Characteristics of people with epilepsy in three Eastern African countries – a pooled analysis

Epilepsy is affecting approximately 46 million people globally and therefore is one of the most common neurological disorders worldwide [1]. If one accounts for family members and relatives of persons with epilepsy (PWE), whose lives are likewise socially and economically affected, this number will increase considerably. The majority of PWE are suspected to live in low-income and middle-income countries (LMIC) [2]. However, epilepsy prevalence estimates are varying notably, probably due to a wide range of different aetiologies including genetic, environmental and behavioural risk factors. Taenia solium neurocysticercosis (NCC) is known to be one of the leading causes of epilepsy in LMIC [3]. However, there is still a large research gap concerning the contribution of other infectious diseases like cerebral malaria, meningitis or HIV/AIDS to the prevalence of epilepsy in low-resource settings. Same applies for the raising burden of cerebrovascular diseases due to the epidemiological transition in many LMIC [4‐8].

As neuroimaging, electroencephalography (EEG) or direct observations of epileptic seizures are rare, diagnosis of epilepsy mostly is made based on reports and descriptions of epileptic events by the patients themselves or observers. Consequently, reliable estimates on epilepsy prevalence and causes are difficult to ascertain. Furthermore, other medical conditions like syncope, movement or sleep disorders may be difficult to distinguish from epileptic seizures, especially by non-specialists. Additionally, underreporting may occur due to potential stigma and discrimination of PWE, especially in rural areas [9‐11].

Despite cheap and effective anti-seizure medication (ASM) being available, and often being free of charge, access to sustained medical treatment is limited for many people in LMIC [12]. Large treatment gaps were already reported before, i.e. PWE not being treated with ASM or treated with insufficient dosage, resulting in up to more than 60% of PWE in Africa not receiving adequate treatment [13‐16]. Reasons are partly patient-related, particularly concerning cultural beliefs and stigma about epilepsy; but also financial constraints from both a patient and a system perspective, or stock-out of ASM play an important role [11, 17, 18].

Knowledge about geographic, demographic, and clinical characteristics, types and frequency of epileptic seizures, relevant co-morbidities as well as the underlying causes of epilepsy is crucial for good clinical practice and appropriate management of PWE as well as adequate planning of resource allocation. That is why this study aimed to pool these factors from four studies on epilepsy in three African countries.

Characteristics and methodology of this pooled analysis have been described elsewhere [19].

In short, the current study was part of a large study that focused on neurocysticercosis in PWE from four study sites of three eastern sub-Saharan African countries. Here we report on the pooled epilepsy data. PWE (n = 1179) were examined in-depth including demographic, clinical, semiological (related to epileptic seizures), neuroradiological and therapeutic (related to anti-seizure medication) variables. Two of the four studies were conducted in hospital-based settings in Tanzania (Haydom and Dar es Salaam) [3, 20]. The other two studies were community-based; one was conducted in northern Uganda and one in Balaka district in Malawi.

A flowchart of included patients by site is displayed in Fig. 1 and the detailed methodology can be found in the Supplement.

Overall, 2749 PWE were included in the four studies. In the community-based studies, epilepsy prevalence was 1.1% (95%CI 1.0–1.1%) in Malawi and 3.3% (95%CI 3.1–3.4%) in Uganda (Table 1). After exclusion of patients who were not eligible for further clinical work-up, 1179 patients remained. In Tanzania 514 (hospital-based; Dar es Salaam: 302, Haydom: 212), in Malawi 365 (community-based) and in Uganda 300 (community-based). For more details refer to Fig. 1. Of the 1179 PWE, 581 (49.3%) were female, and median age of patients was 22 years (IQR 15 to 32 years). Patients from Malawi were in the median younger (18 years [IQR 12 to 31 years]) than patients in the other three studies. In the urban Dar es Salaam study site, more patients were single than in the other rural study sites. In Haydom and Uganda, around 90% of patients were Christians; in Dar es Salaam and Malawi the percentage was smaller (51% and 58%) and there were proportionally more Muslims included. 941 (80%) of the 1179 patients had a CT scan (Table 1).

In this study, we pooled the results of four studies on epilepsy in eastern Africa to describe the demographic, clinical, semiological, and neuroradiological characteristics, as well as treatment of PWE.

