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Epilepsia, 54(4):757–763, 2013 doi: 10.1111/epi.

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FULL-LENGTH ORIGINAL RESEARCH

Epidemiology of epilepsy in rural Benin: Prevalence, incidence, mortality, and follow-up
*Dismand Houinato, *†‡§¶Luce-Perrine Yemadje, *Ghislaine Glitho, *Constant Adjien, *Gilbert Avode, †‡§¶Michel Druet-Cabanac, and †‡§¶Pierre-Marie Preux
*Department of Neurology, School of Health Sciences, University of Abomey Calavi, Cotonou, Benin; †INSERM UMR1094, Tropical Neuroepidemiology, Limoges, France; ‡School of Medicine, Institute of Neuroepidemiology and Tropical Neurology, University of Limoges, Limoges, France; §CNRS FR 3503 GEIST, Limoges, France; and ¶CHU Limoges, Limoges, France

SUMMARY
Purpose: Epilepsy is a major clinical and social issue in Africa. This study was conducted to estimate the prevalence, incidence, mortality, and therapeutic outcome in rural Djidja in Benin. Methods: This was a two-phase study with a cross-sectional phase and 18 months of follow-up. In the first phase, information was obtained using door-to-door surveys, reports from key informants, and medical sources. People were interviewed using a validated screening questionnaire for epilepsy in tropical regions. The diagnosis of epilepsy was confirmed by a neurologist. We used a capture– recapture method to estimate the number of people with epilepsy (PWE). PWE were followed every month for 18 months after the cross-sectional survey. We asked the health services, the general population, and village leaders in the study area to identify suspected cases of epilepsy occurring during the follow-up. New cases were updated every month after confirmation. Antiepileptic drugs were prescribed to PWE.

Key Findings: We surveyed 11,668 subjects (male-tofemale ratio 0.9) and identified 123 PWE, yielding a prevalence of 10.5 per 1,000 (95% confidence interval (CI) 8.8– 12.6/1,000). Combining the three sources, we found 148 PWE and a prevalence of 12.7 per 1,000 (95% CI 10.7– 14.9/1,000). After application of the capture–recapture method, the prevalence was estimated to be as high as 38.4 per 1,000 (95% CI 34.9–41.9/1,000). The cumulative incidence was 104.2 per 100,000 and the mean annual incidence was 69.4 per 100,000. The mean annual mortality was 20.8 per 1,000. After treatment, 45% of PWE had total seizure remission and 35% had a decrease in the number of seizures. Significance: This study shows that door-to-door survey findings could be improved by using information from other sources. The follow-up suggests that epilepsy could be controlled. Continuous drug delivery and regular follow-up are key. KEY WORDS: Prevalence, Incidence, Mortality, Followup, Epilepsy, Benin.

Epilepsy is a major and common neurologic disorder that affects around 70 million people worldwide (Ngugi et al., 2010). Ninety percent of people with epilepsy (PWE) live in developing countries in Africa, Asia, or Latin America (WHO, 2012). Health care delivery structures are still in their infancy in many African regions because of economic challenges. The median prevalence of epilepsy in sub-Saharan Africa is 15.0 per 1,000, which is twofold to threefold higher than that observed in industrialized countries (<8.0/1,000 inhabitants; Forsgren et al., 2005; Preux & Druet-Cabanac, 2005). There are fewer data on the incidence of epilepsy and mortality of
Accepted November 19, 2012; Early View publication January 25, 2013. Address correspondence to Pierre-Marie Preux, Unit e Inserm UMR1094 – Neuro epid emiogie Tropicale, Facult e de Medecine, Institut d’Epid emiologie neurologique et Neurologie Tropicale, 2, rue du Dr Marcland, 87025 Limoges Cedex, France. E-mail: preux@unilim.fr Wiley Periodicals, Inc. © 2013 International League Against Epilepsy

