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) immunoglobulin (Ig) M/IgG before (Pre-pandemic: October-December 2019) and during the pandemic (Pre-wave 1: February-June 2020; Post-wave 1: October-December 2020, Post-wave 2: May-June 2021; and Post-wave 3: 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% confidence interval (0.2, 4.9) in Pre-pandemic; 4.1% (1.4, 11.4) in Pre-wave 1; 31.1% (25.2, 37.7) in Post-wave 1; 62.5% (55.8, 68.8) in Post-wave 2 and 90.0% (85.1, 93.5) in Post-wave 3. 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-wave 1, S-protein IgG seroprevalence was higher at Post-wave 2 and Post-wave 3, (prevalence difference 13.5 [0.1, 26.8] and prevalence ratio 1.5 [1.0, 2.3] in Post-wave 2; and 22.9 [9.2, 36.6] and 1.4 [1.1, 1.8] in Post-wave 3 respectively, P <0.001). CONCLUSION: SARS-CoV-2 transmission in The Gambia during the first 3 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.

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

BACKGROUND: In Sub-Saharan Africa, the prevalence of obesity, cardiovascular disease (CVD) and impaired physical function are increasing due to rapid urbanization. We investigated sex differences in associations between cardiac workload, arterial stiffness, peripheral vascular calcification (PVC) and physical function in Gambian adults. METHODS: A total of 488 Gambians aged 40-75+ years were recruited (men: 239; and women: 249). Supine blood pressure and heart rate were measured to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia peripheral quantitative computed tomography scans. Physical function was assessed by chair rise test (CRT), single two-legged jump (s2LJ) and hand grip strength (HGS). Body composition was measured by dual-energy x-ray absorptiometry; body size corrections were used to calculate fat mass index (FMI) and appendicular lean mass index (ALMI). Estimated glomerular filtration rate (eGFR) was measured from fasting blood samples. The relationship between rate pressure product, pulse pressure or presence of PVC (independent variable) with physical function parameters (dependent variable) was tested using linear regression. Sex-interactions were tested (p-int) adjusting for age, eGFR and ALMI/FMI. Results were expressed as mean differences between men and women with 95% confidence intervals. Mediation analyses used ALMI/FMI as mediator. RESULTS: Women weighed less (54.7 kg ± 10.3 vs. 59.9 kg ± 10.3) and were shorter (157.8 cm ± 6.0 vs. 169.2 cm ± 7.0) compared with men (both P < 0.0001). Women had higher FMI (6.8 kg/m2  ± 2.9 vs. 2.9 kg/m2  ± 2.0, P < 0.0001) and eGFR (263.7 mL/min/1.73 m2  ± 133.1 vs. 237.6 mL/min/1.73 m2  ± 134.6), but lower ALMI (6.2 kg/m2  ± 0.7 vs. 8.02 kg/m2  ± 1.0, P < 0.0001) compared with men. There were significant mean differences between men and women in rate pressure product and s2LJ power (-1.08 [-1.21, -0.95]) and force (-0.57 [-0.63, -0.51]), only after adjusting for age, eGFR and FMI. There were significant mean differences in the associations between pulse pressure and CRT power (-0.28 [-0.31, -0.25]), s2LJ power (-1.07 [-1.20, -0.93]) and HGS (-11.94 [-13.35, -10.54]); these differences were greater after adjusting for age, eGFR and FMI, than ALMI. There were similar differences in the associations between PVC and physical function parameters. In men, FMI mediated the association between rate pressuree product and CRT power (P = 0.002), s2LJ force (P < 0.001) and s2LJ power (P = 0.001). ALMI did not mediate associations for either men or women. CONCLUSIONS: Multiple risk factors for CVD were associated with poorer physical function in men and were mediated by FMI. There is a need to identify strategies to slow/prevent the rising CVD burden and poor physical function in Sub-Saharan Africa.

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).

Exploring influences on adolescent diet and physical activity in rural Gambia, West Africa: food insecurity, culture and the natural environment.

