Evaluation of Kilifi epilepsy education programme: a randomized controlled trial.

OBJECTIVES: 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). METHODS: Seven hundred thirty-eight people with epilepsy (PWE) and their designated supporter were randomized to either the intervention (education) or nonintervention group. Data were collected at baseline and 1 year after the education intervention was administered to the intervention group. There were 581 PWE assessed at both time points. At the end of the study, 105 PWE from the intervention group and 86 from the nonintervention group gave blood samples, which were assayed for the most commonly used AEDs (phenobarbital, phenytoin, and carbamazepine). The proportions of PWE with detectable AED levels were determined using a standard blood assay method. The laboratory technicians conducting the assays were blinded to the randomization. Secondary outcomes were evaluated using questionnaires administered by trained field staff. Modified Poisson regression was used to investigate the factors associated with improved adherence (transition from nonoptimal AED level in blood at baseline to optimal levels at follow-up), reduced seizures, and improved KEBAS, which was done as a post hoc analysis. This trial is registered in ISRCTN register under ISRCTN35680481. RESULTS: There was no significant difference in adherence to AEDs based on detectable drug levels (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 0.74-2.90, p = 0.28) or by self-reports (OR 1.00, 95% CI 0.71-1.40, p = 1.00) between the intervention and nonintervention group. The intervention group had significantly fewer beliefs about traditional causes of epilepsy, cultural treatment, and negative stereotypes than the nonintervention group. There was no difference in seizure frequency. A comparison of the baseline and follow-up data showed a significant increase in adherence-intervention group (36-81% [p < 0.001]) and nonintervention group (38-74% [p < 0.001])-using detectable blood levels. The number of patients with less frequent seizures (≤3 seizures in the last 3 months) increased in the intervention group (62-80% [p = 0.002]) and in the nonintervention group (67-75% [p = 0.04]). Improved therapeutic adherence (observed in both groups combined) was positively associated with positive change in beliefs about risks of epilepsy (relative risk [RR] 2.00, 95% CI 1.03-3.95) and having nontraditional religious beliefs (RR 2.01, 95% CI 1.01-3.99). Reduced seizure frequency was associated with improved adherence (RR 1.72, 95% CI 1.19-2.47). Positive changes in KEBAS were associated with having tertiary education as compared to none (RR 1.09, 95% CI 1.05-1.14). SIGNIFICANCE: Health education improves knowledge about epilepsy, but once only contact does not improve adherence. However, sustained education may improve adherence in future studies.

The reasons for the epilepsy treatment gap in Kilifi, Kenya: using formative research to identify interventions to improve adherence to antiepileptic drugs.

Many people with epilepsy (PWE) in resource-poor countries do not receive appropriate treatment, a phenomenon referred to as the epilepsy treatment gap (ETG). We conducted a qualitative study to explore the reasons for this gap and to identify possible interventions in Kilifi, Kenya. Focus group discussions (FGDs) were carried out of PWE and their caregivers. Individual interviews were conducted of PWE, their caregivers, traditional healers, community health workers and leaders, nurses and doctors. In addition, a series of workshops was conducted, and four factors contributing to the ETG were identified: 1) lack of knowledge about the causes, treatment and prognosis of epilepsy; 2) inaccessibility to antiepileptic drugs; 3) misconceptions about epilepsy derived from superstitions about its origin; 4) and dissatisfaction with the communication skills of health providers. These data indicated possible interventions: 1) education and support for PWE and their caregivers; 2) communication skills training for health providers; 3) and improved drug provision.

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

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.

Development and validation of the Kilifi Epilepsy Beliefs and Attitude Scale.

Epilepsy remains misunderstood, particularly in resource poor countries (RPC). We developed and validated a tool to assess beliefs and attitudes about epilepsy among people with epilepsy (PWE) in Kilifi, Kenya. The 50-item scale was developed through a literature review and qualitative study findings, and its reliability and validity were assessed with 673 PWE. A final scale of 34 items had Cronbach's alpha scores for the five subscales: causes of epilepsy (α=0.71); biomedical treatment of epilepsy (α=0.70); cultural treatment of epilepsy (α=0.75); risk and safety concerns about epilepsy (α=0.56); and negative attitudes about epilepsy (α=0.76) and entire scale (α=0.70). Test-retest reliability was acceptable for all the subscales. The Kilifi Epilepsy Beliefs and Attitude Scale is a reliable and valid tool that measures beliefs and attitudes about epilepsy. It may be useful in other RPC or as a tool to assess the effectiveness of interventions to improve knowledge, beliefs, and attitudes about epilepsy.

Development and validation of the Kilifi Stigma Scale for Epilepsy in Kenya.

