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.

Abnormal intra-aural pressure waves associated with death in African children with acute nontraumatic coma.

BACKGROUND: We explored the relationship between tympanic membrane displacement (TMD) measurements, a tool to monitor intracranial pressure noninvasively, and clinical features and death in children with acute coma in Kilifi, Kenya. METHODS: Between November 2007 and September 2009, we made serial TMD measurements and clinical observations on children with acute coma (Blantyre coma score (BCS) ≤ 2) on the pediatric high dependency unit of Kilifi District Hospital, and on well children presenting to the hospital's outpatient department for routine follow-up. We examined middle ear function using tympanometry and measured cardiac pulse (CPA) and respiratory pulse pressure amplitudes (RPA) using the TMD analyzer. RESULTS: We recruited 75 children (32 (43%) females; median age 3.3 (IQR: 2.0, 4.3) years). Twenty-one (28%) children died. Higher TMD measurements predicted death. Adjusting for diagnosis, every 50 nl rise in both semirecumbent and recumbent CPA was associated with increased odds of death associated with intracranial herniation (OR: 1.61, 95% confidence interval (CI): 1.07, 2.41; P = 0.02 and OR: 1.35, 95% CI: 1.10, 1.66; P ≤ 0.01 respectively). CONCLUSION: Raised TMD pulse pressure measurements are associated with death and may be useful in detecting and monitoring risk of intracranial herniation and intracranial pressure in childhood coma.

Value of Plasmodium falciparum histidine-rich protein 2 level and malaria retinopathy in distinguishing cerebral malaria from other acute encephalopathies in Kenyan children.

BACKGROUND: The diagnosis of cerebral malaria is problematic in malaria-endemic areas because encephalopathy in patients with parasitemia may have another cause. Abnormal retinal findings are thought to increase the specificity of the diagnosis, and the level of histidine-rich protein 2 (HRP2) may reflect the parasite biomass. METHODS: We examined the retina and measured plasma HRP2 levels in children with acute nontraumatic encephalopathy in Kenya. Logistic regression, with HRP2 level as an independent variable and World Health Organization-defined cerebral malaria and/or retinopathy as the outcome, was used to calculate malaria-attributable fractions (MAFs) and retinopathy-attributable fractions (RAFs). RESULTS: Of 270 children, 140 (52%) had peripheral parasitemia, 80 (30%) had malaria retinopathy, and 164 (61%) had an HRP2 level of >0 U/mL. During 2006-2011, the incidence of HRP2 positivity among admitted children declined by 49 cases per 100 000 per year (a 78% reduction). An HRP2 level of >0 U/mL had a MAF of 93% for cerebral malaria, with a MAF of 97% observed for HRP2 levels of ≥ 10 U/mL (the level of the best combined sensitivity and specificity). HRP2 levels of >0 U/mL had a RAF of 77% for features of retinopathy combined, with the highest RAFs for macular whitening (99%), peripheral whitening (98%), and hemorrhages (90%). CONCLUSION: HRP2 has a high attributable fraction for features of malarial retinopathy, supporting its use in the diagnosis of cerebral malaria. HRP2 thresholds improve the specificity of the definition.

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.

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

PURPOSE: 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. METHODS: We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. KEY FINDINGS: Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. SIGNIFICANCE: There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed.

The validation of a three-stage screening methodology for detecting active convulsive epilepsy in population-based studies in health and demographic surveillance systems.

