Machine-learning Prognostic Models from the 2014-16 Ebola Outbreak: Data-harmonization Challenges, Validation Strategies, and mHealth Applications.Ebola virus disease (EVD) plagues low-resource and difficult-to-access settings. Machine learning prognostic models and mHealth tools could improve the understanding and use of evidence-based care guidelines in such settings. However, data incompleteness and lack of interoperability limit model generalizability. This study harmonizes diverse datasets from the 2014-16 EVD epidemic and generates several prognostic models incorporated into the novel Ebola Care Guidelines app that provides informed access to recommended evidence-based guidelines. PMID: 31312805 PMCID: PMC6610774 DOI: 10.1016/j.eclinm.2019.06.003
Dissecting in silico Mutation Prediction of Variants in African Genomes: Challenges and Perspectives. Genomic medicine is set to drastically improve clinical care globally due to high throughput technologies which enable speedy in silicodetection and analysis of clinically relevant mutations. However, the variability in the in silico prediction methods and categorization of functionally relevant genetic variants can pose specific challenges in some populations. In silico mutation prediction tools could lead to high rates of false positive/negative results, particularly in African genomes that harbor the highest genetic diversity and that are disproportionately underrepresented in public databases and reference panels. PMID: 31293624 PMCID: PMC6603221 DOI: 10.3389/fgene.2019.00601
Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa. Hydroxyurea (HU) is clinically beneficial in sickle cell disease (SCD) through fetal hemoglobin (HbF) induction; however, the mechanism of HU is not yet fully elucidated. Selected miRNAs have been associated with HU-induced HbF production. We have investigated differential HU-induced global miRNA expression in peripheral blood of adult SCD patients in patients from Congo, living in South Africa. PMID: 31231425 PMCID: PMC6568309 DOI: 10.3389/fgene.2019.00509
Nasopharyngeal Carriage of Antimicrobial-Resistant Pneumococci in an Intensively Sampled South African Birth Cohort.Nasopharyngeal (NP) colonization by Streptococcus pneumoniae (pneumococcus) precedes the development of respiratory tract infection. Colonization by antimicrobial-resistant pneumococci, especially in infants, is a major public health concern. We longitudinally investigated antimicrobial-resistance amongst pneumococci colonizing the nasopharynx of South African infants immunized with the 13-valent pneumococcal conjugate vaccine (PCV13). PMID: 30972052 PMCID: PMC6446970 DOI: 10.3389/fmicb.2019.00610
C9orf72 repeat expansions in South Africans with amyotrophic lateral sclerosis.The hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic variant found in individuals with sporadic amyotrophic lateral sclerosis (ALS), occurring at a frequency of between 7 and 11% in cohorts of European ancestry. While limited data suggest that C9-expansions (>30 repeats) are less frequent in African-Americans with ALS, there is no data on the frequency of C9-expansions among ALS subjects residing in Africa. We therefore investigated the frequency of this expansion mutation (using repeat-primed PCR) in a cohort of 143 South Africans (SA) with ALS. PMID: 31009932 PMCID: PMC6556408 [Available on 2020-06-15] DOI: 10.1016/j.jns.2019.04.026
Expanding Research Capacity in Sub-Saharan Africa Through Informatics, Bioinformatics, and Data Science Training Programs in Mali.Bioinformatics and data science research have boundless potential across Africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, HIV and AIDS, Ebola virus disease, and Lassa fever. This work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. PMID: 31031807 PMCID: PMC6473184 DOI: 10.3389/fgene.2019.00331
Influence of Socio-Economic and Psychosocial Profiles on the Human Breast Milk Bacteriome of South African Women. The human breast milk (HBM) bacteriome is an important, continuous source of microbes to the neonate in early life, playing an important role in shaping the infant’s intestinal bacteriome. Study of the composition of the HBM bacteriome is an emerging area of research, with little information available, particularly from low- and middle-income countries. The aim of this study was to characterize the diversity of bacterial communities in HBM samples collected between 6-10 weeks postpartum from lactating South African women and to study potential influencing factors of the bacteriome. PMID: 31226873
