Analysis of Erythrocyte Invasion Mechanisms of Plasmodium falciparum Clinical Isolates Across 3 Malaria-Endemic Areas in Ghana.

BACKGROUND: Plasmodium falciparum invades human erythrocytes by using an array of ligands that interact with several receptors, including sialic acid (SA), complement receptor 1 (CR1), and basigin. We hypothesized that in malaria-endemic areas, parasites vary invasion pathways under immune pressure. Therefore, invasion mechanisms of clinical isolates collected from 3 zones of Ghana with different levels of endemicity (from lowest to highest, Accra, Navrongo, and Kintampo) were compared using standardized methods. METHODS: Blood samples were collected from children aged 2-14 years in whom malaria was diagnosed, and erythrocyte invasion phenotypes were determined using the enzymes neuraminidase, chymotrypsin, and trypsin, which differentially cleave receptors from the erythrocyte surface. In addition, antibodies against CR1 and basigin were used to determine the contributions of these receptors to invasion. Gene expression levels of P. falciparum invasion ligands were also examined. RESULTS: The parasites generally expressed SA-independent invasion phenotypes across the malaria-endemic areas, with parasites from Kintampo showing the highest invasion rates in neuraminidase-treated erythrocytes. CR1 was a major mediator of SA-independent invasion, while basigin was essential for both SA-dependent and SA-independent invasion mechanisms. Furthermore, expression of the basigin ligand PfRh5 was the best predictor of donor parasitemia. CONCLUSIONS: Erythrocyte invasion phenotypes expressed by P. falciparum are influenced by endemicity levels, and the PfRh5-basigin pathway is a potential vaccine target

Distribution and clustering of Oesophagostomum bifurcum and hookworm infections in northern Ghana

Human Oesophagostomum infections are locally common in northern Ghana. The present study describes the results of a cross-sectional survey involving 1011 subjects, selected by a compound-based random sampling method from 1227 compounds in 24 villages. Selected persons were examined by both Kato and coproculture methods. Hookworm-like eggs, representing ova of Oesophagostomum bifurcum and hookworm were detected in 87.5% of the Kato smears. The geometric mean egg count of the infected subjects was 1018. Upon coproculture, third-stage larvae of O. bifurcum and hookworm were detected in 53.0% and 86.9% of subjects respectively. Oesophagostomum infections were clustered but no clear explanation for aggregation of infections could be found as yet. Subjects infected with hookworm had a 5-fold higher risk of being infected with O. bifurcum. Infection rates in adult women were higher than in adult men. No association was found with family size, level of hygiene or with the presence of animals in the compounds. Representatives of the Bimoba-tribe were significantly more infected than those of the other tribes. It appears, however, that this tribal association is a geographical phenomenon: Bimoba are mostly living in villages with the highest infection rate

Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima‐Media Thickness: An Individual Participant Data Meta‐Analysis

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid‐intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross‐sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B‐mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 1‐stage individual participant data meta‐analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09–0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01–0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06–0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High‐density lipoprotein‐cholesterol had significant protective effects in African American (beta coefficient, −0.31; 95% CI, −0.42 to −0.21) and African (beta coefficient, −0.26; 95% CI, −0.31 to −0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race‐ ethnicity‐specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations

Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima-Media Thickness : An Individual Participant Data Meta-Analysis

BACKGROUND: The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid-intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. METHODS AND RESULTS: Cross-sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B-mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 2-stage individual participant data meta-analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coeffi-cient, 0.39; 95% CI, 0.09– 0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01– 0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06– 0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High-density lipoprotein-cholesterol had significant protective effects in African American (beta coefficient, −0.31; 95% CI, −0.42 to −0.21) and African (beta coefficient, −0.26; 95% CI, −0.31 to −0.19) populations only. CONCLUSIONS: The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race-ethnicity-specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations

Classical Cardiovascular Risk Factors and HIV are Associated With Carotid Intima-Media Thickness in Adults From Sub-Saharan Africa: Findings From H3Africa AWI-Gen Study

Background Studies on the determinants of carotid intima-media thickness ( CIMT ), a marker of sub-clinical atherosclerosis, mostly come from white, Asian, and diasporan black populations. We present CIMT data from sub-Saharan Africa, which is experiencing a rising burden of cardiovascular diseases and infectious diseases. Methods and Results The H3 (Human Hereditary and Health) in Africa's AWI-Gen (African-Wits-INDEPTH partnership for Genomic) study is a cross-sectional study conducted in adults aged 40 to 60 years from Burkina Faso, Kenya, Ghana, and South Africa. Cardiovascular disease risk and ultrasonography of the CIMT of right and left common carotids were measured. Multivariable linear and mixed-effect multilevel regression modeling was applied to determine factors related to CIMT. Data included 8872 adults (50.8% men), mean age of 50±6 years with age- and sex-adjusted mean (±SE) CIMT of 640±123μm. Participants from Ghana and Burkina Faso had higher CIMT compared with other sites. Age (β = 6.77, 95%CI [6.34-7.19]), body mass index (17.6[12.5-22.8]), systolic blood pressure (7.52[6.21-8.83]), low-density lipoprotein cholesterol (5.08[2.10-8.06]) and men (10.3[4.75- 15.9]) were associated with higher CIMT. Smoking was associated with higher CIMT in men. High-density lipoprotein cholesterol (-12.2 [-17.9- -6.41]), alcohol consumption (-13.5 [-19.1--7.91]) and HIV (-8.86 [-15.7--2.03]) were inversely associated with CIMT. Conclusions Given the rising prevalence of cardiovascular diseases risk factors in sub-Saharan Africa, atherosclerotic diseases may become a major pan-African epidemic unless preventive measures are taken particularly for prevention of hypertension, obesity, and smoking. HIV -specific studies are needed to fully understand the association between HIV and CIMT in sub-Saharan Africa

Enabling the genomic revolution in Africa

H3Africa is developing capacity for health-related genomics research in Afric

Research capacity. Enabling the genomic revolution in Africa.

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