In the two community-based studies (Malawi and Uganda), a screening of people living in the target area was conducted first, comprising more than 100,000 people. Then, screen positives were seen by a neurologist to confirm diagnosis. Lifetime epilepsy prevalence reported in Malawi (1.1% [1.0–1.3%]) and Uganda (3.3% [3.1–3.4%]) were comparable, yet slightly higher than those from a previously published meta-analysis, which found a pooled lifetime prevalence of 0.7% (0.6–0.9%) for epilepsy in eastern Africa [23]. This could be due to our screening questionnaire, which may also have captured more patients with focal onset seizures, which are often not captured at all. Another explanation could be a higher prevalence of risk factors in our cohorts, e.g. NCC. In addition, other studies previously have reported even higher lifetime prevalence estimates for epilepsy of up to 8% [24, 25].

In general, studies estimate that in LMIC around 50% of PWE have secondary epilepsy [11]. In our study, we found a large proportion of people with seizure onset after adolescence which may indicate a predominance of secondary epilepsy. Unfortunately, we were not able to assess the exact proportion of persons with secondary epilepsy in our study. On the one hand because not many patients showed remarkable findings on CT scan, and for those who did, the temporal association could not be established. On the other hand, patients with obvious traumatic brain injury or perinatal hypoxic brain injury were excluded from further work-up due to study protocol, so that (CT) data on these aetiologies are not representative and most likely vastly underrepresented.

Nevertheless, CT data of almost 950 PWE were available, which to our knowledge represents the largest and most detailed analysis in sub-Saharan Africa. The rate of remarkable CT scan findings was highest in patients with focal onset seizures. Most common findings were neurocysticercosis-associated lesions, but interestingly, an even higher proportion of post-ischaemic lesions could be observed. This finding indicates that cerebrovascular events and post-stroke epilepsy have to be considered as an emerging aetiology for epilepsy in sub-Saharan Africa.

Another frequent CT pathology was cerebral atrophy, which is a common finding in PWE, but the significance and aetiology is hard to determine [26]. The rate of this pathology was higher in patients with general onset seizures, which is also known from previous studies, where patients with idiopathic generalised and genetic seizure syndromes showed diffuse and wide-spread alterations of brain morphology [26‐28]. Detailed MRI analyses in these patients sometimes also reveal (wide-spread) cerebral malformations such as lissencephaly with pachygyria or microgyria potentially causing both focal and generalized seizures [29]. Further imaging studies in LMIC are needed to characterize the prevalence and significance of these findings.

The majority of PWE in the four studies had generalised onset seizures according to the ILAE criteria. In this analysis, we also assessed seizures according to the classification by Winkler et al. [22], which looks at epileptic seizures in low-resource settings in a more nuanced way, according to local contexts and needs, and tries to imply information on aetiologies and epilepsy syndromes based on seizure type and occurrence without accessory diagnostic. According to that adjusted classification by Winkler et al., most PWE with generalised seizure onset had generalised seizures within a specific age range, which represents the category in which a possible genetic background can be assumed. PWE of this group are suspected to suffer from idiopathic generalised epilepsies in a large proportion of cases. Consequently, our data suggest that despite a known high prevalence of risk factors for secondary epilepsy and previously reported high prevalence of focal epilepsies [30], genetic and idiopathic epilepsy syndromes also seem to play an important role in LMIC. This finding is of note, although a proportion of 30 to 58% among PWE might represent a certain overestimation in our study due to exclusion criteria for some types of secondary epilepsy as mentioned above. Nevertheless, as genetic origins are various and investigations in such a large and diverse cohort could reveal valuable results for both low-income and high-income countries, our results support the view, that it could be the time for initiating genetic epilepsy research in Africa [31] .

Despite a certain proportion of PWE with focal onset seizures in our analysis, most seizures were accompanied by a loss of consciousness and resulted in tonic–clonic seizures. Additionally, injuries during seizures were frequently observed, with a rate of up to 56% in the community-based studies. This is much higher than studies in high-income countries suggest [32, 33] and also is a possible explanation for high epilepsy-associated mortality rates in LMIC [34].

This lack of seizure control may display a lack in adequate ASM therapy. ASM treatment concerning both type and dosage differed substantially between and within countries. In Malawi and Uganda, phenobarbital and phenytoin were almost the only ASM prescribed; they were also still very common in Tanzania. In Tanzania, however, the majority of patients was treated with carbamazepine. Valproic acid was basically not available in any of the countries. These findings display the common picture of ASM treatment status in sub-Saharan Africa [35]. These findings, however, are not only limited to LMIC but can also be observed in high income countries [36]. Treatment choice in Africa very often depends on availability and cost of treatment and phenobarbital/phenytoin are often cheaper than carbamazepine or valproic acid [17]. Even though ASM are widely available, supply chain is often not sustained which results in stock-outs of medication [17, 37]. Nevertheless, stock-out of medication was not the main reason for changing ASM, but inadequate treatment effect and side-effects. Phenobarbital, in particular, is now rarely prescribed in high-income countries due to its relatively strong side effects and has been replaced by newer ASM [38]. Yet, it is still recommended by the World Health Organization (WHO) as first-line treatment in LMIC because of its cost advantage and broad spectrum of activity [35, 39]. Nevertheless, even in low-resource settings, phenobarbital has a higher risk to be withdrawn due to side-effects than carbamazepine, phenytoin, or valproic acid [39‐41].