OBJECTIVE: To explore, from the perspectives of adolescents and caregivers, and using qualitative methods, influences on adolescent diet and physical activity in rural Gambia. DESIGN: Six focus group discussions (FGD) with adolescents and caregivers were conducted. Thematic analysis was employed across the data set. SETTING: Rural region of The Gambia, West Africa. PARTICIPANTS: Participants were selected using purposive sampling. Four FGD, conducted with forty adolescents, comprised: girls aged 10-12 years; boys aged 10-12 years; girls aged 15-17 years, boys aged 15-17 years. Twenty caregivers also participated in two FGD (mothers and fathers). RESULTS: All participants expressed an understanding of the association between salt and hypertension, sugary foods and diabetes, and dental health. Adolescents and caregivers suggested that adolescent nutrition and health were shaped by economic, social and cultural factors and the local environment. Adolescent diet was thought to be influenced by: affordability, seasonality and the receipt of remittances; gender norms, including differences in opportunities afforded to girls, and mother-led decision-making; cultural ceremonies and school holidays. Adolescent physical activity included walking or cycling to school, playing football and farming. Participants felt adolescent engagement in physical activity was influenced by gender, seasonality, cultural ceremonies and, to some extent, the availability of digital media. CONCLUSIONS: These novel insights into local understanding should be considered when formulating future interventions. Interventions need to address these interrelated factors, including misconceptions regarding diet and physical activity that may be harmful to health.

'I should be disease free, healthy and be happy in whatever I do': a cross-country analysis of drivers of adolescent diet and physical activity in different low- and middle-income contexts.

OBJECTIVE: To explore perceptions of how context shapes adolescent diet and physical activity in eight low- and middle-income (LMIC) sites at different stages of societal and economic transition. DESIGN: Novel qualitative secondary analysis of eight data sets generated as part of the international Transforming Adolescent Lives through Nutrition (TALENT) collaboration. SETTING: Diverse sites in India and Sub-Saharan Africa. PARTICIPANTS: Fifty-two focus group discussions with 491 participants (303 adolescents aged 10-17 years; 188 caregivers). RESULTS: Analysis of pooled qualitative data identified three themes: (1) transitions in generational nutrition education and knowledge; (2) transition in caregiver-adolescent power balance and (3) the implications of societal and economic transition for diet and physical activity. Adolescents in urban and peri-urban areas could readily access 'junk' food. Diets in rural settings were determined by tradition, seasonality and affordability. Physical activity was inhibited by site-specific factors including lack of space and crime in urban settings, and the prioritisation of academic performance. Gender influenced physical activity across all sites, with girls afforded fewer opportunities. CONCLUSIONS: Interventions to improve adolescent diet and physical activity in LMIC need to be complex, context-specific and responsive to transitions at the individual, economic and societal levels. Moreover, solutions need to acknowledge gender inequalities in different contexts, as well as structural and cultural influences on diet and physical activity in resource-limited settings. Programmes need to be effective in engaging and reconciling adolescents' and caregivers' perspectives. Consequently, there is a need for action at both the community-household level and also through policy.

Anthropometric nutritional status, and social and dietary characteristics of African and Indian adolescents taking part in the TALENT (Transforming Adolescent Lives through Nutrition) qualitative study.

OBJECTIVE: To describe the anthropometry, socioeconomic circumstances, diet and screen time usage of adolescents in India and Africa as context to a qualitative study of barriers to healthy eating and activity. DESIGN: Cross-sectional survey, including measured height and weight and derived rates of stunting, low BMI, overweight and obesity. Parental schooling and employment status, household assets and amenities, and adolescents' dietary diversity, intake of snack foods, mobile/smartphone ownership and TV/computer time were obtained via a questionnaire. SETTING: Four settings each in Africa (rural villages, West Kiang, The Gambia; low-income urban communities, Abidjan, Cote D'Ivoire; low/middle-class urban communities, Jimma, Ethiopia; low-income township, Johannesburg, South Africa) and India (rural villages, Dervan; semi-rural villages, Pune; city slums, Mumbai; low-middle/middle-class urban communities, Mysore). PARTICIPANTS: Convenience samples (n 41-112 per site) of boys and girls, half aged 10-12 years and another half aged 15-17 years, were recruited for a qualitative study. RESULTS: Both undernutrition (stunting and/or low BMI) and overweight/obesity were present in all settings. Rural settings had the most undernutrition, least overweight/obesity and greatest diet diversity. Urban Johannesburg (27 %) and Abidjan (16 %), and semi-rural Pune (16 %) had the most overweight/obesity. In all settings, adolescents reported low intakes of micronutrient-rich fruits and vegetables, and substantial intakes of salted snacks, cakes/biscuits, sweets and fizzy drinks. Smartphone ownership ranged from 5 % (West Kiang) to 69 % (Johannesburg), higher among older adolescents. CONCLUSIONS: The 'double burden of malnutrition' is present in all TALENT settings. Greater urban transition is associated with less undernutrition, more overweight/obesity, less diet diversity and higher intakes of unhealthy/snack foods.

