Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Strategies to improve healthcare services for patients with sickle cell disease in Nigeria: The perspectives of stakeholders.

Background: Sickle cell disease (SCD) continues to pose physical and psychosocial burdens to patients, caregivers and health workers. Stakeholder engagement in the processes of policy making and implementation is increasingly becoming the cornerstone of best practices in healthcare. Aim and Objectives: To engage stakeholders with a view to assessing the knowledge of SCD; ascertain the challenges associated with accessibility and affordability of healthcare services; improve the quality of care, and thereby effect behavioral change through increasing attendance and follow-up of patients in the clinics. Methodology: A Stakeholders' Engagement meeting organized by the Sickle Pan Africa Research Consortium Nigeria Network (SPARC-NEt) was attended by patients, caregivers and members of patient support groups, healthcare providers and management/policymakers. The engagement was through PowerPoint presentations, structured questionnaires and an interactive session. The structured questionnaire assessed the knowledge of stakeholders about SCD; the quality of healthcare services; challenges with access and affordability; and SCD-related government policies. Results: Three hundred and twelve stakeholders attended the engagement meeting. Of the 133 that participated in the study, medical workers were the most represented. The majority had good knowledge of what causes SCD (96.2%) and the best place to get help during SCD crisis (98.5%). However, knowledge of the specific preventive measures of SCD and its crisis was not optimal. In terms of the role of community engagement and education, only about one-quarter of the study participants, 34 (25.6%) knew about their positive role in reducing the prevalence of SCD and alleviating SCD crises. Challenges identified include inadequate healthcare personnel and facilities, delay in obtaining laboratory results, long waiting time in the clinic, poor communication, absence of holistic consultation, uncoordinated healthcare services, high cost of care, ignorance, non-prioritization of SCD by government, lack of multisectoral collaboration and partnership with NGOs and international organizations. Strategies proffered to improve healthcare services include, community/stakeholder engagement and health education, sickle cell daycare services, access to a willing and dedicated multidisciplinary workforce, collaboration with support groups and government policies and programs. Conclusion: There is need for regular stakeholder engagement to improve access to healthcare services for SCD patients in Nigeria.

Determinants of hydroxyurea use among doctors, nurses and sickle cell disease patients in Nigeria.

BACKGROUND: Hydroxyurea (HU) is an evidence-based therapy that is currently the most effective drug for sickle cell disease (SCD). HU is widely used in high-income countries with consequent reduction of morbidity and mortality. In Nigeria, HU is prescribed by physicians while nurses are mainly involved in counseling the patients to ensure adherence. The extent of utilization and the determinant factors have not been sufficiently evaluated in Nigeria. OBJECTIVE: To assess the frequency of use of HU and factors affecting utilization among healthcare providers, patients, and caregivers for SCD. METHODS: A questionnaire was administered online and in- person to assess the frequency of HU use and the factors that promote and limit its use. The data were analyzed by descriptive statistics using IBM SPSS software version 23 and the result was presented in frequency tables and percentages. RESULT: A total of 137 physicians, 137 nurses, and 237 patients/caregivers responded to the survey. The rate of prescription of HU by doctors in the past 6 months was 64 (46.7%), 43 (31.4%) nurses provided counseling and 36 (15.6%) patients were on HU. Among doctors, adequate knowledge (91.3%), clinical benefits and safety (94.8%), and inclusion of HU in management guidelines (86.9%) were motivators for prescribing it while inadequate knowledge (60.9%) and unawareness of treatment guidelines (68.6%) constituted barriers. Among nurses, reduction of crisis (91.6%) and safety (64.8%) were the major motivators while barriers were high cost (79.1%) and intensive monitoring (63.1%) of HU treatment. Among the patients, the major motivator was the reduction of crises (80.3%) while poor knowledge (93.2%), high cost of the drug (92.2%) while monitoring (91.2%), non-availability (87.7%) and side effects (83.9%) were the major barriers for the utilization of HU. CONCLUSION: HU prescription and utilization are still poor among healthcare providers and patients. Inadequate knowledge, non-availability and high cost of HU as well as unawareness of treatment guidelines constitute major barriers to prescription and utilization.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.

