Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.

Magnetic resonance imaging findings in Kenyans and South Africans with active convulsive epilepsy: An observational study.

OBJECTIVE: Focal epilepsy is common in low- and middle-income countries. The frequency and nature of possible underlying structural brain abnormalities have, however, not been fully assessed. METHODS: We evaluated the possible structural causes of epilepsy in 331 people with epilepsy (240 from Kenya and 91 from South Africa) identified from community surveys of active convulsive epilepsy. Magnetic resonance imaging (MRI) scans were acquired on 1.5-Tesla scanners to determine the frequency and nature of any underlying lesions. We estimated the prevalence of these abnormalities using Bayesian priors (from an earlier pilot study) and observed data (from this study). We used a mixed-effect modified Poisson regression approach with the site as a random effect to determine the clinical features associated with neuropathology. RESULTS: MRI abnormalities were found in 140 of 240 (modeled prevalence = 59%, 95% confidence interval [CI]: 53%-64%) of people with epilepsy in Kenya, and in 62 of 91 (modeled prevalence = 65%, 95% CI: 57%-73%) in South Africa, with a pooled modeled prevalence of 61% (95% CI: 56%-66%). Abnormalities were common in those with a history of adverse perinatal events (15/23 [65%, 95% CI: 43%-84%]), exposure to parasitic infections (83/120 [69%, 95% CI: 60%-77%]) and focal electroencephalographic features (97/142 [68%, 95% CI: 60%-76%]), but less frequent in individuals with generalized electroencephalographic features (44/99 [44%, 95% CI: 34%-55%]). Most abnormalities were potentially epileptogenic (167/202, 82%), of which mesial temporal sclerosis (43%) and gliosis (34%) were the most frequent. Abnormalities were associated with co-occurrence of generalized non-convulsive seizures (relative risk [RR] = 1.12, 95% CI: 1.04-1.25), lack of family history of seizures (RR = 0.91, 0.86-0.96), convulsive status epilepticus (RR = 1.14, 1.08-1.21), frequent seizures (RR = 1.12, 1.04-1.20), and reported use of anti-seizure medication (RR = 1.22, 1.18-1.26). SIGNIFICANCE: MRI identified pathologies are common in people with epilepsy in Kenya and South Africa. Mesial temporal sclerosis, the most common abnormality, may be amenable to surgical correction. MRI may have a diagnostic value in rural Africa, but future longitudinal studies should examine the prognostic role.

Relationships between trauma types and psychotic symptoms: A network analysis of patients with psychotic disorders in a large, multi-country study in East Africa.

BACKGROUND: The link between trauma exposure and psychotic disorders is well-established. Further, specific types of trauma may be associated with specific psychotic symptoms. Network analysis is an approach that can advance our understanding of the associations across trauma types and psychotic symptoms. METHODS: We conducted a network analysis with data from 16,628 adult participants (mean age [standard deviation] = 36.3 years [11.5]; 55.8% males) with psychotic disorders in East Africa recruited between 2018 and 2023. We used the Life Events Checklist and the Mini International Neuropsychiatric Interview to determine whether specific trauma types experienced over the life course and specific psychotic symptoms were connected. We used an Ising model to estimate the network connections and bridge centrality statistics to identify nodes that may influence trauma types and psychotic symptoms. RESULTS: The trauma type "exposure to a war zone" had the highest bridge strength, betweenness, and closeness. The psychotic symptom "odd or unusual beliefs" had the second highest bridge strength. Exposure to a war zone was directly connected to visual hallucinations, odd or unusual beliefs, passivity phenomena, and disorganized speech. Odd or unusual beliefs were directly connected to transportation accidents, physical assault, war, and witnessing sudden accidental death. CONCLUSION: Specific trauma types and psychotic symptoms may interact bidirectionally. Screening for psychotic symptoms in patients with war-related trauma and evaluating lifetime trauma in patients with odd or unusual beliefs in clinical care may be considered points of intervention to limit stimulating additional psychotic symptoms and trauma exposure. This work reaffirms the importance of trauma-informed care for patients with psychotic disorders.