Inactive alleles of cytochrome P450 2C19 may be positively selected in human evolution.

BACKGROUND: Cytochrome P450 CYP2C19 metabolizes a wide range of pharmacologically active substances and a relatively small number of naturally occurring environmental toxins. Poor activity alleles of CYP2C19 are very frequent worldwide, particularly in Asia, raising the possibility that reduced metabolism could be advantageous in some circumstances. The evolutionary selective forces acting on this gene have not previously been investigated.We analyzed CYP2C19 genetic markers from 127 Gambians and on 120 chromosomes from Yoruba, Europeans and Asians (Japanese + Han Chinese) in the Hapmap database. Haplotype breakdown was explored using bifurcation plots and relative extended haplotype homozygosity (REHH). Allele frequency differentiation across populations was estimated using the fixation index (FST) and haplotype diversity with coalescent models. RESULTS: Bifurcation plots suggested conservation of alleles conferring slow metabolism (CYP2C19*2 and *3). REHH was high around CYP2C19*2 in Yoruba (REHH 8.3, at 133.3 kb from the core) and to a lesser extent in Europeans (3.5, at 37.7 kb) and Asians (2.8, at -29.7 kb). FST at the CYP2C19 locus was low overall (0.098). CYP2C19*3 was an FST outlier in Asians (0.293), CYP2C19 haplotype diversity < = 0.037, p <0.001. CONCLUSIONS: We found some evidence that the slow metabolizing allele CYP2C19*2 is subject to positive selective forces worldwide. Similar evidence was also found for CYP2C19*3 which is frequent only in Asia. FST is low at the CYP2C19 locus, suggesting balancing selection overall. The biological factors responsible for these selective pressures are currently unknown. One possible explanation is that early humans were exposed to a ubiquitous novel toxin activated by CYP2C19. The genetic adaptation took place within the last 10,000 years which coincides with the development of systematic agricultural practices.

Effects of genetic variation at the CYP2C19/CYP2C9 locus on pharmacokinetics of chlorcycloguanil in adult Gambians.

AIMS: Antimalarial biguanides are metabolized by CYP2C19, thus genetic variation at the CYP2C locus might affect pharmacokinetics and so treatment outcome for malaria. MATERIALS & METHODS: Polymorphisms in CYP2C19 and CYP2C9 in 43 adult Gambians treated with chlorproguanil/dapsone for uncomplicated malaria were assessed. Chlorcycloguanil pharmacokinetics were measured and associations with CYP2C19 and CYP2C9 alleles and CYP2C19 metabolizer groups investigated. RESULTS: All CYP2C19/CYP2C9 alleles obeyed Hardy-Weinberg equilibrium. There were 15 CYP2C19/2C9 haplotypes with a common haplotype frequency of 0.23. Participants with the CYP2C19*17 allele had higher chlorcycloguanil area under the concentration versus curve at 24 h (AUC(0-24)) than those without (geometric means: 317 vs 216 ng.h/ml; ratio of geometric means: 1.46; 95% CI: 1.03 to 2.09; p = 0.0363) and higher C(max) (geometric mean ratio: 1.52; 95% CI: 1.13 to 2.05; p = 0.0071). CONCLUSION: CYP2C19*17 determines antimalarial biguanide metabolic profile at the CYP2C19/CYP2C9 locus.