Epilepsy care cascade, treatment gap and its determinants in rural South Africa.

PURPOSE: The percentage of people who are diagnosed with epilepsy (diagnostic gap), access, receive and adhere (treatment gap) to anti-seizure medication (ASM) in low- and middle- income countries remains low. We explored the epilepsy care cascade, measured the diagnostic and treatment gaps, and examined socio-demographic factors associated with adherence to ASMs in rural South Africa. METHODS: Utilizing a population-based cohort of 311 people with active convulsive epilepsy (ACE) residing in rural northeastern South Africa, a questionnaire was administered to examine associations between demographic and socioeconomic factors and the epilepsy treatment gap. Blood was taken to measure levels of ASMs. RESULTS: Of the 311 individuals diagnosed, 93 % of individuals reported being previously told they had epilepsy and 94 % reported previously attending a health facility for their epilepsy. ASMs were detected in 138 individuals (76 %) and optimal levels were detected in 67 individuals, resulting in a treatment gap of 63 % (95 % confidence interval [95 %CI]: 56 %-70 %). Self-reported specificity of ASM use was 23 % (95 %CI: 12-39 %) and individuals ≥18 years were significantly more likely to report taking ASM than children and were significantly (p = 0.011) more likely to be adherent. CONCLUSION: Most people with epilepsy in rural South Africa had been previously diagnosed with epilepsy and had accessed care for epilepsy, yet the level of ASM adherence remained low, significantly lower amongst children. Understanding ways of improving knowledge of and adherence to ASM in rural South Africa is necessary, especially amongst children. The epilepsy care cascade can be useful in identifying gaps in care and targeting interventions to reduce these gaps.

Magnitude and factors associated with nonadherence to antiepileptic drug treatment in Africa: A cross-sectional multisite study.

Objectives: The epilepsy treatment gap is large in low- and middle-income countries, but the reasons behind nonadherence to treatment with antiepileptic drugs (AEDs) across African countries remain unclear. We investigated the extent to which AEDs are not taken and associated factors in people with active convulsive epilepsy (ACE) identified in cross-sectional studies conducted in five African countries. Methods: We approached 2,192 people with a confirmed diagnosis of ACE for consent to give blood voluntarily. Participants were asked if they were taking AEDs, and plasma drug concentrations were measured using a fluorescence polarization immunoassay analyzer. Information about possible risk factors was collected using questionnaire-based clinical interviews. We determined factors associated with nonadherence to AED treatment in children and adults, as measured by detectable and optimal levels, using multilevel logistic regression. Results: In 1,303 samples assayed (43.7% were children), AEDs were detected in 482, but only 287 had optimal levels. Of the 1,303 samples, 532 (40.8%) were from people who had reported they were on AEDs. The overall prevalence of nonadherence to treatment was 63.1% (95% confidence interval [CI] 60.5-65.6%) as measured by detectable AED levels and 79.1% (95% CI 73.3-84.3%) as measured by optimal AED levels; self-reported nonadherence was 65.1% (95% CI 45.0-79.5%). Nonadherence was significantly (p < 0.001) more common among the children than among adults for optimal and detectable levels of AEDs, as was the self-reported nonadherence. In children, lack of previous hospitalization and learning difficulties were independently associated with nonadherence to treatment. In adults, history of delivery at home, absence of burn marks, and not seeking traditional medicine were independently associated with the nonadherence to AED treatment. Significance: Only about 20% of people with epilepsy benefit fully from antiepileptic drugs in sub-Saharan Africa, according to optimum AEDs levels. Children taking AEDs should be supervised to promote compliance.

Sodium Disturbances in Children Admitted to a Kenyan Hospital: Magnitude, Outcome and Associated Factors.