Psychometric properties of the mini international neuropsychiatric interview (MINI) psychosis module: a Sub-Saharan Africa cross country comparison.

BACKGROUND: The Mini International Neuropsychiatric Inventory 7.0.2 (MINI-7) is a widely used tool and known to have sound psychometric properties; but very little is known about its use in low and middle-income countries (LMICs). This study aimed to examine the psychometric properties of the MINI-7 psychosis items in a sample of 8609 participants across four countries in Sub-Saharan Africa. METHODS: We examined the latent factor structure and the item difficulty of the MINI-7 psychosis items in the full sample and across four countries. RESULTS: Multiple group confirmatory factor analyses (CFAs) revealed an adequate fitting unidimensional model for the full sample; however, single group CFAs at the country level revealed that the underlying latent structure of psychosis was not invariant. Specifically, although the unidimensional structure was an adequate model fit for Ethiopia, Kenya, and South Africa, it was a poor fit for Uganda. Instead, a 2-factor latent structure of the MINI-7 psychosis items provided the optimal fit for Uganda. Examination of item difficulties revealed that MINI-7 item K7, measuring visual hallucinations, had the lowest difficulty across the four countries. In contrast, the items with the highest difficulty were different across the four countries, suggesting that MINI-7 items that are the most predictive of being high on the latent factor of psychosis are different for each country. CONCLUSIONS: The present study is the first to provide evidence that the factor structure and item functioning of the MINI-7 psychosis vary across different settings and populations in Africa.

Scoping review and expert-based consensus recommendations for assessment and management of psychogenic non-epileptic (functional) seizures (PNES) in children: A report from the Pediatric Psychiatric Issues Task Force of the International League Against Epilepsy.

Limited guidance exists regarding the assessment and management of psychogenic non-epileptic seizures (PNES) in children. Our aim was to develop consensus-based recommendations to fill this gap. The members of the International League Against Epilepsy (ILAE) Task Force on Pediatric Psychiatric Issues conducted a scoping review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SR) standards. This was supplemented with a Delphi process sent to pediatric PNES experts. Consensus was defined as ≥80% agreement. The systematic search identified 77 studies, the majority (55%) of which were retrospective (only one randomized clinical trial). The primary means of PNES identification was video electroencephalography (vEEG) in 84% of studies. Better outcome was associated with access to counseling/psychological intervention. Children with PNES have more frequent psychiatric disorders than controls. The Delphi resulted in 22 recommendations: Assessment-There was consensus on the importance of (1) taking a comprehensive developmental history; (2) obtaining a description of the events; (3) asking about potential stressors; (4) the need to use vEEG if available parent, self, and school reports and video recordings can contribute to a "probable" diagnosis; and (5) that invasive provocation techniques or deceit should not be employed. Management-There was consensus about the (1) need for a professional with expertise in epilepsy to remain involved for a period after PNES diagnosis; (2) provision of appropriate educational materials to the child and caregivers; and (3) that the decision on treatment modality for PNES in children should consider the child's age, cognitive ability, and family factors. Comorbidities-There was consensus that all children with PNES should be screened for mental health and neurodevelopmental difficulties. Recommendations to facilitate the assessment and management of PNES in children were developed. Future directions to fill knowledge gaps were proposed.

