Rachael Odhiambo

Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors: Cross-sectional and case-control studies

Summary Background The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world, but estimates vary substantially for unknown reasons. We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region. Methods We did large population-based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres: Kilifi, Kenya (Dec 3, 2007–July 31, 2008); Agincourt, South Africa (Aug 4, 2008–Feb 27, 2009); Iganga-Mayuge, Uganda (Feb 2, 2009–Oct 30, 2009); Ifakara, Tanzania (May 4, 2009–Dec 31, 2009); and Kintampo, Ghana (Aug 2, 2010–April 29, 2011). We used a three-stage screening process to identify people with active convulsive epilepsy. Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages. For each case, an age-matched control individual was randomly selected from the relevant centres census database. Fieldworkers masked to the status of the person they were interviewing administered questionnaires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Blood samples were taken from a randomly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. We estimated odds ratios (ORs) with logistic regression, adjusted for age, sex, education, employment, and marital status. Results 586 607 residents in the study areas were screened in stage one, of whom 1711 were diagnosed as having active convulsive epilepsy. Prevalence adjusted for attrition and sensitivity varied between sites: 7·8 per 1000 people (95% CI 7·5–8·2) in Kilifi, 7·0 (6·2–7·4) in Agincourt, 10·3 (9·5–11·1) in Iganga-Mayuge, 14·8 (13·8–15·4) in Ifakara, and 10·1 (9·5–10·7) in Kintampo. The 1711 individuals with the disorder and 2032 control individuals were given questionnaires. In children (aged <18 years), the greatest relative increases in prevalence were associated with difficulties feeding, crying, or breathing after birth (OR 10·23, 95% CI 5·85–17·88; p<0·0001); abnormal antenatal periods (2·15, 1·53–3·02; p<0·0001); and head injury (1·97, 1·28–3·03; p=0·002). In adults (aged ≥18 years), the disorder was significantly associated with admission to hospital with malaria or fever (2·28, 1·06–4·92; p=0·036), exposure to T canis (1·74, 1·27–2·40; p=0·0006), exposure to T gondii (1·39, 1·05–1·84; p=0·021), and exposure to O volvulus (2·23, 1·56–3·19; p<0·0001). Hypertension (2·13, 1·08–4·20; p=0·029) and exposure to T solium (7·03, 2·06–24·00; p=0·002) were risk factors for adult-onset disease. Interpretation The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors. Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region. Funding Wellcome Trust, University of the Witwatersrand, and South African Medical Research Council.

Risk factors associated with the epilepsy treatment gap in Kilifi, Kenya: a cross-sectional study

Summary Background Many people with epilepsy in low-income countries do not receive appropriate biomedical treatment. This epilepsy treatment gap might be caused by patients not seeking biomedical treatment or not adhering to prescribed antiepileptic drugs (AEDs). We measured the prevalence of and investigated risk factors for the epilepsy treatment gap in rural Kenya. Methods All people with active convulsive epilepsy identified during a cross-sectional survey of 232 176 people in Kilifi were approached. The epilepsy treatment gap was defined as the percentage of people with active epilepsy who had not accessed biomedical services or who were not on treatment or were on inadequate treatment. Information about risk factors was obtained through a questionnaire-based interview of sociodemographic characteristics, socioeconomic status, access to health facilities, seizures, stigma, and beliefs and attitudes about epilepsy. The factors associated with people not seeking biomedical treatment and not adhering to AEDs were investigated separately, adjusted for age. Findings 673 people with epilepsy were interviewed, of whom 499 (74%) reported seeking treatment from a health facility. Blood samples were taken from 502 (75%) people, of whom 132 (26%) reported taking AEDs, but 189 (38%) had AEDs detectable in the blood. The sensitivity and specificity of self-reported adherence compared with AEDs detected in blood were 38·1% (95% CI 31·1–45·4) and 80·8% (76·0–85·0). The epilepsy treatment gap was 62·4% (58·1–66·6). In multivariable analysis, failure to seek biomedical treatment was associated with a patient holding traditional animistic religious beliefs (adjusted odds ratio 1·85, 95% CI 1·11–2·71), reporting negative attitudes about biomedical treatment (0·86, 0·78–0·95), living more than 30 km from health facilities (3·89, 1·77–8·51), paying for AEDs (2·99, 1·82–4·92), having learning difficulties (2·30, 1·29–4·11), having had epilepsy for longer than 10 years (4·60, 2·07–10·23), and having focal seizures (2·28, 1·50–3·47). Reduced adherence was associated with negative attitudes about epilepsy (1·10, 1·03–1·18) and taking of AEDs for longer than 5 years (3·78, 1·79–7·98). Interpretation The sensitivity and specificity of self-reported adherence is poor, but on the basis of AED detection in blood almost two-thirds of patients with epilepsy were not on treatment. Education about epilepsy and making AEDs freely available in health facilities near people with epilepsy should be investigated as potential ways to reduce the epilepsy treatment gap. Funding Wellcome Trust.

Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa

Background Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52–2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23–1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04–1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30–2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.

Premature mortality in active convulsive epilepsy in rural Kenya Causes and associated factors

Objective: We estimated premature mortality and identified causes of death and associated factors in people with active convulsive epilepsy (ACE) in rural Kenya. Methods: In this prospective population-based study, people with ACE were identified in a cross-sectional survey and followed up regularly for 3 years, during which information on deaths and associated factors was collected. We used a validated verbal autopsy tool to establish putative causes of death. Age-specific rate ratios and standardized mortality ratios were estimated. Poisson regression was used to identify mortality risk factors. Results: There were 61 deaths among 754 people with ACE, yielding a rate of 33.3/1,000 persons/year. Overall standardized mortality ratio was 6.5. Mortality was higher across all ACE age groups. Nonadherence to antiepileptic drugs (adjusted rate ratio [aRR] 3.37), cognitive impairment (aRR 4.55), and age (50+ years) (rate ratio 4.56) were risk factors for premature mortality. Most deaths (56%) were directly related to epilepsy, with prolonged seizures/possible status epilepticus (38%) most frequently associated with death; some of these may have been due to sudden unexpected death in epilepsy (SUDEP). Possible SUDEP was the likely cause in another 7%. Conclusion: Mortality in people with ACE was more than 6-fold greater than expected. This may be reduced by improving treatment adherence and prompt management of prolonged seizures and supporting those with cognitive impairment.

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

Epilepsy is common in sub‐Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital‐based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross‐sectional community‐based surveys in SSA, to understand the proximate causes, features, and consequences.

Evaluation of Kilifi Epilepsy Education Programme: A randomized controlled trial

The epilepsy treatment gap is largest in resource‐poor countries. We evaluated the efficacy of a 1‐day health education program in a rural area of Kenya. The primary outcome was adherence to antiepileptic drugs (AEDs) as measured by drug levels in the blood, and the secondary outcomes were seizure frequency and Kilifi Epilepsy Beliefs and Attitudes Scores (KEBAS).

Burden, causes, and outcomes of people with epilepsy admitted to a rural hospital in Kenya

People with epilepsy (PWE) develop complications and comorbidities often requiring admission to hospital, which adds to the burden on the health system, particularly in low‐income countries. We determined the incidence, disability‐adjusted life years (DALYs), risk factors, and causes of admissions in PWE. We also examined the predictors of prolonged hospital stay and death using data from linked clinical and demographic surveillance system.

Burden, risk factors, and comorbidities of behavioural and emotional problems in Kenyan children: a population-based study

