Onoja Akpa

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.

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.

Management of Conflicts Arising From Disclosure of HIV Status Among Married Women in Southwest Nigeria

This study examined if disclosure to their spouses by married women living with HIV/AIDS resulted in conflicts. Fifty-seven women completed a questionnaire on conflict indicators. While 93% disclosed their status within 6 months of diagnosis, 12.3% did so through a third party. More than thirty-six percent (36.8%) confirmed that disclosure led to conflict. Although 19.3% had their conflicts resolved through a third party, 10% suffered separation. Marital status and fear of stigma significantly influence time to disclose (p <.01 and p <.05), while type of marriage strongly influences whether status will be disclosed (p <.01). Programs for women with HIV should consider conflicts that may arise from disclosure.

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 Among Young West Africans: Evidence From the SIREN (Stroke Investigative Research and Educational Network) Large Multisite Case–Control Study

Background and Purpose— Stroke in lower and middle-income countries affects a young and productive age group. Data on factors associated with stroke in the young are sorely lacking from lower and middle-income countries. Our objective is to characterize the nature of stroke and its risk factors among young West Africans aged <50 years old. Methods— The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case–control study involving 15 sites in Nigeria and Ghana. Cases included adults aged ≥18 years with computed tomography/magnetic resonance imaging-confirmed stroke. Controls were age-and gender-matched stroke-free adults recruited from the communities in catchment areas of cases. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed. We used conditional logistic regression to estimate odds ratios and population attributable risks with 95% confidence intervals. Results— Five hundred fifteen (24.3%) out of 2118 cases enrolled were <50 years old. Among subjects <50 years old, hemorrhagic stroke proportion was 270 (52.5%) versus 245 (47.5%) for ischemic strokes. Etiologic subtypes of ischemic strokes included large artery atherosclerosis (40.0%), small vessel disease (28.6%), cardioembolism (11.0%), and undetermined (20.4%). Hypertension (91.7%), structural lesions (3.4%), and others (4.9%) were causally associated with hemorrhagic stroke. Six topmost modifiable factors associated with stroke in descending order of population attributable risk (95% confidence interval) were hypertension: 88.7% (82.5%–94.8%), dyslipidemia: 48.2% (30.6%–65.9%), diabetes mellitus: 22.6% (18.7%–26.5%), low green vegetable consumption: 18.2% (−6.8%–43.2%), stress: 14.5% (4.9%–24.1%), and cardiac disease: 8.4% (5.8%–11.1%). Conclusions— The high and rising burden of stroke among young Africans should be curtailed via aggressive, population-wide vascular risk factor control.

Can common carotid intima media thickness serve as an indicator of both cardiovascular phenotype and risk among black Africans

Background It is not known whether common carotid intima media thickness (CIMT) can serve as a surrogate marker of cardiovascular risk among black Africans. Therefore, we examined whether CIMT differed significantly among individuals with distinct cardiovascular phenotype and correlated significantly with traditional cardiovascular risk factors in a black African population. Methods CIMT was measured in 456 subjects with three distinct cardiovascular phenotypes – 175 consecutive Nigerian African stroke patients, 161 hypertensive patients without stroke and 120 normotensive non-smoking adults. For each pair of cardiovascular phenotypes, c-statistics were obtained for CIMT and traditional vascular risk factors (including age, gender, weight, waist circumference, smoking, alcohol, systolic and diastolic blood pressures, fasting plasma glucose, fasting total cholesterol). Pearson’s correlation coefficients were calculated to quantify bivariate relationships. Findings Bilaterally, CIMT was significantly different among the three cardiovascular phenotypes (right: p < 0.001, F = 33.8; left: p < 0.001, F = 48.6). CIMT had a higher c-statistic for differentiating stroke versus normotension (c = 0.78 right; 0.82 left, p < 0.001) and hypertension versus normotension (c = 0.65 right; 0.71 left, p < 0.001) than several traditional vascular risk factors. Bilaterally, combining all subjects, CIMT was the only factor that correlated significantly (right: 0.12 ≤ r ≤ 0.41, 0.018 ≤ p < 0.0001; left: 0.18 ≤ r ≤ 0.41, 0.005 ≤ p < 0.0001) to all the traditional cardiovascular risk factors assessed. Conclusion Our findings support CIMT as a significant indicator of both cardiovascular risk and phenotype among adult black Africans. However, specific thresholds need to be defined based on prospective studies.

