Opening decision spaces: A case study on the opportunities and constraints in the public health sector of Mpumalanga Province, South Africa.

BACKGROUND: Decentralised and evidence-informed health systems rely on managers and practitioners at all levels having sufficient 'decision space' to make timely locally informed and relevant decisions. Our objectives were to understand decision spaces in terms of constraints and enablers and outline opportunities through which to expand them in an understudied rural context in South Africa. METHODS: This study examined decision spaces within Mpumalanga Province, using data and insights generated through a participatory action research process with local communities and health system stakeholders since 2015, which was combined with published documents and research team participant observation to produce findings on three core domains at three levels of the health system. RESULTS: Although capacity for decision making exists in the system, accessing it is frequently made difficult due to a number of intervening factors. While lines of authority are generally well-defined, personal networks take on an important dimension in how stakeholders can act. This is expressed through a range of informal coping strategies built on local relationships. There are constraints in terms of limited formal external accountability to communities, and internal accountability which is weak in places for individuals and focused more on meeting performance targets set at higher levels and less on enabling effective local leadership. More generally, political and personal factors are clearly identified at higher levels of the system, whereas at sub-district and facility levels, the dominant theme was constrained capacity. CONCLUSIONS: By examining the balance of authority, accountability and capacity across multiple levels of the provincial health system, we are able to identify emergent decision space and areas for enlargement. Creating spaces to support more constructive relationships and dialogue across system levels emerges as important, as well as reinforcing horizontal networks to problem solve, and developing the capacity of link-agents such as community health workers to increase community accountability.

Mid-Life Household Food Insecurity and Subsequent Memory Function and Rate of Decline in Rural South Africa, 2004-2022.

INTRODUCTION: We aimed to investigate mid-life food insecurity over time in relation to subsequent memory function and rate of decline in Agincourt, rural South Africa. METHODS: Data from the longitudinal Agincourt Health and Socio-Demographic Surveillance System (Agincourt HDSS) were linked to the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI). Food insecurity (yes vs. no) and food insecurity intensity (never/rarely/sometimes vs. often/very often) in the past month were assessed every 3 years from 2004 to 2013 in Agincourt HDSS. Cumulative exposure to each food insecurity measure was operationalized as 0, 1, and ≥2 time points. Episodic memory was assessed from 2014/15 to 2021/22 in HAALSI. Mixed-effects linear regression models were fitted to investigate the associations of each food insecurity measure with memory function and rate of decline over time. RESULTS: A total of 3,186 participants (mean age [SD] in 2004: 53 [12.87]; range: 30-96) were included and 1,173 (36%) participants experienced food insecurity in 2004, while this figure decreased to 490 (15%) in 2007, 489 (15%) in 2010, and 150 (5%) in 2013. Experiencing food insecurity at one time point (vs. never) from 2004 to 2013 was associated with lower baseline memory function (ß = -0.095; 95% CI: -0.159 to -0.032) in 2014/15 but not rate of memory decline. Higher intensity of food insecurity at ≥2 time points (vs. never) was associated with lower baseline memory function (ß = -0.154, 95% CI: -0.338 to 0.028), although the estimate was imprecise. Other frequencies of food insecurity and food insecurity intensity were not associated with memory function or decline in the fully adjusted models. CONCLUSION: In this setting, mid-life food insecurity may be a risk factor for lower later-life memory function, but not decline.

Double malnutrition and associated factors in a middle-aged and older, rural South African population.

