Estimating vaccine coverage in conflict settings using geospatial methods: a case study in Borno state, Nigeria.

Reliable estimates of subnational vaccination coverage are critical to track progress towards global immunisation targets and ensure equitable health outcomes for all children. However, conflict can limit the reliability of coverage estimates from traditional household-based surveys due to an inability to sample in unsafe and insecure areas and increased uncertainty in underlying population estimates. In these situations, model-based geostatistical (MBG) approaches offer alternative coverage estimates for administrative units affected by conflict. We estimated first- and third-dose diphtheria-tetanus-pertussis vaccine coverage in Borno state, Nigeria, using a spatiotemporal MBG modelling approach, then compared these to estimates from recent conflict-affected, household-based surveys. We compared sampling cluster locations from recent household-based surveys to geolocated data on conflict locations and modelled spatial coverage estimates, while also investigating the importance of reliable population estimates when assessing coverage in conflict settings. These results demonstrate that geospatially-modelled coverage estimates can be a valuable additional tool to understand coverage in locations where conflict prevents representative sampling.

Rationale, Design, and the Baseline Characteristics of the RHDGen (The Genetics of Rheumatic Heart Disease) Network Study†.

BACKGROUND: The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries. METHODS: RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented. Biological samples were collected for conducting genetic analyses, including a discovery case-control genome-wide association study (GWAS) and a replication trio family study. Additional biological samples were also collected, and processed, for the measurement of biomarker analytes and the biomarker analyses are underway. RESULTS: Participants were enrolled into RHDGen between December 2012 and March 2018. For GWAS, 2548 RHD cases and 2261 controls (3301 women [69%]; mean age [SD], 37 [16.3] years) were available. RHD cases were predominantly Black (66%), Admixed (24%), and other ethnicities (10%). Among RHD cases, 34% were asymptomatic, 26% had prior valve surgery, and 23% had atrial fibrillation. The trio family replication arm included 116 RHD trio probands and 232 parents. CONCLUSIONS: RHDGen presents a rare opportunity to identify relevant patterns of genetic factors and biomarkers in Africans that may be associated with differential RHD risk. Furthermore, the RHDGen Network provides a platform for further work on fully elucidating the causes and mechanisms associated with RHD susceptibility and development.

Secondhand smoke exposure is independently associated with stroke among non-smoking adults in West Africa.

BACKGROUND: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans. OBJECTIVE: To evaluate the association of SHSE with stroke among indigenous Africans. METHODS: We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05. RESULTS: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes. CONCLUSION: Culturally relevant primary prevention strategies targeted at SHSE might be promising in preventing stroke among Africans.

Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.

BACKGROUND: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. METHODS: We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. RESULTS: Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. CONCLUSIONS: These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.

Risk Factor Characterization of Ischemic Stroke Subtypes Among West Africans.

BACKGROUND AND PURPOSE: To identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI. RESULTS: There were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001). CONCLUSIONS: Traditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

Unraveling the risk factors for spontaneous intracerebral hemorrhage among West Africans.

OBJECTIVE: To characterize risk factors for spontaneous intracerebral hemorrhage (sICH) occurrence and severity among West Africans. METHODS: The 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. RESULTS: Of 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). CONCLUSIONS: Population-level control of the dominant factors will substantially mitigate the burden of sICH in West Africa.

Subclinical atherosclerosis and associated risk factors among HIV-infected adults in Jos, North Central Nigeria: a cross-sectional study.

