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.

Cerebral palsy in African paediatric populations: A scoping review.

AIM: To review the epidemiology and outcomes of African children with cerebral palsy (CP) over a 21-year period. METHOD: The PubMed, Scopus, and Web of Science online databases were searched for original research on African children with CP aged 18 years and younger published from 2000 to 2021. RESULTS: A total of 1811 articles underwent review against explicit criteria; 93 articles were selected for inclusion in the scoping review. The reported prevalence of CP ranged from 0.8 to 10 per 1000 children. Almost half had perinatal risk factors, but up to 26% had no identifiable risk factor. At least one-third of children with CP had one or more comorbidities, most commonly epilepsy, intellectual disability, and malnutrition. African children with CP demonstrated excess premature mortality approximately 25 times that of the general population, predominantly from infections. Hospital-based and younger populations had larger proportions of children with severe impairments. African children with CP had inadequate access to care and education, yet showed functional improvements compared to controls for all evaluated interventions. INTERPRETATION: The prevalence of CP in Africa remains uncertain. African children with CP have different risk profiles, greater premature mortality, and more severe functional impairments and comorbidities compared to the Global North. Several barriers prevent access to optimal care. Larger African studies on validated and effective interventions are needed.

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.

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.

Emotional and Behavioral Outcomes in Childhood for Survivors of Invasive Group B Streptococcus Disease in Infancy: Findings From 5 Low- and Middle-Income Countries.

BACKGROUND: Survivors of invasive group B Streptococcus (iGBS) disease, notably meningitis, are at increased risk of neurodevelopmental impairment. However, the limited studies to date have a median follow-up to 18 months and have mainly focused on moderate or severe neurodevelopmental impairment, with no previous studies on emotional-behavioral problems among iGBS survivors. METHODS: In this multicountry, matched cohort study, we included children aged 18 months to 17 years with infant iGBS sepsis and meningitis from health demographic surveillance systems, or hospital records in Argentina, India, Kenya, Mozambique, and South Africa. Children without an iGBS history were matched to iGBS survivors for sex and age. Our primary outcomes were emotional-behavioral problems and psychopathological conditions as measured with the Child Behavior Checklist (CBCL). The CBCL was completed by the child's primary caregiver. RESULTS: Between October 2019 and April 2021, 573 children (mean age, 7.18 years) were assessed, including 156 iGBS survivors and 417 non-iGBS comparison children. On average, we observed more total problems and more anxiety, attention, and conduct problems for school-aged iGBS survivors compared with the non-iGBS group. No differences were found in the proportion of clinically significant psychopathological conditions defined by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). CONCLUSIONS: Our findings suggested that school-aged iGBS survivors experienced increased mild emotional behavioral problems that may affect children and families. At-risk neonates including iGBS survivors need long-term follow-up with integrated emotional-behavioral assessments and appropriate care. Scale-up will require simplified assessments that are free and culturally adapted.

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.

Common perinatal mental disorders and post-infancy child development in rural Ethiopia: A population-based cohort study.

OBJECTIVE: To investigate whether maternal common mental disorders (CMD) in the postnatal period are prospectively associated with child development at 2.5 and 3.5 years in a rural low-income African setting. METHODS: This study was nested within the C-MaMiE (Child outcomes in relation to Maternal Mental health in Ethiopia) population-based cohort in Butajira, Ethiopia, and conducted from 2005 to 2006. The sample comprised of 496 women who had recently given birth to living, singleton babies with recorded birth weight measurements, who were 15 to 44 years of age, and residing in six rural sub-districts. Postnatal CMD measurements were ascertained 2 months after delivery. Language, cognitive, and motor development were obtained from the child 2.5 and 3.5 years after birth using a locally adapted version of the Bayley Scales of Infant Development (3rd Ed). Maternal CMD symptoms were measured using a locally validated WHO Self-Reporting Questionnaire. A linear mixed-effects regression model was used to analyze the relationship between postnatal CMD and child development. RESULTS: After adjusting for confounders, there was no evidence for an association between postnatal CMD and overall child development or the cognitive sub-domain in the preschool period. There was no evidence of effect modification by levels of social support, socioeconomic status, stunting, or sex of the child. CONCLUSIONS: Previous studies from predominantly urban and peri-urban settings in middle-income countries have established a relationship between maternal CMD and child development, which contrasts with the findings from this study. The risk and protective factors for child development may differ in areas characterized by high social adversity and food insecurity. More studies are needed to investigate maternal CMD's impact on child development in low-resource and rural areas.

The worldwide epilepsy treatment gap: A systematic review and recommendations for revised definitions - A report from the ILAE Epidemiology Commission.