PWE in sub-Saharan Africa. Population-based studies that used door-to-door methods in Benin have yielded high prevalences: 21.1 per 1,000 in Zinvie (n = 3,134), 15.9 per 1,000 in Savalou, and 10.6 per 1,000 among employees of five companies in South Benin (n = 1,232; Avode et al., 1996; Debrock et al., 2000; Houinato et al., 2007). Epilepsy-related challenges in Benin include the lack of treatment, which is significantly related to the high frequency of seizures, the seroprevalence of human cysticercosis, the social stigma related to epilepsy (still widely seen as a supernatural phenomenon), the high levels of anxiety and depression associated with epilepsy, and the higher prevalence of malnutrition among epilepsy patients than controls (22.1% vs. 9.2%, p = 0.0006) in Djidja (Zoli et al., 2003; Nubukpo et al., 2004; Crepin et al., 2007). The aim of this study is to assess the main epidemiologic parameters of epilepsy in rural Djidja in central Benin and to evaluate a treatment program.

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Phase 1: cross-sectional study A door-to-door survey was performed covering the entire Djidja population. traditional healers (14). Investigators used the validated five-item epilepsy screening questionnaire of Limoges Neuroepidemiology Institute. U. 5. We prescribed antiepileptic drugs to PWE on a monthly basis. An active search Epilepsia. and spiritual leaders (14). U. CA.A. Confidence intervals (Cis) were estimated at 95%. ILAE. The model chosen was the one having less interaction terms.500 inhabitants. 2013 doi: 10. Anyone with suspected epilepsy was further examined by the neurologist to confirm or reject the diagnosis. and Pan African Association of Neurological Sciences (PAANS) (Preux.05 was considered statistically significant.623 (48. Results Cross-sectional study phase: characteristics of the study population The study area population is 14. Phase 2: longitudinal study In the second phase. The population density is 38 inhabitants/km2.045 . Houinato et al. 1951. All people investigated gave informed verbal consent.2%) were male and 6.S. health care services identified and recorded all potential cases of epilepsy that occurred. teachers (30). 1997). Methods Study setting This study was carried out in the Djidja community of the Zou region in Central Benin.758 D. with a Bio Medical Data Package (BMDP procedure 4F.and non–epilepsyrelated) that occurred during the follow-up phase of this study. “N Weighted DIC” was calculated by taking into account all N estimates (Draper. Hook & Regal. Los Angeles. The chi-square test was used to compare qualitative variables. Therapeutic outcome All neurologist-confirmed epilepsy patients were treated daily from the end of the cross-sectional phase to the end of the longitudinal study phase. The population is primarily rural and is dependent mainly on subsistence farming. The second phase consisted of a longitudinal study conducted between January 2006 and June 2007. This region is also marked by the highest level of poverty in Benin (National Institute of Statistics and Economic Analysis. comprising 10 villages and 14.S. A p-value < 0. A participant was considered to have epilepsy if he or she had had at least two epileptic seizures unprovoked by any immediate identified cause. the cross-sectional survey was supplemented with information from two sources: medical and nonmedical.. Mortality We considered all deaths (epilepsy. 1993). 1970). 1997).. The estimation of the total number of PWE and the evaluation of the dependence of the three sources were determined using log-linear models analysis. Carbamazepine at a progressively increasing dose was given to adults who had only partial seizures. 1). Sakamoto et al. During the follow-up. We interviewed 72 key informants: village heads (11). We used a capture–recapture method to estimate the completeness of each source and the number of PWE in Djidja. 80. Subjects who had presented with an isolated seizure were excluded. Data management and analysis Data were recorded and analyzed using Epi-Info (version 6. Data were gathered by 17 investigators familiar with the language of the region and accustomed to administration of the questionnaire. 1995).1111/epi. Statistical Software Inc.12082 was undertaken for new cases involving the general population and village leaders and making use of global sensitization of the community. PWE were followed for 18 months from January 2006. The first phase.4% of the total (Fig. 54(4):757–763. Study design The study was in two phases. Bayesian information criterion (BIC). Hook & Regal.A.668 individuals. that is. Definition of epilepsy We used the International League Against Epilepsy (ILAE) definition of epilepsy (ILAE. 2000). and phenobarbitone 100 mg was given to children (1 tablet/day) and adults (2 tablets/day) with generalized or secondarily generalized seizures. 2002). An update of the new cases was made every month. was conducted in 2005. Seber.500 and we were able to survey 11. Those who had a diagnosis of epilepsy were treated and followed monthly to identify any epilepsy-related death(s) and elucidate the posttreatment evolution of epilepsy. Among them. community leaders (3). a crosssectional study. Ethical agreement was obtained from the ethics committee of the government health department in Benin. Continuous variables were expressed as means Æ standard deviation (SD) and qualitative variables as percentages. and best goodness of fit with the observed data (likelihood ratio statistic non-significant) and lowest information criteria: Akaike information criterion (AIC).). and Draper information criterion (DIC. Anyone who gave at least one positive response to the screening questionnaire was further examined by the neurologist to confirm or reject the diagnosis of epilepsy. we conducted a longitudinal study involving all PWE who were screened during the first phase and people without epilepsy or any other neurologic disorder who agreed to participate in the follow-up. 1986.04d. Centers for Disease Control. We used a capture–recapture method to estimate the number of PWE not identified by the three sources (Chapman. Atlanta. To identify all PWE.

