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Background: Optimal blood pressure control is essential in averting complications and associated cardiovascular risks. Although a 5-mmHg reduction in systolic blood pressure (SBP) is associated with better health outcomes, individual-level and health facility dynamics might influence optimal blood pressure control. We explored individual and health facility-level factors of SBP changes among patients with hypertension in Ghana. Methods: We recruited 15 health facilities that provided hypertension care and from each facility, 15 patients who were currently receiving hypertension care during their clinic appointment. We explored patient-level (adherence to treatment, length of time with hypertension diagnosis, and sociodemographic factors) and health-facility level (accessibility of care, health facility management, bed capacity, provider training, and provider-patient ratio) predictors. We fitted two-level mixed-effect linear regression models to identify predictors of SBP changes. Results: We included 222 patients, 81% were female, and 48% had achieved blood pressure control of < 140/90 mmHg. At the patient level, secondary-level education was associated with a 7.5 mmHg (95% CI: -14.74, -0.28) greater reduction in SBP than a primary or lower level of education (Table). Patients treated at private facilities had on average 15.8 mmHg (95% CI: 4.97, 26.62) higher SBP than those in government health facilities. Patients who were receiving care at health facilities where a physician or physician assistant treated ≥ 280 patients/month had 28.4 mmHg (95% CI: 9.77, 46.97) higher SBP than those receiving care from a physician/physician assistant who cared for < 140 patients/month. Conclusion: Health system interventions to address individual barriers, the shortage of healthcare providers, and team-based care strategies are needed to address the burden of hypertension in Ghana.

Objective: To identify the determinants of systolic blood pressure variability (SBPV) among Ghanaians.Design: We undertook a secondary analysis of data collected in a prospective studySetting: The study involved patients with hypertension and or diabetes receiving care in five hospitals in GhanaMain outcome measures: We assessed determinants of SBPV among 2,785 Ghanaian patients. We calculated the standard deviation (SD) of systolic BP recordings of 3 to 10 visits per patient over 18 months as a measure of SBPV. A multivariate linear regression analysis was fitted to identify factors independently associated with risk visit-to-visit SBP standard deviation.Results: The mean SD of individual patient visit-to-visit SBP overall was 14.8± 6.3 mm Hg. Those with hypertension and diabetes had the highest SD of 15.4 ±6.2 mm Hg followed by 15.2 ±6.5 mm Hg among those with hypertension only and then 12.0 ± 5.2 mm Hg among those with diabetes only, p

Stroke is a major cause of death in Sub-Saharan Africa (SSA) and genetic factors appear to play a part. This led to the development of stroke bio-banking and genomics research in SSA. Existing stroke studies have focused on causes, incidence rates, fatalities and effects. However, scant attention has been paid to the legal issues about stroke bio-banking and genomics research in the sub-region. Therefore, this article examines how genomics research and stroke bio-banking in SSA can be regulated through legislation. The article reports that there are germane issues to be addressed such as appropriate consent model, commercial use of biological samples, ownership right in biological samples and return of research results but that the position of the law on these issues is not satisfactory because there are no statute directly regulating them while existing regulations in these countries are either absent, outdated, conservative or difficult to navigate. The article therefore applies the theory of symbolic legislation and argues for legislative intervention through positive symbolic approach. It recommends that the statute to be enacted should only address policy issues by way of legal rules without being detailed while the understanding of the rules should be fostered in explanatory notes. The explanatory notes should contain examples borne of decided cases, cases settled out of court and the ethical guidelines prepared by Human Heredity and Health in Africa (H3 Africa). Where they are inadequate, recourse may be had to other ethical guidelines subject to the demands of local circumstances.

Objectives: To identify the prevalence and associated factors of anxiety in people living with HIV/AIDS in a tertiary centre in Ghana.Design: The study employed a cross-sectional design.Setting: The study was conducted in the outpatient HIV clinic of a tertiary hospital.Participants: Participants were adult PLWHA receiving OPD care, including those established on combined an-tiretroviral therapy (cART) and newer patients who were not on cART. Four hundred ninety-five participants aged ≥30 years were consecutively enrolled on the study.Interventions: Demographic and clinical data were collected using standard questionnaires and patient files. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression analysis was done to identify associated factors.Main outcome measure: Proportion of PLWHA who had HADS score of ≥8Results: Overall prevalence of anxiety was 61.0% (95%CI: 56.6 – 65.3), with no significant difference between re-cently diagnosed (≤ 6 months, 64.3%) and those with established diagnoses (>6 months, 59.1%). Urban residence (aOR: 1.67, 95%CI: 1.12 – 2.51), alcohol use (aOR: 1.64, 95%CI: 1.13 – 2.38) and depression (aOR: 13.62, 95%CI: 7.91 – 23.45) were independently associated with anxiety.Conclusion: In this sample, 6 in 10 Ghanaian PLWHA had evidence of anxiety. Liaison with the national mental health service for more comprehensive and integrated care and further research into the mental health of PLWHA is recommended to reduce this high burden of anxiety.

