Sex-Specific Associations Between Cardiac Workload, Peripheral Vascular Calcification, and Bone Mineral Density: The Gambian Bone and Muscle Aging Study

Noncommunicable diseases (NCD) are rapidly rising in Africa, with multimorbidity increasing the burden on health and social care. Osteoporosis and cardiovascular disease (CVD) share common risk factors; both often remain undiagnosed until a major life-threatening event occurs. We investigated the associations between cardiac workload, peripheral vascular calcification (PVC), and bone parameters in Gambian adults. The Gambian Bone and Muscle Aging Study (GamBAS) recruited 249 women and 239 men aged 40 to 75+ years. Body composition and areal bone mineral density (aBMD) were measured using dual-energy X-ray absorptiometry; peripheral quantitative computed tomography (pQCT) scans were performed at the radius and tibia. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia pQCT scans. Sex interactions were tested (denoted as p-int); adjustments were made for residuals of appendicular lean mass (ALM) and fat mass (FM). There were negative associations between rate pressure product and aBMD in women only, all p-int < .05; after adjustment for ALM residuals, for every 10% increase in rate pressure product, aBMD was lower at the whole body (-0.6% [-1.2, -0.1]), femoral neck (-0.9% [-1.8, -0.05]), L1 to L4 (-0.6% [-1.7, 0.5]), and radius (-1.9% [-2.8, -0.9]); there were similar associations when adjusted for FM residuals. Similar negative associations were found between pulse pressure and aBMD in women only. PVC were found in 26.6% men and 22.5% women; women but not men with calcification had poorer cardiac health and negative associations with aBMD (all sites p-int < .001). There were consistent associations with cardiac parameters and pQCT outcomes at the radius and tibia in women only. Multiple markers of cardiac health are associated with poorer bone health in Gambian women. In the context of epidemiological transition and changing NCD burden, there is a need to identify preventative strategies to slow/prevent the rising burden in CVD and osteoporosis in Sub-Saharan Africa. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Sustained Ex Vivo Susceptibility of Plasmodium falciparum to Artemisinin Derivatives but Increasing Tolerance to Artemisinin Combination Therapy Partner Quinolines in The Gambia.

Antimalarial interventions have yielded a significant decline in malaria prevalence in The Gambia, where artemether-lumefantrine (AL) has been used as a first-line antimalarial for a decade. Clinical Plasmodium falciparum isolates collected from 2012 to 2015 were analyzed ex vivo for antimalarial susceptibility and genotyped for drug resistance markers (pfcrt K76T, pfmdr1 codons 86, 184, and 1246, and pfk13) and microsatellite variation. Additionally, allele frequencies of single nucleotide polymorphisms (SNPs) from other drug resistance-associated genes were compared from genomic sequence data sets from 2008 (n = 79) and 2014 (n = 168). No artemisinin resistance-associated pfk13 mutation was found, and only 4% of the isolates tested in 2015 showed significant growth after exposure to dihydroartemisinin. Conversely, the 50% inhibitory concentrations (IC50s) of amodiaquine and lumefantrine increased within this period. pfcrt 76T and pfmdr1 184F mutants remained at a prevalence above 80%. pfcrt 76T was positively associated with higher IC50s to chloroquine. pfmdr1 NYD increased in frequency between 2012 and 2015 due to lumefantrine selection. The TNYD (pfcrt 76T and pfmdr1 NYD wild-type haplotype) also increased in frequency following AL implementation in 2008. These results suggest selection for pfcrt and pfmdr1 genotypes that enable tolerance to lumefantrine. Increased tolerance to lumefantrine calls for sustained chemotherapeutic monitoring in The Gambia to minimize complete artemisinin combination therapy (ACT) failure in the future

SARS-CoV-2 seroprevalence in pregnant women during the first three COVID-19 waves in The Gambia