BACKGROUND: There are few studies on the epidemiology of epilepsy in large populations in Low and Middle Income Countries (LMIC). Most studies in these regions use two-stage population-based screening surveys, which are time-consuming and costly to implement in large populations required to generate accurate estimates. We examined the sensitivity and specificity of a three-stage cross-sectional screening methodology in detecting active convulsive epilepsy (ACE), which can be embedded within on-going census of demographic surveillance systems.We validated a three-stage cross-sectional screening methodology on a randomly selected sample of participants of a three-stage prevalence survey of epilepsy. Diagnosis of ACE by an experienced clinician was used as 'gold standard'. We further compared the expenditure of this method with the standard two-stage methodology. RESULTS: We screened 4442 subjects in the validation and identified 35 cases of ACE. Of these, 18 were identified as false negatives, most of whom (15/18) were missed in the first stage and a few (3/18) in the second stage of the three-stage screening. Overall, this methodology had a sensitivity of 48.6% and a specificity of 100%. It was 37% cheaper than a two-stage survey. CONCLUSION: This was the first study to evaluate the performance of a multi-stage screening methodology used to detect epilepsy in demographic surveillance sites. This method had poor sensitivity attributed mainly to stigma-related non-response in the first stage. This method needs to take into consideration the poor sensitivity and the savings in expenditure and time as well as validation in target populations. Our findings suggest the need for continued efforts to develop and improve case-ascertainment methods in population-based epidemiological studies of epilepsy in LMIC.

Behavioral problems in children with epilepsy in rural Kenya.

The aims of this study were to record behavioral problems in children with epilepsy (CWE), compare the prevalence with that reported among healthy children without epilepsy, and investigate the risk factors. A child behavioral questionnaire for parents comprising 15 items was administered to the main caregiver of 108 CWE and 108 controls matched for age in Kilifi, Kenya. CWE had a higher mean score for reported behavioral problems than controls (6.9 vs 4.9, t=4.7, P<0.001). CWE with active epilepsy also recorded more behavioral problems than those with inactive epilepsy (8.2 vs 6.2, t=-2.9, P=0.005). A significantly greater proportion of CWE (49% vs 26% of controls) were reported to have behavioral problems. Active epilepsy, cognitive impairment, and focal seizures were the most significant independent covariates of behavioral problems. Behavioral problems in African CWE are common and need to be taken into consideration in planning comprehensive clinical services in this region.

Prevalence and mortality of epilepsies with convulsive and non-convulsive seizures in Kilifi, Kenya.

OBJECTIVES: The prevalence of all epilepsies (both convulsive and non-convulsive seizures) in Low- and Middle-Income Countries (LMIC), particularly sub-Saharan Africa is unknown. Under estimation of non-convulsive epilepsies in data from these countries may lead to inadequate and sub-optimal allocation of resources to control and prevent epilepsy. We determined the prevalence of all types of epilepsies and compared the mortality between convulsive seizures and non-convulsive seizures in a resource limited rural area in Kenya. METHODS: Trained clinicians identified cases of epilepsy in a randomly selected sample of 4,441 residents in the Kilifi Health and Demographic Surveillance System site using a cross-sectional survey design. Seizure types were classified by epileptologists using the current guidelines of the International League Against Epilepsy (ILAE). We estimated prevalence for epilepsy with convulsive seizures and non-convulsive seizures and for epilepsy with non-convulsive seizures only and compared premature mortality between these groups of seizures. RESULTS: Of the 4441 people visited, 141 had lifetime epilepsy and 96 active epilepsy, which is a crude prevalence of 31.7/1,000 persons (95% CI: 26.6-36.9) and 21.6/1,000 (95% CI: 17.3-25.9), respectively. Both convulsive and non-convulsive seizures occurred in 7% people with epilepsy (PWE), only convulsive seizures in 52% and only non-convulsive seizures in 35% PWE; there was insufficient information to classify epilepsy in the remainder 6%. The age- and sex-adjusted prevalence of lifetime people was 23.5/1,000 (95% CI: 11.0-36.0), with the adjusted prevalence of epilepsy with non-convulsive seizures only estimated at 8.2/1,000 (95%CI:3.9-12.6). The mortality rate in PWE was 6.3/1,000 (95%CI: 3.4-11.8), compared to 2.8/1,000 (2.3-3.3) in those without epilepsy; hazard ratio (HR) =2.31 (1.22-4.39; p=0.011). The annual mortality rate was 11.2/1,000 (95%CI: 5.3-23.4) in PWE with convulsive and non-convulsive seizures and none died in PWE with non-convulsive seizures alone. CONCLUSIONS: Our study shows that epilepsy with non-convulsive seizures is common and adds to the prevalence of previously reported estimates of active convulsive epilepsy. Both epilepsy with convulsive seizures and that with non-convulsive seizures should be identified for optimising treatment and for planning resource allocation.

