A Second Population-Based Cohort Study in Cameroon Confirms the Temporal Relationship Between Onchocerciasis and Epilepsy.
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ABSTRACT:
SUBMITTER: Chesnais CB
PROVIDER: S-EPMC7304933 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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A Second Population-Based Cohort Study in Cameroon Confirms the Temporal Relationship Between Onchocerciasis and Epilepsy.
Chesnais Cédric B CB Bizet Charlotte C Campillo Jérémy T JT Njamnshi Wepnyu Y WY Bopda Jean J Nwane Philippe P Pion Sébastien D SD Njamnshi Alfred K AK Boussinesq Michel M
Open forum infectious diseases 20200602 6
To confirm our earlier evidence of a temporal and dose-response relationship between onchocerciasis and epilepsy, we conducted another cohort study in a different setting in Cameroon. Individuals whose <i>Onchocerca volvulus</i> microfilarial density (<i>Ov</i>-MFD) was measured in 1992-1994 when they were children were revisited in 2019 to determine if they acquired epilepsy. With reference to individuals with no microfilariae in 1992-1994, the relative risks of acquiring epilepsy were 0.96, 2. ...[more]
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Project description:BackgroundA strong association between epilepsy and onchocerciasis endemicity has been reported. We sought to document the epidemiology of epilepsy in onchocerciasis-endemic villages of the Ntui Health District in Cameroon and investigate how this relates to the prevalence of onchocerciasis.MethodsIn March 2022, door-to-door epilepsy surveys were conducted in four villages (Essougli, Nachtigal, Ndjame, and Ndowe). Ivermectin intake during the 2021 session of community-directed treatment with ivermectin (CDTI) was investigated in all participating village residents. Persons with epilepsy (PWE) were identified through a two-step approach: administration of a 5-item epilepsy screening questionnaire followed by clinical confirmation by a neurologist. Epilepsy findings were analyzed together with onchocerciasis epidemiological data previously obtained in the study villages.ResultsWe surveyed 1663 persons in the four study villages. The 2021 CDTI coverage for all study sites was 50.9%. Overall, 67 PWE were identified (prevalence of 4.0% (IQR: 3.2-5.1) with one new-onset case during the past 12 months (annual incidence of 60.1 per 100,000 persons). The median age of PWE was 32 years (IQR: 25-40), with 41 (61.2%) being females. The majority (78.3%) of PWE met the previously published criteria for onchocerciasis-associated epilepsy (OAE). Persons with a history of nodding seizures were found in all villages and represented 19.4% of the 67 PWE. Epilepsy prevalence was positively correlated with onchocerciasis prevalence (Spearman Rho = 0.949, p = 0.051). Meanwhile, an inverse relationship was observed between distance from the Sanaga river (blackfly breeding site) and the prevalence of both epilepsy and onchocerciasis.ConclusionThe high epilepsy prevalence in Ntui appears to be driven by onchocerciasis. It is likely that decades of CDTI have likely contributed to a gradual decrease in epilepsy incidence, as only one new case occurred in the past year. Therefore, more effective elimination measures are urgently needed in such endemic areas to curb the OAE burden.
| S-EPMC7614422 | biostudies-literature
Project description:ObjectiveA systematic review and meta-analysis of all available case-control studies on the relationship between onchocerciasis and epilepsy. Because age and level of onchocerciasis endemicity in the area of residence are major determinants for infection, an additional analysis was performed, restricted to studies achieving control of these confounding factors.Data sourcesMedical databases, the "African Neurology Database, Institute of Neuroepidemiology and Tropical Neurology, Limoges," reference lists of relevant articles, commercial search engines, up to May 2012.MethodsWe searched for studies examining infection status with Onchocerca volvulus in persons with epilepsy (PWE) and without epilepsy (PWOE) providing data suitable for the calculation of pooled odds ratios (ORp) and/or standardized mean differences (SMD) using random-effects models.ResultsEleven studies providing data of qualitative skin biopsies for diagnosis of onchocerciasis were identified. Combined analysis on the total sample of 876 PWE and 4712 PWOE resulted in an ORp of 2.49 (95% confidence interval (95%CI): 1.61-3.86, p<0.001). When this analysis was restricted to those studies achieving control for age, residence and sex (367 PWE, 624 PWOE), an ORp of 1.29 (95% CI: 0.93-1.79; p = 0.139) was found. Presence of nodules for diagnosis of onchocerciasis was analyzed in four studies (225 PWE, 189 PWOE; ORp 1.74; 95%CI: 0.94-3.20; p<0.076), including two studies of the restricted analysis (106 PWE, 106 PWOE; ORp 2.81; 95%CI: 1.57-5.00; p<0.001). One study examined quantitative microfilariae counts in patients without preceding microfilaricidal treatment and demonstrated significantly higher counts in PWE than in PWOE.InterpretationOur results strengthen the hypothesis that, in onchocerciasis foci, epilepsy and infection with O. volvulus are associated. Analysis of indicators giving information on infection intensity, namely nodule palpation and quantitative microfilaria count in untreated patients, support the hypothesis that intensity of infection with O. volvulus is involved in the etiology of epilepsy.
