Lukman Owolabi

The burden of stroke in Africa: a glance at the present and a glimpse into the future.

Summary Objective Information on the current burden of stroke in Africa is limited. The aim of this review was to comprehensively examine the current and projected burden of stroke in Africa. Methods We systematically reviewed the available literature (PubMed and AJOL) from January 1960 and June 2014 on stroke in Africa. Percentage change in age-adjusted stroke incidence, mortality and disability-adjusted life years (DALYs) for African countries between 1990 and 2010 were calculated from the Global Burden of Diseases (GBD) model-derived figures. Results Community-based studies revealed an age-standardised annual stroke incidence rate of up to 316 per 100 000 population, and age-standardised prevalence rates of up to 981 per 100 000. Model-based estimates showed significant mean increases in age-standardised stroke incidence. The peculiar factors responsible for the substantial disparities in incidence velocity, ischaemic stroke proportion, mean age and case fatality compared to high-income countries remain unknown. Conclusions While the available study data and evidence are limited, the burden of stroke in Africa appears to be increasing.

Neurocognitive impairment in HIV-1-infected adults in Sub-Saharan Africa: a systematic review and meta-analysis

OBJECTIVE To estimate the burden of HIV neurocognitive impairment (NCI) among adult patients on and off antiretroviral therapy (ART) in Sub-Saharan Africa. METHODS Estimates were derived from a random effects meta-analysis of prospective studies reporting HIV status, utilization of ART, and the presence of NCI determined using the International HIV Dementia Scale. RESULTS Sixteen studies with quality data from seven countries in Sub-Saharan Africa up to June 2012 were included. Among HIV patients, the frequency of NCI pre-ART was 42.37% (95% confidence interval (CI) 32.18-52.56%), and among those on ART for ≥6 months was 30.39% (95% CI 13.17-47.61%). Respective NCI estimates in studies from Uganda were 46.49% (95% CI 30.62-62.37%) and 28.50% (95% CI -1.31-58.30%). NCI was more common among patients with a concomitant psychiatric ailment. HIV-positive patients compared to HIV-negative controls were predisposed to NCI (odds ratio (OR) 6.49, 95% CI 1.68-25.08); the estimated unadjusted attributable risk of HIV infection leading to NCI was 85%. Meta-regression showed no associations between age, gender, CD4 cell counts, or years of education with NCI. Patients on ART were less likely to have NCI compared to HIV-infected pre-ART patients, with OR 0.36 (95% CI 0.19-0.69). In longitudinal studies with the same patients followed before and at ≥6 months after ART, the OR of NCI after ART compared to pre-ART was 0.23 (95% CI 0.14-0.37). The combined burden of NCI among pre-ART and on-ART patients in Sub-Saharan Africa was estimated at 8,121,910 (95% CI 5,772,140-10,471,680). No publication bias was observed, although residual confounding from differing environmental factors, stages of HIV infection, and viral clades might be a limitation. CONCLUSIONS HIV strongly predisposes to NCI leading to a huge burden in Sub-Saharan Africa, and scale-up of ART can substantially reduce it.

Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol

Background: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research. Methods: SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. Study Significance: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.

Stroke genomics in people of African ancestry: charting new paths.

Abstract One in six people worldwide will experience a stroke in his/her lifetime. While people in Africa carry a disproportionately higher burden of poor stroke outcomes, compared to the rest of the world, the exact contribution of genomic factors to this disparity is unknown. Despite noteworthy research into stroke genomics, studies exploring the genetic contribution to stroke among populations of African ancestry in the United States are few. Furthermore, genomics data in populations living in Africa are lacking. The wide genomic variation of African populations offers a unique opportunity to identify genomic variants with causal relationships to stroke across different ethnic groups. The Stroke Investigative Research and Educational Network (SIREN), a component of the Human Health and Heredity in Africa (H3Africa) Consortium, aims to explore genomic and environmental risk factors for stroke in populations of African ancestry in West Africa and the United States. In this article, we review the literature on the genomics of stroke with particular emphasis on populations of African origin.