000). Longitudinal study phase: characteristics of the study population The longitudinal study included 11. This yielded a cumulative incidence rate of 104.8–181. The estimated exhaustivity rates were 27.4 per 100.520.000 (95% CI 8. five female) were identified among the nonepilepsy population of 11. Seven cases were identified during the first 6 months of follow-up.9–41.php136.0– http://intranet:8080/cmsimple/index.000 (Table 1). Incidence rates After the follow-up of 18 months.000) and a mean annual incidence of 69.5% for door-to-door.3% for medical sources. The sex-specific prevalences were therefore higher among male (16. 150 were followed up (Fig. Door-to-door survey found 123 PWE.000).9/1. 1). Using a capture–recapture method.6/1. and 33.9 and the mean age was 20.000). The sex ratio was 0. Most of new cases (n = 10) were younger than 20 years of age.4 years. Flowchart of participants in the prevalence study of epilepsy in Djidja. Benin.1).8%) female.000) than female (13. 12 new cases of epilepsy (seven male.000) individuals.8–12.8/100.668 subjects.520 subjects who did not have epilepsy at the start of the follow-up and PWE identified during the first phase study. 2). but this difference was not statistically significant (p = 0. refusal to participate Figure 1. The crude prevalence of epilepsy obtained by combining the three sources was 12. yielding a prevalence of 10. The majority of cases were male (sex ratio 1.000 (95% CI 10. The total number of PWE in the chosen model was estimated to be as high as 448 (95% CI 407–488) and the prevalence was 38. Medical sources revealed 20 PWE.759 Epidemiology of epilepsy in rural Benin (51.1 Æ 18.6 to 16.5 per 1. and two during the third 6-month period. three during the second 6-month period. we evaluated the goodness of fit of the log-linear models and estimated the total number of PWE (Table 3).7– 14.000).2 per 100.1111/epi.000 (95% CI 34. and 5 PWE were identified by key informants (Fig.21).2/1.0% for the three sources combined. 54(4):757–763. 148 were confirmed to have epilepsy.12082 . 6.000 (95% CI 53. 2013 doi: 10. The prevalence is significantly higher for people older than 20 years than for the younger age group (Table 2). The “N weighted DIC” was estimated at 544 (95% CI 500–588).4/1.9/1. 5. Prevalence of epilepsy in investigated villages ranged from 6. Prevalence Of the 11.8% for nonmedical sources.4 per 1.9 per 1.7 per 1.000 (95% CI 30. Characteristics of follow-up cases Of 160 epilepsy cases identified in this study (148 in the first study phase and 12 new cases during the follow-up). Epilepsia ILAE Epilepsia. Follow-up was not possible in 10 cases due to inability to participate (5).9/100. 2005.