| S-EPMC3610636 | biostudies-literature
Project description:ObjectiveEpilepsy is highly prevalent in onchocerciasis-endemic African regions. Various types of epilepsy have been described in such regions based essentially on clinical characteristics.MethodsWe conducted a clinical, neurophysiological and neuropsychological study of epilepsy in the onchocerciasis-endemic region of Ntui, Sanaga-Mbam area, Cameroon.ResultsOne hundred and eighty-seven persons with presumed epilepsy were recruited in an epilepsy clinic in Ntui. Epilepsy was clinically confirmed in 144 (79%) subjects, 69 (46.0%) of them met the onchocerciasis-associated epilepsy (OAE) criteria, and 51 of 106 tested (48.1%) presented Ov16 antibodies. Electroencephalograms (EEG) were recorded in 91 participants, of which 36 (33%) were considered abnormal and 27 of 36 (75%) revealed bifrontotemporal spike and slow waves. Concerning the neuropsychological evaluation, 29% showed severe global cognitive impairment, 28% severe episodic memory impairment, and 66% severe frontal cognitive impairment. Half of the persons with epilepsy (PWE) suffered from a mental disorder.SignificanceIn PWE in the Sanaga-Mbam area in Cameroon, we observed EEG patterns similar to those described among persons with OAE, including nodding syndrome in other onchocerciasis-endemic areas. Most PWE presented with severe cognitive impairment. We hypothesize that onchocerciasis may induce neurocognitive disorders and epilepsy via a mechanism that involves mainly the frontal and temporal regions of the brain.
| S-EPMC8408605 | biostudies-literature
Project description:BackgroundA high prevalence of epilepsy has been observed in several onchocerciasis-endemic villages in the Sanaga River basin, Cameroon. Recent studies suggest that ivermectin, a drug that is distributed annually with the aim of eliminating onchocerciasis, may have a protective effect against acquiring onchocerciasis-associated epilepsy (OAE). This study, therefore, provides an in-depth understanding of both the complex therapeutic landscape for epilepsy as well as the experiences related to the 'community-directed treatment with ivermectin' (CDTI) campaign in order to identify a more trenchant path forward in the fight against epilepsy.Methodology/principal findingsBased on a mixed methods study combining a qualitative strand with a quantitative survey, we found that epilepsy was perceived to have had an epidemic emergence in the past and was still considered an important health issue in the study area. Socio-economic status, availability and accessibility of drugs and practitioners, as well as perceived aetiology shaped therapeutic itineraries for epilepsy, which included frequenting (in)formal biomedical health care providers, indigenous and/or faith healing practitioners. Ivermectin uptake for onchocerciasis was generally well known and well regarded. The CDTI faced structural and logistical bottlenecks undermining equal access and optimal adherence to the drug.Conclusions/significanceLocally accessible, uninterrupted, sustainable and comprehensive health-service delivery is essential to help alleviate the epilepsy burden on afflicted households. Addressing structural challenges of CDTI and communicating the potential link with epilepsy to local populations at risk could optimize the uptake of this potentially significant tool in OAE prevention.