A novel mutation in the GARS gene in a Malian family with Charcot-Marie-Tooth disease. Charcot-Marie-Tooth (CMT) disease is a very heterogeneous neurological condition with more than 90 reported genetic entities. It is the most common inherited peripheral neuropathy; however, cases are rarely reported in sub-Saharan Africa. In addition, only few families, mostly of Caucasian ancestry, have been reported to have Charcot-Marie-Tooth disease type 2D (CMT2D) mutations. To date no case of CMT2D was reported in Africa. We present here a consanguineous family with CMT phenotype in which a novel mutation in the GARS (glycyl-tRNA synthetase) gene was identified. PMID: 31173493
How to use relevant data for maximal benefit with minimal risk: digital health data governance to protect vulnerable populations in low-income and middle-income countries.Globally, the volume of private and personal digital data has massively increased, accompanied by rapid expansion in the generation and use of digital health data. These technological advances promise increased opportunity for data-driven and evidence-based health programme design, management and assessment; but also increased risk to individuals of data misuse or data breach of their sensitive personal data, especially given how easily digital data can be accessed, copied and transferred on electronic platforms if the appropriate controls are not implemented. This is particularly pertinent in low-income and middle-income countries (LMICs), where vulnerable populations are more likely to be at a disadvantage in negotiating digital privacy and confidentiality given the intersectional nature of the digital divide. PMID: 31139457PMCID: PMC6509603 DOI: 10.1136/bmjgh-2019-001395
Role of genomics literacy in reducing the burden of common genetic diseases in Africa.In Africa, health practitioners and the current knowledge of the public on genetics and genomics is still very low and yet this has potential to reduce the burden of common genetic diseases. Many initiatives have promoted genomic research, infrastructure, and capacity building in Africa. What remains to be done is to improve genomics literacy among populations and communities while utilizing an array of strategies. Genomic literacy and awareness are key in the management of genetic diseases which includes diagnosis, prevention of complications and therapy. Africa is characterized by great cultural and language diversity thereby requiring a multidisciplinary approach to improving public and community genomics literacy and engagement. However, this is further complicated by having the fact that sub-Saharan Africa is comprised of countries with the lowest literacy rates in the world. PMID: 31131548 DOI: 10.1002/mgg3.776
Hereditary spastic paraplegia type 35 in a family from Mali.Variants in FA2H have been associated with a wide range of phenotypes including hereditary spastic paraplegia type 35 (SPG35); however, genetically confirmed cases have not been reported in Africa. We report here the first African family with a variant in the FA2H gene causing SPG35. Four affected siblings with consanguineous parents presented with walking difficulty at age 2-3 and progressive limb weakness. They became wheelchair-bound 2 years after disease onset. PMID: 31087769 PMCID: PMC6557683 DOI: 10.1002/ajmg.a.61179
Complimentary Methods for Multivariate Genome-Wide Association Study Identify New Susceptibility Genes for Blood Cell Traits.Genome-wide association studies (GWAS) have found hundreds of novel loci associated with full blood count (FBC) phenotypes. However, most of these studies were performed in a single phenotype framework without putting into consideration the clinical relatedness among traits. In this work, in addition to the standard univariate GWAS, we also use two different multivariate methods to perform the first multiple traits GWAS of FBC traits in ∼7000 individuals from the Ugandan General Population Cohort (GPC). PMID: 31080455 PMCID: PMC6497788 DOI: 10.3389/fgene.2019.00334
Sharing with Strangers: Governance Models for Borderless Genomic Research in a Territorial World.One of the practices that has defined the ethos of genomic research to date is a commitment to open and rapid sharing of genomic data and resources. As genomic research evolves into an international enterprise, this commitment is being challenged by the need to respect the interests of those it involves and implicates, from individual scientists and subjects to institutions and nations. In this essay, we first describe the types of claims that different stakeholders are making about the disposition of genomic data and samples. Next, we illustrate the complexities of these multiple claims by applying them to the case of one ongoing international genomics initiative, the H3Africa Consortium. Finally, in the light of these complexities, we conclude by comparing and contrasting four governance models for future international data-sharing policy and practices in genomics. PMID: 31080178 DOI: 10.1353/ken.2019.0000
Differential Impact of Risk Factors on Stroke Occurrence Among Men Versus Women in West Africa.