8 per 1.and second-degree relatives was reported for 54% PWE (Table 4). PWE were predominantly men (54. one during the second 6 months. Two deaths occurred during the first 6-month period.000 6.7 14. 2005). Previous studies conducted in Benin show similar prevalences in Zinkanme and Savalou. five deaths (three due to epilepsy) were observed among the PWE identified in Djidja.000 (95% CI 10.3%).. Discussion Prevalence This study used three sources of information and yielded a prevalence of 12.12082 .3–17.7 per 1.3%). neighboring Benin (Grunitzky et al.2 7. Benin.0%).3 per 1.110 959 958 742 1. respectively (Avode et al. The study Figure 2. The mean annual mortality was 20. Therapeutic follow-up During the 18 months of follow-up. 68 achieved total remission of seizures (45%) and 53 achieved a reduction in seizures (35.0%).5 13.760 D.6 4. 1996. Table 1.5–29. The differences between treated and untreated patients could also influence the probability of a case being reported by a source.6%).7 6. and all suspected cases were confirmed by a neurologist. at 14. however.000 and 15. 2005). 2013 doi: 10. Compared with studies outside Benin.9 8.000. the entire population was not interviewed. Case definitions were identical for the three sources.6 (2).000.5 per 1.5 13. and two during the third 6 months. despite repeated visits to the villages to meet as many villagers as possible. 2004).5–24.0–38. possibly because of small numbers in some cells of the contingency table.3 14. The population could be considered as closed during the study period because the majority of the villagers were farmers and did not travel.095 1.9 10. One of the three deaths due to epilepsy occurred during a fishing excursion on a boat. Sociodemographic and clinical characteristics of the 150 PWE in Djidja are summarized in Table 4.000—close to the median prevalence of epilepsy in sub-Saharan Africa countries (Preux & Druet-Cabanac.4 11.3–16..3/ 1.000). Participants in door-to-door survey and prevalence of epilepsy in each investigated village Village Madjavi Sovlegni Hounvi Kome Ye Aligoudo Wogbaye Agonhohoun Sanwlakpa Dona Total Number 4. Independence within the sources is the principal condition underlying this method. Distribution of specific and common cases of epilepsy according to three sources of information in Djidja. In this study.7–20.9 15.2/ 1.0 6.000) in Togo. Debrock et al. and (12.5 6. 1996. and unmarried (75.2/1.668 PWE 27 10 9 11 10 22 8 8 9 9 123 Prevalence/1. Our figure was lower than that found using the same methodology in Zinvie in rural Benin (21.2 per 1. Epilepsia ILAE Epilepsia. and was taken into account by the log-linear method. Houinato et al.3–9. A family history of epilepsy in first.8–31.2–29. change was favorable for 121 of 150 PWE followed (80. one during the night when a patient living alone had a seizure. 54(4):757–763. corresponding to a mortality of 31.. 2005.6–20. The prevalence calculated from door-to-door survey findings only was 10.000 (95% CI 10. 2000).6 8.4/1.5 95% CI 4. the numbers of PWE estimated by log-linear models and the “N weighted DIC” were very high and widely variable.2–28.0 9.0/1. and during a recurrence of epileptic seizures lasting more than 5 min.8 per 1.000) during the 18 months of follow-up.8 16.8 7. and death before starting the follow-up (3). These estimations seem unreliable.5 4. <40 years old (81..000). Senegal (14. Mortality During the 18 months of follow-up.000.2–71.607 559 536 570 532 11.1111/epi. The validity of the capture–recapture method requires that certain conditions be fulfilled. Ndoye et al. Zohoun. Among them.7 5.8–12. the prevalence was similar to that in Pikine.6 9.