Co-morbid mental health conditions in people with epilepsy and association with quality of life in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Comorbid mental health conditions are common in people with epilepsy and have a significant negative impact on important epilepsy outcomes, although the evidence is mostly from high-income countries. This systematic review aimed to synthesise evidence on the association between comorbid mental health conditions and quality of life and functioning among people with epilepsy living in low- and middle income countries (LMICs). METHODS: We searched PubMed, EMBASE, CINAHL, Global Index medicus (GID) and PsycINFO databases from their dates of inception to January 2022. Only quantiative observational studies were included. Meta-analysis was conducted for studies that reported the same kind of quality of life and functioning outcome. Cohen's d was calculated from the mean difference in quality-of-life score between people with epilepsy who did and did not have a comorbid depression or anxiety condition. The protocol was registered with PROSPERO: CRD42020161487. RESULTS: The search strategy identified a total of 2,101 articles, from which 33 full text articles were included. Depression was the most common comorbid mental health condition (33 studies), followed by anxiety (16 studies). Meta-analysis was conducted on 19 studies reporting quality of life measured with the same instrument. A large standardized mean effect size (ES) in quality of life score was found (pooled ES = -1.16, 95% confidence interval (CI) - 1.70, - 0.63) between those participants with comorbid depression compared to non-depressed participants. There was significant heterogeneity between studies (I2 = 97.6%, p < 0.001). The median ES (IQR) was - 1.20 (- 1.40, (- 0.64)). An intermediate standard effect size for anxiety on quality of life was also observed (pooled ES = -0.64, 95% CI - 1.14, - 0.13). There was only one study reporting on functioning in relation to comorbid mental health conditions. CONCLUSION: Comorbid depression in people with epilepsy in LMICs is associated with poor quality of life although this evidence is based on highly heterogeneous studies. These findings support calls to integrate mental health care into services for people with epilepsy in LMICs. Future studies should use prospective designs in which the change in quality of life in relation to mental health or public health interventions across time can be measured.

Risk of suicidality in mental and neurological disorders in low and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Both fatal and nonfatal suicidal behaviours are important complications of mental, neurological, and substance use disorders (MNSDs) worldwide. We aimed at quantifying the association of suicidal behaviour with MNSDs in Low and Middle Income Countries (LMICs) where varying environmental and socio-cultural factors may impact outcome. METHODS: We conducted a systematic review and meta-analysis to report the associations between MNSDs and suicidality in LMICs and the study-level factors of these associations. We searched the following electronic databases: PUBMED, PsycINFO, MEDLINE, CINAHL, World Cat, and Cochrane library for studies on suicide risk in MNSDs, with a comparison/control group of persons without MNSDs, published from January 1, 1995 to September 3, 2020. Median estimates were calculated for relative risks for suicide behaviour and MNSDs, and when appropriate, these were pooled using random effects metanalytic model. This study was registered with PROSPERO, CRD42020178772. RESULTS: The search identified 73 eligible studies: 28 were used for quantitative synthesis of estimates and 45 for description of risk factors. Studies included came from low and upper middle-income countries with a majority of these from Asia and South America and none from a low-income country. The sample size was 13,759 for MNSD cases and 11,792 hospital or community controls without MNSD. The most common MNSD exposure for suicidal behaviour was depressive disorders (47 studies (64%)), followed by schizophrenia spectrum, and other psychotic disorders (28 studies (38%)). Pooled estimates from the meta-analysis were statistically significant for suicidal behaviour with any MNSDs (odds ratios (OR) = 1∙98 (95%CI = 1∙80-2∙16))) and depressive disorder (OR = 3∙26 (95%CI = 2∙88-3∙63))), with both remaining significant after inclusion of high-quality studies only. Meta-regression identified only hospital-based studies (ratio of OR = 2∙85, CI:1∙24-6∙55) and sample size (OR = 1∙00, CI:0∙99-1∙00) as possible sources of variability in estimates. Risk for suicidal behaviour in MNSDs was increased by demographic factors (e.g., male sex, and unemployment), family history, psychosocial context and physical illness. INTERPRETATION: There is an association between suicidal behaviour and MNSDs in LMICs, the association is greater for depressive disorder in LMICs than what has been reported in High Income Countries (HICs). There is urgent need to improve access for MNSDs care in LMICs. FUNDING: None.

Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014-2018: A cohort study.