BACKGROUND: Perturbations of blood sodium are the most frequently encountered electrolyte disorder in sick children, and may influence fluid therapy. We examined the frequency of blood sodium perturbations, and factors and outcomes associated with hyponatremia in children admitted to a rural Kenyan hospital and investigated the risk factors associated with deaths in hyponatremic children. METHODS: Plasma sodium levels and other laboratory parameters were measured in children admitted to a rural Kenyan hospital. Clinical measurements were collected using standard forms and entered into a computer database. The proportion of children admitted with hyponatremia was determined. Logistic regression models were used to investigate factors associated with hyponatremia, and death in those with hyponatremia. RESULTS: Abnormal plasma sodium occurred in 46.6% (95% confidence interval (95%CI) 43.5-49.6%) of 1026 pediatric admissions. Hyponatremia occurred in 44.4% (95%CI 41.4-47.5%) and hypernatremia in 2.1% (95%CI 1.3-3.0%). Malaria (40.8%) was the most common underlying primary diagnosis in hyponatremic children. Malaria, hyperglycemia, wasting, high creatinine levels and preserved consciousness were associated with hyponatremia. Pallor and seizures were associated with increased mortality in hyponatremic children. CONCLUSIONS: Sodium disturbances are common in pediatric admissions to a County hospital in rural Kenya. Seizures and pallor were predictors of mortality in hyponatremic children.

Factors influencing the utilization of focused antenatal care services in Malindi and Magarini sub-counties of Kilifi county, Kenya.

INTRODUCTION: Globally, pregnancy related complications contribute to more than half of the deaths among women annually. Antenatal care (ANC) is important for the prevention of maternal and fetal mortality and morbidity. This study identifies the socio-demographic and economic characteristics; knowledge and attitude and; health service provision for focused antenatal care (FANC) services. METHODS: A cross-sectional comparative study conducted among 385 women of reproductive age who visited 5 public health facilities in Malindi and Magarini Sub Counties. Data collection was conducted between June 2013 and September 2013 through structured questionnaires, Key Informant Interviews (KIIs) and Focused Group Discussions (FGDs) and analyzed through descriptive summary statistics and test of associations of the various variables using chi square. RESULTS: About 35% of women sought 1st and 2nd ANC services at the health facilities. These women went ahead to complete the recommended 4 minimum visits as recommended by World Health Organization (WHO). Compared to Catholics, Muslims were less likely to attend a rural health facility (Odds ratio (OR) = 0.25, 95% Confidence Interval (CI) 0.10, 0.62, p=0.003). According to education levels, those with secondary (OR=0.07, 95% CI 0.03, 0.18, p<0.001) or tertiary (OR=0.09, 95% CI 0.03-0.17, p<0.001) levels of education were less likely to seek FANC at rural facility. Women seeking rural ANC services started at 2nd or 3rd trimester (OR=5.40 95% CI 2.97-10.06, p<0.001) while those in urban setup start at 1st trimester. Among the women who were aware of FANC, only 27% utilized its services. Long waiting hours, unavailability of services, and departmental disharmony were major causes of dissatisfaction to mothers visiting the facilities. CONCLUSION: Utilization and awareness of FANC services in both rural and urban health facilities among women in Malindi and Magarini Sub Counties continues to be low which is associated by socio-demographic characteristics, and health facility inefficiencies. Thus there is need to standardize services across health facilities and increase awareness on FANC in both rural and urban.

Differing Methods and Definitions Influence DALY estimates: Using Population-Based Data to Calculate the Burden of Convulsive Epilepsy in Rural South Africa.

BACKGROUND: The disability adjusted life year (DALY) is a composite measure of disease burden that includes both morbidity and mortality, and is relevant to conditions such as epilepsy that can limit productive functioning. The 2010 Global Burden of Disease (GBD) study introduced a number of new methods and definitions, including a prevalence-based approach and revised disability weights to calculate morbidity and new standard life expectancies to calculate premature mortality. We used these approaches, and local, population-based data, to estimate the burden of convulsive epilepsy in rural South Africa. METHODS & FINDINGS: Comprehensive prevalence, incidence and mortality data on convulsive epilepsy were collected within the Agincourt sub-district in rural northeastern South Africa between 2008 and 2012. We estimated DALYs using both prevalence- and incidence-based approaches for calculating years of life lived with disability. Additionally, we explored how changing the disease model by varying the disability weights influenced DALY estimates. Using the prevalence-based approach, convulsive epilepsy in Agincourt resulted in 332 DALYs (95% uncertainty interval (UI): 216-455) and 4.1 DALYs per 1,000 individuals (95%UI: 2.7-5.7) annually. Of this, 26% was due to morbidity while 74% was due to premature mortality. DALYs increased by 10% when using the incidence-based method. Varying the disability weight from 0.072 (treated epilepsy, seizure free) to 0.657 (severe epilepsy) caused years lived with disability to increase from 18 (95%UI: 16-19) to 161 (95%UI: 143-170). CONCLUSIONS: DALY estimates are influenced by both the methods applied and population parameters used in the calculation. Irrespective of method, a significant burden of epilepsy is due to premature mortality in rural South Africa, with a lower burden than rural Kenya. Researchers and national policymakers should carefully interrogate the methods and data used to calculate DALYs as this will influence policy priorities and resource allocation.