Clinical and neurophysiologic features of active convulsive epilepsy in rural Kenya: a population-based study.

PURPOSE: Epilepsy is common in sub-Saharan Africa but is poorly characterized. Most studies are hospital-based, and may not reflect the situation in rural areas with limited access to medical care. We examined people with active convulsive epilepsy (ACE), to determine if the clinical features could help elucidate the causes. METHODS: We conducted a detailed descriptive analysis of 445 people with ACE identified through a community-based survey of 151,408 people in rural Kenya, including the examination of electroencephalograms. RESULTS: Approximately half of the 445 people with ACE were children aged 6 to 18 years. Seizures began in childhood in 78% of those diagnosed. An episode of status epilepticus was recalled by 36% cases, with an episode of status epilepticus precipitated by fever in 26%. Overall 169 had an abnormal electroencephalogram, 29% had focal features, and 34% had epileptiform activity. In the 146 individuals who reported generalized tonic-clonic seizures only, 22% had focal features on their electroencephalogram. Overall 71% of patients with ACE had evidence of focal abnormality, documented by partial onset seizures, focal neurologic deficits, or focal abnormalities on the electroencephalogram. Increased seizure frequency was strongly associated with age and cognitive impairment in all ages and nonattendance at school in children (p < 0.01). DISCUSSION: Children and adolescents bear the brunt of epilepsy in a rural population in Africa. The predominance of focal features and the high proportion of patients with status epilepticus, suggests that much of the epilepsy in this region has identifiable causes, many of which could be prevented.

An overview of mental health care system in Kilifi, Kenya: results from an initial assessment using the World Health Organization's Assessment Instrument for Mental Health Systems.

BACKGROUND: Little is known about the state of mental health systems in Kenya. In 2010, Kenya promulgated a new constitution, which devolved national government and the national health system to 47 counties including Kilifi County. There is need to provide evidence from mental health systems research to identify priority areas in Kilifi's mental health system for informing county health sector decision making. We conducted an initial assessment of state of mental health systems in Kilifi County and documented resources, policy and legislation and spectrum of mental, neurological and substance use disorders. METHODS: This was a pilot study that used the brief version of the World Health Organization's Assessment Instrument for Mental Health Systems Version 2.2 to collect data. Data collection was based on the year 2014. RESULTS: Kilifi county has two public psychiatric outpatient units that are part of general hospitals. There is no standalone mental hospital in Kilifi. There are no inpatients or community based facilities for people with mental health problems. Although the psychiatric facilities in Kilifi have an essential drugs list, supply of drugs is erratic with frequent shortages. There is no psychiatrist or psychologist in Kilifi with only two psychiatric nurses for a population of approximately 1.2 million people. Schizophrenia was the commonest reason for visiting outpatient facilities (47.1%) while suicidal ideation was the least common (0.4%). Kenya's mental health policy, which is being used by Kilifi County, is outdated and does not cater for the current mental health needs of Kilifi. There is no specific legislation to protect the rights of people with mental health problems. No budget exists specifically for mental health care. There have been no efforts to integrate mental health care into primary care in Kilifi, and there is no empirical research work to evaluate its feasibility. CONCLUSION: There is an urgent need to increase resources allocated for mental health in particular infrastructure and human resource. Policy and legislations need to be established to protect the rights of people with mental illnesses, and mental health should be integrated with primary care to increase access to services.

Adverse perinatal events, treatment gap, and positive family history linked to the high burden of active convulsive epilepsy in Uganda: A population-based study.