BACKGROUND: Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown and given the lack of diagnostic facilities in routine care it is possible that CHIKV is an unrecognized etiology among children with encephalitis or other neurological illness. METHODS AND FINDINGS: We estimated the incidence of CHIKV infection among children hospitalized with neurological disease in Kilifi County, coastal Kenya. We used reverse transcriptase polymerase chain reaction (RT-PCR) to systematically test for CHIKV in cerebrospinal fluid (CSF) samples from children aged <16 years hospitalized with symptoms of neurological disease at Kilifi County Hospital between January 2014 and December 2018. Clinical records were linked to the Kilifi Health and Demographic Surveillance System and population incidence rates of CHIKV infection estimated. There were 18,341 pediatric admissions for any reason during the 5-year study period, of which 4,332 (24%) had CSF collected. The most common clinical reasons for CSF collection were impaired consciousness, seizures, and coma (47%, 22%, and 21% of all collections, respectively). After acute investigations done for immediate clinical care, CSF samples were available for 3,980 admissions, of which 367 (9.2%) were CHIKV RT-PCR positive. Case fatality among CHIKV-positive children was 1.4% (95% CI 0.4, 3.2). The annual incidence of CHIKV-associated neurological disease varied between 13 to 58 episodes per 100,000 person-years among all children <16 years old. Among children aged <5 years, the incidence of CHIKV-associated neurological disease was 77 per 100,000 person-years, compared with 20 per 100,000 for cerebral malaria and 7 per 100,000 for bacterial meningitis during the study period. Because of incomplete case ascertainment due to children not presenting to hospital, or not having CSF collected, these are likely minimum estimates. Study limitations include reliance on hospital-based surveillance and limited CSF sampling in children in coma or other contraindications to lumbar puncture, both of which lead to under-ascertainment of incidence and of case fatality. CONCLUSIONS: In this study, we observed that CHIKV infections are relatively more common than cerebral malaria and bacterial meningitis among children hospitalized with neurological disease in coastal Kenya. Given the wide distribution of CHIKV mosquito vectors, studies to determine the geographic extent of CHIKV-associated neurological disease in Africa are essential.

Neurological impairment and disability in children in rural Kenya.

AIM: To investigate geographical change over time in the burden of neurological impairments in school-aged children in a demographic surveillance area. METHOD: We investigated changes in neurological impairment prevalence in five domains (epilepsy and cognitive, hearing, vision, and motor impairments) using similar two-phase surveys conducted in 2001 (n=10 218) and 2015 (n=11 223) and determined changes in location-level prevalence, geographical clustering, and significant risk factors for children aged 6 to 9 years (mean 7y 6mo, SD 1y) of whom 50.4% were males. Admission trends for preterm birth, low birthweight (LBW), and encephalopathy were determined using admission data to a local hospital. RESULTS: Overall prevalence for any neurological impairment decreased from 61 per 1000 (95% confidence interval [CI] 48.0-74.0) in 2001 to 44.7 per 1000 (95% CI 40.9-48.6) in 2015 (p<0.001). There was little evidence of geographical variation in the prevalence of neurological impairments in either survey. The association between neurological impairments and some risk factors changed significantly with year of survey; for example, the increased association of adverse perinatal events with hearing impairments (exponentiated coefficient for the interaction=5.94, p=0.03). Annual admission rates with preterm birth (rate ratio 1.08, range 1.07-1.09), LBW (rate ratio 1.08, range 1.06-1.10), and encephalopathy (rate ratio 1.08, range 1.06-1.09) significantly increased between 2005 and 2016 (p<0.001). INTERPRETATION: There was a significant decline in the prevalence of neurological impairments and differential changes in the associations of some risk factors with neurological impairments over the study period. Limited geographical variation suggests that similar interventions are appropriate across the defined area.

Prevalence, risk factors and behavioural and emotional comorbidity of acute seizures in young Kenyan children: a population-based study.

