Effect of a cash transfer intervention on memory decline and dementia probability in older adults in rural South Africa.

Evidence on cash transfers as a population-level intervention to support healthy cognitive aging in low-income settings is sparse. We assessed the effect of a cash transfer intervention on cognitive aging outcomes in older South African adults. We leveraged the overlap in the sampling frames of a Phase 3 randomized cash transfer trial [HIV Prevention Trial Network (HPTN) 068, 2011-2015] and an aging cohort [Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community (HAALSI), 2014-2022] in rural Mpumalanga Province, South Africa. In 2011/12, young women and their primary caregivers were randomly assigned 1:1 to receive a monthly cash transfer or control. In 2014/2015, 862 adults aged 40+ y living in trial households were enrolled in the HAALSI cohort, with cognitive data collected in three waves over 7 y. We estimated the impact of the intervention on rate of memory decline and dementia probability scores. Memory decline in the cash transfer arm was 0.03 SD units (95% CI: 0.002, 0.05) slower per year than in the control arm. Dementia probability scores were three percentage points lower in the cash transfer arm than the control arm (ß = -0.03; 95% CI: -0.05, -0.001). Effects were consistent across subgroups. A modestly sized household cash transfer delivered over a short period in mid- to later-life led to a meaningful slowing of memory decline and reduction in dementia probability 7 y later. Cash transfer programs could help stem the tide of new dementia cases in economically vulnerable populations in the coming decades.

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.

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.

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.

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.

Obstacles and facilitators to communicating with children about their parents' mental illness: a qualitative study in a sub-district of Mpumalanga, South Africa.

BACKGROUND: Given that common mental disorders are one of the leading causes of disease burden worldwide, it is likely that many children are growing up with a parent or other adult within their family who has anxiety or depression. Parents with a mental illness may not consider it appropriate to discuss their illness with their child, and consequently an absence of communication may lead to stigmatization, shame, misunderstanding their parents' symptoms, and even blaming themselves. There is a scarcity of research exploring the experiences and perceptions of healthcare professionals about communication with children of parents with mental illness in low-resource and African contexts. METHODS: A qualitative study using semi-structured interviews with healthcare professionals (n = 15) was conducted within the Bushbuckridge sub-district of Mpumalanga Province, South Africa. Data were analysed using Thematic Analysis. RESULTS: Four themes were identified relating to the obstacles around communication with children. These included: (1) finding an appropriate language to describe mental illness, as well as the prevailing cultural explanations of mental illness (2) the stigma associated with mental illness (3) the perceived role of children in society and (4) mental health services and staff skills. Two themes that addressed facilitators of communication about parental mental illness were identified: (1) the potential to increase mental health awareness amongst the broader community through social media, the internet, and general psychoeducation (2) healthcare professionals' concerns for the wellbeing and future mental health of patients' children, as well as their hopes for increased mental health awareness amongst future generations. CONCLUSIONS: This study provides insight into healthcare professionals' attitudes and perceptions about talking to patients and families within their community about mental illness. The results provide recommendations about possible ways to promote sharing information about a parent's mental illness with children at an individual and community level. Future research should focus on the collaborative creation of culturally sensitive psychoeducational resources and evidence-based guidelines. This must be supported by systemic and organisational change in order for professionals to successfully facilitate conversations with patients who are parents, and their children.

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.

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.

Effects of Pension Eligibility Expansion on Men's Cognitive Function: Findings from Rural South Africa.

Two-thirds of people living with Alzheimer's disease and related dementias (ADRD) live in low- and middle-income countries, and this figure is expected to rise as these populations are rapidly aging. Since evidence demonstrates links between socioeconomic status and slower rates of cognitive decline, protecting older adults' cognitive function in resource-limited countries that lack the infrastructure to cope with ADRD is crucial to reduce the burden it places on these populations and their health systems. While cash transfers are a promising intervention to promote healthy cognitive aging, factors such as household wealth and level of education often confound the ability to make causal inferences on the impact of cash transfers and cognitive function. This study uses a quasi-experimental design, leveraging an exogenous expansion to the Old Age Pension for men in South Africa, to approximate causal associations with cognitive function. We found evidence that there is a potential benefit of cash transfers at an earlier age for older individuals. As such, transfers such as pensions or other forms of direct basic income transfers may hold promise as potential interventions to promote healthy cognitive aging.

SARS-CoV-2 Seroprevalence after Third Wave of Infections, South Africa.

By November 2021, after the third wave of severe acute respiratory syndrome coronavirus 2 infections in South Africa, seroprevalence was 60% in a rural community and 70% in an urban community. High seroprevalence before the Omicron variant emerged may have contributed to reduced illness severity observed in the fourth wave.

Modeling Combination Interventions to Prevent Human Immunodeficiency Virus in Adolescent Girls and Young Women in South Africa (HIV Prevention Trials Network 068).

BACKGROUND: Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV. METHODS: We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors. RESULTS: Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, -1.4%; 95% confidence interval [CI], -2.7% to -.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by -1.3% (95% CI, -2.6% to -.2%). CONCLUSIONS: To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence.