Skills Capacity Building For Health Care Services and Research Through the Sickle Pan African Research Consortium.

Skills development, the building of human capacity, is key to any sustainable capacity building effort, however, such undertakings require adaptable and tailored strategies. The Sickle Pan-African Research Consortium (SPARCo) is building capacity in sickle cell disease (SCD) management and research in sub-Saharan Africa, including a multi-national SCD patient registry, this is underpinned by skills development activities in data, research, and SCD management. Method: The SPARCo Skills Working Group was set up with the mandate of coordinating skills development activities across the three SPARCo sites in Ghana, Nigeria and Tanzania. To tailor activities to the requirements of the consortium, a needs assessment was conducted at the start of the project which identified skills required for SCD management and research and catalogued existing external and internal training programmes. The needs assessment highlighted differences in skill levels between the sites and different organisational structures which required tailored skills development activities at individual, site and consortium levels. Strategy: Based on the needs and the resources available, different types of training activities were implemented: these included online, blended and face to face activities. In order to create a sustainable skills development programme, existing short, medium, long-term, on-job training activities were used wherever possible. World Sickle Cell Day (19th June) was leveraged for training and health education activities. Results: SPARCo has recorded 1,726 participants in skills development activities across the three sites. Skills have been enhanced in data management, SCD and research to underpin the core deliverables of SPARCo. Conclusion and Lessons Learned: The baseline needs assessments and continual review and adjustment were critical for development of an effective skill development strategy for the consortium. This adaptability was particularly valuable during the COVID-19 pandemic. The sustainability plan leveraged existing programmes and activities and has created a pool of people with required skills for health care and research in SCD. To be effective, skills development programmes need to take into account existing capacity, training opportunities and local conditions. The model was applied to SCD and is adaptable to other skills development in healthcare and research in low and middle- income countries.

Determination of Serum Prostate Specific Antigen Levels Amongst Apparently Healthy Nigerian Males in a University and University Hospital Community in the Federal Capital Territory.

BACKGROUND: Prostate cancer is the commonest cancer among men worldwide and serum prostate specific antigen (PSA) has remained the most commonly applied screening test for the disease till date. Current PSA test results guidelines in our population are informed by reference intervals derived from studies from Caucasians and other racial groups. With scanty data on PSA reference values from our local population, this study evaluated the serum PSA levels of apparently healthy Nigerian male subjects in whom prostate cancer and urinary tract infection have been excluded. METHOD: This study had participants aged 40 to 70 years, with no lower urinary tract symptoms or other symptoms suggestive of prostate disease recruited from the male staff population of the University of Abuja and University of Abuja Teaching Hospital and the adjoining local community. They were physically examined, had prostate ultrasonography, urine analysis, and blood sample collected for PSA testing. Data collected was analyzed using Statistical Package for Social Science (SPSS) version 24. RESULT: Of a total of 210 men who participated in the study, 191 eventually met the inclusion criteria. The average age was 52.9 years, ninety seven percent of them had heard of prostate cancer before now. The mean total PSA was 1.46 ng/mL (SD +/-1.55), while the reference interval was .23-5.60 ng/mL. The average prostate size was 41.8 mL (SD+/-20.11), and there was a positive correlation between the PSA and the prostate size (.418) as well as the age of the subjects (.446). There was no significant difference in the mean PSA value for those with or without family history of prostate cancer (P=.979). CONCLUSION: The reference range of PSA in Nigeria is higher than in other races, hence utilizing a local value in decision making would help to reduce unnecessary invasive procedures.

Overall and central obesity and prostate cancer risk in African men.

PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multi-center, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI ≥ 30 kg/m2), 26% and 90% had WC > 97 cm and WHR > 0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive PCa, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR = 1.38, 95% CI 0.99-1.93), and central obesity (WC > 97 cm: OR = 1.60, 95% CI 1.10-2.33; and WHtR > 0.59: OR = 1.68, 95% CI 1.24-2.29) were positively associated with D'Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

Prevalence, patterns and predictors of dyslipidaemia in Nigeria: a report from the REMAH study.