BACKGROUND: Acute symptomatic seizures and febrile seizures are common in children admitted to hospitals in Africa and may be markers of brain dysfunction. They may be associated with behavioural and emotional problems, but there are no published community-based studies in Africa. METHODS: We screened 7047 children aged 1-6 years (randomly sampled from 50,000 in the community) for seizures (using seven questions) and invited those who screened positive and a proportion of negatives for a clinical assessment. Risk factors were identified using a parental questionnaire. Behavioural and emotional problems were examined using the Child Behaviour Checklist (CBCL) in 3273 children randomly selected from 7047. Generalised linear models with appropriate link functions were used to determine risk factors and associations between behavioural or emotional problems and acute seizures. Sobel-Goodman mediation tests were used to investigate if the association between acute seizures and CBCL scores was mediated by co-diagnosis of epilepsy. RESULTS: Acute seizures were identified in 429 (6.1%) preschool children: 3.2% (95% confidence interval CI: 2.9-3.5%) for symptomatic seizures, and 2.9% (95% CI: 2.6-3.3%) for febrile seizures. Risk factors for acute seizures included family history of febrile seizures (odds ratio OR = 3.19; 95% CI: 2.03-5.01) and previous hospitalisation (OR = 6.65; 95% CI: 4.60-9.63). Total CBCL problems occurred more frequently in children with acute seizures (27%; 95% CI: 21-34%) than for those without seizures (11%; 95% CI: 11-12%; chi-squared p ≤ 0.001). Acute seizures were associated with total CBCL problems (adjusted risk ratio (aRR) = 1.92; 95% CI: 1.34-2.77), externalising problems (aRR = 1.82; 95% CI: 1.21-2.75) and internalising problems (aRR = 1.57; 95% CI: 1.22-2.02), with the proportion of the comorbidity mediated by a co-diagnosis of epilepsy being small (15.3%; 95% CI: 4.5-34.9%). Risk factors for this comorbidity included family history of febrile seizures (risk ratio (RR) = 3.36; 95% CI: 1.34-8.41), repetitive acute seizures (ß = 0.36; 95% CI: 0.15-0.57) and focal acute seizures (RR = 1.80; 95% CI: 1.05-3.08). CONCLUSIONS: Acute seizures are common in preschool children in this area and are associated with behavioural and emotional problems. Both conditions should be assessed and addressed in children.

Quality of antiepileptic drugs in sub-Saharan Africa: A study in Gabon, Kenya, and Madagascar.

OBJECTIVE: Epilepsy is a major public health issue in low- and middle-income countries, where the availability and accessibility of quality treatment remain important issues, the severity of which may be aggravated by poor quality antiepileptic drugs (AEDs). The primary objective of this study was to measure the quality of AEDs in rural and urban areas in 3 African countries. METHODS: This cross-sectional study was carried out in Gabon, Kenya, and Madagascar. Both official and unofficial supply chains in urban and rural areas were investigated. Samples of oral AEDs were collected in areas where a patient could buy or obtain them. Pharmacological analytical procedures and Medicine Quality Assessment Reporting Guidelines were used to assess quality. RESULTS: In total, 102 batches, representing 3782 units of AEDs, were sampled. Overall, 32.3% of the tablets were of poor quality, but no significant difference was observed across sites: 26.5% in Gabon, 37.0% in Kenya, and 34.1% in Madagascar (P = .7). The highest proportions of substandard medications were found in the carbamazepine (38.7%; 95% confidence interval [CI] 21.8-57.8) and phenytoin (83.3%; 95% CI 35.8-99.5) batches, which were mainly flawed by their failure to dissolve. Sodium valproate was the AED with the poorest quality (32.1%; 95% CI 15.8-42.3). The phenobarbital (94.1%; 95% CI 80.3-99.2) and diazepam (100.0%) batches were of better quality. The prevalence of substandard quality medications increased in samples supplied by public facilities (odds ratio [OR] 9.9; 95% CI 1.2-84.1; P < .04) and manufacturers located in China (OR 119.8; 95% CI 8.7-1651.9; P < .001). The prevalence of AEDs of bad quality increased when they were stored improperly (OR 5.4; 95% CI 1.2-24.1; P < .03). SIGNIFICANCE: No counterfeiting was observed. However, inadequate AED storage conditions are likely to lead to ineffective and possibly dangerous AEDs, even when good-quality AEDs are initially imported.