Objective: To determine the prevalence of active convulsive epilepsy (ACE) and describe the clinical characteristics and associated factors among a rural Ugandan population. Methods: The entire population in Iganga/Mayuge Health Demographic Surveillance Site (IM-HDSS) was screened using two questions about seizures during a door-to-door census exercise. Those who screened positive were assessed by a clinician to confirm diagnosis of epilepsy. A case control study with the patients diagnosed with ACE as the cases and age/sex-matched controls in a ratio of 1:1 was conducted. Results: A total of 64,172 (92.8%) IM-HDSS residents, with a median age of 15.0 years (interquartile range [IQR]: 8.0-29.0), were screened for epilepsy. There were 152 confirmed ACE cases, with a prevalence of 10.3/1,000 (95% confidence interval [CI]: 9.5-11.1) adjusted for nonresponse and screening sensitivity. Prevalence declined with age, with the highest prevalence in the 0-5 years age group. In an analysis of n = 241 that included cases not identified in the survey, nearly 70% were unaware of their diagnosis. Seizures were mostly of focal onset in 193 (80%), with poor electroencephalogram (EEG) agreement with seizure semiology. Antiepileptic drug use was rare, noted in 21.2% (95% CI: 16.5-25.8), and 119 (49.3%) reported using traditional medicines. History of an abnormal antenatal period (adjusted odds ratio [aOR] 10.28; 95%CI 1.26-83.45; p = 0.029) and difficulties in feeding, crying, breathing in the perinatal period (aOR 10.07; 95%CI 1.24-81.97; p = 0.031) were associated with ACE in children. In adults a family history of epilepsy (aOR 4.38 95%CI 1.77-10.81; p = 0.001) was the only factor associated with ACE. Significance: There is a considerable burden of epilepsy, low awareness, and a large treatment gap in this population of rural sub-Saharan Africa. The identification of adverse perinatal events as a risk factor for developing epilepsy in children suggests that epilepsy burden may be decreased by improving obstetric and postnatal care.

Electroencephalographic features of convulsive epilepsy in Africa: A multicentre study of prevalence, pattern and associated factors.

OBJECTIVE: We investigated the prevalence and pattern of electroencephalographic (EEG) features of epilepsy and the associated factors in Africans with active convulsive epilepsy (ACE). METHODS: We characterized electroencephalographic features and determined associated factors in a sample of people with ACE in five African sites. Mixed-effects modified Poisson regression model was used to determine factors associated with abnormal EEGs. RESULTS: Recordings were performed on 1426 people of whom 751 (53%) had abnormal EEGs, being an adjusted prevalence of 2.7 (95% confidence interval (95% CI), 2.5-2.9) per 1000. 52% of the abnormal EEG had focal features (75% with temporal lobe involvement). The frequency and pattern of changes differed with site. Abnormal EEGs were associated with adverse perinatal events (risk ratio (RR)=1.19 (95% CI, 1.07-1.33)), cognitive impairments (RR=1.50 (95% CI, 1.30-1.73)), use of anti-epileptic drugs (RR=1.25 (95% CI, 1.05-1.49)), focal seizures (RR=1.09 (95% CI, 1.00-1.19)) and seizure frequency (RR=1.18 (95% CI, 1.10-1.26) for daily seizures; RR=1.22 (95% CI, 1.10-1.35) for weekly seizures and RR=1.15 (95% CI, 1.03-1.28) for monthly seizures)). CONCLUSIONS: EEG abnormalities are common in Africans with epilepsy and are associated with preventable risk factors. SIGNIFICANCE: EEG is helpful in identifying focal epilepsy in Africa, where timing of focal aetiologies is problematic and there is a lack of neuroimaging services.

Prevalence and factors associated with convulsive status epilepticus in Africans with epilepsy.

OBJECTIVE: We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. METHODS: We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. RESULTS: The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died. CONCLUSIONS: CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE.

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.

Long-term survival and outcome in children admitted to kilifi district hospital with convulsive status epilepticus.