INTRODUCTION: Double malnutrition (co-existing overnutrition and undernutrition) is increasingly prevalent in sub-Saharan Africa due to rapid epidemiological and nutritional transitions. In this region, studies of double malnutrition have largely been conducted at country and household level, with individual-level studies primarily limited to children and women of reproductive age. We investigated the prevalence and determinants of individual-level double malnutrition in middle-aged and older adults who constitute an increasing proportion of the sub-Saharan African population. METHODS: 250 individuals aged 40-70 years (50% women) and resident in the Agincourt Health and socio-Demographic Surveillance System in rural Mpumalanga province, South Africa, were randomly selected. Double malnutrition was defined as overweight/obesity and anaemia only, overweight/obesity and iodine insufficiency, or overweight/obesity and any micronutrient deficiency (anaemia and/or iodine insufficiency). The Chi-squared goodness of fit test was used to compare the expected and observed numbers of individuals with the type of double malnutrition. Logistic regression was used to investigate determinants of each type of double malnutrition. RESULTS: Double malnutrition was present in 22-36% of participants, depending on the definition used. All types of double malnutrition were more common in women than in men (overweight/obesity and anaemia: 34% vs. 10.2%, p < 0.01; overweight/obesity and iodine insufficiency: 32% vs. 12.2%, p < 0.01 and overweight/obesity and any micronutrient deficiency: 50.5% vs. 20.4%, p < 0.01). There were no differences between the overall expected and observed numbers of individuals with combinations of overweight and micronutrient deficiencies [overweight/obesity and anaemia (p = 0.28), overweight/obesity and iodine insufficiency (p = 0.27) or overweight/obesity and any micronutrient deficiency (p = 0.99)]. In models adjusted for socio-demographic factors, HIV and antiretroviral drug status, and food security or dietary diversity, men were 84-85% less likely than women to have overweight/obesity and anaemia, 65% less likely to have overweight/obesity and iodine insufficiency and 74% less likely to have overweight/obesity and any micronutrient deficiency. CONCLUSIONS: Individual-level double malnutrition is prevalent in middle-aged and older adults in a rural sub-Saharan African community. Interventions to improve nutrition in similar settings should target individuals throughout the life course and a focus on women may be warranted.

Genetic association and transferability for urinary albumin-creatinine ratio as a marker of kidney disease in four Sub-Saharan African populations and non-continental individuals of African ancestry.

Background: Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts. Methods: Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations. Results: Two genome-wide significant (P < 5 × 10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained. Conclusion: This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes.

The Impact of Old Age Pension Eligibility on Alcohol Consumption: Evidence From a Population-Based Study in Rural South Africa.

Background and Objectives: Alcohol causes more than 3 million deaths a year globally and contributes to over 5% of global disease and injury. Heavy drinking and alcohol use disorders among older adults have increased in the last 10-15 years. For individuals living in low-income countries, where wages are low and unemployment is high, old age pensions may provide a significant increase in household income. In turn, the receipt of supplementary income may increase spending on alcohol. Earlier life factors and socioeconomic status may affect alcohol consumption, making it difficult to directly assess the impact of income on alcohol consumption. This study reduces the potential for endogeneity with other life factors by exploiting an exogenous increase in income from old age pensions to isolate the impact of extra income on alcohol consumption for older adults. Research Design and Methods: We used a regression discontinuity design to assess changes in drinking patterns among rural, low-income adults who were 3 years below and 3 years above South Africa's Old Age Pension Grant eligibility threshold (age 60). We assessed this relationship separately by gender and for employed and unemployed individuals. Results: We observed a significantly increased alcohol use associated with the Old Age Pension Grant eligibility for employed men (ß = 4.57, 95% confidence interval: 1.72-12.14). We did not observe this same trend for unemployed men or for women. Discussion and Implications: The analysis in this study indicates that increased income from reaching the pension eligibility age may contribute to an increase in alcohol consumption for employed men. Interventions, such as informational campaigns on the risks of alcohol consumption for older adults or age-appropriate health interventions to help individuals reduce alcohol consumption, targeted around the time of pension eligibility age for employed men may help to reduce alcohol-related harms in low-income, rural sub-Saharan African settings.

Expanding the human gut microbiome atlas of Africa.

Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ~84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population. Using shotgun metagenomic sequencing, we find that study site explains substantially more microbial variation than disease status. We identify taxa with strong geographic and lifestyle associations, including loss of Treponema and Cryptobacteroides species and gain of Bifidobacterium species in urban populations. We uncover a wealth of prokaryotic and viral novelty, including 1,005 new bacterial metagenome-assembled genomes, and identify phylogeography signatures in Treponema succinifaciens. Finally, we find a microbiome signature of HIV infection that is 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 to date, and paired with extensive clinical biomarkers, demographic data, and lifestyle information, provides extensive opportunity for microbiome-related discovery and research.

