35 research outputs found
Characterization of DNA Methylation in Giardia intestinalis
No full textAbstract G. intestinalis is an intestinal protozoan parasite that causes 180 million symptomatic diarrheacases (giardiasis) and more than 0.5 billion asymptomatic infections per year. Symptomaticinfections are usually treated with metronidazole (Flagyl). However, resistance is emerging, andan alternative treatment is required. The mechanism to which the parasite causes the disease is notunderstood and, neither is the regulation of encystation (a process where trophozoites differentiateto cyst) However, preliminary data suggest that an epigenetic mechanism is involved. DNAmethylation is an important epigenetic regulator in many organisms, but it is not known if theDNA is methylated in Giardia. The main goal of this project was to characterize DNA methylationin G. intestinalis and, if it exists, study if it is linked to cell differentiation and use it as a target fordrug treatment. We found out using the dot blot technique complemented withimmunofluorescence assays, that 6mA and 5mC DNA methylation exists on the genomic DNA ofthe assemblage A G. intestinalis isolate WB. 6mA methylation was also found on RNA. However,no major differences were detected between trophozoites and cysts. Assemblage B Giardia isolates(GS and H3) also have methylated genomic DNA, but we detected lower levels of methylation. Abioinformatic search was performed in the G. intestinalis WB genome in an attempt to identifyDNA methylases. Expression levels through-out the life cycle, sequence similarities and structuralmodelling using iTASSER identified six putative DNA methylases in the WB genome. The sixDNA methylases were over-expressed in Giardia, three were lethal and three localized to thenucleus. 5-azacytidine and 5-aza-2’-deoxycytidine nucleoside analog drugs prevent methylationand are incorporated into RNA and DNA, respectively. We tested these two drugs on Giardiatrophozoites, and both have effects on the trophozoite stage (IC50 1.46±0.46 μM for 5-aza-2’-deoxycytidine and 111±24 μM for 5-Azacytidine). The 5-aza-2’-deoxycytidine drug is actuallymore effective than metronidazole, showing that nucleoside analogs affecting DNA methylationcould be alternative drugs for treatment of giardiasis
Adiposity phenotypes and subclinical atherosclerosis in adults from sub-saharan Africa: An H3Africa awi-gen study
No full textBackground: Obesity and adipose tissue distribution contribute to an increased risk of cardiovascular disease (CVD) by promoting atherosclerosis. This association has been poorly studied in sub–Saharan Africa (SSA) despite the rising prevalence of cardiovascular disease.Objectives: We determined the association between various adiposity phenotypes and carotid intima–media thickness (CIMT), a proxy of subclinical atherosclerosis, in a large SSA population.Methods: A population–based cross–sectional study was performed from 2013–2016 in Burkina Faso, Ghana, Kenya and South Africa. Body mass index (BMI), waist (WC), hip circumferences (HC), visceral (VAT) and subcutaneous adipose tissue (SCAT) using B-mode ultrasound were measured. Ultrasonography of left and right far wall CIMT of the common carotid artery was used as an indicator of subclinical atherosclerosis. Individual participant data meta–analyses were used to determine the associations between adiposity phenotypes and CIMT in the pooled sample while adjusted multivariable linear regression analyses were used for site specific analyses.Results: Data were obtained from 9,010 adults (50.3% women and a mean age of 50± 6years). Men had higher levels of visceral fat than women while women had higher BMI, waist and hip circumference and subcutaneous fat than men at all sites except Burkina Faso. In the pooled analyses, BMI (â–value [95% CIs]: 19.5 [16.8, 22.3] ìm) showed the strongest relationship with CIMT followed by VAT (5.86 [4.65, 7.07] ìm), SCAT (5.00 [2.85, 7.15] ìm), WC (1.27 [1.09, 1.44] ìm) and HC (1.23 [1.04, 1.42] ìm). Stronger associations were observed in men than in women.Conclusion: Obesity within SSA will likely result in higher levels of atherosclerosis and promote the occurrence of cardio- and cerebrovascular events, especially in males, unless addressed through primary prevention of obesity in both rural and urban communities across Africa. The inverse association of VAT with CIMT in Burkina Faso and Ghana requires further investigation.Highlights: All adiposity phenotypes were positively associated with common carotid intima-media thickness (CIMT) in the entire cohort (pooled analyses).BMI had the strongest association with CIMT compared to other phenotypes.The magnitude of association between adiposity phenotypes and CIMT was higher in men than in women.Subcutaneous adipose tissue was inversely associated with CIMT only in women.An unexpected finding was the inverse association of visceral adipose tissue with CIMT in Burkina Faso and Ghana