OBJECTIVE: In order to more appropriately apply and understand the "epilepsy treatment gap" (ETG) concept in current health systems, revised conceptual and operational definitions of ETG are timely and necessary. This article therefore systematically reviews worldwide studies of the ETG, distinguishing high-, middle-, and low-income regions, and provides recommendations for an updated International League Against Epilepsy (ILAE) definition of ETG. METHODS: A systematic review of the ETG was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was conducted from January 1990 to July 2019, in the online databases of Ovid MEDLINE and Embase. Identified abstracts were reviewed in duplicate and data independently extracted using a standard proforma. Data describing treatment gap information including both diagnostic and therapeutic aspects of access to epilepsy treatment were recorded. Descriptive statistics are presented. RESULTS: The treatment gap reported in the 45 distinctive populations represented 33 countries. Treatment gap definitions varied widely. The reported ETGs ranged broadly from 5.6% in Norway to 100% in parts of Tibet, Togo, and Uganda. The wide range of reported ETGs was multifactorial in origin including true differences in the availability and utilization of health care among study populations, variations in operational definitions of the epilepsy treatment gap, and methodological differences in sampling and identifying representative epilepsy cases in populations. Significance and recommendations For the ETG to be a useful metric to compare levels of unmet epilepsy care across different countries and regions, a standardized definition must be adapted, recognizing some of the limitations of the current definitions. Our proposed definition takes into account the lack of effective health care insurance, the diagnostic gap, the therapeutic gap, quality-of-care, and other unmet health care needs."

The global cost of epilepsy: A systematic review and extrapolation.

OBJECTIVE: Global action for epilepsy requires information on the cost of epilepsy, which is currently unknown for most countries and regions of the world. To address this knowledge gap, the International League Against Epilepsy Commission on Epidemiology formed the Global Cost of Epilepsy Task Force. METHODS: We completed a systematic search of the epilepsy cost-of-illness literature and identified studies that provided a comprehensive set of direct health care and/or indirect costs, followed standard methods of case identification and cost estimation, and used data on a representative population or subpopulation of people with epilepsy. Country-specific costs per person with epilepsy were extracted and adjusted to generate an average cost per person in 2019 US dollars. For countries with no cost data, estimates were imputed based on average costs per person of similar income countries with data. Per person costs for each country were then applied to data on the prevalence of epilepsy from the Global Burden of Disease collaboration adjusted for the treatment gap. RESULTS: One hundred one cost-of-illness studies were included in the direct health care cost database, 74 from North America or Western Europe. Thirteen studies were used in the indirect cost database, eight from North America or Western Europe. The average annual cost per person with epilepsy in 2019 ranged from $204 in low-income countries to $11 432 in high-income countries based on this highly skewed database. The total cost of epilepsy, applying per person costs to the estimated 52.51 million people in the world with epilepsy and adjusting for the treatment gap, was $119.27 billion. SIGNIFICANCE: Based on a summary and extrapolations of this limited database, the global cost of epilepsy is substantial and highly concentrated in countries with well-developed health care systems, higher wages and income, limited treatment gaps, and a relatively small percentage of the epilepsy population.

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.

Correlates of health-related quality of life in primary caregivers of perinatally HIV infected and HIV exposed uninfected adolescents at the Kenyan Coast.

BACKGROUND: Mothers and other primary caregivers play a crucial role in looking after perinatally HIV infected, and HIV exposed uninfected adolescents in sub-Saharan Africa. Day- to-day caregiving in the context of limited instrumental support and added biomedical risk (HIV seropositivity) may expose these caregivers to adverse states of health. Unfortunately, very few studies have examined their health-related quality of life (HRQoL). Our study documents the HRQoL profile, and associated factors in primary caregivers of perinatally HIV infected, perinatally HIV exposed but uninfected and HIV unexposed/uninfected adolescents aged 12-17 years at the Kenyan Coast. METHODS: This was a cross-sectional analysis of 485 primary caregivers: 195 of perinatally HIV infected adolescents, 128 of perinatally HIV exposed but uninfected adolescents and 162 of HIV unexposed/uninfected adolescents. All caregivers completed a self-report measure of HRQoL (having 8 subscales), depressive symptoms, and parenting stress. They also provided their sociodemographic information and that of the care recipients. We used one-way analysis of variance to assess statistical differences among the groups. Linear regression analyses were used to identify correlates of HRQoL. RESULTS: Overall, caregivers of HIV unexposed/uninfected adolescents reported significantly higher mean HRQoL scores than the other caregivers in the overall HRQoL domain and majority of the subscales. There were no statistical differences in the overall HRQoL scores and most subscales between caregivers of HIV exposed adolescents. Linear regression analyses across the sample indicated that depressive symptoms, increasing age of caregiver, and caring for an adolescent perinatally exposed to HIV were significantly associated with reduced HRQoL at both the overall and sub-scale level. Having a professional job relative to subsistence farming was the only factor associated with improved overall HRQoL. At subscale level, higher socioeconomic status correlated positively with HRQoL while being a grandparent, level of education, parenting stress were negatively associated with HRQoL. CONCLUSIONS: Caregivers in this sample, especially those who are ageing, at risk of mental ill-health, and taking care of adolescents perinatally exposed to HIV, appear to be vulnerable to poor quality of life. Inclusive and multi-component interventions tailored to the caregivers' psychosocial and mental needs will potentially enhance their quality of life.