Characteristics of infections with ancestral, Beta and Delta variants of SARS-CoV-2 in the PHIRST-C community cohort study, South Africa, 2020-2021.

BACKGROUND: Data on the characteristics of individuals with mild and asymptomatic infections with different SARS-CoV-2 variants are limited. We therefore compared the characteristics of individuals infected with ancestral, Beta and Delta SARS-CoV-2 variants in South Africa. METHODS: We conducted a prospective cohort study in a rural and an urban site during July 2020-August 2021. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Differences in demographic and clinical characteristics, shedding and cycle threshold (Ct) value of infection episodes by variant were evaluated using multinomial regression. Overall and age-specific incidence rates of infection were compared by variant. RESULTS: We included 1200 individuals from 222 households and 648 rRT-PCR-confirmed infection episodes (66, 10% ancestral, 260, 40% Beta, 322, 50% Delta). Symptomatic proportion was similar for ancestral (7, 11%), Beta (44, 17%), and Delta (46, 14%) infections (p=0.4). After accounting for previous infection, peak incidence shifted to younger age groups in successive waves (40-59 years ancestral, 19-39 years Beta, 13-18 years Delta). On multivariable analysis, compared to ancestral, Beta infection was more common in individuals aged 5-12 years (vs 19-39)(adjusted odds ratio (aOR) 2.6, 95% confidence interval (CI)1.1-6.6) and PCR cycle threshold (Ct) value <30 (vs >35)(aOR 3.2, 95%CI 1.3-7.9), while Delta was more common in individuals aged <5 (aOR 6.7, 95%CI1.4-31.2) and 5-12 years (aOR 6.6 95%CI2.6-16.7)(vs 19-39) and Ct value <30 (aOR 4.5, 95%CI 1.3-15.5) and 30-35 (aOR 6.0, 95%CI 2.3-15.7)(vs >35). CONCLUSIONS: Consecutive SARS-CoV-2 waves with Beta and Delta variants were associated with a shift to younger individuals. Beta and Delta infections were associated with higher peak viral loads, potentially increasing infectiousness.

Mid-life employment trajectories and subsequent memory function and rate of decline in rural South Africa, 2000-22.

AIM: To investigate mid-life employment trajectories in relation to later-life memory function and rate of decline in rural South Africa. METHODS: Data from the Agincourt Health and Socio-Demographic Surveillance System were linked to the 'Health and Ageing in Africa: A Longitudinal Study of an INDEPTH Community in South Africa' (HAALSI) in rural Agincourt, South Africa (N = 3133). Employment was assessed every 4 years over 2000-12 as being employed (0, 1, 2 and ≥3 time points), being employed in a higher-skill occupation (0, 1, 2 and ≥3 time points) and dynamic employment trajectories identified using sequence analysis. Latent memory z-scores were assessed over 2014-22. Mixed-effects linear regression models were fitted to examine the associations of interest. RESULTS: Sustained mid-life employment from 2000-12 (ß = 0.052, 95% CI: -0.028 to 0.132, 1 vs 0 time points; ß = 0.163, 95% CI: 0.077 to 0.250, 2 vs 0 time points; ß = 0.212, 95% CI: 0.128 to 0.296, ≥3 vs 0 time points) and greater time spent in a higher-skill occupation (ß = 0.077, 95% CI: -0.020 to 0.175, 1 vs 0 time points; ß = 0.241, 95% CI: 0.070 to 0.412, 2 vs 0 time points; ß = 0.361, 95% CI: 0.201 to 0.520, ≥3 vs 0 time points) were associated with higher memory scores in 2014/15, but not subsequent rate of memory decline. Moving from a lower-skill to higher-skill occupation was associated with higher memory function, but a faster rate of decline over 2014-22. CONCLUSIONS: Sustained mid-life employment, particularly in higher-skill occupations, may contribute to later-life memory function in this post-Apartheid South African setting.