Carotid atherosclerosis, microalbuminuria, and estimated 10-year atherosclerotic cardiovascular disease risk in sub-saharan Africa
No full textImportance Carotid atherosclerosis and microalbuminuria are associated with atherosclerotic cardiovascular disease (ASCVD) but are understudied in sub-Saharan Africa.Objective To evaluate the association of carotid atherosclerosis and microalbuminuria with 10-year ASCVD risk in middle-aged sub-Saharan African individuals.Design, Setting, and Participants This cross-sectional study conducted analyses of baseline data from the African-Wits-INDEPTH (International Network for the Demographic Evaluation of Populations and Their Health in Low- and Middle-Income Countries) genomic study (AWI-Gen). Women and men aged 40 to 60 years without baseline CVD and drawn from Burkina Faso, Ghana, Kenya, and South Africa were included.Main Outcomes and Measures Hypotheses for the analyses were formulated after data collection. The main exposures were carotid atherosclerosis, assessed using carotid intima-media thickness (CIMT) using B-mode ultrasonography, and microalbuminuria, measured using spot urine albumin (SUA) and urine albumin-creatinine ratio (uACR). The main outcome was high ASCVD risk, defined as a 2018 Pooled Cohort Equations score of 7.5% or greater. Associations were estimated using adjusted multivariable logistic regression analyses.Findings A total of 9010 participants with a mean (SD) age of 50 (6) years and 4533 (50.3%) women were included. High CIMT, SUA, and uACR were each associated with older age (eg, mean [SD] age of participants with high vs reference range CIMT: 55 [5] years vs 50 [6] years; P < .001) and high prevalence of both diabetes and hypertension (eg, hypertension among those with high vs reference range SUA: 213 of 1117 [19.1%] vs 356 of 2549 [14.0%]; P < .001). Smokers were likely to have higher vs reference range SUA (210 [18.8%] vs 407 [16.0%]) and uACR (138 of 707 [19.5%] vs 456 of 2797 [16.3%]). Carotid atherosclerosis was common in Burkina Faso (82 of 262 [31.3%]) and Ghana (91 [34.7%]), while microalbuminuria, measured by SUA, was common in Kenya (272 [24.4%]) and South Africa (519 [46.5%]). SUA was associated with higher odds of carotid atherosclerosis (odds ratio [OR], 1.77; 95% CI, 1.04-3.01) compared with uACR (OR, 0.51; 95% CI, 0.27-0.95). Common CIMT, SUA, and uACR were associated with 10-year ASCVD risk, with CIMT having a stronger association with 10-year ASCVD risk in both women (OR, 1.95; 95% CI, 1.78-2.14) and men (OR, 1.73; 95% CI, 1.55-1.93) than SUA (women: OR, 1.29; 95% CI, 1.12-1.43; men: OR, 1.46; 95% CI, 1.26-1.55) and uACR (women: OR, 1.32; 95% CI, 1.10-1.54; men: OR, 1.35; 95% CI, 1.15-1.46).Conclusions and Relevance The presence of microalbuminuria measured by SUA may indicate risk of subclinical carotid atherosclerosis and high 10-year ASCVD risk in middle-aged residents of sub-Saharan Africa. These data should be confirmed in longitudinal studies of cardiovascular events
Author Correction: High-depth African genomes inform human migration and health
No full textIn this Article, the affiliation ‘South African National Bioinformatics Network, University of the Western Cape, Bellville, South Africa’, which is associated with authors Gordon Wells and Judit Kumuthini, should be ‘South African National Bioinformatics Institute, University of the Western Cape, Bellville, South Africa’. In addition, author Gordon Wells should be associated with an additional affiliation, ‘Africa Health Research Institute, Durban, South Africa’. In Fig. 1a, the circle representing the data for South Africa should be dark grey (indicating the AGVP data source) rather than light grey (indicating the 1000G data source). The Article has been corrected online
Genomic and environmental risk factors for cardiometabolic diseases in Africa: methods used for Phase 1 of the AWI-Gen population crosssectional study
No full texthttps://doi.org/10.1080/16549716.2018.1507133There is an alarming tide of cardiovascular and metabolic disease (CMD) sweeping across Africa. This may be a result of an increasingly urbanized lifestyle characterized by the growing consumption of processed and calorie-dense food, combined with physical inactivity and more sedentary behaviour. While the link between lifestyle and public health has been extensively studied in Caucasian and African American populations, few studies have been conducted in Africa. This paper describes the detailed methods for Phase 1 of the AWI-Gen study that were used to capture phenotype data and assess the associated risk factors and end points for CMD in persons over the age of 40 years in sub-Saharan Africa (SSA). We developed a population-based cross-sectional study of disease burden and phenotype in Africans, across six centres in SSA. These centres are in West Africa (Nanoro, Burkina Faso, and Navrongo, Ghana), in East Africa (Nairobi, Kenya) and in South Africa (Agincourt, Dikgale and Soweto). A total of 10,702 individuals between the ages of 40 and 60 years were recruited into the study across the six centres, plus an additional 1021 participants over the age of 60 years from the Agincourt centre. We collected socio-demographic, anthropometric, medical history, diet, physical activity, fat distribution and alcohol/tobacco consumption data from participants. Blood samples were collected for disease-related biomarker assays, and genomic DNA extraction for genome-wide association studies. Urine samples were collected to assess kidney function. The study provides base-line data for the development of a series of cohorts with a second wave of data collection in Phase 2 of the study. These data will provide valuable insights into the genetic and environmental influences on CMD on the African continent