Background: The association of vegetable consumption with hypertension remains poorly described in sub-Saharan Africa. This study assessed the relationship between vegetable consumption and hypertension among indigenous Africans. Methods: We harmonized data on the frequency of vegetable consumption (servings/week) and hypertension (defined as systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg or previous diagnosis or use of antihypertensive medications) from 16,445 participants across five African countries (Ghana, Burkina Faso, Kenya, Nigeria and South Africa) from the SIREN and AWI-Gen studies. Using the recommendation of at least five servings/day (35 servings/week) adapted from the World Health Organization recommendations, and vegetable consumption was classified as 'inadequate' (P Results: The mean age of participants was 53.0±10.7years, 45.9% (7,552 of 16,445) were males, and 42.9% (7,070 of 16,445) were hypertensives. Adequate vegetable consumption was associated with lower odds of hypertension; OR: 0.86 (95%CI: 0.76, 0.97). The sex-stratified odds was; OR: 0.87 (95%CI: 0.73, 1.02) for females and 0.84 (95%CI: 0.71, 1.00) for males. Conclusion: These findings provide new evidence for promoting regular vegetable consumption in the guidelines for the primary prevention of hypertension among Africans.

Background: Hypertension continues to be a growing health burden in Sub-Saharan Africa (SSA). The health systems in SSA are ill-equipped to manage patients with hypertension. The current study explored hypertension service readiness at the health facilities in Kumasi, Ghana. Methods: We purposively recruited 11 (out of over 200) health facilities that provide hypertension services in Kumasi, Ghana. At each facility, we administered the Hypertension Service Availability and Readiness tool. The main outcome of interest was hypertension service readiness regarding the availability of hypertension guidelines, provider and their training, equipment, diagnostics, and anti-hypertensive medications. We used descriptive analysis and reported counts (%) and median (Interquartile Range). Results: Five facilities (46%) were of medium size with 50-100 bed-capacity, four (36%) were government-owned, five (46%) treated patients with hypertension in a hypertension clinic while the rest managed them in the general outpatient department (Table). At least one provider had received cardiovascular disease training at 7 (64%) facilities. Hypertension-related patient education materials and treatment guidelines were available in 6 (54%) and 8 (72%) facilities, respectively. Also, 7 (64%) had all of the first-line anti-hypertensive medications (as stipulated in Ghana Standard Treatment Guidelines) available. Conclusion: We identified gaps in provider training, patient education, and first-line medication availability related to hypertension in Ghana. This study calls for policy changes to improve hypertension management and prevention of cardiovascular diseases.

Background: Secondhand smoking (SHS) is the exposure to smoke arising from a burning cigarette or exhaled by a smoker. It is a significant public health problem worldwide and whether it is associated with hypertension, particularly among Africans, is yet to be clearly understood. This study evaluated the relationship between SHS and hypertension among stroke-free adults who are non-smokers in the Stroke Investigation Research and Educational Network (SIREN) study. Methods: We identified 3905 adults (≥18years who had never smoked) in the SIREN study conducted in Ghana and Nigeria. Participants reported a history of SHS exposure in an indoor environment. Hypertension was defined as one of the following conditions; mean SBP≥140mmHg, DBP≥90mmHg or use of antihypertensive medications. Logistic regression was used to estimate the multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension by SHS exposure at a two-sided P Results: Overall, mean age was 55.8±14.9years, 18.2% (712 of 3905) had SHS exposure, with a higher proportion among males 20.0% (360 of 1803) than females 16.7% (352 of 2102). SHS was associated with higher odds of having hypertension in the overall population; OR: 1.2 (95%CI: 1.0, 1.5) among females; OR: 1.6 (95%CI: 1.2, 2.1), but not among males; OR: 0.9 (95%CI: 0.7, 1.2). Conclusion: SHS was associated with higher odds of hypertension, particularly among females in this sample. The viability of public interventions in mitigating the potential effect of SHS cannot be underestimated in managing the hypertension burden among Africans, pending longitudinal studies to establish causal associations between SHS and hypertension.

See Poewe and Espay (doi:10.1093/brain/awaa226) for a scientific commentary on this article. Cilia et al. describe the natural course of motor symptoms in drug-naïve patients with Parkinson’s disease and the effects of long-term levodopa on motor disability progression in the overnight OFF-state. Compared to natural progression, levodopa reduces the annual decline in OFF-state UPDRS-III scores by almost one third., The natural pattern of progression of Parkinson’s disease is largely unknown because patients are conventionally followed on treatment. As Parkinson’s disease progresses, the true magnitude of the long-duration response to levodopa remains unknown, because it can only be estimated indirectly in treated patients. We aimed to describe the natural course of motor symptoms by assessing the natural OFF in consecutive Parkinson’s disease patients never exposed to treatment (drug-naïve), and to investigate the effects of daily levodopa on the progression of motor disability in the OFF medication state over a 2-year period. In this prospective naturalistic study in sub-Saharan Africa, 30 Parkinson’s disease patients (age at onset 58 ± 14 years, disease duration 7 ± 4 years) began levodopa monotherapy and were prospectively assessed using the Unified Parkinson’s disease Rating Scale (UPDRS). Data were collected at baseline, at 1-year and 2-years follow-up. First-ever levodopa intake induced a significant improvement in motor symptoms (natural OFF versus ON state UPDRS-III 41.9 ± 15.9 versus 26.8 ± 15.1, respectively; P