Akpalu A, Gebregziabher M, Ovbiagele B, Sarfo F, Iheonye H, Akinyemi R, Akpa O, Tiwari HK, Arnett D, Wahab K, Lackland D, Abiodun A, Ogbole G, Jenkins C, Arulogun O, Akpalu J, Obiako R, Olowoyo P, Fawale M, Komolafe M, Osaigbovo G, Obiabo Y, et al.
Background and Purpose- The interplay between sex and the dominant risk factors for stroke occurrence in sub-Saharan Africa has not been clearly delineated. We compared the effect sizes of risk factors of stroke by sex among West Africans. Methods- SIREN study (Stroke Investigative Research and Educational Networks) is a case-control study conducted at 15 sites in Ghana and Nigeria. Cases were adults aged >18 years with computerized tomography/magnetic resonance imaging confirmed stroke, and controls were age- and sex-matched stroke-free adults. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed using validated tools. We used conditional logistic regression to estimate odds ratios and reported risk factor specific and composite population attributable risks with 95% CIs. Results- Of the 2118 stroke cases, 1193 (56.3%) were males. The mean±SD age of males was 58.1±13.2 versus 60.15±14.53 years among females. Shared modifiable risk factors for stroke with adjusted odds ratios (95% CI) among females versus males, respectively, were hypertension [29.95 (12.49-71.77) versus 16.1 0(9.19-28.19)], dyslipidemia [2.08 (1.42-3.06) versus 1.83 (1.29-2.59)], diabetes mellitus [3.18 (2.11-4.78) versus 2.19 (1.53-3.15)], stress [2.34 (1.48-3.67) versus 1.61 (1.07-2.43)], and low consumption of green leafy vegetables [2.92 (1.89-4.50) versus 2.00 (1.33-3.00)]. However, salt intake and income were significantly different between males and females. Six modifiable factors had a combined population attributable risk of 99.1% (98.3%-99.6%) among females with 9 factors accounting for 97.2% (94.9%-98.7%) among males. Hemorrhagic stroke was more common among males (36.0%) than among females (27.6%), but stroke was less severe among males than females. Conclusions- Overall, risk factors for stroke occurrence are commonly shared by both sexes in West Africa favoring concerted interventions for stroke prevention in the region. PMID:30879432 | PMCID:PMC6433514
Longitudinal Population Dynamics of Staphylococcus aureus in the Nasopharynx During the First Year of Life.
Abdulgader SM, Robberts L, Ramjith J, Nduru PM, Dube F, Gardner-Lubbe S, Zar HJ, Nicol MP.
Background: Staphylococcus aureus colonization is a risk factor for invasive disease. Few studies have used strain genotype data to study S. aureus acquisition and carriage patterns. We investigated S. aureus nasopharyngeal carriage in infants in an intensively sampled South African birth cohort. Methods: Nasopharyngeal swabs were collected at birth and fortnightly from 137 infants through their first year of life. S. aureus was characterized by spa-typing. The incidence of S. aureus acquisition, and median carriage duration for each genotype was determined. S. aureus carriage patterns were defined by combining the carrier index (proportion of samples testing positive for S. aureus) with genotype diversity measures. Persistent or prolonged carriage were defined by a carrier index ≥0.8 or ≥0.5, respectively. Risk factors for time to acquisition of S. aureus were determined. Results: Eighty eight percent (121/137) of infants acquired S. aureus at least once. The incidence of acquisition at the species and genotype level was 1.83 and 2.8 episodes per child-year, respectively. No children had persistent carriage (defined as carrier index of >0.8). At the species level 6% had prolonged carriage, while only 2% had prolonged carriage with the same genotype. Carrier index correlated with the absolute number of spa-CCs carried by each infant (r = 0.5; 95% CI 0.35-0.62). Time to first acquisition of S. aureus was shorter in children from households with ≥5 individuals (HR 1.06, 95% CI 1.07-1.43), with S. aureus carrier mothers (HR; 1.5, 95% CI 1.2-2.47), or with a positive tuberculin skin test during the first year of life (HR; 1.81, 95% CI 0.97-3.3). Conclusion: Using measures of genotype diversity, we showed that S. aureus NP carriage is highly dynamic in infants. Prolonged carriage with a single strain occurred rarely; persistent carriage was not observed. A correlation was observed between carrier index and genotype diversity. PMID:30930937 | PMCID:PMC6428701
C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort.
