African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Common hepatitis B virus genotypes among blood donors in Lagos, Nigeria.

Background: Hepatitis B virus (HBV) infection is one of the public health diseases causing global health problems. It is a leading cause of cirrhosis and hepatocellular carcinoma. Blood transfusion is a major route of its transmission and screening of blood is suboptimal in our environment. Occult HBV infection describes the presence of HBV DNA in blood or liver tissue in patients who are hepatitis B surface antigen (HBsAg) seronegative. This study documented the common genotypes of HBV a blood-borne infection in the population of blood donors in Lagos. Methods: This was a cross-sectional study carried out at the blood donor clinics of ten Lagos State Government-owned hospitals in Lagos State. A total of 1400 participants were recruited consecutively from November 2020 to June 2021. All participants' samples were screened using Diaspot Rapid Test Kit (RTK) and Dialabenzyme enzyme-linked immunosorbent assay (ELISA) kit. Furthermore, some of the plasma samples were used for HBV DNA extraction and genotyping using the real time-polymerase chain reaction. Statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS) software version 26 and P value was considered significant at ≤0.05. Results: The sero-prevalence of HBsAg using RTK and ELISA was 19.9% and 22.4%, respectively. The prevalence of occult HBV infection was 5.2%. A total of 278 and 313 HBsAg RTK and ELISA positive samples were obtained, respectively. HBV genotype result had A (46.6%) as the most prevalent followed closely by B (44.7%), E (23.8%), D (20.9%) and C (11.2%). Conclusion: HBV infection has a high prevalence among blood donors. ELISA is a more sensitive screening tool and its use should be advocated nationally. HBV genotype A is the most prevalent genotype from our study.

Prevalence, pattern and determinants of contraceptive use among pregnant women attending antenatal clinic (ANC) in a secondary health facility in Kebbi State: a cross-sectional study.

Introduction: rapidly rising population in Africa is of great concern, especially in Nigeria because of its impact on social stability. Nigeria has been unable to meet the set targets in respect of scaling up access to contraception, and increasing contraceptive prevalence. Thus, being projected to be the third most populous country by 2050 amidst a rising unemployment rate and a shrinking economy. Methods: a cross-sectional study was conducted among 350 pregnant women attending antenatal clinic (ANC) in General Hospital Argungu, Kebbi State, and data were obtained using an interviewer-administered questionnaire and analyzed using IBM SPSS version 22. Results: most 318 (90.9%) of the 350 respondents were aware of contraception. The prevalence of previous use of contraceptives among the respondents was 59.4%, while 70% of them intend to use contraception in the future. Concerns about the return of fertility 56 (50.9) after contraceptive use was a major reason given by respondents who had never used any form of contraceptive. Educational attainment, age at marriage, and occupation were the factors that were associated with awareness, previous use, and future use of contraception. Conclusion: this study underscores the need to promote girl-child education as a cardinal strategy in increasing the level of contraception among the populace.

Translating research to usual care of children with sickle cell disease in Northern Nigeria: lessons learned from the SPRING Trial Team.

OBJECTIVES: Evidence-based practice for stroke prevention in high-income countries involves screening for abnormal transcranial Doppler (TCD) velocity and initiating regular blood transfusions for at least 1 year, followed by treatment with hydroxyurea. This practice has not been transferred to low-resource settings like Nigeria, the country with the highest global population density of SCD. Following a multi-center randomized controlled trial among children with SCA in northern Nigeria, screening for stroke and initiation of hydroxyurea was established as standard of care at the clinical trial sites and other locations. We aim to describe the critical steps we took in translating research into practice for stroke prevention in SCA in Nigeria. Guided by the PRISM framework, we describe how we translated results from a randomized controlled trial for primary prevention of stroke in children with sickle cell anemia into usual care for children with SCA in Kaduna, Nigeria. RESULTS: Findings from this study demonstrate the importance of organizational support and stakeholder involvement from the onset of a clinical trial. Having the dual objective of conducting an efficacy trial while simultaneously focusing on strategies for future implementation can significantly decrease the lag time between discovery and routine practice.

Establishing Sickle Cell Disease Stroke Prevention Teams in Africa is Feasible: Program Evaluation Using the RE-AIM Framework.