0–27.12082 . Similar observations were made in two studies.6 BIC 0. Mortality Mortality data are very scarce in sub-Saharan Africa.0–239.11 0.37 8.5 years (Tekle-Haimanot et al. S1S2a S1. estimation of total number of cases. S1S3.000 inhabitants-years.5%) was observed for the door-to-door survey.26 0.000. a Chosen model with lowest AIC. S2S3 S2.000 habitants per years) was calculated through a comparison of two crosssectional studies. 1997).6 À1. S3 d.6 per 1. S2S3 S1S3. d.000.8–12. 54(4):757–763. Bayesian information criterion.212–1.0 À1.000 (28. S2.000 5. S1S3 S3.8 7.5 95% CI 3.6/ 1.00 0..8 per 1.6 À3.95 2. Benin.274 641 1.72 21. The mean annual incidence of epilepsy in our study was 69.668 PWE 21 20 36 26 10 10 123 Prevalence/1.0/100.9 20. Goodness of fit of the log-linear models and estimation of the total number of epilepsy patients in Djidja.6 6. Incidence To our knowledge. This could be considered surprisingly low and may be due to several causes: concealment due to stigma or underrecognition by household informants.7 4. very few previous studies have estimated the incidence of epilepsy in sub-Saharan Africa. In addition. the capture–recapture method is based on a statistical model.000 inhabitants-years.3 15.6 5.4 13.4 per 100.53 2. Incidence of epilepsy in Ethiopia (64/100. Age-specific epilepsy prevalence in rural Djidja.724 1.5 À0.4 15.3 14.5 17.6 3. DIC.5 0.6 area population was 14.f..1111/epi. which is significantly lower than the crude mortality (31. 1998).3 2. close to that observed in Burkina Faso (83.000) reported in a 2-year Ethiopian study (316 epilepsy Table 3.5 À0.5–28.7 À1.5–17. Debouverie et al.5–11.. 2005 Model S1S2.000 inhabitants per year obtained after a follow-up of the population twice a year in Togo (Grunitzky et al.6 9.3 19.5 À2. 1988).00 0. S3.069 11.5 11. for example.4–29.3 6.6 12.5 À3. G2. Draper information criterion.000 inhabitants per year (Kaiser et al.00 0.. degrees of freedom. Epilepsia.668 (80.0 À7. 1993) or the median incidence of epilepsy 81. the second conducted after an average period of 3. and DIC..f. 2013 doi: 10. AIC.48 21. S2S3 S1.1–7.24 0.278 663 534 175 241 177 448 241 95% CI 1. BIC. 2011). since other sources of case ascertainment such as medical records or referral from key informants may not be sufficiently complete.58 8. Our incidence estimate was also slightly different from the 119 per 100. and the low numbers of cases in some combinations of sources could lead to overestimation of the capture– recapture estimate. door-to-door survey.8 5. wherein a protocol that used key informants as the only source yielded a prevalence of 3.and middle-income countries (Ngugi et al.01 0. N. 1996).150 2. Akaike information criterion. S2S3 S1S2. S2.1 N 1. The highest exhaustivity rate (27.4%) of the total.58 p-value 1. Benin 2005 Age (years) 0–9 10–19 20–29 30–39 40–49 ! 50 Total Number 4. rather than active ascertainment or a second cross-sectional survey. Calculation of incidence requires long-term monitoring of large numbers of patients or the possibility of a sufficiently reliable retrospective estimation. whereas using the doorto-door survey the estimated prevalence was 18. in Uganda where the rate age standardized on the world population was 156 per 100. BIC. which may differ from study to study. nonmedical source. Several factors. Door-to-door surveys are ideal in developing countries.1 8. 0 1 1 1 2 2 2 3 G2 0.00 AIC 0.2 per 1. It is possible that our estimate is low as we relied on health care services to identify PWE.3 15.500.810 1. such as lack of awareness of seizure types and poor cooperation among traditional healers may partially explain underestimation of prevalence. S1S3 S1S2. thus yielding varied incidence results.344 614–712 490–578 149–201 211–271 151–203 407–488 211–271 S1.4 10. and we surveyed 11. medical source.45 1. and consequently underestimation of exhaustiveness.7 per 100.761 Epidemiology of epilepsy in rural Benin Table 2.5 4..000 in the same population (Kaamugisha & Feski. The annual mortality observed in our study was 20. likelihood ratio statistic.1 7.5) in low. Our estimate is different from that observed in other African countries.6 DIC 0.