Background: Lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hs-CRP) levels are associated with cardiovascular disease (CVD) in the general population, even after adjusting for conventional CVD risk factors. However, data are limited regarding the distribution of Lp(a) and hs-CRP among patients with HIV in Ghana. We explored levels of Lp(a), hs-CRP and other cardiovascular risk factors among people who were HIV positive (HIV+) on ART (HIV+ART+), HIV+ART–, and HIV–ART– in a Ghanaian population.Methods: We conducted a cross sectional study, recruited individuals who were HIV+ART+ and HIV+ART– from the largest HIV clinic in central Ghana between August 2018 and December 2019. HIV negative controls were recruited from communities and adjoining suburbs of Kumasi. Lipoprotein(a) was measured using Immunoturbidimetric assay and high sensitive-CRP concentrations were determined using particle-enhanced turbidimetric assay. We compared levels of Lp(a), hs-CRP, and conventional CVD risk factors among these groups and used multivariable stepwise logistic regression models to explore associations between them.Results: Among HIV+ART+ (n = 156), HIV+ART– (n = 131), and HIV–ART– (n = 147), mean(SD) ages were 48 (9.1) years, 41 (11.1) years and 45 (11.9) years, p = 30mg/dL) were 70%, 48% and 62% among HIV+ART+,HIV+ART– and HIV–ART– participants respectively. Diabetes mellitus, dyslipidemia, waist-to-hip ratio and metabolic syndrome were associated with higher hs-CRP levels. Compared to HIV–ART–, HIV+ patients had higher odds of having hs-CRP > 3mg/L while HIV+ART+ patients had higher odds of elevated Lp(a) than HIV+ART– after multivariable adjustment.Conclusion: PLWHA in Ghana are associated with higher odds of elevated hs-CRP, regardless of ART use. HIV+ART+ is significantly associated with higher odds of elevated Lp(a) levels compared to HIV+ART–; even after multivariable adjustments. Reasons for this and potential clinical implications merit further study.

ObjectiveTo characterize risk factors for spontaneous intracerebral hemorrhage (sICH) occurrence and severity among West Africans.MethodsThe Stroke Investigative Research and Educational Network (SIREN) study is a multicenter case-control study involving 15 sites in Ghana and Nigeria. Patients were adults ≥18 years old with CT-confirmed sICH with age-, sex-, and ethnicity-matched stroke-free community controls. Standard instruments were used to assess vascular, lifestyle, and psychosocial factors. Factors associated with sICH and its severity were assessed using conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% confidence intervals (CIs) for factors.ResultsOf 2,944 adjudicated stroke cases, 854 were intracerebral hemorrhage (ICH). Mean age of patients with ICH was 54.7 ± 13.9 years, with a male preponderance (63.1%), and 77.3% were nonlobar. Etiologic subtypes of sICH included hypertension (80.9%), structural vascular anomalies (4.0%), cerebral amyloid angiopathy (0.7%), systemic illnesses (0.5%), medication-related (0.4%), and undetermined (13.7%). Eight factors independently associated with sICH occurrence by decreasing order of PAR with their adjusted OR (95% CI) were hypertension, 66.63 (20.78–213.72); dyslipidemia, 2.95 (1.84–4.74); meat consumption, 1.55 (1.01–2.38); family history of CVD, 2.22 (1.41–3.50); nonconsumption of green vegetables, 3.61 (2.07–6.31); diabetes mellitus, 2.11 (1.29–3.46); stress, 1.68 (1.03–2.77); and current tobacco use, 14.27 (2.09–97.47). Factors associated with severe sICH using an NIH Stroke Scale score >15 with adjusted OR (95% CI) were nonconsumption of leafy green vegetables, 2.03 (1.43–2.88); systolic blood pressure for each mm Hg rise, 1.01 (1.00–1.01); presence of midline shift, 1.54 (1.11–2.13); lobar ICH, 1.72 (1.16–2.55); and supratentorial bleeds, 2.17 (1.06–4.46).ConclusionsPopulation-level control of the dominant factors will substantially mitigate the burden of sICH in West Africa.

Background: There is paucity of data on the epidemiology of post-stroke cognitive impairment among African stroke survivors. The aim of this study is to report the profile and risk factors of post- stroke cognitive impairment among stroke survivors participating in the Stroke Investigative Research and Education Network (SIREN) Study. Methods: 1566 were evaluated with the Montreal Cognitive Assessment (MoCA) tool, the Community Screening Instrument for Dementia (CSID) and the Stick Design Test three months after the index stroke. Domain scores were derived for executive function, language memory and visuo-constructive/visuospatial domains. Cut off scores were derived from normative cognitive data obtained from comparable healthy stroke-free control subjects. We used conditional logistic regression to estimate odds ratios (OR) with 95% CIs. Results: Of 1566 stroke survivors [mean age 57.7 (13.4) years] who were assessed 3 months after stroke, 37% were impaired in global cognition and 18-43% were impaired in different domains of cognition (executive, memory, language and visuo-constructive). Stroke severity measured by modified NIHSS score had a strong significant negative association with cognitive function in all domains OR 1.96(1.32-2.91). Older age 1.04 (1.02-2.05), male gender 0.69 (0.50 -0.96), low intake of green leafy vegetables 2.83 (2.03 -3.95) and cardiac disease 1.86 (1.31 -2.75) were associated with poorer cognitive performance in different cognitive domains. Conclusion: The frequency of post-stroke cognitive impairment was high among African stroke survivors three months after the ictus. Diet low in green leafy vegetables is a potentially modifiable risk factor for post-stroke cognitive impairment among West Africans.