Multilingual Validation of the Questionnaire for Verifying Stroke-Free Status in West Africa

Background and Purpose— The Questionnaire for Verifying Stroke-Free Status (QVSFS), a method for verifying stroke-free status in participants of clinical, epidemiological, and genetic studies, has not been validated in low-income settings where populations have limited knowledge of stroke symptoms. We aimed to validate QVSFS in 3 languages, Yoruba, Hausa and Akan, for ascertainment of stroke-free status of control subjects enrolled in an on-going stroke epidemiological study in West Africa. Methods— Data were collected using a cross-sectional study design where 384 participants were consecutively recruited from neurology and general medicine clinics of 5 tertiary referral hospitals in Nigeria and Ghana. Ascertainment of stroke status was by neurologists using structured neurological examination, review of case records, and neuroimaging (gold standard). Relative performance of QVSFS without and with pictures of stroke symptoms (pictograms) was assessed using sensitivity, specificity, positive predictive value, and negative predictive value. Results— The overall median age of the study participants was 54 years and 48.4% were males. Of 165 stroke cases identified by gold standard, 98% were determined to have had stroke, whereas of 219 without stroke 87% were determined to be stroke-free by QVSFS. Negative predictive value of the QVSFS across the 3 languages was 0.97 (range, 0.93–1.00), sensitivity, specificity, and positive predictive value were 0.98, 0.82, and 0.80, respectively. Agreement between the questionnaire with and without the pictogram was excellent/strong with Cohen k=0.92. Conclusions— QVSFS is a valid tool for verifying stroke-free status across culturally diverse populations in West Africa.

Interleukin–6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men

BACKGROUND Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub - Saharan African populations. Interleukin-6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. AIM Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6, CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. METHODS Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of the 23 SNPs in rigorously phenotyped cases (N=429) of ischemic stroke (Men=198; Women=231) and stroke- free (N=483) controls (Men=236; Women=247). RESULTS Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans=8.6%) was significantly associated with ischemic stroke in men (OR=2.006, 95% CI=[1.065, 3.777], p=0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans=1.7%) was also associated with ischemic stroke in men (OR=2.550, 95% CI=[1.027, 6.331], p=0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke. CONCLUSION Polymorphisms rs1800796 in IL6 gene and rs2383207 in CDKN2A/CDKN2B gene have significant associations with ischemic stroke in indigenous West African men. CDKN2A/CDKN2B SNP rs2383207 is independently associated with ischemic stroke in indigenous West African men. Further research should focus on the contributions of inflammatory genes and other genetic polymorphisms, as well as the influence of sex on the neurobiology of stroke in people of African ancestry.

Validation of the 8-item questionnaire for verifying stroke free status with and without pictograms in three West African languages

Background The Questionnaire for Verifying Stroke-free Status (QVSFS) has been validated in Western populations as a method for verifying stroke-free status in participants of clinical, epidemiological and genetic studies. This instrument has not been validated in low-income settings where populations have limited knowledge of stroke symptoms and literacy levels are low. Objective To simultaneously validate the 8-item QVSFS in 3 languages spoken in West Africa (Yoruba, Hausa and Akan) for ascertainment of stroke-free status of control subjects in SIREN. Methods Using a cross-sectional study design, 100 participants each from the 3 linguistic groups will be consecutively recruited from neurology and general medicine clinics of 5 tertiary referral hospitals in Nigeria and Ghana. Ascertainment of stroke status will be determined by neurologists using structured neurological examination, review of case records and neuro-imaging (Gold standard). The relative performance of QVSFS without and with pictures of stroke symptoms (pictograms) will be assessed using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Conclusion The proposed study will provide valuable data on the performance of the QVSFS in resource-limited settings.

Epilepsy and Education in developing countries: a survey of school teachers’ knowledge about epilepsy and their attitude towards students with epilepsy in Northwestern Nigeria

Introduction Students living with epilepsy still find themselves confronted with social barriers that prevent them from academic achievements. Objective The aim of this study was to evaluate knowledge and attitudes of school teachers and to determine the factors associated with good knowledge and positive attitude among nursery, primary and secondary school teachers in Kano, Northwestern Nigeria. Methods A 20-item validated semi-structured questionnaire was self-administered to 200 teachers, selected through multistage sampling technique, in Kano, Northwestern Nigeria. Results The respondents comprised 124 (62%) males and 76(38%) females. Their age ranged between 17 and 55 with a median age of 26 years. All the respondents have heard or read about epilepsy, 13% have had students with epilepsy in their classes before, fifty one (25.5%) of them would object to having an epileptic child in their class. To one hundred and seventy one (85.5%) all seizures were convulsive, 81% of them admitted to not havingadequate knowledge of the initial procedure should their student develop epileptic seizure, 60% believed that epileptic student should be separated from non-epileptic students in the classroom and 44.5% of them preferred alternative medicine. Overall, fifty nine (29.5%) teachers had fair to good knowledge about epilepsy. and one hundred and sixty four (82%) had positive attitude to students with epilepsy. Statistically significant association was found between level of education attained by the respondents and good knowledge about epilepsy as well as between female gender and good attitude. However, none of the variables was statistically significant predictor of knowledge or attitude among the respondents. Conclusion There was low level of knowledge and misconceptions about epilepsy but fair attitude towards epileptic students in Northwestern Nigeria. Higher level of education of the teachers was significantly associated with good attitude.