INTRODUCTION: human immunodeficiency virus (HIV) is evolving into a leading cause of cardiovascular diseases (CVD) in sub-Saharan Africa (SSA) where the burden of HIV remains high. Atherosclerosis underlie progression to CVD. We therefore examined the prevalence of subclinical atherosclerosis and its association with traditional and non-traditional risk factors for CVD in Nigerian HIV-infected adults. METHODS: this was a cross-sectional study involving randomly selected stable HIV-infected patients with undetectable viral load attending HIV clinics at the Jos University Teaching Hospital and Faith Alive Foundation in Jos, Nigeria. Demographic data, biophysical measurements, cardiovascular risk factors and information regarding HIV-related factors, fasting serum lipid profile, fasting plasma glucose, high-sensitivity C-reactive protein and Carotid-Intima-Media-Thickness (CIMT) were assessed. Subclinical atherosclerosis was defined using a cut-off value of mean CIMT ≥ 0.78 mm. Data were analyzed with the Statistical Package for Social Sciences® (SPSS) software version 23.0 (IBM Corp., Chicago, Illinois, USA). Bivariate analysis and multivariate logistic regression were used to examine the association between risk factors of CVD and subclinical atherosclerosis. The statistical significance level was set at p ≤ 0.05. RESULTS: a total of 148 HIV adults (70.9% being females) on Anti-Retroviral Therapy (ART) were included in this study. The prevalence of subclinical atherosclerosis was 7.4%. Among subjects with subclinical atherosclerosis (SCA), 63.6% were males and 81.8% were hypertensive. Elevated blood glucose, lipids and high-sensitivity C-reactive protein, body mass index (BMI), HIV-related parameters (duration of HIV infection, antiretroviral regimen, CD4+ cell count), current smoking status, alcohol use, were not significantly associated with subclinical atherosclerosis (p>0.05). Male gender [OR(95%CI=4.91(1.36-17.77)], age [OR(95%CI)=1.14(1.06-1.23)], hypertension [OR(95%CI=14.4(3.03-71.86)] and metabolic syndrome [OR(95%CI=8.34(1.73-40.18)] were significantly associated with SCA at bivariate analysis. After adjusting for age, sex and antiretroviral regimen, only increasing age [Adjusted Odds Ratio (AOR) (95% confidence interval (CI)] = 1.12(1.01-1.25)] and hypertension [AOR (95%CI)=10.67 (1.31-87.18)], remained as independent predictors of subclinical atherosclerosis (SCA). CONCLUSION: the prevalence of subclinical atherosclerosis among HIV-infected adults is high in Nigeria. It is significantly associated with increasing age and hypertension. Traditional CVD risk factors such as dyslipidaemia, diabetes mellitus and obesity were not associated with subclinical atherosclerosis in this population.

Echocardiographic Abnormalities and Determinants of 1-Month Outcome of Stroke Among West Africans in the SIREN Study.

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<0.001) and posterior wall thickness at systole (18.9 versus 21.5, 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.

Elastomeric pump malfunction resulting in over-infusion of local anesthetic.

A 70 year-old female patient presented for a right humeral head replacement. Preoperatively an interscalene catheter was placed and postoperatively connected to an elastomeric pump for continuous infusion at 8 mL/h of Ropivacaine 0.2% with an additional 5 mL patient activated bolus available every 30 min. About 17 h after the elastomeric pump was connected to the catheter, the 550 mL reservoir was found to be empty, indicating the pump's infusion rate was more than 32 mL/h despite the pump still being set at an infusion rate of 8 mL/h with a possible 5 mL bolus every 30 min. There was no visible damage or leak in the pump system, and the insertion site was dry. The patient denied any changes to the pump settings. She was alert and oriented and denied any signs of local anesthetic toxicity. The catheter was immediately pulled and the manufacturer notified. The manufacturer found a red tab broken inside the patient-controlled bolus remote resulting in the over-infusion. Despite the dependability of elastomeric pumps, healthcare providers must be aware of their possible complications and malfunctions.

Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study.