We found a quite large proportion of patients who had epileptic seizures more often than monthly, especially in the community-based studies, possibly reflecting the lower rates of ASM treatment compared to the hospital-based settings. However, we also found high frequencies of seizures even in patients receiving ASM, which may be due to barriers to accessing healthcare services, supply shortages, or the cost of ASM (mainly to hospitals and sometimes to patients, although ASM are often available free of charge), but also due to underdosage of ASM, which was common in our study. A large part of PWE in our pooled analysis received ≤ 60 mg phenobarbital or ≤ 400 mg carbamazepine per day.

Interestingly, seizure control varied considerably even among the two hospital-based studies, although both showed high treatment rates and treatment with carbamazepine was available. Haydom in rural Tanzania had a high proportion of patients with seizures only yearly or even less often, and no patients with seizures more frequent than monthly, despite underdosage was present in a certain proportion of patients. In contrast, PWE in urban Dar es Salaam showed high seizure rates, comparable to the community-based settings. This could be a result of the study settings, as PWE in Haydom were primarily recruited by a doctor and invited to follow-up visits in the clinic, probably getting access to ASM for the first time in some cases, resulting in good treatment effect, whereas patients in Dar es Salaam were recruited directly from the clinic. One could suspect a high proportion of patients with regular clinic visits due to difficulties to reach seizure control. This might be also reflected by the fact that this was the study site with the highest number of PWE receiving a combination therapy and having a history of prior change in ASM treatment. More studies comparing rural and urban healthcare settings are needed to assess the possible differences and contributing factors.

Many PWE across studies also received alternative treatment for their seizures. This shows the still very prevalent disbelieves about epilepsy as supernatural or witchcraft. In many regions of Africa, PWE are still being stigmatized which makes it difficult to analyse community-based prevalence and which may be the cause of the prevalent undertreatment of PWE.

Epilepsy has a big impact on social life as shown by the fact that many PWE dropped out of school, especially in Malawi and Uganda. In contrast, > 90% of PWE went to school in urban Dar es Salaam despite inadequate seizure control. One could hypothesize that disbelieves and stigmatization is less frequent in urban areas, although alternative non-ASM treatments were equally present in this group.

We report a rather large proportion of PWE who suffer from psychiatric disorders. Studies estimate that up to 50% of all PWE suffer from mental disorders, most commonly from depression, anxiety or dementia [42‐45]. This proportion, however, is likely an overestimation as phenomena during seizures may be mischaracterised as mood disorders [46]. Those studies were mainly conducted in high-income countries, and only one was from Sierra Leone. For sub-Saharan Africa, data are still scarce. In our analysis, the proportion of patients with psychiatric disorders differed substantially between studies, which may be due to different assessors, as the questionnaire was the same across countries. Interestingly, prevalence of psychiatric disorders was highest in the urban study site of Dar es Salaam. Differences in education and work as well as different degrees of stigmatization of psychiatric disorders may be a possible explanation. In the four studies, only a small proportion of patients suffered from chronic diseases other than psychiatric illnesses, which is not unusual in sub-Sahara Africa, mostly because diseases can be diagnosed with less certainty.

In this large and comprehensive study, data on demographic, semiological, clinical, neuroradiological and therapeutic findings of four studies among PWE in eastern Africa were pooled. Overall, epilepsy is common in sub-Saharan Africa and PWE suffer from high seizure rates and subsequent injuries as well as from socio-economic consequences, such as drop out from school. ASM treatment rates are rather low, especially in rural areas, and underdosage is common. Secondary epilepsy plays an important role with CT imaging revealing both, neurocysticercosis-associated and post-ischaemic lesions as the main findings in our study setting. Nevertheless, a large proportion of PWE can also be assumed to suffer from genetic epilepsy syndromes, although study setting might have overestimated this group.

This pooled analysis contributes to the evaluation and understanding of the burden of epilepsy and the persisting treatment gap in sub-Saharan Africa. Our results demonstrate the need of structural programmes, addressing both, acquisition of material resources and transfer of expert knowledge, for adequate identification, education, and treatment of PWE.