SARS-CoV-2 Seroprevalence in a Rural and Urban Household Cohort during First and Second Waves of Infections, South Africa, July 2020-March 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may be underestimated because of limited access to testing. We measured SARS-CoV-2 seroprevalence in South Africa every 2 months during July 2020-March 2021 in randomly selected household cohorts in 2 communities. We compared seroprevalence to reported laboratory-confirmed infections, hospitalizations, and deaths to calculate infection-case, infection-hospitalization, and infection-fatality ratios in 2 waves of infection. Post-second wave seroprevalence ranged from 18% in the rural community children <5 years of age, to 59% in urban community adults 35-59 years of age. The second wave saw a shift in age distribution of case-patients in the urban community (from persons 35-59 years of age to persons at the extremes of age), higher attack rates in the rural community, and a higher infection-fatality ratio in the urban community. Approximately 95% of SARS-CoV-2 infections were not reported to national surveillance.

Poor cardiovascular health is associated with subclinical atherosclerosis in apparently healthy sub-Saharan African populations: an H3Africa AWI-Gen study.

BACKGROUND: The cardiovascular health index (CVHI) introduced by the American Heart Association is a valid, accessible, simple, and translatable metric for monitoring cardiovascular health in a population. Components of the CVHI include the following seven cardiovascular risk factors (often captured as life's simple 7): smoking, dietary intake, physical activity, body mass index, blood pressure, glucose, and total cholesterol. We sought to expand the evidence for its utility to under-studied populations in sub-Saharan Africa, by determining its association with common carotid intima-media thickness (CIMT). METHODS: We conducted a cross-sectional study involving 9011 participants drawn from Burkina Faso, Ghana, Kenya, and South Africa. We assessed established classical cardiovascular risk factors and measured carotid intima-media thickness of the left and right common carotid arteries using B-mode ultrasonography. Adjusted multilevel mixed-effect linear regression was used to determine the association of CVHI with common CIMT. In the combined population, an individual participant data meta-analyses random-effects was used to conduct pooled comparative sub-group analyses for differences between countries, sex, and socio-economic status. RESULTS: The mean age of the study population was 51 ± 7 years and 51% were women, with a mean common CIMT of 637 ± 117 µm and CVHI score of 10.3 ± 2.0. Inverse associations were found between CVHI and common CIMT (ß-coefficients [95% confidence interval]: Burkina Faso, - 6.51 [- 9.83, - 3.20] µm; Ghana, - 5.42 [- 8.90, - 1.95]; Kenya, - 6.58 [- 9.05, - 4.10]; and South Africa, - 7.85 [- 9.65, - 6.05]). Inverse relations were observed for women (- 4.44 [- 6.23, - 2.65]) and men (- 6.27 [- 7.91, - 4.64]) in the pooled sample. Smoking (p < 0.001), physical activity (p < 0.001), and hyperglycemia (p < 0.001) were related to CIMT in women only, while blood pressure and obesity were related to CIMT in both women and men (p < 0.001). CONCLUSION: This large pan-African population study demonstrates that CVHI is a strong marker of subclinical atherosclerosis, measured by common CIMT and importantly demonstrates that primary prevention of atherosclerotic cardiovascular disease in this understudied population should target physical activity, smoking, obesity, hypertension, and hyperglycemia.

Community health workers to improve adherence to anti-seizure medication in rural South Africa: Is it cost-effective?

OBJECTIVE: Epilepsy is a common, chronic neurological disorder that disproportionately affects individuals living in low- and middle-income countries (LMICs), where the treatment gap remains high and adherence to medication remains low. Community health workers (CHWs) have been shown to be effective at improving adherence to chronic medications, yet no study assessing the costs of CHWs in epilepsy management has been reported. METHODS: Using a Markov model with age- and sex-varying transition probabilities, we determined whether deploying CHWs to improve epilepsy treatment adherence in rural South Africa would be cost-effective. Data were derived using published studies from rural South Africa. Official statistics and international disability weights provided cost and health state values, respectively, and health gains were measured using quality adjusted life years (QALYs). RESULTS: The intervention was estimated at International Dollars ($) 123 250 per annum per sub-district community and cost $1494 and $1857 per QALY gained for males and females, respectively. Assuming a costlier intervention and lower effectiveness, cost per QALY was still less than South Africa's Gross Domestic Product per capita of $13 215, the cost-effectiveness threshold applied. SIGNIFICANCE: CHWs would be cost-effective and the intervention dominated even when costs and effects of the intervention were unfavorably varied. Health system re-engineering currently underway in South Africa identifies CHWs as vital links in primary health care, thereby ensuring sustainability of the intervention. Further research on understanding local health state utility values and cost-effectiveness thresholds could further inform the current model, and undertaking the proposed intervention would provide better estimates of its efficacy on reducing the epilepsy treatment gap in rural South Africa.

Alcohol Consumption and Sexual Risk Behavior in an Aging Population in Rural South Africa.

