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.

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.

HIV virological non-suppression is highly prevalent among 18- to 24-year-old youths on antiretroviral therapy at the Kenyan coast.

BACKGROUND: In sub-Saharan Africa, data on virologic outcomes of young people living with HIV (YLWH) enrolled on antiretroviral therapy (ART) remains scarce. In this study, we describe the prevalence of HIV virological non-suppression (VNS) and its associated factors among YLWH aged 18-24 years from the Kenyan coast. METHODS: Data were analyzed for 384 YLWH who participated in a larger cross-sectional study conducted between November 2018 and September 2019 in two counties at the Kenyan coast (Kilifi and Mombasa). Descriptive statistics were used to summarize sample characteristics and logistic regression was used for statistical modeling of factors associated with VNS. In this study, VNS was defined as plasma viral load ≥ 1000 copies/mL. RESULTS: Among these YLWH with a mean age of 20.7 years (SD = 2.2); 55.5% females, the overall prevalence of VNS was 32.0% (95% Confidence interval (95% CI): 27.5, 36.9%). In the multivariable logistic regression analysis, being from a largely rural setting (adjusted Odds Ratio (aOR) 1.73, 95% CI 1.10, 2.71; p = 0.02), underweight (aOR 1.87, 95% CI 1.16, 3.01; p = 0.01) and low self-reported ART adherence (aOR 2.83, 95% CI 1.34, 6.00; p = 0.01) were significantly associated with higher odds of VNS in YLWH. CONCLUSIONS: In this study, high levels of VNS were observed among YLWH and this was significantly associated with rural residency, nutritional and ART adherence problems. ART adherence counselling and nutritional support and education should be intensified in this setting targeting YLWH residing mostly in rural areas. Given the high frequency of VNS, there is need to closely monitor viral load and profile HIV drug resistance patterns in youths from the Kenyan coast with confirmed virologic failure. The latter will help understand whether drug resistance also contributes to poor viral suppression in addition to, or exclusive of suboptimal ART adherence.

Psychosocial and mental health challenges faced by emerging adults living with HIV and support systems aiding their positive coping: a qualitative study from the Kenyan coast.

BACKGROUND: In sub-Saharan Africa, there is little data on the challenges faced by young people living with HIV transitioning into adult life. Adapting the socio-ecological framework, this qualitative study investigated the challenges faced by emerging adults living with HIV from a rural Kenyan setting. Additionally, the study explored support systems that aid positive coping among these young adults. METHODS: In April 2018, in-depth interviews were conducted with a convenience sample of 22 young adults living with HIV (12 females), 18-24 years old, from rural Kilifi, coast of Kenya. Data were analyzed thematically using NVIVO 11 software. RESULTS: Young adults living with HIV from this setting face various challenges at different levels of the social ecosystem. At the individual level, key challenges they reported included acceptance of HIV positive status, antiretroviral adherence, economic burden associated with access to healthcare, building an intimate relationship, mental health problems, and HIV status disclosure. At the family level, death of parents, poverty, and being unaccepted were the commonly mentioned challenges. At the community level, socialization difficulties and long waiting time at the HIV clinic were highlighted. HIV stigma and discrimination were frequently reported across the different levels. Economic independence, social support (from families, friends, organizations, healthcare providers and peer meetings), and reliance on spirituality aided positive coping among these young adults amidst the challenges of living with HIV. CONCLUSIONS: In this rural setting, emerging adults living with HIV face various challenges at the individual, family, and community level, some of which are cross-cutting. Our findings underscore the need for designing multi-level youth-friendly interventions that can address modifiable challenges encountered by emerging adults living with HIV in this and similar settings. Such interventions should incorporate appropriate context-specific support structures that may help these young people smoothly transit into adult life.

Prevalence, risk and protective indicators of common mental disorders among young people living with HIV compared to their uninfected peers from the Kenyan coast: a cross-sectional study.