Background: The risk factors associated with the occurrence of the distinct pathophysiologic subtypes of ischemic stroke are unknown among indigenous Africans. Objective: To identify and quantify the contributions of risk factors for occurrence of ischemic stroke and its etiologic subtypes among West Africans. Methods: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Nigeria and Ghana. Cases included adults aged >18 years with CT/MRI confirmed stroke and ischemic strokes were etiologically subtyped using the TOAST protocol. 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 using standard instruments. We used conditional logistic regression to estimate odds ratios (OR) with 95% CIs. Results: There were 1,721 ischemic stroke cases with a mean age of 62.19 ± 14.03 vs 60.86 ± 13.71 for controls. Using the TOAST etiologic scheme, 867 (50.3%) were small vessel occlusions, 425(24.7%) were large-artery atherosclerotic, 181(10.5%) were cardio-embolic, 204(11.9%) were undetermined and 44(2.6%) were of other determined etiology. The 7 dominant risk factors for ischemic strokes aOR (95%CI) were hypertension 10.76(7.15-16.20), dyslipidemia 5.30(3.86-7.29), diabetes 3.61(2.72-4.80), psychosocial stress 1.68(1.20-2.35), cardiac disease 1.94 (1.25-3.02), meat consumption 2.02(1.54-2.65), green vegetable consumption 0.44(0.33-0.59). Hypertension, dyslipidemia, diabetes, meat consumption and green vegetable intake were confluent factors shared by small-vessel, large-vessel and cardio-embolic ischemic stroke subtypes. Conclusion: We provide empiric evidence of risk factors to be targeted for stroke prevention. Our findings open a vista into future studies aimed at elucidating the genetic factors linked with pathophysiologic subtypes of stroke among Africans.

Background The burden of stroke among hypertensive and diabetic population in sub-Saharan Africa remains high. We sought to identify the risk factors associated with stroke occurrence in these high-risk population groups. Methods A prospective cohort study involving adults with hypertension and or type II diabetes mellitus at 5 public hospitals in Ghana who were stroke-free at enrollment. Patients were followed every 2 months at clinic for 18 months and assessed clinically for first ever stroke by physicians. We calculated crude incidence rates for stroke and assessed the factors associated with stroke occurrence using a multivariate Cox Proportional Hazards regression models. Results Of 3220 eligible participants with 3805 person-years of follow-up, there were 54 clinically confirmed new strokes. Incidence rate of stroke was 14.19 events per 1000 person-years [95% CI: 10.77–18.38], with rates among diabetics with hypertension being 16.64 [10.58–25.00], hypertension of 13.77 [9.33–19.64] and diabetes was 9.81 [3.59–21.74]. Two factors independently associated with stroke occurrence were previous cigarette smoking with adjusted HR (95% CI) of 2.59 (1.18–5.67) and physical inactivity, 1.81 (1.06–3.10). In secondary analysis, stage II hypertension compared with optimal BP was associated with aHR of 3.04 (1.00–9.27), p = .05 for stroke occurrence. Conclusion Incident stroke among Ghanaians with hypertension and diabetes is quite high. Stricter control of blood pressure and engaging in regular physical activities are strongly recommended to reduce the risk of strokes., Highlights • The first prospective cohort study to assess factors associated with incident strokes among Ghanaians • 3220 participants stroke free adults with hypertension or diabetes were followed for an average of 14 months • There were 54 strokes with incidence rate of 14.19 events per 1000 person-years • Patients with both diabetes with hypertension had highest stroke rates • Previous cigarette smoking and physical inactivity were independently associated with incident strokes

Objectives 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. Materials and methods We assessed baseline data being collected as part of an intervention to improve one-year blood pressure control among recent (≤1 month) stroke survivors in SSA. Anxiety in this patient population was measured using the Hospital Anxiety and Depression Scale (HADS), while the community screening instrument for dementia was used to evaluate cognitive functioning. Independent associations were assessed using logistic regression analysis. Results Among 391 participants, clinically significant anxiety (HADS anxiety score≥11) was found in 77 (19.7%). Anxiety was comorbid with depression in 55 (14.1%). Female stroke survivors were more likely than males to have anxiety (OR=2.4, 95% CI=1.5-4.0). Anxiety was significantly associated with the presence of cognitive impairment after adjusting for age, gender and education (OR=6.8, 95% CI=2.6-18.0). Conclusions One in five recent stroke survivors in SSA has clinically significant anxiety, and well over 70% of those with anxiety also have depression. Future studies will need to determine what specific impact post-stroke anxiety may have on post-stroke clinical processes and outcomes.

Background Little is known about the relationship between echocardiographic abnormalities and outcome among patients with acute stroke. We investigated the pattern and association of baseline echocardiographic variables with 1‐month disability and mortality among patients with stroke in the SIREN (Stroke Investigative Research and Education Network) study. Methods and Results We enrolled and followed up consecutive 1020 adult patients with acute stroke with baseline transthoracic echocardiography from west Africa. To explore the relationship between echocardiographic variables and 1‐month disability (using modified Rankin scale >3) and fatality, regression models were fitted. Relative risks were computed with 95% CIs. The participants comprised 60% men with a mean age of 59.2±14.6 years. Ischemic stroke was associated with smaller aortic root diameter (30.2 versus 32.5, P =0.018) and septal (16.8 versus 19.1, P P =0.004). Over 90% of patients with stroke had abnormal left ventricular (LV) geometry with eccentric hypertrophy predominating (56.1%). Of 13 candidate variables investigated, only baseline abnormal LV geometry (concentric hypertrophy) was weakly associated with 1‐month disability (unadjusted relative risk, 1.80; 95% CI , 0.97–5.73). Severe LV systolic dysfunction was significantly associated with increased 1‐month mortality (unadjusted relative risk, 3.05; 95% CI , 1.36–6.83). Conclusions Nine of 10 patients with acute stroke had abnormal LV geometry and a third had systolic dysfunction. Severe LV systolic dysfunction was significantly associated with 1 month mortality. Larger studies are required to establish the independent effect and unravel predictive accuracy of this association.