We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate a Stroke Prevention Team's readiness to prevent strokes in children with sickle cell anemia living in northern Nigeria. The NIH sponsored Stroke Prevention Trial in Nigeria included a goal of a sustainable stroke prevention program. The program's 1-year reach for transcranial Doppler screening was 14.7% (4710/32,000) of which 6.0% (281/4710) had abnormal velocities (≥200 cm/s). All participants with abnormal transcranial Doppler velocities were started on hydroxyurea (effectiveness). The leaders of all 5 hospitals agreed to adopt the program. After 1 year, program-implementation and maintenance rates were 100%, demonstrating the program's feasibility and short-term sustainability.

Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial.

BACKGROUND: In high-income countries, standard care for primary stroke prevention in children with sickle cell anaemia and abnormal transcranial Doppler velocities results in a 92% relative risk reduction of strokes but mandates initial monthly blood transfusion. In Africa, where regular blood transfusion is not feasible for most children, we tested the hypothesis that initial moderate-dose compared with low-dose hydroxyurea decreases the incidence of strokes for children with abnormal transcranial Doppler velocities. METHODS: SPRING is a double-blind, parallel-group, randomised, controlled, phase 3 trial of children aged 5-12 years with sickle cell anaemia with abnormal transcranial Doppler velocities conducted at three teaching hospitals in Nigeria. For randomisation, we used a permuted block allocation scheme with block sizes of four, stratified by sex and site. Allocation was concealed from all but the pharmacists and statisticians. Participants were assigned in a 1:1 ratio to low-dose (10 mg/kg per day) or moderate-dose (20 mg/kg per day) oral hydroxyurea taken once daily with monthly clinical evaluation and laboratory monitoring. The primary outcome was initial stroke or transient ischaemic attack, centrally adjudicated. The secondary outcome was all-cause hospitalisation. We used the intention-to-treat population for data analysis. The trial was stopped early for futility after a planned minimum follow-up of 3·0 years to follow-up for participants. This trial was registered with ClinicalTrials.gov, number NCT02560935. FINDINGS: Between Aug 2, 2016, and June 14, 2018, 220 participants (median age 7·2 years [IQR 5·5-8·9]; 114 [52%] female) were randomly allocated and followed for a median of 2·4 years (IQR 2·0-2·8). All participants were Nigerian and were from the following ethnic groups: 179 (82%) people were Hausa, 25 (11%) were Fulani, and 16 (7%) identified as another ethnicity. In the low-dose hydroxyurea group, three (3%) of 109 participants had strokes, with an incidence rate of 1·19 per 100 person-years and in the moderate-dose hydroxyurea group five (5%) of 111 had strokes with an incidence rate of 1·92 per 100 person-years (incidence rate ratio 0·62 [95% CI 0·10-3·20], p=0·77). The incidence rate ratio of hospitalisation for any reason was 1·71 (95% CI 1·15-2·57, p=0·0071), with higher incidence rates per 100 person-years in the low-dose group versus the moderate-dose group (27·43 vs 16·08). No participant had hydroxyurea treatment stopped for myelosuppression. INTERPRETATION: Compared with low-dose hydroxyurea therapy, participants treated with moderate-dose hydroxyurea had no difference in the stroke incidence rate. However, secondary analyses suggest that the moderate-dose group could lower incidence rates for all-cause hospitalisations. These findings provide an evidence-based guideline for the use of low-dose hydroxyurea therapy for children with sickle cell anaemia at risk of stroke. FUNDING: National Institute of Neurological Disorders and Stroke.

Acute urinary tract infection in patients with underlying benign prostatic hyperplasia and prostate cancer.

INTRODUCTION: the occurrence of urinary tract infection in patients with obstructing prostate causes reduction in their health-related quality of life and overall well-being. The objective of this study was to determine the prevalence, risk factors and antimicrobial sensitivity pattern of pathogens causing urinary tract infection in patients with benign prostatic hyperplasia and prostate cancer. METHODS: all patients who presented to our urology division with bladder outlet obstruction secondary to benign prostatic hyperplasia or prostate cancer between January 2016 and January 2019 were included. Information on age, co-morbid conditions, presence of an indwelling catheter, bacteriologic analysis, imaging findings and histological diagnosis were obtained and analyzed using SPSS version 20. RESULTS: de-novo urinary tract infection occurred in 35.6% of patients while recurrent infection occurred in 5.9% of them. The most commonly isolated organisms were gram-negative bacteria with Escherichia coli, Klebsiella spp, Citrobacter spp and Aerobacter spp accounting for 62.2%, 27.0%, 8.1% and 2.7% respectively. Nitrofurantoin (64.3%), Ceftriaxone (46.3%) and Genticin (42.9%) were the three most sensitive antimicrobials to the organisms isolated. Only the presence of an indwelling catheter in the bladder was an independent predictor of urinary tract infection in the study population. CONCLUSION: about one-third of patients with benign prostatic hyperplasia and prostate cancer develop urinary tract infection. The predominant bacterial cause was Escherichia coli, which had a high degree of sensitivity to Nitrofurantoin. The presence of an indwelling catheter was the only independent predictor of this infection. Appropriate measures should be re-enforced to prevent the occurrence of catheter-associated infections.