| S-EPMC7946181 | biostudies-literature
Project description:BackgroundSurveys conducted in 1991-1992 in the Mbam Valley (Cameroon) revealed that onchocerciasis was highly endemic, with community microfilarial loads (CMFL) > 100 microfilariae/snip in some villages. Also in 1991-1992, a survey of suspected cases of epilepsy (SCE) found 746 SCE using a questionnaire administered to individuals identified by key informants, with prevalences reaching 13.6% in some communities. From 1998, annual community-directed treatment with ivermectin (CDTI) was implemented to control onchocerciasis. In 2017, a door-to-door household survey was conducted in three of the villages visited in 1991-1992, using a standardized 5-item epilepsy screening questionnaire.ResultsIn 2017, a total of 2286 individuals living in 324 households were screened (582 in Bayomen, 553 in Ngongol and 1151 in Nyamongo) and 112 SCE were identified (4.9%). Neurologists examined 92 of these SCE and confirmed the diagnosis of epilepsy for 81 of them (3.5%). Between the surveys in 1991-1992 and 2017, the prevalence of SCE decreased from 13.6% to 2.5% in Bayomen (P = 0.001), from 8.7% to 6.6% in Ngongol (P = 0.205) and from 6.4% to 5.4% in Nyamongo (P = 0.282). The median age of SCE shifted from 20 (IQR: 12-23) to 29 years (IQR: 18-33; P = 0.018) in Bayomen, from 16 (IQR: 12-21) to 26 years (IQR: 21-39; P < 0.001) in Ngongol and from 16 (IQR: 13-19) to 24 years (IQR: 19-32; P < 0.001) in Nyamongo. The proportions of SCE aged < 10, 10-19, 20-29 and ≥ 30 years shifted from 9.5, 58.3, 25.0 and 7.1% in 1991-1992 to 2.7, 20.5, 39.3 and 37.5% in 2017, respectively.ConclusionsSCE prevalence decreased overall between 1991-1992 and 2017. The age shift observed is probably due to a decrease in the number of new cases of epilepsy resulting from the dramatic reduction of Onchocerca volvulus transmission after 19 years of CDTI.
| S-EPMC6423875 | biostudies-literature
Project description:BackgroundOnchocerciasis elimination currently relies on repeated ivermectin-based preventive chemotherapy. Current World Health Organization's guidelines strongly recommend, though with low evidence of certainty, the use of Ov16 serology testing in children younger than 10 years old to assess whether mass drugs administration can be safely stopped. Therefore, more evidences are needed to support the use of this marker as sero-evaluation tool. This study aimed at determining the relationship between microfilaridermia and anti-Ov16 IgG4, and their variation according to age, gender and ivermectin intake history.MethodologyA cross-sectional survey was conducted in an area where ivermectin-based MDA has been implemented since more than 20 years. A questionnaire was used to record ivermectin intake history for the last 5 years. All volunteers aged ≥2 years were tested for microfilaridermia. IgG4 antibodies against Ov16 antigen were determined using the Standard Diagnostic Ov16 IgG4 ELISA kits and the recombinant anti-Ov16 AbD19432 antibodies. Prevalences, microfilaridermia counts and IgG4 concentrations were compared with regards to age, gender and history of ivermectin intake.Principal findingsThe prevalence of skin microfilariae was 23.4% (95% CI: 23.4-30.8), whereas Ov16 seroprevalence was 53.2% (95% CI: 47.9-58.4). A moderate positive percentage agreement (50.4%) and a high negative percentage agreement (69.2%) was found between skin snip and Ov16 serology in the whole population, while in children aged <10 years, the agreements were higher (positive percentage agreement: 62.6%; negative percentage agreement: 83.5%). In addition, no associations were found between ivermectin intake, Mf counts and estimated IgG4 concentration of participants. Anti-Ov16 IgG4 were higher in individuals harboring microfilariae than their negative counterparts (p<0.0001), though a negative correlation was found between skin microfilarial counts and anti-Ov16 IgG4 levels (r = -0.2400; p = 0.03). No variation in microfilarial counts according to age and gender was observed. Though positively correlated with age (r = 0.4020; p<0.0001), IgG4 was significantly different between the different age classes (p<0.0001).Conclusion/significanceOur results revealed moderate positive and negative agreements between parasitological and immunological parameters of onchocerciasis infection after several rounds MDA. Anti-Ov16 IgG4 levels increased with age but decreased with microfilarial counts, suggesting a variation of anti-Ov16 IgG4 as a result of constant exposure and accumulation of infection. This brings evidence sustaining the use of Ov16 serology in children as evaluation tool. However, additional investigations are needed to further reshape the appropriate age range among children aged <10 years old.