Background Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is associated with neuropsychiatric toxicity. Little is known about the risk of short- and long-term neuropsychiatric toxicity in sub-Saharan Africa, where NNRTIs are widely used in first-line combination ART. This observational study assessed the risk of neuropsychiatric toxicity in Ghanaian patients starting first-line ART between 2004 and 2010 at a single centre. Methods In this retrospective observational study, frequencies of documented neuropsychiatric toxicity events were assessed and time to events calculated using a Kaplan–Meier analysis. Associations of neuropsychiatric toxicity with specific NNRTIs and other explanatory variables were examined using Cox proportional hazards modelling. Results Of 3999 patients initiating NNRTI-based ART, who were followed for a median of 30 (0.25–90) months (11,237 person years), 218 (5.5%) reported symptoms of neuropsychiatric toxicity at a rate of 21.4 events per 1000 person-years (95% CI, 18.8–24.2/1000 py). Events were more common with efavirenz than nevirapine (7.6% versus 2.4%), were usually reported within the first 2 months of ART initiation and persisted up to 84 months in a few patients. The most commonly reported neuropsychiatric adverse drug reactions were insomnia (50%), headaches (8%), dizziness (7%) and abnormal dreams (6%). The factors independently associated with neuropsychiatric toxicity were BMI, Highlights • Millions of patients living with HIV AIDS in sub-Saharan Africa are initiated on an efavirenz-based combination antiretroviral therapy which is frequently associated with neuropsychiatric toxicity. • In this retrospective study involving 3999 Ghanaian HIV-infected patients initiating therapy between 2004 and 2010, neuropsychiatric toxicity was documented in 5.5% with a higher incidence among efavirenz recipients (7.6%) compared with nevirapine recipients (2.4%). • Peak neuropsychiatric adverse events occurred within the first two months upon initiating therapy with some few further events occurring as later on during 90 months of follow-up. • Up to 17% of patients reporting neuropsychiatric toxicity had treatment modifications as a result.

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., Highlights • This study seeks to evaluate the performance of the 8-item QVSFS in Akan, Yoruba and Hausa for the ascertainment of stroke-free status among West Africans. • A line pictogram has been developed to determine its impact on the relative performance of the 8-item QVSFS.

Background Graves disease (GD) has increased in prevalence over the past decade in Africa. Despite this, the condition is not well described, especially in sub-Saharan Africa. Objective We have described the clinical characteristics and associated factors of GD in a cohort of patients attending a resource-limited setting tertiary hospital. Methods Patients were examined thoroughly and systematically tested for the degree of clinical and biochemical thyroid status. Thyroid volume, characteristics, and blood flow were assessed at presentation using ultrasonography. Factors associated with an inability to achieve clinical and biochemical thyroid remission were evaluated using multiple logistic regression analysis. Results Overall, 182 patients were studied, 152 (83.5%) were women with a female:male ratio of 5.1:1.0. The mean age at presentation was 39.9 ± 14.7 years with women significantly older than men. Thyroid-associated orbitopathy (TAO) was observed in 56% of the participants and pretibial myxoedema in 6%. About 84% of the participants were hyperthyroid at presentation, 9% were euthyroid, 4% were hypothyroid, and 3% had subclinical hyperthyroidism. Inability to achieve biochemical and clinical remission at 24 months was associated with increased thyroid volume (odds ratio [OR]: 2.35, 95% confidence interval [CI]: 1.85-2.52, P < .001), presence of TAO (OR: 2.15, 95% CI: 2.12-2.33, P < .001), increased FT3/FT4 ratio (OR: 1.33, 95% CI: 1.24-2.56, P = .004), and missed clinic appointment (OR: 5.2, 95% CI: 4.55-7.89, P < .001). Conclusions Graves disease among Ghanaians is associated with significant signs at presentation. Inability to achieve remission within the first 24 months is associated with increased thyroid volume, TAO, an increased FT3/FT4 ratio, as well as missed clinic appointment.

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 P P P P 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.