The aim of this study was to develop and validate a tool to measure perceived stigma among people with epilepsy (PWE) in Kilifi, Kenya. We reviewed existing scales that measured stigma, particularly of epilepsy. We conducted a qualitative study to determine salient concerns related to stigma in Kilifi. Themes were generated, and those related to stigma were used to construct an 18-item stigma scale. A descriptive cross-sectional survey was then conducted among 673 PWE to assess the reliability and validity of the scale. Internal consistency was calculated using Cronbach's alpha and test-retest reliability with an interclass correlation coefficient. The final scale had 15 items, which had high internal consistency (Cronbach's α=0.91) and excellent test-retest reliability (r=0.92). Factor analysis indicated that the scale was unidimensional with one factor solution explaining 45.8% of the variance. The Kilifi Stigma Scale for Epilepsy is a culturally appropriate measure of stigma with strong psychometric properties.

Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage.

BACKGROUND: Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage. METHODS: An everyday memory battery was administered on 152 children with cerebral malaria (CM) (mean age, 7 y 4 months [SD 13 months]; 77 males) 156 children (mean age, 7 y 4 months [SD, 14 months]; 72 males) with malaria plus complex seizures (MS) and 179 children (mean age, 7 y 6 months [SD, 13 months]; 93 males) unexposed to either condition. RESULTS: CM was associated with poorer everyday memory [95% CI, -2.46 to -0.36, p = 0.004] but not MS [95% CI, -0.91 to 1.16, p = 1.00] compared to unexposed children. Children with exposure to CM performed more poorly in recall [95% CI, -0.79 to -0.04, p = 0.024] and recognition subtests [95% CI, -0.90 to -0.17, p = 0.001] but not in prospective memory tests compared to controls. The health factors that predicted impaired everyday memory outcome in children with exposure to CM was profound coma [95% CI, 0.02 to 0.88, p = 0.037] and multiple episodes of hypoglycaemia [95% CI, 0.05 to 0.78, p = 0.020], but not seizures. DISCUSSION: The findings show that exposure to CM was associated with a specific impairment of everyday memory. Seizures commonly observed in severe malaria may not have a causal relationship with poor outcome, but rather be associated with profound coma and repeated metabolic insults (multi-hypoglycaemia) that are strongly associated with impaired everyday memory.

The epilepsy treatment gap in developing countries: a systematic review of the magnitude, causes, and intervention strategies.

SUMMARY: In many developing countries, people with epilepsy do not receive appropriate treatment for their condition, a phenomenon called the treatment gap (TG). We carried out a systematic review to investigate the magnitude, causes, and intervention strategies to improve outcomes in developing countries. We systematically searched MEDLINE, EMBASE, and PsycINFO databases, supplemented by a hand search of references in the key papers. The degree of heterogeneity and a pooled TG estimate were determined using metaanalysis techniques. The estimates were further stratified by continent and location of study (urban, rural). Twenty-seven studies met the inclusion criteria: twelve from Africa, nine from Asia and six from Latin America. We observed a high degree of heterogeneity and inconsistency between studies. The overall estimate of the TG was 56/100 [95% confidence interval (CI) 31.1-100.0]. The variation in estimates could possibly be explained by nonuniform TG estimation methods and the diverse study populations, among other factors. The TG was mainly attributed to inadequate skilled manpower, cost of treatment, cultural beliefs, and unavailability of antiepileptic drugs (AEDs). These factors have been addressed using different intervention strategies, such as education and supply of AEDs. Future research should estimate the TG coherently and develop sustainable interventions that will address the causes.

Child development: risk factors for adverse outcomes in developing countries.

Poverty and associated health, nutrition, and social factors prevent at least 200 million children in developing countries from attaining their developmental potential. We review the evidence linking compromised development with modifiable biological and psychosocial risks encountered by children from birth to 5 years of age. We identify four key risk factors where the need for intervention is urgent: stunting, inadequate cognitive stimulation, iodine deficiency, and iron deficiency anaemia. The evidence is also sufficient to warrant interventions for malaria, intrauterine growth restriction, maternal depression, exposure to violence, and exposure to heavy metals. We discuss the research needed to clarify the effect of other potential risk factors on child development. The prevalence of the risk factors and their effect on development and human potential are substantial. Furthermore, risks often occur together or cumulatively, with concomitant increased adverse effects on the development of the world's poorest children.

Dietary whey protein lowers serum C-peptide concentration and duodenal SREBP-1c mRNA abundance, and reduces occurrence of duodenal tumors and colon aberrant crypt foci in azoxymethane-treated male rats.