BACKGROUND: In sub-Saharan Africa, common mental disorders (CMDs) like depression and anxiety are under-investigated amongst young people living with HIV (YLWH). To address the gap, in Kenya we: a) determined the prevalence of CMDs among YLWH compared to their uninfected peers; b) investigated HIV status as an independent predictor of CMDs in young people; c) investigated CMDs risk and protective indicators with more focus on YLWH. METHODS: Between November 2018 and September 2019, 819 young people aged 18-24 years (407 HIV-infected) were recruited from two Counties on the Kenyan coast. Locally adapted pre-existing mental health measures, Patient Health Questionnaire (9-item) and Generalized Anxiety Disorder scale (7-item), were administered among other questionnaires via audio computer-assisted self-interview. Logistic regression was used to determine the correlates of CMDs. RESULTS: Prevalence of CMDs was significantly elevated among YLWH compared to their uninfected peers i.e. 29% vs. 12%; p < 0.001 for depressive symptoms, 19% vs. 8%; p < 0.001 for anxiety symptoms, and 16% vs. 5%; p < 0.001 for comorbid depressive and anxiety symptoms. HIV status independently predicted depressive symptoms and its co-occurrence with anxiety symptoms. Among YLWH, negative life events, higher perceived HIV-related stigma and low adherence to antiretroviral therapy were the risk indicators for elevated CMDs. Among HIV-uninfected youths, death of both parents was a risk indicator for elevated depressive symptoms. Protective indicators against CMDs among youths with and without HIV included higher social support and health-related quality of life. CONCLUSION: At the Kenyan coast, YLWH have significantly higher burden of CMDs compared to their uninfected peers. Being HIV-positive as a youth in this setting is predictive of more depressive symptoms and its comorbidity with anxiety symptoms. YLWH at high risk of CMDs in coastal Kenya can benefit from early detection, referral and treatment if routine screening for CMDs is integrated in their care package. The mental wellbeing of bereaving HIV-unaffected youths could be improved through continued support to help them come to terms with their loss. At the community level, programmes strengthening the social capital or improving the overall quality of life of youths with or without HIV may be beneficial to their mental health.

Correlates of health-related quality of life among adults receiving combination antiretroviral therapy in coastal Kenya.

BACKGROUND: Health-related quality of life (HRQoL) is an important metric of perceived wellbeing in people living with HIV/AIDS (PLWHA). However, research on HRQoL among PLWHA in sub-Saharan Africa is limited. This study investigates factors associated with HRQoL among PLWHA in Kilifi, coast of Kenya. METHODS: Between February and April 2018, 450 adults living with HIV and on combined antiretroviral therapy (cART) between 18 to 60 years were sequentially recruited from an HIV-specialized clinic. The Functional Assessment of HIV Infection (FAHI) questionnaire, previously adapted for assessing HRQoL in this setting, was slightly modified and administered to participants alongside other measures of sociodemographic, health and treatment characteristics in a face-to-face interview. RESULTS: Linear regression analyses indicated that depressive symptoms, HIV-related stigma, non-disclosure of HIV status, living alone, clinic inaccessibility, and presence of any current opportunistic infection were significantly associated with lower HRQoL scores at both the FAHI overall and sub-scale level. Higher physician empathy, male sex, and higher body mass index were significantly associated with better HRQoL scores at both FAHI overall and sub-scale level. Age and longer duration on cART were significantly associated with better HRQoL only at the sub-scale level. CONCLUSIONS: Interventions aimed at reducing depressive symptoms and HIV stigma, making HIV-related services more accessible, addressing opportunistic infections, strengthening social support systems, serostatus disclosure and put in place caring, respectful, and compassionate model of care are necessary to improve the HRQoL of PLWHA.

The reliability, validity and factorial structure of the Swahili version of the 7-item generalized anxiety disorder scale (GAD-7) among adults living with HIV from Kilifi, Kenya.

BACKGROUND: Generalized Anxiety Disorder (GAD) is under-investigated in people living with HIV/AIDS from sub-Saharan Africa. In part, this is due to paucity of culturally appropriate measures for GAD which are psychometrically robust. This study aimed to evaluate the reliability, factorial structure, and validity of Swahili version of the 7-item GAD questionnaire (GAD-7) among adults living with HIV. STUDY DESIGN: Descriptive cross-sectional study. METHODS: 450 adults receiving comprehensive care from an HIV specialized clinic in Kilifi County, coastal Kenya, were consecutively recruited. Swahili versions of GAD-7, Patient Health Questionnaire (PHQ-9) and a 12-item HIV stigma scale were administered alongside measures of psychosocial and health-related characteristics. Internal consistency, test-retest reliability, factorial structure, convergent validity, and discriminant validity of Swahili GAD-7 were examined using Cronbach's alpha (α), intra-class correlation coefficient (ICC), Confirmatory Factor Analysis (CFA), Pearson's correlation, and analysis of covariance (ANCOVA), respectively. RESULTS: Internal consistency of Swahili GAD-7 was good, α = 0.82 (95% CI 0.78, 0.85). Its test-retest reliability (2 weeks apart) was acceptable, ICC = 0.70 (95% CI 0.55, 0.81). A confirmatory analysis of a one-factor solution indicated an excellent fit to the hypothesized structure (RMSEA = 0.00 [95% confidence interval 0.00, 0.05], CFI = 1.00, TLI = 1.00). Multi-group CFA substantiated factorial invariance for sex and age for the one-factor structure of Swahili GAD-7. Scores of GAD-7, Swahili version, significantly correlated with those of PHQ-9 (r = 0.73; p < 0.001) and the HIV stigma scale (r = 0.36; p < 0.001) suggesting good convergent validity. Statistically significant differences were observed between participants on first-line antiretroviral therapy compared to those on second-line treatment (F [1, 441] = 5.55, p = 0.02) indicative of good discriminant validity of Swahili GAD-7. CONCLUSION: GAD-7 Swahili version retained its original unidimensional latent structure with good psychometric properties among adults living with HIV from Kilifi, Kenya. It can be used to identify symptoms of GAD in similar research settings. However, to confidently identify those in need of mental health treatment or referral services in HIV primary care clinics, more research on the validity of Swahili GAD-7 is needed especially its discriminant validity and diagnostic accuracy at different cut-off scores.