Objectives. The incidence of convulsive status epilepticus (CSE) is high in Africa but the long-term outcome is unknown. We examined the neurocognitive outcome and survival of children treated for CSE in a Kenyan hospital 3 to 4 years after discharge. Methods. The frequency and nature of neurological deficits among this group of children were determined and compared to a control group. The children were screened with the Ten Questions Questionnaire for neurodevelopmental impairment if alive and those that screened positive were invited for further assessment to determine the pattern and extent of their impairment. A verbal autopsy was performed to determine the cause of death in those that died. Results. In the 119 cases followed-up, 9 (8%) died after discharge, with the majority having seizures during their fatal illness. The 110 survivors (median age 5 years) had significantly more neurological impairments on the screening compared to 282 controls (34/110 (30.9%) versus 11/282 (3.9%), OR = 11.0, 95% CI 5.3-22.8). Fifteen percent of the cases had active epilepsy. Conclusions. This study demonstrates the considerable burden of CSE in African children. Strategies to manage children with CSE that are acceptable to the community need to be explored to improve the longer-term outcome.

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.

Unexpected relationship between tympanometry and mortality in children with nontraumatic coma.

OBJECTIVE: We sought to further examine the relationship between tympanometry and mortality after noting an unexpected association on assessment of baseline data of a study whose primary aim was to investigate the utility of noninvasive tympanic membrane displacement measurement for monitoring intracranial pressure in childhood coma. METHODS: We recruited children who presented with acute nontraumatic coma to the high-dependency unit of Kilifi District Hospital on the rural coast of Kenya. We excluded children with sickle cell disease, epilepsy, and neurodevelopmental delay. We performed tympanometry on the right ear before tympanic membrane displacement analyzer measurements. All children were managed according to standard World Health Organization guidelines. RESULTS: We recruited 72 children with a median age of 3.2 years (interquartile range [IQR]: 2.0-4.3 years); 31 (43%) were female. Thirty-eight (53%) had cerebral malaria, 8 (11%) acute bacterial meningitis, 4 (6%) sepsis, and 22 (30%) encephalopathy of unknown etiology. Twenty (28%) children died. Tympanometry was normal in 25 (35%) children. Adjusting for diagnosis and clinical features of increased intracranial pressure, both associated with death on univariable analysis, children with abnormal tympanometry had greater odds of dying than did those with normal tympanometry (adjusted odds ratio: 17.0; 95% confidence interval: 1.9-152.4; P = .01). Children who died had a lower compliance (0.29 mL; IQR: 0.09-0.33 mL) compared with those who survived (0.48 mL; IQR: 0.29-0.70 mL) (P < .01). CONCLUSIONS: Abnormal tympanometry appears to be significantly associated with death in children with acute nontraumatic coma. This finding needs to be explored further through a prospective study that incorporates imaging and intensive physiologic monitoring.

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

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 centre's 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.

Fosphenytoin for seizure prevention in childhood coma in Africa: a randomized clinical trial.

PURPOSE: We conducted a double-blind trial to determine whether a single intramuscular injection of fosphenytoin prevents seizures and neurologic sequelae in children with acute coma. METHODS: We conducted this study at Kilifi District Hospital in coastal Kenya and Kondele Children's Hospital in western Kenya. We recruited children (age, 9 months to 13 years) with acute nontraumatic coma. We administered fosphenytoin (20 phenytoin equivalents/kg) or placebo and examined the prevalence and frequency of clinical seizures and occurrence of neurocognitive sequelae. RESULTS: We recruited 173 children (median age, 2.6 [interquartile range, 1.7-3.7] years) into the study; 110 had cerebral malaria, 8 had bacterial meningitis, and 55 had encephalopathies of unknown etiology. Eighty-five children received fosphenytoin and 88 received placebo. Thirty-three (38%) children who received fosphenytoin had at least 1 seizure compared with 32 (36%) who received placebo (P = .733). Eighteen (21%) and 15 (17%) children died in the fosphenytoin and placebo arms, respectively (P = .489). At 3 months after discharge, 6 (10%) children in the fosphenytoin arm had neurologic sequelae compared with 6 (10%) in the placebo arm (P = .952). CONCLUSION: A single intramuscular injection of fosphenytoin (20 phenytoin equivalents/kg) does not prevent seizures or neurologic deficits in childhood acute nontraumatic coma.