Cognition, mood and quality-of-life outcomes among low literacy adults living with epilepsy in rural Kenya: A preliminary study.

Epilepsy is frequently associated with neurocognitive impairments, mental health, and psychosocial problems but these are rarely documented in low- and middle-income countries. The aim of this study was to examine the neurocognitive outcomes, depressive symptoms, and psychosocial adjustments of people with epilepsy (PWE) in Kilifi, Kenya. We evaluated the impact of these outcomes on health-related quality of life. Self-report, interviewer-administered measures of depression (Major Depression Inventory) and quality of life (RAND SF-36) were administered to 63 PWE and 83 community controls. Neurocognitive functioning was assessed using Raven's Standard Progressive Matrices, Digit Span, and Contingency Naming Test. The results show that PWE have poorer scores for executive function, working memory, intelligence quotient (IQ), depression, and quality of life than controls. Twenty-seven (27%) of PWE had depressive symptoms, which was significantly greater than in controls (6%); P < 0.001. Quality-of-life scores were significantly lower in PWE with depressive symptoms than in those without depressive symptoms (Mean QoL scores (standard deviation (SD)): 46.43 (13.27) versus 64.18 (17.69); P = 0.01. On adjusted linear regression models, depression affected total quality-of-life scores (P = 0.07) as well as individual health indicator domains touching on pain (P = 0.04), lethargy/fatigue (P = 0.01), and emotional well-being (P = 0.02). Our results show that epilepsy is associated with a significant burden of mental health and neurocognitive impairments in the community; however, community-based studies are needed to provide precise estimates of these disorders.

Suicide in a rural area of coastal Kenya.

BACKGROUND: Suicide accounts for approximately 1.4% of deaths globally and is the 15th leading cause of death overall. There are no reliable data on the epidemiology of completed suicide in rural areas of many developing countries, yet suicide is an indicator of the sustainable development goals on health. METHODS: Using data collected between 2008 and 2016 from the Kilifi Health and Demographic Surveillance System in rural Kenya, we retrospectively determined the incidence rate and risk factors for completed suicide. RESULTS: During the period, 104 people died by suicide, contributing to 0.78% (95% CI = 0.74-1.10) of all deaths. The mean annual incidence rate of suicide was 4.61 (95% CI = 3.80-5.58) per 100,000 person years of observation (pyo). The annual incidence rate for men was higher than that of women (IRR = 3.05, 95% CI = 1.98-4.70, p < 0.001) and it increased with age (IRR = 2.73, 95% CI = 2.30-3.24, p < 0.001). People aged > 64 years had the highest mean incidence rate of 18.58 (95% CI = 11.99-28.80) per 100,000 pyo. Completed suicide was associated with age, being male, and living in a house whose wall is made of scrap material, which is a proxy marker of extreme poverty in this region (OR = 5.5, 95% CI = 4.0-7.0, p = 0.02). Most cases (76%) completed suicide by hanging themselves. Spatial heterogeneity of rates of suicides was observed across the enumeration zones of the KHDSS. CONCLUSIONS: Suicide is common in this area, but the incidence of completed suicide in rural Kenya may be an underestimate of the true burden. Like in other studies, suicide was associated with older age, being male and poverty, but other medical and neuropsychiatric risk factors should be investigated in future studies.

The Association Between Childhood Seizures and Later Childhood Emotional and Behavioral Problems: Findings From a Nationally Representative Birth Cohort.