Transcranial Doppler and Magnetic Resonance in Tanzanian Children With Sickle Cell Disease.

Background and Purpose- We determined prevalences of neurological complications, vascular abnormality, and infarction in Tanzanian children with sickle cell disease. Methods- Children with sickle cell disease were consecutively enrolled for transcranial Doppler; those with slightly elevated (>150 cm/s), low (<50 cm/s) or absent cerebral blood flow velocity (CBFv) were invited for brain magnetic resonance imaging and magnetic resonance angiography. Results- Of 200 children (median age 9; range 6-13 years; 105 [2.5%] boys), 21 (11%) and 15 (8%) had previous seizures and unilateral weakness, respectively. Twenty-eight (14%) had elevated and 39 (20%) had low/absent CBFv, all associated with lower hemoglobin level, but not higher indirect bilirubin level. On multivariable analysis, CBFv>150 cm/s was associated with frequent painful crises and low hemoglobin level. Absent/low CBFv was associated with low hemoglobin level and history of unilateral weakness. In 49 out of 67 children with low/absent/elevated transcranial Doppler undergoing magnetic resonance imaging, 43% had infarction, whereas 24 out of 48 (50%) magnetic resonance angiographies were abnormal. One had hemorrhagic infarction; none had microbleeds. Posterior circulation infarcts occurred in 14%. Of 11 children with previous seizure undergoing magnetic resonance imaging, 10 (91%) had infarction (5 silent) compared with 11 out of 38 (29%) of the remainder ( P=0.003). Of 7 children with clinical stroke, 2 had recurrent stroke and 3 died; 4 out of 5 had absent CBFv. Of 193 without stroke, 1 died and 1 had a stroke; both had absent CBFv. Conclusions- In one-third of Tanzanian children with sickle cell disease, CBFv is outside the normal range, associated with frequent painful crises and low hemoglobin level, but not hemolysis. Half have abnormal magnetic resonance angiography. African children with sickle cell disease should be evaluated with transcranial Doppler; those with low/absent/elevated CBFv should undergo magnetic resonance imaging/magnetic resonance angiography.

Prevalence and correlates of depressive symptoms among adults living with HIV in rural Kilifi, Kenya.

BACKGROUND: Published research on depression among people living with HIV/AIDS (PLWHA) from Africa is increasing, but data from Kenya remains scarce. This cross-sectional study measured the prevalence and correlates of depressive symptoms among PLWHA in rural Kilifi, on the Kenyan coast. METHODS: Between February and April 2018, we consecutively recruited and interviewed 450 adults living with HIV and on combination antiretroviral therapy (cART). Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9), with a positive depression screen defined as PHQ-9 score ≥ 10. Measures of psychosocial, health, and treatment characteristics were also administered. RESULTS: The overall prevalence of depressive symptoms was 13.8% (95% Confidence Interval (95%CI): 10.9, 17.3). Multivariable logistic regression analysis identified current comorbid chronic illness (adjusted Odds Ratio (aOR) 5.72, 95% CI: 2.28, 14.34; p < 0.001), cART regimen (aOR 6.93, 95%CI: 2.34, 20.49; p < 0.001), perceived HIV-related stigma (aOR 1.10, 95%CI: 1.05, 1.14, p < 0.001) and difficulties accessing HIV care and treatment services (aOR 2.37, 95%CI: 1.14, 4.91; p = 0.02) as correlates of depressive symptoms. CONCLUSION: The prevalence of depressive symptoms among adults living with HIV on the Kenyan coast is high. Those at high risk for elevated depressive symptoms (e.g., with comorbid chronic illnesses, on second-line cART, experiencing perceived HIV-stigma or with problems accessing HIV care) may benefit from early identification, treatment or referral, which requires integration of mental health programmes into HIV primary care.

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.

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.

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.

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.