Chikowore T, Sahibdeen V, Hendry LM, Norris SA, Goedecke JH, Micklesfield LK, Lombard Z. AIM:
To evaluate the association between loss-of-function (LOF) PCSK9 variants (A433T/rs28362263 and C679X/rs28362286) and biomarkers of cardiometabolic risk, specifically fasting glucose and low density lipoprotein cholesterol (LDL-C) concentrations. METHODS:
Our study comprised 757 male and female black South African adolescents (mean age 18.0 ± 0.5 years) who are part of the Birth to Twenty Plus Cohort and had been genotyped for the two above-mentioned variants. Anthropometric measures were completed and fasting plasma glucose and lipid analysis were performed using standard procedures. RESULTS:
The median and interquartile range of fasting glucose and LDL-C for the whole group were 4.60 (4.36-4.88) mmol/L and 1.67 (1.25-2.14) mmol/L, respectively. After adjusting for sex, association between the biomarkers and A443T was not significant. However, C679X carriers displayed 0.30 [95% CI (-0.57, -0.02); p = 0.035] mmol/L lower fasting glucose and 0.50 [95% CI (-0.74, -0.26); p < 0.001) mmol/L lower LDL-C concentrations compared to non-carriers. CONCLUSIONS:
Our results indicate for the first that the C679X variants associated with low fasting glucose levels during adolescents as had been known for LDL-C. In view that a similar finding was reported in older black South African adults, therefore, the correlation of lower fasting glucose and LDL-C levels with C679X is observed from an early age to adulthood. PMID:30899674 | PMCID:PMC6407309
Indoor air pollution and tobacco smoke exposure: impact on nasopharyngeal bacterial carriage in mothers and infants in an African birth cohort study.
Vanker A, Nduru PM, Barnett W, Dube FS, Sly PD, Gie RP, Nicol MP, Zar HJ.
Indoor air pollution (IAP) or environmental tobacco smoke (ETS) exposure may influence nasopharyngeal carriage of bacterial species and development of lower respiratory tract infection (LRTI). The aim of this study was to longitudinally investigate the impact of antenatal or postnatal IAP/ETS exposure on nasopharyngeal bacteria in mothers and infants. A South African cohort study followed mother-infant pairs from birth through the first year. Nasopharyngeal swabs were taken at birth, 6 and 12 months for bacterial culture. Multivariable and multivariate Poisson regression investigated associations between nasopharyngeal bacterial species and IAP/ETS. IAP exposures (particulate matter, carbon monoxide, nitrogen dioxide, volatile organic compounds) were measured at home visits. ETS exposure was measured through maternal and infant urine cotinine. Infants received the 13-valent pneumococcal and Haemophilus influenzae B conjugate vaccines. There were 881 maternal and 2605 infant nasopharyngeal swabs. Antenatal ETS exposure was associated with Streptococcus pneumoniae carriage in mothers (adjusted risk ratio (aRR) 1.73 (95% CI 1.03-2.92)) while postnatal ETS exposure was associated with carriage in infants (aRR 1.14 (95% CI 1.00-1.30)) Postnatal particulate matter exposure was associated with the nasopharyngeal carriage of H. influenzae (aRR 1.68 (95% CI 1.10- 2.57)) or Moraxella catarrhalis (aRR 1.42 (95% CI 1.03-1.97)) in infants. Early-life environmental exposures are associated with an increased prevalence of specific nasopharyngeal bacteria during infancy, which may predispose to LRTI. PMID:30740462 | PMCID:PMC6360211
Stroke, cerebrovascular diseases and vascular cognitive impairment in Africa.
