as all published papers, and compared project findings with results of previous research on NS.ResultsFindings from the NSETHIO project showed that NS is only one of the clinical manifestations in the wide spectrum of onchocerciasis-associated epilepsy (OAE) that could be prevented by strengthening onchocerciasis elimination programs. NSETHIO demonstrated that OAE is an important neglected public health problem in onchocerciasis-endemic areas with no or a sub-optimally functioning onchocerciasis control strategies.Conclusions.Today there is overwhelming evidence that NS together with the Nakalanga syndrome is clinical presentations of OAE, a condition that could be prevented by strengthening onchocerciasis elimination programs. While research needs to continue to elucidate the pathophysiological mechanisms causing NS, new strategies to accelerate onchocerciasis elimination coupled with community-based surveillance and treatment programs for epilepsy are urgently needed in areas of high Onchocerca volvulus transmission.

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“…An association between onchocerciasis (river blindness) and epilepsy was reported as early as 1938 [1]. This association was later documented in many cross-sectional studies [2][3][4][5], but the causal relationship between onchocerciasis and epilepsy remains controversial. A recent cohort study performed in an onchocerciasis-endemic region in Cameroon strongly suggested that infection with Onchocerca volvulus is able to cause epilepsy depending on the microfilarial (mf) density [6].…”

Section: Introductionmentioning

confidence: 99%

Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo

Mandro¹,

Fodjo

Dusabimana

et al. 2020

Pathogens

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Background: There is anecdotal evidence that ivermectin may decrease seizure frequency in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods: In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy experiencing ≥2 seizures/month were randomly allocated to receive, over a one-year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs. Data was analyzed using multiple logistic regression. Results: We enrolled 197 participants. In an intent-to-treat analysis (data from group 1 and 2 combined), seizure freedom was more likely among OIPWE treated with ivermectin thrice (OR: 5.087, 95% CI: 1.378–19.749; p = 0.018) and twice (OR: 2.471, 95% CI: 0.944–6.769; p = 0.075) than in those treated once. Similarly, >50% seizure reduction was more likely among those treated with ivermectin twice (OR: 4.469, 95% CI: 1.250–16.620) and thrice (OR: 2.693, 95% CI: 1.077–6.998). Absence of microfilariae during the last 4 months increased the odds of seizure freedom (p = 0.027). Conclusions: Increasing the number of ivermectin treatments was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures.

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Onchocerca volvulus as a risk factor for developing epilepsy in onchocerciasis endemic regions in the Democratic Republic of Congo: a case control study

Cited by 24 publications

References 17 publications

Onchocerciasis-associated epilepsy in the Democratic Republic of Congo: Clinical description and relationship with microfilarial density

Onchocerciasis-associated epilepsy in the Democratic Republic of Congo: Clinical description and relationship with microfilarial density

Nodding syndrome research, lessons learned from the NSETHIO project

Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo

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