Summary Background Three-quarters of the burden of mental health problems occurs in low-and-middle-income countries, but few epidemiological studies of these problems in preschool children from sub-Saharan Africa have been published. Behavioural and emotional problems often start in early childhood, and this might be particularly important in Africa, where the incidence of perinatal and early risk factors is high. We therefore aimed to estimate the prevalence and risk factors of behavioural and emotional problems in young children in a rural area on the Kenyan coast. Methods We did a population-based epidemiological study to assess the burden of behavioural and emotional problems in preschool children and comorbidities in the Kilifi Health and Demographic Surveillance System (KHDSS, a database formed of the population under routine surveillance linked to admissions to Kilifi County Hospital). We used the Child Behaviour Checklist (CBCL) to assess behavioural and emotional problems. We then determined risk factors and medical comorbidities associated with behavioural and emotional problems. The strength of associations between the risk factors and the behavioural and emotional problems was estimated using generalised linear models, with appropriate distribution and link functions. Findings 3539 families were randomly selected from the KHDSS. Of these, 3273 children were assessed with CBCL. The prevalence of total behavioural and emotional problems was 13% (95% CI 12–14), for externalising problems was 10% (9–11), and for internalising problems was 22% (21–24). The most common CBCL syndrome was somatic problems (21%, 20–23), whereas the most common DSM-IV-oriented scale was anxiety problems (13%, 12–14). Factors associated with total problems included consumption of cassava (risk ratio 5·68, 95% CI 3·22–10·03), perinatal complications (4·34, 3·21–5·81), seizure disorders (2·90, 2·24–3·77), and house status (0·11, 0·08–0·14). Seizure disorders, burn marks, and respiratory problems were important comorbidities of behavioural and emotional problems. Interpretation Behavioural and emotional problems are common in preschool children in this Kenyan rural area and are associated with preventable risk factors. Behavioural and emotional problems and associated comorbidities should be identified and addressed in young children. Funding Wellcome Trust.

Incidence and risk factors for neonatal tetanus in admissions to Kilifi County Hospital, Kenya.

Background Neonatal Tetanus (NT) is a preventable cause of mortality and neurological sequelae that occurs at higher incidence in resource-poor countries, presumably because of low maternal immunisation rates and unhygienic cord care practices. We aimed to determine changes in the incidence of NT, characterize and investigate the associated risk factors and mortality in a prospective cohort study including all admissions over a 15-year period at a County hospital on the Kenyan coast, a region with relatively high historical NT rates within Kenya. Methods We assessed all neonatal admissions to Kilifi County Hospital in Kenya (1999–2013) and identified cases of NT (standard clinical case definition) admitted during this time. Poisson regression was used to examine change in incidence of NT using accurate denominator data from an area of active demographic surveillance. Logistic regression was used to investigate the risk factors for NT and factors associated with mortality in NT amongst neonatal admissions. A subset of sera from mothers (n = 61) and neonates (n = 47) were tested for anti-tetanus antibodies. Results There were 191 NT admissions, of whom 187 (98%) were home deliveries. Incidence of NT declined significantly (Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81–0.89), P<0.001) but the case fatality (62%) did not change over the study period (P = 0.536). Younger infant age at admission (P = 0.001) was the only independent predictor of mortality. Compared to neonatal hospital admittee controls, the proportion of home births was higher among the cases. Sera tested for antitetanus antibodies showed most mothers (50/61, 82%) had undetectable levels of antitetanus antibodies, and most (8/9, 89%) mothers with detectable antibodies had a neonate without protective levels. Conclusions Incidence of NT in Kilifi County has significantly reduced, with reductions following immunisation campaigns. Our results suggest immunisation efforts are effective if sustained and efforts should continue to expand coverage.

Evaluation of Psychometric Properties and Factorial Structure of ADHD Module of K-SADS-PL in Children From Rural Kenya:

Objective: We determined the reliability of The Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime (K-SADS-PL) for screening and diagnosing ADHD in children. Method: K-SADS-PL was administered to 2,074 children in the community. Psychometric properties, factorial structure, and clinical validity of K-SADS-PL in screening or diagnosis of ADHD were examined. Results: Internal consistency was excellent for items in the screening interview (Macdonald’s Omega [ω] = 0.89; 95% confidence interval [CI] [0.87, 0.94]) and diagnostic supplement (ω = 0.95; 95% CI [0.92, 0.99]). The standardized coefficients for items in the screening interview were acceptable (0.59-0.85), while fit indices for single factorial structure reached acceptable levels. Screening items were associated with high sensitivity (97.8%; 95% CI [97.2, 98.5%]) and specificity (94.0%; 95% CI [93.0, 95.0%]) for diagnosis of ADHD in the supplement. The test-retest and interinformant reliability as measured by intraclass correlation coefficient was good for most of the items. Conclusion: This large study shows that K-SADS-PL can be reliably used to screen and diagnose ADHD in children in Kenya.