BACKGROUND: It is crucial to assess genomic literacy related to stroke among Africans in preparation for the ethical, legal and societal implications of the genetic revolution which has begun in Africa. OBJECTIVE: To assess the knowledge, attitudes and practices (KAP) of West Africans about stroke genetic studies. METHODS: A comparative cross-sectional study was conducted among stroke patients and stroke-free controls recruited across 15 sites in Ghana and Nigeria. Participants' knowledge of heritability of stroke, willingness to undergo genetic testing and perception of the potential benefits of stroke genetic research were assessed using interviewer-administered questionnaire. Descriptive, frequency distribution and multiple regression analyses were performed. RESULTS: Only 49% of 2029 stroke patients and 57% of 2603 stroke-free individuals knew that stroke was a heritable disorder. Among those who knew, 90% were willing to undergo genetic testing. Knowledge of stroke heritability was associated with having at least post-secondary education (OR 1.51, 1.25-1.81) and a family history of stroke (OR 1.20, 1.03-1.39) while Islamic religion (OR=0.82, CI: 0.72-0.94), being currently unmarried (OR = 0.81, CI: 0.70-0.92), and alcohol use (OR = 0.78, CI: 0.67-0.91) were associated with lower odds of awareness of stroke as a heritable disorder. Willingness to undergo genetic testing for stroke was associated with having a family history of stroke (OR 1.34, 1.03-1.74) but inversely associated with a medical history of high blood pressure (OR = 0.79, 0.65-0.96). CONCLUSION: To further improve knowledge of stroke heritability and willingness to embrace genetic testing for stroke, individuals with less formal education, history of high blood pressure and no family history of stroke require targeted interventions.

Domestic solid fuel combustion in an adult population in Nigeria: A cross sectional analysis of association with respiratory symptoms, quality of life and lung function.

BACKGROUND AND OBJECTIVES: We examined the association of respiratory symptoms, health status, and lung function with the use of solid fuel (wood, charcoal, coal or crop residue) for cooking or heating in a predominantly non-smoking population. METHODS: Using the protocol of the Burden of Obstructive Lung Diseases (BOLD) initiative, we collected representative population data using questionnaires and spirometry tests. We categorized solid fuel use into 'never user', 'ex user' and 'current user' based on responses to the survey. We developed regression models to evaluate the relation between use of solid fuel and the prevalence of respiratory symptoms, quality of life and lung function adjusting for confounding variables. RESULTS: Out of 1147 respondents with complete information on domestic fuel type, 33% were 'never-users', 19% were 'ex-users' while 48% reported current use of solid fuel for domestic cooking and/or indoor heating. Compared with never-users, current solid fuel users were more likely to report cough (OR: 1.7, 95% CI: 1.0, 2.9), cough or phlegm (OR: 1.6, 95% CI: 1.0, 2.5) and the association was stronger among women (OR: 3.0, 95% CI: 1.3, 7.1 and OR: 2.3, 95% CI: 1.1, 5.2, respectively). Current solid fuel users also had lower mental health status (coefficient: ?1.5, 95% CI: ?2.8, - 0.2) compared with the group of never-users. Current or previous domestic use of solid fuels for cooking or heating was not associated with higher prevalence of chronic airflow obstruction (FEV1/FVC < LLN). CONCLUSIONS: Using solid fuel for domestic cooking or heating was associated with a higher risk of cough or phlegm and a lower mental quality of life. However we found no significant effect in the prevalence of chronic airflow obstruction in Ife, Nigeria.

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

BACKGROUND: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. METHODS: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. RESULTS: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries. CONCLUSIONS: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.

Aortic aneurysm with valvular insufficiency: is it due to Marfan syndrome or hypertension? A case report and review of literature.

Aortic aneurysm can result from both Marfan syndrome (MFS) and hypertension. Hypertension is more easily detected by the use of ubiquitous sphygmomanometer but MFS diagnosis requires a summation of a set of clinical features, including increased cardiac output from aortic regurgitation. A common complication of aortic aneurysm may result in apparent elevation in systolic pressure in a MFS patient with aortic root dilatation and regurgitation. Thus a patient with MFS presenting with aortic regurgitation may be misdiagnosed as having hypertensive heart disease. Clinical case presentation of a 47-year-old woman referred to the cardiology unit with the diagnosis of aortic aneurysm with regurgitation secondary to hypertension was found to have MFS. Relevant literature on diagnostic criteria of MFS and differences in aortic root disease secondary to MFS and that secondary to hypertension was reviewed. Physicians should have a high index of suspicion and consider MFS as a differential diagnosis of aortic aneurysm, especially in younger patients.