Background HCV RNA screening of large sample repositories provides data on HCV epidemic patterns that may help guide control policies. In resource-limited settings, shipment of frozen samples to molecular laboratory facilities and testing of individual samples may be prohibitively expensive. Objective Our aim was to detect and sequence HCV RNA in a large HIV-positive cohort from Kumasi, Ghana, using pooled and individual dried plasma spots (DPS) produced from samples stored at −80 °C. Study design In the validation phase, replicate DPS were prepared with six dilutions (500–10,000 IU/ml) of the 4th International Standard for HCV and tested in three independent experiments. In the testing phase, DPS prepared with plasma samples from 875 HIV-positive subjects were pooled for screening, followed by testing of individual DPS of positive pools. Input from individual DPS was two 6 mm punches; pools comprised two punches from each of five DPS. Genotypes were determined by Sanger sequencing of HCV core and NS5B. Results With the dilution series, sensitivity of HCV RNA detection was ≥2500 IU/ml. Replicate DPS gave intra-assay and inter-assay coefficients of variation ≤1.4%. With the stored samples, HCV RNA was detected in 5/175 DPS pools and in one DPS from each positive pool, yielding a HCV RNA prevalence of 5/875 (0.57%; 95% confidence interval 0.07-1.07%). The five samples were sequenced as HCV genotypes 2l and 2r. Discussion DPS allowed reproducible HCV RNA detection, and pooling effectively contained the cost and labour of screening a previously untested, low-prevalence cohort. DPS were also suitable for HCV sequencing.

Introduction: The relative contributions of racial and environmental factors to the higher risk of stroke in people of African ancestry are not clear due to limited opportunities to evaluate stroke type and risk among indigenous Africans, in comparison with Africans in diaspora and their host populations. This knowledge could provide insights into avenues for similar vs. unique approaches to managing stroke risk in Africans. Objective: To compare the pattern of stroke and contribution of vascular risk factors to stroke among indigenous Africans, African Americans and European Americans. Methods: SIREN is a large multicenter case-control study involving several sites in West Africa, the ancestral home of 71% African Americans, whilst REGARDS is a cohort study including African and European Americans in the United States. Stroke diagnosis and type were confirmed using CT or MRI scan. Traditional vascular risk factors were assessed using history, physical examination and laboratory investigations. We compared data from acute stroke cases age≥55 years in SIREN and REGARDS in the distribution of key socio-demographic and clinical risk factors based on harmonized standard definitions. Results: There were 811 stroke subjects in the SIREN population (A) and 452 African Americans (B) and 665 European Americans (C) from the REGARDS study with a progressive increment in mean age of 68.0 ± 9.3, 73.0 ± 8.3 and 76.0 ± 8.3 years respectively, p Conclusion: Environmental risk factors such as cigarette smoking may contribute to the higher proportion of ischemic stroke in African-Americans compared to indigenous Africans, while racial factors may contribute to the higher proportion of hypertension among stroke subjects of African ancestry.

Background. Ghana began mandatory iodization of salt in 1996. This study compares the prevalence of thyroid disorders before and after the introduction of iodization. Methods. This is a retrospective study of thyroid cases from the middle belt of Ghana between 1982 and 2014. To demonstrate a link between iodization and hyperthyroidism and autoimmunity, we compared the prevalence of hyperthyroidism and autoimmune thyroid disorders before and after the iodization programme. Results. A total of 10,484 (7548 females, 2936 males) cases were recorded. The rate of thyroid cases seen was 343/100,000. Nontoxic nodular goiters (25.7%) and toxic nodular goiters (22.5%) represented the second commonest thyroid disorders recorded. The prevalence of hyperthyroid disorders seen after 1996 was significantly higher than the prevalence seen before the iodization (40.0 versus 21.1%, p<0.001). The prevalence of autoimmune disorders recorded after iodization was significantly higher than that before the iodization programme started (22.3% versus 9.6%, p<0.001). Conclusions. This study has revealed a significant increase in thyroid admissions in Central Ghana over the decades. A connection between iodine fortification and iodine-induced hyperthyroidism and between iodine fortification and autoimmune thyroiditis has been shown in this study.

During August 2010–December 2012, we conducted a study of patients in Ghana who had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co-infected with Mansonella perstans nematodes; 13% of controls also had M. perstans infection. M. perstans co-infection should be considered in the diagnosis and treatment of Buruli ulcer.

This study was conducted to determine the frequency and pattern of cognitive impairment in the elderly at the outpatients clinic of the Holy Family Hospital, Techiman, Ghana. The study was a descriptive cross-sectional study. Cognitive impairment was assessed using modified versions of the ‘test

Buruli ulcer (BU) is an infectious skin disease that occurs mainly in West and Central Africa. It can lead to severe disability and stigma because of scarring and contractures. Effective treatment with antibiotics is available, but patients often report to the hospital too late to prevent surgery and the disabling consequences of the disease. In a highly endemic district in Ghana, intensified public health efforts, mainly revolving around training and motivating community-based surveillance volunteers (CBSVs), were implemented. As a result, 70% of cases were reported in the earliest—World Health Organization category I—stage of the disease, potentially minimizing the need for surgery. CBSVs referred more cases in total and more cases in the early stages of the disease than any other source. CBSVs are an important resource in the early detection of BU.