Bull Soc Pathol Exot 89:45–47.7 77.3 24. (1951) Some properties of the hypergeometric distribution with applications to zoological sample censuses.7% (n = 63) of PWE were lost 1 year after the start of the follow-up. Benin. Feksi et al. it must be fully integrated in the primary health care system. Our results suggest that the care of patients with epilepsy in Africa requires not only the strengthening of human and material resources. 1989.762 D. determination of mortality based on very small numbers of cases yielded a wide confidence interval. . in our study.0 46. Treatment Our study yielded a high proportion of seizure-free cases (45%) and of cases with a decreased seizure frequency (35%).3 show that the deaths were not caused by the seizures themselves but related to their consequences (drowning. Whatever the intervention.0 9. Table 4. cases. Information from door-to-door cross-sectional surveys is usefully complemented by data from other sources in order to identify the total number of PWE in low. the chances of remission are also high and it is therefore probable that young PWE will be able to actively contribute to society. Watts. but also an effort to ensure continuous follow-up and thereby improve health care status and quality of life..4 65.0 54. Gandaho P. Regular follow-up of PWE is absolutely necessary to improve the health status of PWE and their care. high level commitment is needed from governmental agencies to guarantee that epilepsy continues to be a priority and that the supply of drugs is ensured. Tekle-Haimanot et al. (1996) Epilepsie provoqu ee par la cysticercose.0 8. The circumstances under which the deaths occurred Epilepsia.3 44.3 24. and the types of epileptic seizures. A propos d’une enqu^ ete sociologique et culturelle r ealis ee  a Savalou au B enin.3 53. Bouteille B. and a reduction in 26%. In our study a lower rate of loss was observed after 18 months of follow-up (n = 10. Characteristics of the PWE followed in Djidja.0 4.7 4. continuous.7 2. 6.0 14. In a previous study conducted in Zinvie in Benin.7 4. This study has provided some promising results. References Avode DG. Therefore. 2005 Characteristic Sex Men Women Age (years) <10 10–19 20–29 30–39 40–49 ! 50 Marital status Unmarried Married Occupation Active Not active Religion Animist Christian Muslim Ethnic group Fon Adja Other Antecedents Familial epilepsy Alcoholism Head injury Cerebrovascular disease Infection None declared Age at seizure onset <20 20–29 30–39 ! 40 Type of seizure Generalized Partial secondarily generalized Partial simple/complex Chronic complications Depression (deep sadness) Problems of concentration/memory (based on declaration) N = 105 81 69 21 20 36 26 10 10 113 37 79 71 80 66 4 137 7 6 81 7 3 2 20 37 116 14 6 14 98 46 6 8 80 % 54. 54(4):757–763.7 6.3 4.. In addition. 2013 doi: 10. Dumas M.7 52. treatment compliance.7 91. Univ Calif Public Stat 1:131–160. In addition.0 53. Houinato et al. More than half of the deaths were epilepsy related..3 24. although the mortality depends upon many factors such as availability of suitable drugs. health personnel also need to be trained and motivated to treat epilepsy to the same degree as they are for other health problems. Our study also revealed a significant monthly decline in the number of seizures. 31. Chapman DG.0 13.7 47.3 30.3%).3 6.3 13.3 4. However. Although mortality is high among PWE. These figures are close to those reported in studies from Malawi (seizure remission in 56% of PWE) and Kenya (total remission in 53% of PWE. Capo-Chichi OB.12082 Disclosure None of the authors has any conflict of interest to disclose.0 1. the differences could be due to the different sample sizes. 1997) or in a 10-year followup of 128 PWE in rural Cameroon where 37 PWE died (Kamgno et al. solitude). drug quality and the state of health care delivery in the region.0 17. which may differ between populations or studies. This study showed that the maintenance of regular and timely follow-up is needed to ensure the effectiveness of antiepileptic treatment. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this paper is consistent with those guidelines.and middleincome countries. 1991). This lower rate suggests that the follow-up was reliable.0 2.3 9. and sufficient. 2003).1111/epi.7 75. as long as there are sufficient resources and commitment.

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