We evaluated partially hydrolyzed whey protein (WPH) for inhibitory effects on the development of colon aberrant crypt foci (ACF) and intestinal tumors in azoxymethane (AOM)-treated rats. Pregnant Sprague-Dawley rats and their progeny were fed AIN-93G diets containing casein (CAS, control diet) or WPH as the sole protein source. Colons and small intestines from the male progeny were obtained at 6, 12, 20 and 23 weeks after AOM treatment. At 6 and 23 weeks, post-AOM, WPH-fed rats had fewer ACF than did CAS-fed rats. Intestinal tumors were most frequent at 23 weeks, post-AOM. At this time point, differences in colon tumor incidence with diet were not observed; however, WPH-fed rats had fewer tumors in the small intestine (7.6% vs. 26% incidence, P=.004). Partially hydrolized whey protein suppressed circulating C-peptide concentration (a stable indicator of steady-state insulin secretion) at all four time points relative to the corresponding CAS-fed animals. The relative mRNA abundance for the insulin-responsive, transcription factor gene, SREBP-1c, was reduced by WPH in the duodenum but not colon. Results indicate potential physiological linkages of dietary protein type with circulating C-peptide (and by inference insulin), local expression of SREBP-1c gene and propensity for small intestine tumorigenesis.

The effect of Plasmodium falciparum on cognition: a systematic review.

OBJECTIVE: Systematic review to investigate the relationship between Plasmodium falciparum infection and cognitive function. METHOD: We searched MEDLINE, EMBASE and PsycINFO, and hand-searched journals and PhD theses. The inclusion criteria were (1) use of standardized tests for the specific populations and/or appropriate controls; (2) clear differentiation between children and adults. Eighteen studies were eligible, of which three gave information on all cognitive domains considered in the review. RESULTS: Deficits in attention, memory, visuo-spatial skills, language and executive functions may occur after malaria infection. These deficits are not only caused by cerebral falciparum malaria, but also appear to occur in less severe infections. P. falciparum seems to affect the brain globally, not in a localised fashion. Outcome depends on both biological and social risk factors. CONCLUSION: Future research should seek to establish the extent of these cognitive deficits using culturally appropriate techniques and well-defined criteria of disease.

Severe falciparum malaria and acquired childhood language disorder.

Language disorders have been reported after severe falciparum malaria but the deficits have not been described in detail. We assessed language outcome in three groups of children aged 6 to 9 years (n=487): those previously admitted to Kilifi District Hospital, Kenya, with cerebral malaria (CM; n=152; mean age 7y 4 mo [SD 1y 1mo]; 77 males, 75 females); or those with malaria and complicated seizures (M/S; n=156; mean age 7y 4mo [SD 1y 2mo]; 72 males, 84 females); and those unexposed to either condition (n=179; mean age 7y 6mo [SD 1y 1mo]; 93 males, 86 females). Median age at hospital admission was 28 months (interquartile range [IQR] 19 to 44 mo) among children with a history of CM and 23 months (IQR 12 to 35mo) among children with a history of M/S. A battery of eight assessments covering the major facets of speech and language was used to measure language performance. Cognitive performance, neurological/motor skills, behaviour, hearing, and vision were also measured. Eighteen (11.8%) of the CM group, 14 (9%) of the M/S group, and four (2.2%) of the unexposed group were found to have a language impairment. CM (odds ratio 3.68, 95% confidence interval 1.09 to 12.4, p=0.04) was associated with significantly increased odds of an impairment-level score relative to the unexposed group. The results suggest that falciparum malaria is one of the most common causes of acquired language disorders in the tropics.

Issues in the development of cross-cultural assessments of speech and language for children.

BACKGROUND: There is an increasing demand for the assessment of speech and language in clinical and research situations in countries where there are few assessment resources. Due to the nature of cultural variation and the potential for cultural bias, new assessment tools need to be developed or existing tools require adaptation. However, there are few guidelines on how to develop 'culturally appropriate' assessment tools. AIMS: To review the literature on cross-cultural assessment in order to identify the major issues in the development and adaptation of speech and language assessments for children and to illustrate these issues with practical examples from our own research programme in Kenya. METHODS & PROCEDURES: Five broad categories pertaining to cross-cultural assessment development were identified: the influence of culture on performance, familiarity with the testing situation, the effect of formal education, language issues and picture recognition. It was outlined how some of these issues were addressed in our research. The results of the review were integrated to produce a list of ten guidelines highlighting the importance of collaboration with mother tongue speakers; piloting; familiar assessment materials; assessment location; and practice items and prompts. CONCLUSIONS: There are few clinicians and assessors, whether in the UK or abroad, who do not assess or treat children from a culture different to their own. Awareness of cultural variation and bias and cooperative efforts to develop and administer culturally appropriate assessment tools are the foundation of effective, valid treatment programmes.