Towards 2030 Target for Hepatitis B and C Viruses Elimination: Assessing the Validity of Predonation Rapid Diagnostic Tests versus Enzyme-linked Immunosorbent Assay in State Hospitals in Kaduna, Nigeria.

INTRODUCTION: Sub-Saharan Africa accounts for 25% of the estimated global 325 million people with chronic hepatitis B and C virus infections. Weak blood transfusion systems facilitate the spread of both hepatitis B and C virus infections. This is worsened by the absence of sustainable quality assurance programs and perennial shortage of sensitive screening kits. We aim to compare the validity of rapid diagnostic tests (RDTs) with the World Health Organization-recommended quality-assured enzyme-linked immunosorbent assay (ELISA) screening method for these viruses. MATERIALS AND METHODS: We conducted a cross-sectional study on consecutive blood donor samples. Two hundred and sixty-four blood donor samples screened for hepatitis B and C viruses using RDTs were retested at a National blood transfusion service, Kaduna, Nigeria. Data were analyzed using OpenEpi version 3.01 to determine the sensitivity, specificity, and predictive values of RDTs versus ELISA. RESULTS: The sensitivities of the RDTs at 95% confidence interval (CI) were low - 40% (19.8-64.3) and 50.0% (18.8-81.2) - for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody, respectively. The specificities and 95% CI were high - 99.9% (97.8-99.9) and 100.0% (98.5-100) for HBsAg and HCV antibody, respectively. CONCLUSION: Predonation RDTs screening of blood donor samples for hepatitis B virus and HCV in hospital donation units performed poorly compared to quality-assured ELISA screening in Kaduna. The risk of transmitting viral hepatitis through blood transfusion still exists. We recommend quality-assured ELISA screening of all donated units for HBsAg and HCV antibody to reduce the risk of these transfusion-transmitted infections.

The Prevalence of Occult Hepatitis B Infection among Blood Donors in Lagos, Nigeria.

BACKGROUND: In occult hepatitis B virus (HBV) infection, the HBV DNA is present in the blood or liver tissue in patients negative for hepatitis B surface antigen (HBsAg) with or without anti-HBV antibodies. Thus, the absence of HBsAg in the blood only reduces the risk of transmission and is not sufficient enough to ensure the absence of HBV infection. AIM: This study was aimed at determining the prevalence of occult HBV infection among blood donors in Lagos. STUDY DESIGNS: A cross-sectional study was done among 101 consenting blood donors at Lagos State University Teaching Hospital, Ikeja, between November 2016 and January 2017. MATERIALS AND METHODS: HBV DNA analysis and viral load were done at the Molecular Laboratory of National Sickle Cell Centre, Idi Araba, Lagos, for all the HBsAg negative blood donors screened by rapid kit at Ikeja. RESULTS: The prevalence of occult HBV DNA among the participants was 3% consisting of 3% prevalence of HBV DNA surface antigen and 0% prevalence for precore and core of the HBV DNA. CONCLUSION: The low prevalence (3%) of occult HBV seen in our study does not make it cost-effective to routinely screen blood donors or the general population for HBV infection using DNA polymerase chain reaction.

Towards 2030 target for hepatitis B and C viruses elimination: assessing the validity of predonation rapid diagnostic tests versus enzyme-linked immunosorbent assay in state hospitals in Kaduna, Nigeria