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.

Community suicide rates and related factors within a surveillance platform in Western Kenya.

BACKGROUND: Suicide is an important contributor to the burden of mental health disorders, but community-based suicide data are scarce in many low- and middle-income countries (LMIC) including Kenya. Available data on suicide underestimates the true burden due to underreporting related to stigma and legal restrictions, and under-representation of those not utilizing health facilities. METHODS: We estimated the cumulative incidence of suicide via verbal autopsies from the Health and Demographic Surveillance System (HDSS) in Kisumu County, Kenya. We then used content analysis of open history forms among deaths coded as accidents to identify those who likely died by suicide but were not coded as suicide deaths. We finally conducted a case-control study of suicides (both verbal autopsy confirmed and likely suicides) compared to accident-caused deaths to assess factors associated with suicide in this HDSS. RESULTS: A total of 33 out of 4306 verbal autopsies confirmed suicide as the cause of death. Content analysis of a further 228 deaths originally attributed to accidents identified 39 additional likely suicides. The best estimate of suicide-specific mortality rate was 14.7 per 100,000 population per year (credibility window = 11.3 - 18.0). The most common reported method of death was self-poisoning (54%). From the case-control study interpersonal difficulties and stressful life events were associated with increased odds of suicide in both confirmed suicides and confirmed combined with suspected suicides. Other pertinent factors such as age and being male differed depending upon which outcome was used. CONCLUSION: Suicide is common in this area, and interventions are needed to address drivers. The twofold increase in the suicide-specific mortality rate following incorporation of misattributed suicide deaths exemplify underreporting and misclassification of suicide cases at community level. Further, verbal autopsies may underreport suicide specifically among older and female populations.

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.

Long-Term Mental Health and Quality of Life Outcomes of Neonatal Insults in Kilifi, Kenya.

We examined the mental health and quality of life (QoL) outcomes and their correlates of school-aged survivors of neonatal jaundice (NNJ), hypoxic-ischemic encephalopathy (HIE), and a comparison group. The Child Behavior Checklist and the Pediatric Quality of Life Inventory were administered to assess the mental health and QoL of 375 children (134 with NNJ, 107 with HIE, and 134 comparison group) aged 6 to 12 years [Median age 9 (interquartile range 7 to 11)]. The results showed that survivors of NNJ and HIE have mental health problems and QoL similar to the comparison group. Maternal mental health was the predominant covariate of mental health and QoL in survivors of NNJ and HIE. This result could indicate that mothers with mental health problems are more likely to have children with mental health issues, but also that caring for children with these adversities may affect mental health well-being of the caregivers. There is a need for early mental health screening and psychosocial intervention for caregivers and their children to enhance both their mental health and QoL.

Clinical features of bacterial meningitis among hospitalised children in Kenya.

BACKGROUND: Diagnosing bacterial meningitis is essential to optimise the type and duration of antimicrobial therapy to limit mortality and sequelae. In sub-Saharan Africa, many public hospitals lack laboratory capacity, relying on clinical features to empirically treat or not treat meningitis. We investigated whether clinical features of bacterial meningitis identified prior to the introduction of conjugate vaccines still discriminate meningitis in children aged ≥60 days. METHODS: We conducted a retrospective cohort study to validate seven clinical features identified in 2002 (KCH-2002): bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsion age range, focal seizures, impaired consciousness, or fever without malaria parasitaemia and Integrated Management of Childhood Illness (IMCI) signs: neck stiffness, lethargy, impaired consciousness or seizures, and assessed at admission in discriminating bacterial meningitis after the introduction of conjugate vaccines. Children aged ≥60 days hospitalised between 2012 and 2016 at Kilifi County Hospital were included in this analysis. Meningitis was defined as positive cerebrospinal fluid (CSF) culture, organism observed on CSF microscopy, positive CSF antigen test, leukocytes ≥50/µL, or CSF to blood glucose ratio <0.1. RESULTS: Among 12,837 admissions, 98 (0.8%) had meningitis. The presence of KCH-2002 signs had a sensitivity of 86% (95% CI 77-92) and specificity of 38% (95% CI 37-38). Exclusion of 'fever without malaria parasitaemia' reduced sensitivity to 58% (95% CI 48-68) and increased specificity to 80% (95% CI 79-80). IMCI signs had a sensitivity of 80% (95% CI 70-87) and specificity of 62% (95% CI 61-63). CONCLUSIONS: A lower prevalence of bacterial meningitis and less typical signs than in 2002 meant the lower performance of KCH-2002 signs. Clinicians and policymakers should be aware of the number of lumbar punctures (LPs) or empirical treatments needed for each case of meningitis. Establishing basic capacity for CSF analysis is essential to exclude bacterial meningitis in children with potential signs.