AIM: The aim of this study was to determine the prevalence and predictors of dyslipidaemia in adults in Nigeria. METHODS: Using the WHO criteria, we determined dyslipidaemia using serum lipid levels of 3 211 adult Nigerians, aged at least 18 years, obtained between March 2017 and February 2018 from two communities (rural and urban) in a state from each of the six geopolitical zones of Nigeria. RESULTS: The overall prevalence of low high-density lipoprotein cholesterol (l-HDL), elevated low-density lipoprotein cholesterol (e-LDL), hypertriglyceridaemia (h-TG) and hypercholesterolaemia (h-CHL) were 72.5,13.6, 21.4 and 7.5%, respectively. The adjusted odds of h-CHL [odds ratio (95% confidence interval) 1.47 (1.10-1.95)], h-TG [1.89 (1.48-2.41)] and e-LDL [1.51 (1.03-2.15)] increased with obesity. Being a rural dweller increased the odds of h-TG [1.55 (1.29-1.85)], e-LDL [1.38 (1.10-1.73)] and l-HDL [1.34 (1.14-1.58)]. The odds of h-CHL [2.16 (1.59-2.95)], h-TG [1.21 (1.01-1.47)], e-LDL [1.42 (1.13-1.80)] and l-HDL [0.78 (0.65-0.93)] increased with hypertension. Diabetes mellitus doubled only the odds of h-TG [2.04(1.36-3.03)]. CONCLUSION: The prevalence of dyslipidaemia, particularly low HDL-C, is high among adult Nigerians.

Ionised serum calcium reference interval among rural women of reproductive age in Abuja, Nigeria.

BACKGROUND: Various medical conditions in pregnancy may be traced to suboptimal levels of serum calcium during pregnancy. Communities' derivation of normal serum calcium reference interval is imperative. OBJECTIVE: The objective was to determine the normal free (ionised) serum calcium reference interval among women of reproductive age in the federal capital territory (FCT) of Nigeria. MATERIALS AND METHODS: This was a cross-sectional study of 240 women from six primary health-care facilities in Abuja, Nigeria. Their blood samples were collected in serum separator bottles. The outcome measure was the determination of the reference interval of free (ionised) serum calcium among the participants. RESULTS: The obtained normal reference interval of ionised serum calcium (iCa) was 0.88-1.4 mmol/L. The accompanying reference intervals for total protein and albumin were 5.7-9.4 mg/dl and 3.3-5.2 mg/dl, respectively. CONCLUSION: The derived reference interval of iCa in this study was 0.88-1.4 mmol/L, while the total calcium range was 2.18-2.82 mmol/L. These intervals are recommended for use in the Nigerian FCT and its environs as it provides lower intervals compared to the operational values. There is a need for a national derived value as this may change the practice.

Hyperhomocysteinemia and its relations to conventional risk factors for cardiovascular diseases in adult Nigerians: the REMAH study.

BACKGROUND: Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are limited in a sub-Saharan black population. OBJECTIVE: We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians. METHODS: Data of 156 adults aged 18-70 years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy > 10 µmol/L. RESULTS: Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p < 0.05) older (41.5 vs. 40.6yrs), had lower HDL-cholesterol (0.6 vs. 0.8 mmol/L) and higher systolic (145.5 vs. 126.0 mmHg) and diastolic BP (92.9 vs. 79.6 mmHg), compared to those without HHcy. Intake of alcohol and a 1 yr increase in age were respectively and significantly (p < 0.05) associated with a 1.54 and 0.10 µmol/L increase in Hcy. In a multivariable model adjusted for age, sex and body mass index, a 1 µmol/L increase in Hcy, was associated with a 1.69 mmHg and 1.34 mmHg increase in systolic and diastolic pressure (p < 0.0001) respectively; and a 0.01 mmol/L decrease in HDL-cholesterol (p < 0.05). CONCLUSION: HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.

Barriers to Therapeutic Use of Hydroxyurea for Sickle Cell Disease in Nigeria: A Cross-Sectional Survey.