Genetic Association and Transferability for Urinary Albumin-Creatinine Ratio as a Marker of Kidney Disease in four Sub-Saharan African Populations and non-continental Individuals of African Ancestry.

BACKGROUND: Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts. METHODS: Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations. RESULTS: Two genome-wide significant (P<5x10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained. CONCLUSION: This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes. METHODS: Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations. RESULTS: Two genome-wide significant (P<5x10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained. CONCLUSION: This study contributes novel insights into the genetic architecture of kidney function in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations.

Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study.

Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p < 5E-08): systolic BP near P2RY1 (rs77846204; intergenic variant, p = 4.95E-08) and pulse pressure near LINC01256 (rs80141533; intergenic variant, p = 1.76E-08). No genome-wide signals are detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p < 5E-06) are observed for all traits, with 29 SNPs associating with more than one trait and several replicating known associations. Polygenic risk scores (PRSs) developed from studies on different ancestries have limited transferability, with multi-ancestry PRS providing better prediction. This study provides insights into the genetics of BP variation in African populations.

Disease awareness and healthcare utilization in rural South Africa: a comparative analysis of HIV and diabetes in the HAALSI cohort.

BACKGROUND: Studies from rural South Africa indicate that people living with HIV (PLHIV) may have better health outcomes than those without, potentially due to the frequent healthcare visits necessitated by infection. Here, we examined the association between HIV status and healthcare utilization, using diabetes as an illustrative comparator of another high-burden, healthcare-intensive disease. METHODS: Our exposure of interest was awareness of positive disease status for both HIV and diabetes. We identified 742 individuals who were HIV-positive and aware of their status and 305 who had diabetes and were aware of their status. HIV-positive status was further grouped by viral suppression. For each disease, we estimated the association with (1) other comorbid, chronic conditions, (2) health facility visits, (3) household-level healthcare expenditure, and (4) per-visit healthcare expenditure. We used log-binomial regression models to estimate prevalence ratios for co-morbid chronic conditions. Linear regression models were used for all other outcomes. RESULTS: Virally suppressed PLHIV had decreased prevalence of chronic conditions, increased public clinic visits [ß = 0.59, 95% CI: 0.5, 0.7], and reduced per-visit private clinic spending [ß = -60, 95% CI: -83, -6] compared to those without HIV. No differences were observed in hospitalizations and per-visit spending at hospitals and public clinics between virally suppressed PLHIV and non-PLHIV. Conversely, diabetic individuals had increased prevalence of chronic conditions, increased visits across facility types, increased household-level expenditures (ß = 88 R, 95% CI: 29, 154), per-visit hospital spending (ß = 54 R, 95% CI: 7, 155), and per-visit public clinic spending (ß = 31 R, 95% CI: 2, 74) compared to those without diabetes. CONCLUSIONS: Our results suggest that older adult PLHIV may visit public clinics more often than their HIV-negative counterparts but spend similarly on a per-visit basis. This provides preliminary evidence that the positive health outcomes observed among PLHIV in rural South Africa may be explained by different healthcare engagement patterns. Through our illustrative comparison between PLHIV and diabetics, we show that shifting disease burdens towards chronic and historically underfunded diseases, like diabetes, may be changing the landscape of health expenditure inequities.

Forgotten but not gone in rural South Africa: Urinary schistosomiasis and implications for chronic kidney disease screening in endemic countries.