OBJECTIVES: SARS-CoV-2 transmission in Sub-Saharan Africa has probably been underestimated. Population-based seroprevalence studies are needed to determine the extent of transmission in the continent. METHODS: Blood samples from a cohort of Gambian pregnant women were tested for SARS-CoV-2 total receptor binding domain (RBD) IgM/IgG before (Pre-pandemic: October-December 2019), and during the pandemic (Pre-wave1: February-June 2020; Post-wave1: October-December 2020, Post-wave2: May-June 2021; and Post-wave3: October-December 2021). Samples reactive for SARS-CoV-2 total RBD IgM/IgG were tested in specific S1- and nucleocapsid (NCP) IgG assays. RESULTS: SARS-CoV-2 total RBD IgM/IgG seroprevalence was 0.9% 95%CI (0.2, 4.9) in Pre-pandemic; 4.1% (1.4, 11.4) in Pre-wave1; 31.1% (25.2, 37.7) in Post-wave1; 62.5% (55.8, 68.8) in Post-wave2 and 90.0% (85.1, 93.5) in Post-wave3. S-protein IgG and NCP-protein IgG seroprevalence also increased at each Post-wave period. Although S-protein IgG and NCP-protein IgG seroprevalence was similar at Post-wave1, S-protein IgG seroprevalence was higher at Post-wave2 and Post-wave3, [prevalence difference (PD) 13.5 (0.1, 26.8) and prevalence ratio (PR) 1.5 (1.0, 2.3) in Post-wave2; and 22.9 (9.2, 36.6) and 1.4 (1.1, 1.8) in Post-wave3 respectively, p<0.001]. CONCLUSION: SARS-CoV-2 transmission in The Gambia during the first three COVID-19 waves was high, differing significantly from official numbers of COVID-19 cases reported. Our findings are important for policy makers in managing the near-endemic COVID-19

Effects of inactive CYP2C19/CYP2C9 alleles on chlorproguanil pharmacokinetics in adults and treatment outcome in children with uncomplicated malaria following Lapdap treatment

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Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa.

Acknowledgements: The authors wish to acknowledge the contribution of the participants who took part in this study. We thank the men and women of Kiang West and the Kombos, The Gambia, who patiently participated in the study. We acknowledge the enthusiastic work of the study team, especially the research and bone imaging staff, who tirelessly collected the data, and the drivers who transported the participants between facilities. The support of the data management team was greatly appreciated both during and after data collection. We are grateful to Michael Mendy and Mustapha Ceesay for their senior oversight of the bone imaging team. We also thank Dr. Sarah Dalzell for her help in planning the study. This research was jointly funded by the MRC (programme codes U105960371, U123261351, MCA760-5QX00) and the Department for International Development (DFID) under the MRC/DFID Concordat agreement. For the purposes of Open Access, the authors (KAW, AP) have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.Between-scanner differences in measures of bone and body composition can obscure or exaggerate physiological differences in multi-site studies or the magnitude of changes in longitudinal studies. We conducted a cross-calibration study at two bone imaging centres in The Gambia, West Africa where DXA (dual-energy X-ray absorptiometry) and pQCT (peripheral Quantitative-Computed Tomography) are routinely used. Repeat scans were obtained from 64 Gambian adults (58% Male) aged Mean(SD) 30.9 (13.5) years with Mean(SD) body mass index (BMI) 21.7 (4.0) kg/m2, using DXA (GE Lunar iDXA, whole body [WB], total hip [TH], lumbar spine [LS]) and pQCT (Stratec XCT2000L/XCT2000, tibia 4%, 50% sites). Between-scanner differences were tested using paired t tests (p < 0.05). Between-scanner correlation was explored with linear regression, and cross-calibration equations derived. Bland-Altman analysis investigated machine trend/bias. When differences were detected (p < 0.05), cross-calibration equations were applied to urban values, with t tests and Bland Altman analysis repeated. Between-scanner differences exceeded the predefined level of statistical significance (p < 0.05) for WB aBMD and BA; all pQCT measures vBMD, BMC, cortical cross-sectional area (CSA) and stress-strain index (SSI). Between-scanner correlation was high (R2:0.92-0.99), except pQCT Mu.Den (R2 = 0.51). Bland Altman plots indicated bias increased with increasing BMD. Cross-calibration equations attenuated all between-scanner differences and systematic bias. Cross-calibration, particularly of pQCT scanners, is an important consideration in multi-site studies particularly where between population comparisons are intended. Our experiences and findings may be generalisable to other resource-limited settings where the logistics of sourcing parts and in-country repair may result in lengthy scanner downtime