Background: Sickle cell disease, the inherited blood disorder characterized by anemia, severe pain and other vaso-occlusive complications, acute chest syndrome, disproportionate hospitalization, and early mortality, has significant financial, social, and psychosocial impacts and drains individuals, families, and health systems globally. Hydroxyurea could improve the health of the 300,000 individuals born each year with sickle cell disease in sub-Saharan Africa; however, challenges to adoption and adherence persist. This study assessed the barriers to therapeutic use of hydroxyurea for sickle cell disease within the Nigerian healthcare system, specifically from the level of the patient, provider, and health system. Methods: We used purposive sampling to recruit participants from 13 regions in Nigeria. A cross-sectional survey was administered to physicians (n = 70), nurses or counselors (n = 17), and patients or their caregivers (n = 33) at 13 health centers. Findings were mapped onto the appropriate Consolidated Framework for Implementation Research (CFIR) domains. Results: This study was able to identify factors that mapped onto the inner setting, outer setting, and characteristics of individuals domains of CFIR. The majority of physicians (74.3%) prescribe hydroxyurea, and half stated hydroxyurea is the standard of care. Among clinicians, barriers included limited knowledge of the drug, as well as low self-efficacy to prescribe among physicians and to counsel among nurses; perceived side effects; perceived patient preference for traditional medicine; cost for patient and expense of accompanying laboratory monitoring; and limited availability of the drug and equipment for laboratory monitoring. Among patients and caregivers, barriers included lack of knowledge; perceived side effects; cost; religious beliefs of disease causation; and lack of pediatric formulation. Conclusions: Findings suggest that patient, provider, and health systems-level interventions are needed to improve hydroxyurea uptake among providers and adherence among patients with sickle cell disease in Nigeria. Interventions such as patient education, provider training, and policy change could address the disproportionate burden of sickle cell disease in sub-Saharan Africa and thus improve health equity.

Prevalence and Determinants of Masked Hypertension in Nigeria: The REMAH Study.

BACKGROUND: Estimating the burden of hypertension in Nigeria hitherto relied on clinic blood pressure (BP) measurement alone. This excludes individuals with masked hypertension (MH), i.e., normotensive clinic but hypertensive out-of-clinic BP. METHODS: In a nationally representative sample of adult Nigerians, we obtained clinic BP using auscultatory method and out-of-clinic BP by self-measured home BP with semi-automated oscillometric device. Clinic BP was average of 5 consecutive measurements and home BP was average of 3 days duplicate morning and evening readings. MH was clinic BP <140 mm Hg systolic and 90 mm Hg diastolic and home BP ≥135 mm Hg systolic and/or 85 mm Hg diastolic. RESULTS: Among 933 participants, the prevalence of sustained hypertension, MH, and white-coat hypertension was 28.3%, 7.9%, and 11.9%, respectively. Among subjects whose clinic BP were in the normotensive range (n = 558), the prevalence of MH was 13%; 12% among untreated and 27% among treated individuals. The mutually adjusted odds ratios of having MH among all participants with normotensive clinic BP were 1.33 (95% confidence interval, 1.10-1.60) for a 10-year higher age, 1.59 (1.09-2.40) for a 10 mm Hg increment in systolic clinic BP, and 1.16 (1.08-1.28) for a 10 mg/dl higher random blood glucose. The corresponding estimates in the untreated population were 1.24 (1.03-1.51), 1.56 (1.04-2.44), and 1.16 (1.08-1.29), respectively. CONCLUSIONS: MH is common in Nigeria and increasing age, clinic systolic BP, and random blood glucose are the risk factors.

Urinary sodium excretion and its association with blood pressure in Nigeria: A nationwide population survey.

Assessment of level of salt intake in a population is the first step toward planning strategies aimed at salt reduction. As a surrogate of salt intake, we measured a single 24-hour urine sodium (uNa) of free-living 2503 adults in a nationally representative sample of Nigerians drawn from 12 rural and urban communities; and evaluated the community-level association of uNa with blood pressure (BP). Overall, the median (interquartile range (IQR)) of uNa was 99 (105) mmol, ranging from 23.8 (32.4) in rural north-central to 172.8 (131.0) mmol in urban northwestern region. Daily uNa was significantly higher (p < .001) in men compared to women (107.1 vs 93.9 mmol); and urban compared to rural dwellers (114.9 vs 86.0mmol). About one-half of participants excreted uNa in excess of recommended daily maximum value (86mmol). In a model adjusted for age, sex, body mass index (BMI), level of education, place of residence, and use of antihypertensive medication; being a man (odds ratio, OR 1.69, 95% confidence Interval CI, 1.21-2.37, p = .002) and being < 60 years of age (OR 1.74, 95% CI 1.23-2.45, p = .002), were associated with excreting higher than recommended uNa. In a fully adjusted model of the community-level analysis, urinary sodium, potassium, and sodium-to-potassium ratio each showed no significant independent association with both systolic and diastolic BPs. Among adult Nigerians, the median daily uNa excretion was 99 mmol and it had no significant association with blood pressure indices.