Background: Urinary schistosomiasis caused by infection with Schistosoma haematobium ( S. haematobium) remains endemic in Africa and is associated with haematuria and albuminuria/proteinuria. Kidney Disease Improving Global Outcomes clinical guidelines recommend evaluating proteinuria/albuminuria and glomerular filtration rate for chronic kidney disease (CKD) diagnosis. The guidelines are informed by population data outside of Africa but have been adopted in many African countries with little validation. Our study aimed to characterise the burden of urinary schistosomiasis in rural South Africa (SA) and evaluate its relationship with markers of kidney dysfunction with implications for CKD screening. Methods: In this population-based cohort study, we recruited 2021 adults aged 20 - 79 years in the Mpumalanga Province, SA. Sociodemographic data were recorded, urinalysis performed, and serum creatinine and urine albumin and creatinine measured. Kidney dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m 2 and/or urine albumin-creatinine ratio >3.0mg/mmol. S . haematobium infection was determined by urine microscopy. Multivariable analyses were performed to determine relationships between S. haematobium and markers of kidney dysfunction. Results: Data were available for 1226 of 2021 participants. 717 (58.5%) were female and the median age was 35 years (IQR 27 - 47). Prevalence of kidney dysfunction and S. haematobium was 20.2% and 5.1% respectively. S. haematobium was strongly associated with kidney dysfunction (OR 8.66; 95% CI 4.10 - 18.3) and related to albuminuria alone (OR 8.69; 95% CI 4.11 - 18.8), with no evidence of an association with eGFR <90ml/min/1.73m 2 (OR 0.43; 95% CI 0.05 - 3.59). Discussion: The strong association between urinary schistosomiasis and albuminuria requires careful consideration when screening for CKD. Screening for, and treatment of, schistosomiasis should be a routine part of initial work-up for CKD in S. haematobium endemic areas. Urinary schistosomiasis, a neglected tropical disease, remains a public health concern in the Mpumulanga province of SA.

Home-based HIV testing strategies for middle-aged and older adults in rural South Africa.

OBJECTIVE: More than one in four adults over 40 years with HIV in South Africa are unaware of their status and not receiving antiretroviral therapy (ART). HIV self-testing may offer a powerful approach to closing this gap for aging adults. Here, we report the results of a randomized comparative effectiveness trial of three different home-based HIV testing strategies for middle-aged and older adults in rural South Africa. DESIGN: Two thousand nine hundred and sixty-three individuals in the 'Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa (HAALSI)' cohort study were randomized 1 : 1 : 1 to one of three types of home-based and home-delivered HIV testing modalities: rapid testing with counseling; self-testing, and both rapid testing with counselling and self-testing. METHOD: In OLS regression analyses, we estimated the treatment effects on HIV testing and HIV testing frequency at about 1 year after delivery. Finally, we assessed the potential adverse effects of these strategies on the secondary outcomes of depressive symptom as assessed by the CESD-20, linkage to care, and risky sexual behavior. RESULTS: There were no significant differences in HIV testing uptake or testing frequency across groups. However, respondents in the self-testing treatment arms were more likely to shift from testing at home and a facility [self-testing (HIVST), -8 percentage points (pp); 95% confidence interval (CI) -14 to -2 pp; self-testing plus rapid testing and counselling (ST+RT+C); -9 pp, 95% CI -15 to -3 pp] to testing only at home (HIVST 5 pp; 95% CI 2 to 9 pp; ST+RT+C: 5 pp, 95% CI 1 to 9 pp) - suggesting a revealed preference for self-testing in this population. We also found no adverse effects of this strategy on linkage to care for HIV and common comorbidities, recent sexual partners, or condom use. Finally, those in the self-testing only arm had significantly decreased depressive symptom scores by 0.58 points (95% CI -1.16 to -0.01). CONCLUSION: We find HIV self-testing to be a well tolerated and seemingly preferred home-based testing option for middle-aged and older adults in rural South Africa. This approach should be expanded to achieve the UNAIDS 95-95-95 targets.

Trans-ethnic genomic informed risk assessment for Alzheimer's disease: An International Hundred K+ Cohorts Consortium study.

BACKGROUND: As a collaboration model between the International HundredK+ Cohorts Consortium (IHCC) and the Davos Alzheimer's Collaborative (DAC), our aim was to develop a trans-ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD). METHODS: The GIRA model was created to include polygenic risk score calculated from the AD genome-wide association study loci, the apolipoprotein E haplotypes, and non-genetic covariates including age, sex, and the first three principal components of population substructure. RESULTS: We validated the performance of the GIRA model in different populations. The proteomic study in the participant sites identified proteins related to female infertility and autoimmune thyroiditis and associated with the risk scores of AD. CONCLUSIONS: As the initial effort by the IHCC to leverage existing large-scale datasets in a collaborative setting with DAC, we developed a trans-ethnic GIRA for AD with the potential of identifying individuals at high risk of developing AD for future clinical applications.