Hypertension knowledge attitudes and perceptions among adults in the Navrongo Health and Demographic Surveillance Site a mixed methods analysis
No full textExpanding the human gut microbiome atlas of Africa
No full textPopulation studies provide insights into the interplay between the gut microbiome and geographical, lifestyle, genetic and environmental factors. However, low- and middle-income countries, in which approximately 84% of the world’s population lives1, are not equitably represented in large-scale gut microbiome research2,3,4. Here we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,801 women from Burkina Faso, Ghana, Kenya and South Africa. By engaging with communities that range from rural and horticultural to post-industrial and urban informal settlements, we capture a far greater breadth of the world’s population diversity. Using shotgun metagenomic sequencing, we identify taxa with geographic and lifestyle associations, including Treponema and Cryptobacteroides species loss and Bifidobacterium species gain in urban populations. We uncover 1,005 bacterial metagenome-assembled genomes, and we identify antibiotic susceptibility as a factor that might drive Treponema succinifaciens absence in urban populations. Finally, we find an HIV infection signature defined by several taxa not previously associated with HIV, including Dysosmobacter welbionis and Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals so far, and paired with extensive clinical biomarkers and demographic data, provides extensive opportunity for microbiome-related discovery
Distribution of human Oesophagostomum bifurcum, hookworm and Strongyloides stercoralis infections in northern Ghana
No full textA cross-sectional study was carried out in 216 randomly selected, representative rural villages in the northeastern part of Ghana from March 1995 to May 1998. Inhabitants of randomly selected households, stratified by age and gender, were included. The geographical position of villages was recorded with a global positioning system (GPS). The prevalence of Oesophagostomum, hookworm and Strongyloides stercoralis infections in a study population of 20 250 people was determined by microscopic examination of larvae in stool cultures. The overall prevalence was 10.2, 50.6 and 11.6% for the three nematodes, respectively. Hookworm infections were seen in all but one (99.5%) and S. stercoralis in 88.4% of the 216 villages, while Oesophagostomum infections were found to be common in a limited area with prevalences varying from 0 to 75%. An association was found between Oesophagostomum and hookworm infection, both at the individual and at the village level. Spatial analysis of the prevalence data indicated that the endemic area is relatively clearly demarcated to the south of the study area.</p
Autozygosity influences cardiometabolic diseaseassociated traits in the AWI-Gen sub-Saharan African study
No full textThe analysis of the effects of autozygosity, measured as the change of the mean value of a trait among offspring of genetic relatives, reveals the existence of directional dominance or overdominance. In this study we detect evidence of the effect of autozygosity in 4 out of 13 cardiometabolic disease-associated traits using data from more than 10,000 sub-Saharan African individuals recruited from Ghana, Burkina Faso, Kenya and South Africa.
The effect of autozygosity on these phenotypes is found to be sex-related, with inbreeding having a significant decreasing effect in men but a significant increasing effect in women for several traits (body mass index, subcutaneous adipose tissue, low-density lipoproteins and total cholesterol levels). Overall, the effect of inbreeding depression is more intense in men. Differential effects of inbreeding depression are also observed between study sites with different night-light intensity used as proxy for urban development. These results suggest a directional dominant genetic component mediated by environmental interactions and sex-specific differences in genetic architecture for these traits in the Africa Wits-INDEPTH partnership for Genomic Studies (AWI-Gen) cohort
Regional disparities in immunization services in Ghana through a bottleneck analysis approach: implications for sustaining national gains in immunization
No full text