Prevalence, Awareness, Treatment and Control of Hypertension in Nigeria: Data from a Nationwide Survey 2017.

Background: Previous studies that evaluated the prevalence, awareness and treatment of hypertension in Nigeria were either localized to some specific regions of the country or non-standardized thereby making evaluation of trend in hypertension care difficult. Methods: We used the World Health Organization (WHO) STEPwise approach to chronic disease risk factor surveillance to evaluate in a nationally representative sample of 4192 adult Nigerians selected from a rural and an urban community in one state in each of the six geo-political zones of the country. Results: The overall age-standardized prevalence of hypertension was 38.1% and this varied across the geo-political zones as follows: North-Central, 20.9%; North-East, 27.5%; North-West, 26.8%; South-East, 52.8%; South-South, 44.6%; and South-West, 42.1%. Prevalence rate did not differ significantly (p > 0.05) according to place of residence; 39.2% versus 37.5 %; urban vs rural. Prevalence of hypertension increased from 6.8% among subjects less than 30 years to 63.0% among those aged 70 years and above. Awareness was better (62.2% vs. 56.6%; P = 0.0272); treatment rate significantly higher (40.9 % vs. 30.8%; P < 0.0001) and control similar (14 vs. 10.8%) among urban compared to rural residents. Women were more aware of (63.3% vs. 52.8%; P < 0.0001); had similar (P > 0.05) treatment (36.7 vs. 34.3%) and control (33.9% vs. 35.5%) rates of hypertension compared to men. Conclusion: Our results suggest a large burden of hypertension in Nigeria and a closing up of the rural-urban gap previously reported. This calls for a change in public health policies anchored on a primary health care system to address the emerging disease burden occasioned by hypertension.

A Custom Genotyping Array Reveals Population-Level Heterogeneity for the Genetic Risks of Prostate Cancer and Other Cancers in Africa.

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. SIGNIFICANCE: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

Removing the mask on hypertension (REMAH) study: Design; quality of blood pressure phenotypes and characteristics of the first 490 participants.

Purpose: Previous studies that evaluated the prevalence of hypertension in Nigeria were either clinic based, non-standardized or did not include out-of-clinic blood pressure (BP) measurement. Materials and Methods: We selected a rural and an urban community in one state in each of the 6 geopolitical zones of Nigeria. Five consecutive BP of adults older than 18 years were measured in the clinic following which, each participant was provided with a home BP device to obtain duplicate morning and evening BP for 3 days. Result: Out of 556 invited from Anambra State, South-East Nigeria, 490 (88%) consented. Overall, more women participated in both rural (115 vs 61, p < .0001) and urban (213 vs 101; p < .0001) sites. About 35.9% of participants had their home BP monitored. Of the 4890 clinic BP readings, 29.8%, 16.3%, 16.6%, 16.4% and 20.8% ended in 0,2,4,6 and 8 digits respectively. Only 0.8% ended in odd numbers. Of the identical BP readings,5 (0.20%), 6 (0.25%), 56 (2.30%) and 316 (12.9%) SBP and 8 (0.33%), 17 (0.70%), 93 (3.80%), 319 (13.1%) DBP had no difference in five, four, three and two values of the five consecutive readings. Conclusion: REMAH is feasible and the quality of BP will ensure that the final results are robust.

HemoTypeSC, a low-cost point-of-care testing device for sickle cell disease: Promises and challenges.