Developmental impairments following severe falciparum malaria in children.

OBJECTIVE: Neurological deficits are reported in children after cerebral malaria (CM) but little is known about the prevalence and characteristics of persisting neurocognitive consequences. The prevalence of developmental impairments following other complications of falciparum malaria, such as multiple, prolonged or focal seizures, is not known. Thus, our objective was to investigate the long-term developmental outcome of CM and malaria with complicated seizures (M/S). METHODS: We followed up a cohort of children previously exposed to CM or M/S and children unexposed to either condition. All children between 6 and 9 years of age, exposed to CM, and an equal number of children exposed to M/S were identified from databases of hospital admissions from 1991 to 1998. The unexposed group was randomly selected from a census database. The children's performance was measured using assessments of cognition, motor, speech and language, hearing and vision. A parental questionnaire was used to identify children with epilepsy. RESULTS: CM group scores were significantly lower than unexposed group scores on the assessments of higher level language (adjusted mean difference -1.63, 95% CI: -2.99 to -0.27), vocabulary (-0.02, 95% CI: -0.04 to -0.01), pragmatics (OR 2.81, 95% CI: 1.04-7.6) and non-verbal functioning (-0.33, 95% CI: -0.61 to -0.06). The areas of significantly reduced functioning for the M/S group were concentrated on phonology (OR 2.74, 95% CI: 1.26-5.95), pragmatics (OR 3.23, 95% CI: 1.2-8.71) and behaviour (OR 1.8, 95% CI: 1.0-3.23). The performance of the active epilepsy group was significantly poorer than that of the group without epilepsy on the tests of comprehension, syntax, pragmatics, word finding, memory, attention, behaviour and motor skills. CONCLUSIONS: CM and M/S are associated with developmental impairments. If these impairments persist, this may have implications for least 250,000 children in Sub-Saharan Africa each year. Active epilepsy significantly increases the risk of cognitive and behavioural problems in children with a history of severe malaria.

Increased prevalence of epilepsy associated with severe falciparum malaria in children.

PURPOSE: Multiple, prolonged, generalized, or focal seizures are common in children with severe malaria, with or without coma. In other contexts, such seizures have been associated with the development of epilepsy. The relation between falciparum malaria and epilepsy is undetermined; thus we measured the prevalence and characteristics of epilepsy in children with a history of severe malaria. METHODS: We took a detailed epilepsy history from the parents of 487 children (aged 6-9 years) to compare the prevalence of epilepsy between three exposure groups: children with a history of cerebral malaria (CM), malaria and complicated seizures (M/S), or those unexposed to either complication. Each child had an EEG and was classified as having active, inactive, or no epilepsy. RESULTS: An increased prevalence of epilepsy was seen in children previously admitted with CM [9.2%; OR, 4.4; 95% confidence interval (CI), 1.4-13.7] or M/S (11.5%; OR, 6.1; 95% CI, 2.0-18.3) compared with the unexposed group (2.2%). The most commonly reported seizure types were tonic-clonic (42%), focal becoming secondarily generalized (16%), and both (21%). Twenty-six percent of the active epilepsy group initially had EEG abnormalities. CONCLUSIONS: These results suggest that children exposed to CM or M/S have an increased propensity for epilepsy relative to children unexposed to these complications. The prevalence of epilepsy associated with CM is similar to that reported after other severe encephalopathies. The prevalence associated with M/S is more than twice that reported after complicated febrile seizures.

Neuro-cognitive impairment following acquired central nervous system infections in childhood: a systematic review.

The morbid consequences of central nervous system (CNS) infections are often overlooked in the face of high mortality rates. However, neurological impairments not only affect the child's development and future prospects but also place an economic and social burden on communities and countries that often have few resources to deal with such problems. We conducted a systematic review to investigate the occurrence and pattern of persisting neurological impairment after common CNS infections. A comprehensive search of MEDLINE, EMBASE and PsycINFO databases, supplemented by hand-searches of key journals, resulted in forty-six eligible studies, five of which gave information on the spectrum of developmental domains. Despite the lack of comprehensive, methodologically-sound studies, the results show that postinfectious neurological impairment persists, most commonly in cognition and motor functions. Deficits include more subtle problems, which can be difficult to detect on gross neurological assessment but may still be deleterious to the child's social and educational functioning. Higher morbidity for similar mortality in acute bacterial meningitis compared with cerebral malaria in the epidemiological data may suggest future research directions for clinical research to devise more effective interventions.