Perceptions and recommendations by scientists for a potential release of genetically modified mosquitoes in Nigeria

BackgroundThe use of genetically modified mosquitoes (GMMs) for the control of malaria and other mosquito-borne diseases has been proposed in malaria-endemic countries, such as Nigeria, which has the largest burden in Africa. Scientists are major stakeholders whose opinions and perceptions can adversely affect the success of the trials of GMMs if they are not involved early. Unfortunately, information on the awareness of Nigerians scientists and their overall perception of the GMMs is practically non-existent in the literature. Therefore, this study aimed at understanding how receptive Nigerian scientists are to a potential release of GMMs for the control of malaria.MethodsThe sample consisted of 164 scientists selected from academic and research institutions in Nigeria. Data were collected from participants using a semi-structured, self-administered questionnaire. Questions were asked about the cause and prevention of malaria, genetic modification and biotechnology. Specific questions on perception and acceptable conditions for the potential release of GM mosquitoes in Nigeria were also covered.ResultsAll participants cited mosquitoes as one of several causes of malaria and used various methods for household control of mosquitoes. The main concerns expressed by the scientists were that GMMs can spread in an uncontrolled way beyond their release sites (89%) and will mate with other mosquito species to produce hybrids with unknown consequences (94.5%). Most participants (92.7%) agreed that it was important that before approving the release of GMMs in Nigeria, there had to be evidence of contingency measures available to remove the GMMs should a hazard become evident during the course of the release. In general, a majority (83.5%) of scientists who participated in this study were sceptical about a potential release in Nigeria, while 16.5% of the participants were in support.ConclusionsAlthough a majority of the participants are sceptical about GMMs generally, most encourage the use of genetic modification techniques to make mosquitoes incapable of spreading diseases provided that there are contingency measures to remove GMMs if a hazard becomes evident during the course of the release.

Awareness and Utilization of Affordable Medicine Facility-Malaria among Caregivers of Under-Five Children in Ibadan North-West Local Government Area, Oyo State

Introduction. Distribution of Affordable Medicine Facility-malaria Artemisinin Combination Therapies (AMFm-ACTs) started in Nigeria in 2011, but its use at community level has not been documented. Methods. Four hundred seventy-eight caregivers whose under-five children had fever within two weeks prior to the survey were selected using cluster sampling technique. Information on sociodemographic characteristics, treatment seeking for malaria, and awareness and use of AMFm-ACTs was collected using an interviewer administered questionnaire. Result. More than half of the respondents (51.2%) bought AMFm-ACTs without prescription. Awareness of AMFm was low as only 9.1% has heard about the programme. Overall, 29.2% used AMFm-ACTs as their first line choice of antimalarial drug. On bivariate analysis age, group (25–34 years), public servants, respondents with tertiary education, respondents with high socioeconomic status, respondents with poor knowledge of symptoms of malaria, awareness of AMFm-ACTs, availability of AMFm-ACTs, and sources of drug were significantly associated with utilization of AMFm-ACTs (P < 0.05). Logistic regression demonstrated that only people who were aware of AMFM-ACTs predicted its use (AOR: 0.073; CI: 0.032–0.166; P < 0.001). Conclusion. Interventions which targeted at raising awareness of AMFm-ACTs among people at risk of malaria are advocated for implementation.

Prevalence and predictors of anxiety in an African sample of recent stroke survivors.

Studies considering emotional disturbances in the setting of stroke have primarily focused on depression and been conducted in high‐income countries. Anxiety in stroke survivors, which may be associated with its own unique sets of risk factors and clinical parameters, has been rarely investigated in sub‐Saharan Africa (SSA). We assess the characteristics of anxiety and anxiety‐depression comorbidity in a SSA sample of recent stroke survivors.