Association of alcohol use and multimorbidity among adults aged 40 years and above in rural South Africa.

We assessed the prevalence of reported alcohol use and its association with multimorbidity among adults aged 40 years and above in a rural, transitioning South African setting. Findings could potentially inform alcohol interventions integration in the prevention and treatment of chronic conditions. We analysed data from the first wave of The Health and Ageing in Africa-a longitudinal Study in an INDEPTH community (HAALSI) nested within the Agincourt Health and Demographic Surveillance Systems, conducted between November 2014 and November 2015 (n = 5059). We computed descriptive statistics and performed univariate analysis to determine factors independently associated with multimorbidity. Age, Body Mass Index, education, sex, and household wealth status and variables with a p-value < 0.20 in univariate analysis were included in multivariable Modified Poisson regression models. Any factors with a p-value of < 0.05 in the final models were considered statistically significant. The first wave of HAALSI was completed by 5059 participants aged 40 years and above and included 2714 (53.6%) females. The prevalence of reported ever alcohol use was 44.6% (n = 2253) and of these 51.9% (n = 1171) reported alcohol use in the last 30 days. The prevalence of HIV multimorbidity was 59.6% (3014/5059) and for multimorbidity without HIV 52.5% (2657/5059). Alcohol use was associated with HIV multimorbidity among all participants (RR: 1.05, 95% CI: 1.02-1.08), and separately for males (RR: 1.05, 95% CI: 1.00-1.10) and females (RR: 1.06, 95%CI: 1.02-1.11). Similarly, alcohol use was associated with multimorbidity without HIV among all participants (RR: 1.05, 95% CI: 1.02-1.09), and separately for males (RR: 1.06, 95% CI: 1.00-1.12) and females (RR: 1.06, 95% CI: 1.01-1.11). Reported alcohol use was common and associated with HIV multimorbidity and multimorbidity without HIV among older adults in rural northeast South Africa. There is a need to integrate Screening, Brief Interventions, and Referral for alcohol Treatment in the existing prevention and treatment of multimorbidity in South Africa.

Feasibility of an online consensus approach for the diagnosis of cognitive impairment and dementia in rural South Africa.

INTRODUCTION: We describe the development and feasibility of using an online consensus approach for diagnosing cognitive impairment and dementia in rural South Africa. METHODS: Cognitive assessments, clinical evaluations, and informant interviews from Cognition and Dementia in the Health and Aging in Africa Longitudinal Study (HAALSI Dementia) were reviewed by an expert panel using a web-based platform to assign a diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia. RESULTS: Six hundred thirty-five participants were assigned a final diagnostic category, with 298 requiring adjudication conference calls. Overall agreement between each rater's independent diagnosis and final diagnosis (via the portal or consensus conference) was 78.3%. A moderate level of agreement between raters' individual ratings and the final diagnostic outcomes was observed (average κ coefficient = 0.50). DISCUSSION: Findings show initial feasibility in using an online consensus approach for the diagnosis of cognitive impairment and dementia in remote, rural, and low-resource settings.

The adolescent HIV executive function and drumming (AHEAD) study, a feasibility trial of a group drumming intervention amongst adolescents with HIV.