Dominant modifiable risk factors for stroke in Ghana and Nigeria (SIREN): a case-control study

Summary Background Sub-Saharan Africa has the highest incidence, prevalence, and fatality from stroke globally. Yet, only little information about context-specific risk factors for prioritising interventions to reduce the stroke burden in sub-Saharan Africa is available. We aimed to identify and characterise the effect of the top modifiable risk factors for stroke in sub-Saharan Africa. Methods The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study done at 15 sites in Nigeria and Ghana. Cases were adults (aged ≥18 years) with stroke confirmed by CT or MRI. Controls were age-matched and gender-matched stroke-free adults (aged ≥18 years) recruited from the communities in catchment areas of cases. Comprehensive assessment for vascular, lifestyle, and psychosocial factors was done using standard instruments. We used conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% CIs. Findings Between Aug 28, 2014, and June 15, 2017, we enrolled 2118 case-control pairs (1192 [56%] men) with mean ages of 59.0 years (SD 13.8) for cases and 57.8 years (13.7) for controls. 1430 (68%) had ischaemic stoke, 682 (32%) had haemorrhagic stroke, and six (<1%) had discrete ischaemic and haemorrhagic lesions. 98.2% (95% CI 97.2–99.0) of adjusted PAR of stroke was associated with 11 potentially modifiable risk factors with ORs and PARs in descending order of PAR of 19.36 (95% CI 12.11–30.93) and 90.8% (95% CI 87.9–93.7) for hypertension, 1.85 (1.44–2.38) and 35.8% (25.3–46.2) for dyslipidaemia, 1.59 (1.19–2.13) and 31.1% (13.3–48.9) for regular meat consumption, 1.48 (1.13–1.94) and 26.5% (12.9–40.2) for elevated waist-to-hip ratio, 2.58 (1.98–3.37) and 22.1% (17.8–26.4) for diabetes, 2.43 (1.81–3.26) and 18.2% (14.1–22.3) for low green leafy vegetable consumption, 1.89 (1.40–2.54) and 11.6% (6.6–16.7) for stress, 2.14 (1.34–3.43) and 5.3% (3.3–7.3) for added salt at the table, 1.65 (1.09–2.49) and 4.3% (0.6–7.9) for cardiac disease, 2.13 (1.12–4.05) and 2.4% (0.7–4.1) for physical inactivity, and 4.42 (1.75–11.16) and 2.3% (1.5–3.1) for current cigarette smoking. Ten of these factors were associated with ischaemic stroke and six with haemorrhagic stroke occurrence. Interpretation Implementation of interventions targeting these leading risk factors at the population level should substantially curtail the burden of stroke among Africans. Funding National Institutes of Health.

Stroke in Indigenous Africans, African Americans, and European Americans

Background and Purpose— The relative contributions of racial and geographic factors to higher risk of stroke in people of African ancestry have not been unraveled. We compared stroke type and contributions of vascular risk factors among indigenous Africans (IA), African Americans (AA), and European Americans (EA). Methods— SIREN (Stroke Investigative Research and Educational Network) is a large multinational case–control study in West Africa—the ancestral home of 71% AA—whereas REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a cohort study including AA and EA in the United States. Using harmonized assessments and standard definitions, we compared data on stroke type and established risk factors for stroke in acute stroke cases aged ≥55 years in both studies. Results— There were 811 IA, 452 AA, and 665 EA stroke subjects, with mean age of 68.0±9.3, 73.0±8.3, and 76.0±8.3 years, respectively (P<0.0001). Hemorrhagic stroke was more frequent among IA (27%) compared with AA (8%) and EA (5.4%; P<0.001). Lacunar strokes were more prevalent in IA (47.1%), followed by AA (35.1%) and then EA (21.0%; P<0.0001). The frequency of hypertension in decreasing order was IA (92.8%), followed by AA (82.5%) and then EA (64.2%; P<0.0001) and similarly for diabetes mellitus IA (38.3%), AA (36.8%), and EA (21.0%; P<0.0001). Premorbid sedentary lifestyle was similar in AA (37.7%) and EA (34.0%) but lower frequency in IA (8.0%). Conclusions— Environmental risk factors such as sedentary lifestyle may contribute to the higher proportion of ischemic stroke in AA compared with IA, whereas racial factors may contribute to the higher proportion of hypertension and diabetes mellitus among stroke subjects of African ancestry.