OBJECTIVES: Emotional/behavioral disorders are often comorbid with childhood epilepsy, but both may be predicted by social disadvantage and fetal risk indicators (FRIs). We used data from a British birth cohort, to assess the association of epilepsy, single unprovoked seizures, and febrile seizures with the later development of emotional/behavioral problems. METHODS: A total of 17,416 children in the 1958 British birth cohort were followed up until age 16 years. Logistic and modified Poisson regression models were used to determine a) the association of social disadvantage at birth and FRI with epilepsy, single unprovoked seizures, and febrile seizures at 7 years, and emotional/behavioral disorders in later childhood, and (ii) the association of childhood seizures by age 7 years with emotional/behavioral disorders in later childhood, after accounting for social disadvantage and FRI. RESULTS: Higher scores on FRI and social disadvantage were associated with emotional/behavioral problems at 7, 11, and 16 years, but not with seizure disorders at age 7 years. Epilepsy was associated with emotional/behavioral problems at 7 years (odds ratio [OR] = 2.50, 95% confidence interval [CI] = 1.29-4.84), 11 years (OR = 2.00, 95% CI = 1.04-3.81), and 16 years (OR = 5.47, 95% CI = 1.65-18.08), whereas single unprovoked seizures were associated with emotional/behavioral problems at 16 years (OR = 1.44, 95% CI = 1.02-2.01), after adjustment for FRI and social disadvantage. Febrile convulsions were not associated with increased risk for emotional/behavioral problems. CONCLUSIONS: Emotional/behavioral problems in children are related to an earlier diagnosis of epilepsy and single unprovoked seizures after accounting for social disadvantage and FRI, whereas febrile convulsions are not associated with emotional/behavioral problems.

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.

Incidence, causes and phenotypes of acute seizures in Kenyan children post the malaria-decline period.

BACKGROUND: Acute seizures are a common cause of paediatric admissions to hospitals in Africa, and malaria is an important cause of seizures in endemic areas. Malaria has declined in the past decade whilst neonatal admissions have increased, both which may affect the incidence and phenotypes of acute seizures in African children. METHODS: We examined the effect of recent decline in malaria and the increasing burden of neonatal admissions on the incidence, causes and phenotypes of acute seizures admitted to hospital from 2009-2013. We used logistic regression to measure associations and Poisson regression to calculate the incidence and rate ratios. RESULTS: The overall incidence of acute seizures over the 5-year period was 312 per 100,000/year (95% CI, 295-329): 116 per 100,000/year (95% CI, 106-127) for complex seizures and 443 per 100,000 live births (95% CI, 383-512) for neonatal seizures. Over the period, there was an increase in incidence of seizures-attributable to malaria (SAM) (incidence rate ratio (IRR) = 1.25; p < 0.001), but neither non-SAM (IRR = 1.03; p = 0.569) nor neonatal seizures (IRR = 0.99; p = 0.905). Important causes of acute seizures were malaria (33%) and respiratory tract infections (19%); and for neonatal seizures were neonatal sepsis (51%), hypoglycemia (41%) and hypoxic-ischemic encephalopathy (21%). Mortality occurred in 6% of all acute seizures, being more common in complex seizures (8%) and neonatal seizures (10 %) than other seizures (p < 0.001 for both comparisons). CONCLUSIONS: Acute seizures remain common in children despite a decline in the incidence of malaria; suggesting that causes for these seizures need to be prevented in the community.

Community perceptions of developmental and behavioral problems experienced by children living with epilepsy on the Kenyan coast: A qualitative study.

Childhood epilepsy is common in Africa. However, there are little data on the developmental and behavioral problems experienced by children living with epilepsy, especially qualitative data that capture community perceptions of the challenges faced by these children. Identifying these perceptions using qualitative approaches is important not only to help design appropriate interventions but also to help adapt behavioral tools that are culturally appropriate. We documented the description of these problems as perceived by parents and teachers of children with or without epilepsy. The study involved 70 participants. Data were collected using in-depth interviews and focus group discussions and were analyzed using NVIVO to identify major themes. Our analysis identified four major areas that are perceived to be adversely affected among children with epilepsy. These included internalizing and externalizing problems such as aggression, temper tantrums, and excessive crying. Additionally, developmental delay, especially cognitive deficits and academic underachievement, was also identified as a major problematic area. There is a need to supplement these findings with quantitative estimates and to develop psychosocial and educational interventions to rehabilitate children with epilepsy who have these difficulties.