AHEAD feasibility trial assessed the feasibility and acceptability of an 8-session group drumming programme aiming to improve executive function, depression and anxiety symptoms, and perceived social support in adolescents living with HIV in a rural low-income South African setting. Sixty-eight 12- to 19-year-old adolescents participated. They were individually randomised. The intervention arm (n = 34) received weekly hour-long group drumming sessions. Controls (n = 34) received no intervention. Feasibility and acceptability were assessed using rates of: enrolment; retention; attendance; logistical problems; adolescent-reported acceptability. Secondary measures included: five Oxford Cognitive Screen-Executive Function (OCS-EF) tasks; two Rapid Assessment of Cognitive and Emotional Regulation (RACER) tasks; the Self-Reporting Questionnaire-20 (SRQ-20) measuring depression and anxiety symptoms; the Multidimensional Scale of Perceived Social Support (MSPSS). All feasibility criteria were within green progression limits. Enrolment, retention, and acceptability were high. There was a positive effect on adolescent depressed mood with signal for a working memory effect. There were no significant effects on executive function or socio-emotional scales. Qualitative findings suggested socio-emotional benefits including: group belonging; decreased internalised stigma; improved mood; decreased anxiety. Group drumming is a feasible and acceptable intervention amongst adolescents living with HIV in rural South Africa. A full-scale trial is recommended.

Estimating the Prevalence of over- and Under-Reporting in HIV Testing, Status and Treatment in Rural Northeast South Africa: A Comparison of a Survey and Clinic Records.

We assess the accuracy of self-reported testing, HIV status, and treatment responses compared to clinical records in Ehlanzeni District, South Africa. We linked a 2018 population-based survey of adults 18-49 years old with clinical data at local primary healthcare facilities from 2014 to 2018. We calculated self-reported testing, HIV status, and treatment, and triangulated findings with clinic record data. We adjusted testing estimates for known gaps in HIV test documentation. Of 2089 survey participants, 1657 used a study facility and were eligible for analysis. Half of men and 84% of women reported an HIV test in the past year. One third of reported tests could be confirmed in clinic data within 1 year and an additional 13% within 2 years; these fractions increased to 57% and 22% respectively limiting to participants with a verified clinic file. After accounting for gaps in clinic documentation, we found that prevalence of recent HIV testing was closer to 15% among men and 51% in women. Estimated prevalence of known HIV was 16.2% based on self-report vs. 27.6% with clinic documentation. Relative to clinical records among confirmed clinic users, self report of HIV testing and of current treatment were highly sensitive but non-specific (sensitivity 95.5% and 98.8%, specificity 24.2% and 16.1% respectively), while self report of HIV status was highly specific but not sensitive (sensitivity 53.0%, specificity 99.3%). While clinical records are imperfect, survey-based measures should be interpreted with caution in this rural South African setting.

Improvements in Hypertension Control in the Rural Longitudinal HAALSI Cohort of South African Adults Aged 40 and Older, From 2014 to 2019.

BACKGROUND: Over half of the South African adults aged 45 years and older have hypertension but its effective management along the treatment cascade (awareness, treatment, and control) remains poorly understood. METHODS: We compared the prevalence of all stages of the hypertension treatment cascade in the rural HAALSI cohort of older adults at baseline and after four years of follow-up using household surveys and blood pressure data. Hypertension was a mean systolic blood pressure >140 mm Hg or diastolic pressure >90 mm Hg, or current use of anti-hypertension medication. Control was a mean blood pressure <140/90 mm Hg. The effects of sex and age on the treatment cascade at follow-up were assessed. Multivariate Poisson regression models were used to estimate prevalence ratios along the treatment cascade at follow-up. RESULTS: Prevalence along the treatment cascade increased from baseline (B) to follow-up (F): awareness (64.4% vs. 83.6%), treatment (49.7% vs. 73.9%), and control (22.8% vs. 41.3%). At both time points, women had higher levels of awareness (B: 70.5% vs. 56.3%; F: 88.1% vs. 76.7%), treatment (B: 55.9% vs. 41.55; F: 79.9% vs. 64.7%), and control (B: 26.5% vs. 17.9%; F: 44.8% vs. 35.7%). Prevalence along the cascade increased linearly with age for everyone. Predictors of awareness included being female, elderly, or visiting a primary health clinic three times in the previous 3 months, and the latter two also predicted hypertension control. CONCLUSIONS: There were significant improvements in awareness, treatment, and control of hypertension from baseline to follow-up and women fared better at all stages, at both time points.