ntroduction: Sub-Saharan Africa accounts for 25% of the estimated global 325 million people with chronic hepatitis B and C virus infections. Weak blood transfusion systems facilitate the spread of both hepatitis B and C virus infections. This is worsened by the absence of sustainable quality assurance programs and perennial shortage of sensitive screening kits. We aim to compare the validity of rapid diagnostic tests (RDTs) with the World Health Organization-recommended quality-assured enzyme-linked immunosorbent assay (ELISA) screening method for these viruses. Materials and Methods: We conducted a cross-sectional study on consecutive blood donor samples. Two hundred and sixty-four blood donor samples screened for hepatitis B and C viruses using RDTs were retested at a National blood transfusion service, Kaduna, Nigeria. Data were analyzed using OpenEpi version 3.01 to determine the sensitivity, specificity, and predictive values of RDTs versus ELISA. Results: The sensitivities of the RDTs at 95% confidence interval (CI) were low ­ 40% (19.8­64.3) and 50.0% (18.8­81.2) ­ for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody, respectively. The specificities and 95% CI were high ­ 99.9% (97.8­99.9) and 100.0% (98.5­100) for HBsAg and HCV antibody, respectively. Conclusion: Predonation RDTs screening of blood donor samples for hepatitis B virus and HCV in hospital donation units performed poorly compared to quality-assured ELISA screening in Kaduna. The risk of transmitting viral hepatitis through blood transfusion still exists. We recommend quality-assured ELISA screening of all donated units for HBsAg and HCV antibody to reduce the risk of these transfusion-transmitted infections

Metagenomic insights into effects of spent engine oil perturbation on the microbial community composition and function in a tropical agricultural soil.

Analyzing the microbial community structure and functions become imperative for ecological processes. To understand the impact of spent engine oil (SEO) contamination on microbial community structure of an agricultural soil, soil microcosms designated 1S (agricultural soil) and AB1 (agricultural soil polluted with SEO) were set up. Metagenomic DNA extracted from the soil microcosms and sequenced using Miseq Illumina sequencing were analyzed for their taxonomic and functional properties. Taxonomic profiling of the two microcosms by MG-RAST revealed the dominance of Actinobacteria (23.36%) and Proteobacteria (52.46%) phyla in 1S and AB1 with preponderance of Streptomyces (12.83%) and Gemmatimonas (10.20%) in 1S and Geodermatophilus (26.24%), Burkholderia (15.40%), and Pseudomonas (12.72%) in AB1, respectively. Our results showed that soil microbial diversity significantly decreased in AB1. Further assignment of the metagenomic reads to MG-RAST, Cluster of Orthologous Groups (COG) of proteins, Kyoto Encyclopedia of Genes and Genomes (KEGG), GhostKOALA, and NCBI's CDD hits revealed diverse metabolic potentials of the autochthonous microbial community. It also revealed the adaptation of the community to various environmental stressors such as hydrocarbon hydrophobicity, heavy metal toxicity, oxidative stress, nutrient starvation, and C/N/P imbalance. To the best of our knowledge, this is the first study that investigates the effect of SEO perturbation on soil microbial communities through Illumina sequencing. The results indicated that SEO contamination significantly affects soil microbial community structure and functions leading to massive loss of nonhydrocarbon degrading indigenous microbiota and enrichment of hydrocarbonoclastic organisms such as members of Proteobacteria and Actinobacteria.

NT-proBNP as a marker of cardiopulmonary status in sickle cell anaemia in Africa.

N-terminal (NT) pro-brain natriuretic peptide (proBNP) > or =160 ng/l has a 78% positive predictive value for pulmonary hypertension and is associated with increased mortality in US sickle cell disease patients, but the importance in sickle cell disease patients in Africa is not known. In a cross-sectional study at Ahmadu Bello University Teaching Hospital, Shika-Zaria, Nigeria, we studied 133 hydroxycarbamide-naïve Nigerian sickle cell anaemia patients aged 18-52 years at steady-state and 65 healthy controls. Twenty-six percent of patients versus 5% of controls had NT-proBNP > or =160 ng/l (P = 0.0006). By logistic regression among the patients, human immunodeficiency virus seropositivity, higher serum ferritin and lower haemoglobin or higher lactate dehydrogenase independently predicted elevated NT-proBNP. After adjustment for haemoglobin concentration, elevated NT-proBNP concentration was associated with an estimated 7.8-fold increase in the odds of severe functional impairment, defined as an inability to walk more than 300 m in 6 min (95% confidence interval 1.5-32.6; P = 0.005). Similarly, elevated tricuspid regurgitation velocity was associated with an estimated 5.6-fold increase in the odds of functional impairment (95% confidence interval 1.5-21.0; P = 0.011). In conclusion, NT-proBNP elevation is common and is associated with markers of anaemia, inflammation and iron status and with severe functional impairment among sickle cell anaemia patients in Nigeria.