Sex-specific associations between cardiac workload, peripheral vascular calcification and bone mineral density: The Gambian Bone and Muscle Ageing Study

Non‐communicable diseases (NCD) are rapidly rising in Africa, with multi‐morbidity increasing the burden on health and social care. Osteoporosis and cardiovascular disease (CVD) both share common risk factors; both often remain undiagnosed until a major life‐threatening event occurs. We investigated the associations between cardiac workload, peripheral vascular calcification (PVC) and bone parameters in Gambian adults. The Gambian Bone and Muscle Ageing Study (GamBAS) recruited 249 women and 239 men aged 40‐75+ years. Body composition and areal bone mineral density (aBMD) were measured using dual energy x‐ray absorptiometry; peripheral‐ quantitative computed tomography (pQCT) scans were performed at the radius and tibia. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia pQCT scans. Sex‐interactions were tested (denoted as p‐int); adjustments were made for residuals of appendicular lean mass (ALM) and fat mass (FM). There were negative associations between rate pressure product and aBMD in women only, all p‐int&lt;0.05; after adjustment for ALM residuals, for every 10% increase in rate pressure product, aBMD was lower at the: whole‐body (‐0.6%[‐1.2,‐0.1]) , femoral neck (‐0.9%[‐1.8,‐0.05]), L1‐L4 (‐0.6%[‐1.7,0.5]) and radius (‐1.9%[‐2.8,‐0.9]); there were similar associations when adjusted for FM residuals. Similar negative associations were seen between pulse pressure and aBMD in women only. PVC were found in 26.6% men, 22.5% women; women but not men with calcification had poorer cardiac health, and negative associations with aBMD (all sites p‐int&lt;0.001). There were consistent associations with cardiac parameters and pQCT outcomes at the radius and tibia in women only. Multiple markers of cardiac health are associated with poorer bone health in Gambian women. In the context of epidemiological transition and changing NCD burden, there is a need to identify preventative strategies to slow/prevent the rising burden in CVD and osteoporosis in Sub‐Saharan Africa

Sex-specific associations between cardiovascular risk factors and physical function: The Gambian Bone and Muscle Ageing Study.

AimTo examine possible sex differences in the excess risk of myocardial infarction (MI) consequent to a range of conventional risk factors in a large-scale international cohort of patients with diabetes, and to quantify these potential differences both on the relative and absolute scales.Materials and methodsEleven thousand and sixty-five participants (42% women) with type 2 diabetes in the ADVANCE trial and its post-trial follow-up study, ADVANCE-ON, were included. Cox regression models were used to estimate hazard ratios (HRs) for associations between risk factors and MI (fatal and non-fatal) by sex, and the women-to-men ratio of HRs (RHR).ResultsOver a median of 9.6 years of follow-up, 719 patients experienced MI. Smoking status, smoking intensity, higher systolic blood pressure (SBP), HbA1c, total and LDL cholesterol, duration of diabetes, triglycerides, body mass index (BMI) and lower HDL cholesterol were associated with an increased risk of MI in both sexes. Furthermore, some variables were associated with a greater relative risk of MI in women than men: RHRs were 1.75 (95% CI: 1.05-2.91) for current smoking, 1.53 (1.00-2.32) for former smoking, 1.18 (1.02-1.37) for SBP, and 1.13 (95% CI, 1.003-1.26) for duration of diabetes. Although incidence rates of MI were higher in men (9.3 per 1000 person-years) compared with women (5.8 per 1000 person-years), rate differences associated with risk factors were greater in women than men, except for HDL cholesterol and BMI.ConclusionsIn patients with type 2 diabetes, smoking, higher SBP and longer duration of diabetes had a greater relative and absolute effect in women than men, highlighting the importance of routine sex-specific approaches and early interventions in women with diabetes