Akinyemi RO, Owolabi MO, Ihara M, Damasceno A, Ogunniyi A, Dotchin C, Paddick SM, Ogeng’o J, Walker R, Kalaria RN.
With increased numbers of older people a higher burden of neurological disorders worldwide is predicted. Stroke and other cerebrovascular diseases do not necessarily present with different phenotypes in Africa but their incidence is rising in tandem with the demographic change in the population. Age remains the strongest irreversible risk factor for stroke and cognitive impairment. Modifiable factors relating to vascular disease risk, diet, lifestyle, physical activity and psychosocial status play a key role in shaping the current spate of stroke related diseases in Africa. Hypertension is the strongest modifiable risk factor for stroke but is also likely associated with co-inheritance of genetic traits among Africans. Somewhat different from high-income countries, strokes attributed to cerebral small vessel disease (SVD) are higher >30% among sub-Saharan Africans. Raised blood pressure may explain most of the incidence of SVD-related strokes but there are likely other contributing factors including dyslipidaemia and diabetes in some sectors of Africa. However, atherosclerotic and cardioembolic diseases combined also appear to be common subtypes as causes of strokes. Significant proportions of cerebrovascular diseases are ascribed to various forms of infectious disease including complications of human immunodeficiency virus. Cerebral SVD leads to several clinical manifestations including gait disturbance, autonomic dysfunction and depression. Pathological processes are characterized by arteriolosclerosis, lacunar infarcts, perivascular spaces, microinfarcts and diffuse white matter changes, which can now all be detected on neuroimaging. Except for isolated cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL, hereditary arteriopathies have so far not been reported in Africa. Prevalence estimates of vascular dementia (2-3%), delayed dementia after stroke (10-20%) and vascular cognitive impairment (30-40%) do not appear to be vastly different from those in other parts of the world. However, given the current demographic transition in both urban and rural settings these figures will likely rise. Wider application of neuroimaging modalities and implementation of stroke care in Africa will enable better estimates of SVD and other subtypes of stroke. Stroke survivors with SVD type pathology are likely to have low mortality and therefore portend increased incidence of dementia. PMID:29807146 | PMCID:PMC6252289
Applying Mental Model Methods to Characterize Understanding of Gene-Environment Influences: The Case of Podoconiosis in Ethiopia.
Allen CG, McBride CM, Engdawork K, Ayode D, Tadele G.
The rapid pace of genomic discovery has raised public expectation and concerns about the utility of new discoveries and their potential to exacerbate health disparities. Improving literacy concerning gene and environmental (GxE) contributors to disease is needed to avoid commonly observed deterministic misconceptions about genomics. Mental models approaches that incorporate community engagement processes could be used to inform GxE literacy-building interventions. We used a mental models approach to describe and systematically compare expert and lay understanding of GxE interactions, using the example of podoconiosis, a non-infectious lymphedema endemic in highland Ethiopia. Methods included: (1) specifying elicitation questions for a literature review, (2) eliciting an expert model, (3) eliciting a lay model, and (4) comparing the two models. We used a coding scheme to identify lay participants’ knowledge gaps, misunderstandings and extra knowledge relative to the expert standard. Results indicated that lay participants’ viewed poverty as an important susceptibility factor and considered heredity and contagion to have a joint causal influence. Experts did not endorse either of these viewpoints. Conventional expert-based interventions aimed to correct misconceptions about behaviors important for prevention may be stymied by lay views that social environmental factors have more important influences on health outcomes. GxE literacy interventions that consider multiple levels of influence including social determinants of health and personal resilience to augment health education strategies are needed in diverse settings. Novel communication approaches will be needed to help target audiences disentangle long-held conceptions of heredity and contagion. PMID:30853753 | PMCID:PMC6405231
Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study.
Akinyemi RO, Sarfo FS, Akinyemi J, Singh A, Onoja Akpa M, Akpalu A, Owolabi L, Adeoye AM, Obiako R, Wahab K, Sanya E, Komolafe M, Ogbole G, Fawale M, Adebayo P, Osaigbovo G, Sunmonu T, Olowoyo P 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. PMID:30040054