Incidence, Remission and Mortality of Convulsive Epilepsy in Rural Northeast South Africa.

BACKGROUND: Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. METHODS: A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package. RESULTS: The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4)). CONCLUSIONS: The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.

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.

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

OBJECTIVE: 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. METHODS: We studied children and adults admitted to a Kenyan rural hospital, between January 2003 and December 2011, with a diagnosis of epilepsy. Poisson regression was used to compute incidence and rate ratios, logistic regression to determine associated factors, and the DALY package of the R-statistical software to calculate years lived with disability (YLD) and years of life lost (YLL). RESULTS: The overall incidence of admissions was 45.6/100,000 person-years of observation (PYO) (95% confidence interval [95% CI] 43.0-48.7) and decreased with age (p < 0.001). The overall DALYs were 3.1/1,000 (95% CI, 1.8-4.7) PYO and comprised 55% of YLD. Factors associated with hospitalization were use of antiepileptic drugs (AEDs) (odds ratio [OR] 5.36, 95% CI 2.64-10.90), previous admission (OR 11.65, 95% CI 2.65-51.17), acute encephalopathy (OR 2.12, 95% CI 1.07-4.22), and adverse perinatal events (OR 2.87, 95% CI 1.06-7.74). Important causes of admission were epilepsy-related complications: convulsive status epilepticus (CSE) (38%), and postictal coma (12%). Age was independently associated with prolonged hospital stay (OR 1.02, 95% CI 1.00-1.04) and mortality (OR, 1.07, 95% CI 1.04-1.10). SIGNIFICANCE: Epilepsy is associated with significant number of admissions to hospital, considerable duration of admission, and mortality. Improved supply of AEDs in the community, early initiation of treatment, and adherence would reduce hospitalization of PWE and thus the burden of epilepsy on the health system.

Burden of epilepsy in rural Kenya measured in disability-adjusted life years.

OBJECTIVES: The burden of epilepsy, in terms of both morbidity and mortality, is likely to vary depending on the etiology (primary [genetic/unknown] vs. secondary [structural/metabolic]) and with the use of antiepileptic drugs (AEDs). We estimated the disability-adjusted life years (DALYs) and modeled the remission rates of active convulsive epilepsy (ACE) using epidemiologic data collected over the last decade in rural Kilifi, Kenya. METHODS: We used measures of prevalence, incidence, and mortality to model the remission of epilepsy using disease-modeling software (DisMod II). DALYs were calculated as the sum of Years Lost to Disability (YLD) and Years of Life Lost (YLL) due to premature death using the prevalence approach, with disability weights (DWs) from the 2010 Global Burden of Disease (GBD) study. DALYs were calculated with R statistical software with the associated uncertainty intervals (UIs) computed by bootstrapping. RESULTS: A total of 1,005 (95% UI 797-1,213) DALYs were lost to ACE, which is 433 (95% UI 393-469) DALYs lost per 100,000 people. Twenty-six percent (113/100,000/year, 95% UI 106-117) of the DALYs were due to YLD and 74% (320/100,000/year, 95% UI 248-416) to YLL. Primary epilepsy accounted for fewer DALYs than secondary epilepsy (98 vs. 334 DALYs per 100,000 people). Those taking AEDs contributed fewer DALYs than those not taking AEDs (167 vs. 266 DALYs per 100,000 people). The proportion of people with ACE in remission per year was estimated at 11.0% in males and 12.0% in females, with highest rates in the 0-5 year age group. SIGNIFICANCE: The DALYs for ACE are high in rural Kenya, but less than the estimates of 2010 GBD study. Three-fourths of DALYs resulted from secondary epilepsy. Use of AEDs was associated with 40% reduction of DALYs. Improving adherence to AEDs may reduce the burden of epilepsy in this area.

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.

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.