BACKGROUND: Sickle cell disease (SCD) is a neglected burden of growing importance. >312,000 births are affected annually by sickle cell anaemia (SCA). Early interventions such as newborn screening, penicillin prophylaxis and hydroxyurea can substantially reduce the mortality and morbidity associated with SCD. Nevertheless, their implementation in African countries has been mostly limited to pilot projects. Recent development of low-cost point-of-care testing (POCT) devices for sickle haemoglobin (HbS) could greatly facilitate the diagnosis of those affected. METHODS: We conducted the first multi-centre, real-world assessment of a low-cost POCT device, HemoTypeSC, in a low-income country. Between September and November 2017, we screened 1121 babies using both HemoTypeSC and HPLC and confirmed discordant samples by molecular diagnosis. FINDINGS: We found that, in optimal field conditions, the sensitivity and specificity of the test for SCA were 93.4% and 99.9%, respectively. All 14 carriers of haemoglobin C were successfully identified. Our study reveals an overall accuracy of 99.1%, but also highlights the importance of rigorous data collection, staff training and accurate confirmatory testing. It suggests that HPLC results might not be as reliable in a resource-poor setting as usually considered. INTERPRETATION: The use of such a POCT device can be scaled up and routinely used across multiple healthcare centres in sub-Saharan Africa, which would offer great potential for the identification and management of vast numbers of individuals affected by SCD who are currently undiagnosed. FUNDING US: Imperial College London's Wellcome Trust Centre for Global Health Research (grant #WMNP P43370).

Herbal Drug use in Sickle Cell Disease Management; Trends and Perspectives in Sub-Saharan Africa - A Systematic Review.

INTRODUCTION: Nigeria has the largest burden of Sickle Cell Disease (SCD) with estimated 100,000 new born affected annually. SCD is a Hemoglobin (Hb) disorder with the major form resulting from the substitution of a polar glutamate (Glu) by non-polar Valine (Val) in an invariant region of Hbß chain-subunit. Species of Hb found in the sickle cell trait are HbA and HbS in a 60:40 proportion, in SCD only HbS, in the HbC disease only HbC, and in the SC disease it's HbS and HbC in a 50:50 equal proportion. OBJECTIVE: This paper reviews herbal medicines usage in sub-Saharan Africa (sSA) to ameliorate the crisis associated with SCD. The model Hb tetramer suggests a higher membrane affinity of HbS and HbC, promoting dehydration of RBCs, with concomitant in vivo crystallization. Some drawbacks using these herbal drugs include; poor bioavailability and the lack of proper pharmacovigilance monitoring procedures arising from weak governance structure combined with under reporting of herbal usage to physicians were discussed. Probable epigenetic loci that could be targeted using phytomedicines for effective SCD management were also discussed. METHODS: Using search engines, several databases including Google scholar, PubMed, Academic Resource Index were utilized as a source for relevant publications/ literature. The protein coordinates for the Hb tetramer were obtained from the Protein Data Bank (PDB). CONCLUSION: Manipulation of epigenetics to achieve better SCD management involves careful thinking. Herein, we discuss some epigenetic interactions that could be putatively tweaked with a view of enhancing soluble bioactive small molecular components with the potential to reactivate γ -globin genes, thereby boosting immune response in patient with SCD.

Office and Home Blood Pressures as Determinants of Electrocardiographic Left Ventricular Hypertrophy Among Black Nigerians Compared With White Flemish.

BACKGROUND: The association of electrocardiographic left ventricular hypertrophy (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains poorly documented. METHODS: In 225 Black Nigerians and 729 White Flemish, we analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP (duplicate morning and evening readings averaged over 1 week). RESULTS: In multivariable analyses, QRS voltage and voltage-duration indexes were generally higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference among women (17.1%). Precordial voltages and voltage-duration products increased with office and home systolic BP (SBP), and increases were up to 3-fold steeper in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26) vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for office and home BP, respectively, with a significant ethnic gradient (P < 0.05). The risk of ECG-LVH increased more with office and home BP in Blacks than Whites. CONCLUSIONS: Associations of ECG voltages and voltage-duration products and risk of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference population. In resource-poor settings of sub-Saharan Africa, the ECG in combination with office and home BP is an essential instrument in risk stratification across the entire BP range.