OBJECTIVES Information on the long-term effectiveness and tolerability of efavirenz- or nevirapine-based antiretroviral therapy (ART) in Africa is lacking. The primary objective of this retrospective observational study was to compare the long-term clinical and immunological outcomes of efavirenz- versus nevirapine-based first-line ART in a large government clinic in Ghana. PATIENTS AND METHODS The main outcomes were AIDS, death, ART-related toxicity, discontinuation of ART and a composite endpoint of death, AIDS or ART discontinuation. These time-to-event outcomes were compared using a Cox proportional hazards regression model. CD4 counts on ART were compared using a mixed-effects model. RESULTS A total of 3990 patients started non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART between 2004 and 2010, of which 2369 (59%) were on efavirenz. No significant differences were apparent between each NNRTI for subsequent risk of AIDS, death or the composite of treatment failure; however, stavudine use was independently associated with an increased risk of death [adjusted hazard ratio (HR) 1.60 (95% CI: 1.21-2.11)]. There was an increased risk of early toxicity with nevirapine leading to discontinuation [adjusted HR 1.53 (95% CI: 1.23-1.97)], mostly due to excess skin rashes in the first 2 months of treatment; however, overall discontinuation rates were low. CONCLUSIONS There was no difference in the long-term effectiveness of efavirenz- and nevirapine-based ART in this population; however, patients initiating nevirapine were more likely to develop early toxicity and discontinue this drug. The excess mortality observed in patients taking stavudine is of concern and should prompt increased efforts to replace it with alternative antiretroviral drugs in developing countries.

Stroke is the leading cause of neurological hospital admissions in sub-Saharan Africa (SSA) and the second leading cause of death globally. The Stroke Investigative Research and Education Network seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams for research to address and decrease the burden of stroke and other noncommunicable diseases in SSA. One of the first steps to address this goal is to effectively engage the communities that suffer the high burden of disease. The purpose of this article is to describe plans to elucidate information about knowledge, attitudes, beliefs, and practices about stroke and genomics from patients, caregivers, and local leaders, to recruit participation in research activities and dissemination of ongoing results, as well as to facilitate research uptake and impact within the broader communities of scientists, health professionals, policy makers, and others. We describe the (a) study sites and their communities; (b) plans for community advisory boards, focus groups, and surveys; (c) methods for data management in REDCap database; (d) analyses of qualitative data; (e) evaluation of community and public engagement across multiple sites and research teams in SSA and the United States; (f) use of RE-AIM for presentation of evaluation data; and (g) community indicators of success. This is the first of its kind public outreach engagement initiative to evaluate stroke and genomics in SSA, and has implications as a model for assessment in other high–stroke risk populations.

Background: It is projected that Sub-Saharan Africa (SSA) will experience a rising epidemic of cardiovascular diseases (CVD) driven by a surge in rates of major CVD risk factors; while it has been well established for several decades that African Americans have a much higher stroke incidence and mortality than their non-Hispanic White Counterparts. Objective: To compare baseline characteristics of current Black stroke survivors in SSA with Black stroke survivors encountered during a roughly similar epidemiologic stage (i.e. earlier aspects of the “Age of Degenerative and Man-Made Diseases” ) in the United States (US). Methods: We compared baseline data obtained in 1960 from stroke cases within the historical Black Pooling Project (BPP) comprising the Charleston Heart Study and Evans County Heart Study cohorts with baseline data from stroke cases encountered within the ongoing Stroke Investigative Research and Education Network (SIREN) Project taking place at several sites in Nigeria and Ghana. Results: There were 188 stroke cases in the BPP cohort and 422 in the SIREN cohort. We found a similar pattern of events by age (figure 1) between the two study populations with the majority of the strokes occurring before 65 years of age (BPP 67%;SIREN 65%). However, SIREN cases were more common at the age extremes, and BPP cases more common in the middle-age range. Modifiable risk factors were comparable between the groups: hypertension (BPP 89%; SIREN 90%) and diabetes (BPP 3%; SIREN 20%). Conclusion: While baseline hypertension rates of Black American stroke survivors in the 1960s and Black Africans in the 2010s are similar, the former experienced stroke more frequently in mid-life and lower rates of diabetes. Further phenotypic and genotypic comparisons of both these cohorts could provide novel insights into stroke risk among people of African ancestry.

International audience; Infection of human skin with Mycobacterium ulcerans, the causative agent of Buruli ulcer, is associated with the systemic diffusion of a bacterial macrolide named mycolactone. Patients with progressive disease show alterations in their serum proteome, likely reflecting the inhibition of secreted protein production by mycolactone at the cellular level. Here, we used semi-quantitative metabolomics to characterize metabolic perturbations in serum samples of infected individuals, and human cells exposed to mycolactone. Among the 430 metabolites profiled across 20 patients and 20 healthy endemic controls, there were significant differences in the serum levels of hexoses, steroid hormones, acylcarnitines, purine, heme, bile acids, riboflavin and lysolipids. In parallel, analysis of 292 metabolites in human T cells treated or not with mycolactone showed alterations in hexoses, lysolipids and purine catabolites. Together, these data demonstrate that M. ulcerans infection causes systemic perturbations in the serum metabolome that can be ascribed to mycolactone. Of particular importance to Buruli ulcer pathogenesis is that changes in blood sugar homeostasis in infected patients are mirrored by alterations in hexose metabolism in mycolactone-exposed cells. Buruli ulcer (BU) is a necrotizing disease of the skin caused by infection with Mycobacterium ulcerans, the third most prevalent mycobacterial pathogen in humans after M. tuberculosis and M. leprae 1. How M. ulcerans is transmitted to humans is not fully understood, however there is increasing evidence that breaches in the skin barrier and exposure to contaminated environments are both required 2–5. Since the 1980s, BU has spread in low-income developing countries of West Africa 6. If not diagnosed or treated appropriately, it can result in irreversible deformity, functional disability and life-threatening secondary infections. The current diagnosis methods include acid-fast staining, culture or amplification of bacterial DNA from fine needle aspirates, swabs or skin biopsies 7. Treatment consists of the daily administration of rifampicin and streptomycin for eight weeks 8,9 , and excision surgery of large lesions. Although effective, control programs are costly, reactive rather than pro-active, and globally unsuited to field conditions. In order to improve the detection and management of BU, it is essential to improve our understanding of the molecular and cellular mechanisms underpinning BU pathogenesis 10. M. ulcerans is unique amongst human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone 11–14. Bacterial production of mycolactone is essential for BU formation, as shown by the avirulence of mycolactone-deficient strains of M. ulcerans in rodent models of infection. While bacteria grow primarily in host skin tissues, mycolactone gains access to the peripheral circulation 15,16. Foodpad infection of mice with wild-type, but not mycolactone-deficient strains of M. ulcerans, induced intrinsic defects in blood T cells evidenced by their incapacity to produce cytokines