| S-EPMC9098087 | biostudies-literature
Project description:ObjectiveWe sought to evaluate the relationship between onchocerciasis prevalence and that of epilepsy using available data collected at community level.DesignWe conducted a systematic review and meta-regression of available data.Data sourcesElectronic and paper records on subject area ever produced up to February 2008.Review methodsWe searched for population-based studies reporting on the prevalence of epilepsy in communities for which onchocerciasis prevalence was available or could be estimated. Two authors independently assessed eligibility and study quality and extracted data. The estimation of point prevalence of onchocerciasis was standardized across studies using appropriate correction factors. Variation in epilepsy prevalence was then analyzed as a function of onchocerciasis endemicity using random-effect logistic models.ResultsEight studies from west (Benin and Nigeria), central (Cameroon and Central African Republic) and east Africa (Uganda, Tanzania and Burundi) met the criteria for inclusion and analysis. Ninety-one communities with a total population of 79,270 individuals screened for epilepsy were included in the analysis. The prevalence of epilepsy ranged from 0 to 8.7% whereas that of onchocerciasis ranged from 5.2 to 100%. Variation in epilepsy prevalence was consistent with a logistic function of onchocerciasis prevalence, with epilepsy prevalence being increased, on average, by 0.4% for each 10% increase in onchocerciasis prevalence.ConclusionThese results give further evidence that onchocerciasis is associated with epilepsy and that the disease burden of onchocerciasis might have to be re-estimated by taking into account this relationship.
| S-EPMC2691484 | biostudies-literature
Project description:BACKGROUND:A high prevalence and incidence of epilepsy has been reported in onchocerciasis-endemic regions in Central and East Africa. There is compelling epidemiological evidence suggesting that this high burden is caused by onchocerciasis-associated epilepsy (OAE). We hypothesized that OAE had also occured in West African onchocerciasis foci. METHODS:We searched PubMed, the African Journals Online platform and grey literature for population-based epilepsy studies in West African countries. Epilepsy and onchocerciasis prevalence data were extracted. The pre-control onchocerciasis endemicity in the study sites was estimated from historical data of onchocerciasis control programmes. The prevalence of epilepsy in different sites was analysed, taking into account onchocerciasis endemicity and the duration of control. RESULTS:The pooled prevalence of epilepsy in the West African study sites was 13.14 per 1000 (95% confidence interval 11.28-15.00). Higher pre-control endemicity and a shorter duration of onchocerciasis control were both associated with increased epilepsy prevalence (p<0.001). Two studies in Ivory Coast that provided detailed descriptions of persons with epilepsy in onchocerciasis-endemic settings revealed that most of them had features of OAE (73.7% and 83.3%, respectively). CONCLUSIONS:Our findings suggest that before and during the early years of implementing onchocerciasis control in West Africa, high onchocerciasis endemicity resulted in a high prevalence of OAE and that subsequent control efforts significantly reduced the prevalence of OAE.
| S-EPMC7320426 | biostudies-literature
Project description:BackgroundHigh 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.MethodsIn 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.ResultsOf 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).ConclusionIn 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 registrationClinicalTrials.gov NCT03052998.
| S-EPMC6663032 | biostudies-literature
Project description:BackgroundA high epilepsy prevalence has been reported in several onchocerciasis-endemic villages along the Mbam and Sanaga river valleys in Cameroon, including Bilomo and Kelleng. We sought to determine the prevalence of epilepsy in these two villages following more than 13 years of community-directed treatment with ivermectin (CDTI).MethodsDoor-to-door surveys were performed on the entire resident population in the villages in August 2017 and January 2018. Epilepsy was diagnosed using a 2-step approach: administration of a standardized 5-item questionnaire followed by confirmation by a neurologist. Previously published diagnostic criteria for onchocerciasis-associated epilepsy (OAE) were used. Ov16 serology was done for children aged 7-10 years to assess onchocerciasis transmission. Findings were compared with previous data from these two villages.ResultsA total of 1525 individuals (1321 in Bilomo and 204 in Kelleng) in 233 households were surveyed in both villages. The crude prevalence of epilepsy was 4.6% in Bilomo (2017) and 7.8% in Kelleng (2018), including 12 (15.6% of cases) persons with epilepsy (PWE) with nodding seizures. The age and sex-standardized prevalence in Kelleng decreased from 13.5% in 2004 to 9.3% in 2018 (P < 0.001). The median age of PWE shifted from 17 (IQR: 12-22) years to 24 (IQR: 20-30) years in Bilomo (P < 0.001); and slightly from 24 (IQR: 14-34) years to 28 (IQR: 21.25-36.75) years in Kelleng (P = 0.112). Furthermore, 47.6% of all tested children between 7 and 10 years had Ov16 antibodies.ConclusionsThere is a decrease in epilepsy prevalence after 13 years and more of CDTI in both villages. The age-shift observed in PWE suggests that ivermectin may prevent OAE in younger residents. Ov16 seropositivity in children indicates ongoing onchocerciasis transmission possibly due to suboptimal control measures. Our findings support the existence of OAE in Cameroon and highlight the need to strengthen onchocerciasis elimination programs.
| S-EPMC6276171 | biostudies-literature