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.

Buruli ulcer, an ulcerating skin disease caused by Mycobacterium ulcerans infection, is common in tropical areas of western Africa. We determined the clinical and microbiological responses to administration of rifampin and streptomycin for 2 weeks followed by administration of rifampin and clarithromycin for 6 weeks in 43 patients with small laboratory-confirmed Buruli lesions and monitored for recurrence-free healing. Bacterial load in tissue samples before and after treatment for 6 and 12 weeks was monitored by semiquantitative culture. The success rate was 93%, and there was no recurrence after a 12-month follow-up. Eight percent had a positive culture 4 weeks after antibiotic treatment, but their lesions went on to heal. The findings indicate that rifampin and clarithromycin can replace rifampin and streptomycin for the continuation phase after rifampin and streptomycin administration for 2 weeks without any apparent loss of efficacy.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli., Author Summary Mycobacterium ulcerans infection causes Buruli ulcer (BU), a disfiguring skin disease now found principally in poor rural areas of West Africa. M. ulcerans produces a toxin called mycolactone (ML), which destroys fat cells in skin tissue. BU typically first shows as a nodule that eventually ulcerates. The lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills the bacilli and wounds gradually heal. We tried to determine if RS treatment actually stops mycolactone production before killing bacilli. Using a mouse footpad model of M. ulcerans infection where the time of infection and lesion development can be followed in a controlled manner before and after antibiotic treatment, we found that RS treatment rapidly reduced footpad swelling, M. ulcerans numbers, and ML production. Microscopic analysis of footpads revealed that RS treatment resulted in bacilli being destroyed by host cells whereas lack of treatment resulted in extracellular infection, destruction of host cells, and lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans.

HIV/hepatitis B virus (HBV) coinfection is common in Ghana, where first-line antiretroviral therapy (ART) comprises lamivudine with zidovudine or stavudine and nevirapine or efavirenz. Little is known about ART outcomes in the context of coinfection. This study evaluated outcomes of ART among HIV/HBV-coinfected Ghanaians, focusing on locally available parameters.An observational study comparing clinical and virological outcomes in HIV-infected individuals who were either hepatitis B surface antigen (HBsAg) positive or HBsAg negative was conducted over 36 months. Clinical events, hepatic transaminases, CD4 count and body mass index (BMI) were evaluated among 143 HBsAg-positive and 228 HBsAg-negative patients. In a random subset of HBsAg-positive patients, HBV-DNA levels and polymerase sequences were analysed.Comparing HBsAg-positive and HBsAg-negative patients, 44/143 (30.8%) and 83/228 (36.4%) defaulted follow-up, 15/143 (10.5%) and 30/228 (13.2%) experienced a new clinical event, and 8/143 (5.6%) and 11/228 (4.8%) discontinued their initial regimen, respectively. Transaminase levels were higher in HBsAg-positive patients, although elevations were low grade. HBV coinfection was associated with an adjusted 2.04 (95% CI 0.59-3.49) cells/mm(3)/month smaller CD4 cell increase; there was no significant effect on BMI changes. After a median of 9 months of ART, 64/66 (97.0%) patients showed detectable HBV-DNA (median 3.3 log(10) IU/mL; IQR 2.6-6.2); 12/53 (22.6%) of these showed lamivudine-associated resistance mutations.HIV/HBV-coinfected Ghanaians tolerated first-line ART well, but experienced blunted CD4 cell responses. There was evidence of ongoing HBV replication, mild but persistent transaminase elevations and emerging lamivudine resistance in a proportion of treated patients, indicating the potential for progressive liver damage.

It has recently been shown that in a Buruli ulcer (BU) endemic region of southeastern Australia, significant numbers of possums (native tree-dwelling marsupials) have clinical BU disease. Furthermore, based on quantitative PCR (qPCR) analysis, animals with BU lesions (and some without) shed M. ulcerans DNA in their faeces, indicative of bacterial loads of up to 10(8) organisms/gram. These findings led us to propose that humans might also harbour M. ulcerans in their gastrointestinal tract and shed the bacterium in their faeces. We conducted a pilot study and collected faecal swabs from 26 patients with confirmed BU and 31 healthy household controls. Faecal samples were also collected from 10 healthy controls from non-endemic regions in Ghana. All 67 specimens were negative when tested by IS2404 PCR. The detection sensitivity of this method was ≥10(4) bacteria per gram (wet-weight) of human faecal material. We conclude that the human gastrointestinal tract is unlikely to be a significant reservoir of M. ulcerans.

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