We sought to characterize the relationship between alcohol consumption and sexual risk-taking in an aging population in rural South Africa. A cross-sectional analysis was conducted using baseline data from the Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community (HAALSI) cohort. We elicited information on sexual risk behavior and self-reported frequency of alcohol consumption among 5059 adults ≥ 40 years old. Multivariable models showed that more frequent alcohol consumption is associated with a higher number of sexual partners (ß: 1.38, p < .001) and greater odds of having sex for money (OR: 42.58, p < .001) in older adults in South Africa. Additionally, daily drinkers were more likely to have sex without a condom (OR: 2.67, p = .01). Older adults who drank more alcohol were more likely to engage in sexual risk-taking. Behavioral interventions to reduce alcohol intake should be considered to reduce STI and HIV transmission.

The relationship between executive function, risky behaviour and HIV in young women from the HPTN 068 study in rural South Africa.

Executive function (EF) may predict sexual risk-taking and HIV risk in young women in rural South Africa. We tested associations between EF and seven risky behavioural outcomes: binge drinking, illicit substance use, unprotected vaginal sex, concurrent sexual relationships, transactional sex, herpes simplex virus type 2 (HSV-2) infection, and HIV infection. We compared EF in young women with HIV to matched controls. 1080 young women underwent cognitive assessments. Better verbal short-term memory was associated with a lower risk of HSV-2 (OR 0.77; 95% CI 0.69, 0.86; p < 0.001). Uncorrected trends (p < 0.05) were better verbal working memory being associated with a lower risk of concurrency, better planning with a lower risk of illicit drug use, and better affective inhibition with a lower risk of transactional sex. 78 participants with sexually acquired HIV were matched with 153 HIV-negative controls and had poorer verbal working memory than controls (Hedge's g = -0.38; 95% CI -0.66, -0.10; p = 0.0076), but this was non-significant after adjustment. EF's contribution to young women's risky behaviour in this context does not hold when stringent statistical corrections are applied, with only verbal short term memory reaching statistical significance as predictor. Replication in other samples is recommended.

Evaluating chronic kidney disease in rural South Africa: comparing estimated glomerular filtration rate using point-of-care creatinine to iohexol measured GFR.

OBJECTIVES: The prevalence of chronic kidney disease is rising rapidly in low- and middle-income countries. Serum creatinine and estimation of glomerular filtration rate (GFR) are critical diagnostic tools, yet access to centralised laboratory services remains limited in primary care resource-limited settings. The aim of this study was to evaluate point-of-care (POC) technologies for serum creatinine measurement and to compare their performance to a gold standard measurement using iohexol measured GFR (mGFR). METHODS: POC creatinine was measured using iSTAT® and StatSensor® devices in capillary and venous whole blood, and laboratory creatinine was measured using the compensated kinetic Jaffe method in 670 participants from a rural area in South Africa. GFR estimating equations Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (CKD-EPI and MDRD) for POC and laboratory creatinine were compared to iohexol mGFR. RESULTS: Calculated GFR for laboratory and POC creatinine measurements overestimated GFR (positive bias of 1.9-34.1 mL/min/1.73 m2). However, all POC devices had less positive bias than the laboratory Jaffe method (1.9-14.7 vs. 34.1 for MDRD, and 8.4-19.9 vs. 28.6 for CKD-EPI). Accuracy within 30% of mGFR ranged from 0.56 to 0.72 for POC devices and from 0.36 to 0.43 for the laboratory Jaffe method. POC devices showed wider imprecision with coefficients of variation ranging from 4.6 to 10.2% compared to 3.5% for the laboratory Jaffe method. CONCLUSIONS: POC estimated GFR (eGFR) showed improved performance over laboratory Jaffe eGFR, however POC devices suffered from imprecision and large bias. The laboratory Jaffe method performed poorly, highlighting the need for laboratories to move to enzymatic methods to measure creatinine.

The African Genome Variation Project shapes medical genetics in Africa.

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Developing and evaluating a frailty index for older South Africans-findings from the HAALSI study.

BACKGROUND: despite rapid population ageing, few studies have investigated frailty in older people in sub-Saharan Africa. We tested a cumulative deficit frailty index in a population of older people from rural South Africa. METHODS: analysis of cross-sectional data from the Health and Ageing in Africa: Longitudinal Studies of an INDEPTH Community (HAALSI) study. We used self-reported diagnoses, symptoms, activities of daily living, objective physiological indices and blood tests to calculate a 32-variable cumulative deficit frailty index. We fitted Cox proportional hazards models to test associations between frailty category and all-cause mortality. We tested the discriminant ability of the frailty index to predict one-year mortality alone and in addition to age and sex. RESULTS: in total 3,989 participants were included in the analysis, mean age 61 years (standard deviation 13); 2,175 (54.5%) were women. The median frailty index was 0.13 (interquartile range 0.09-0.19); Using population-specific cutoffs, 557 (14.0%) had moderate frailty and 263 (6.6%) had severe frailty. All-cause mortality risk was related to frailty severity independent of age and sex (hazard ratio per 0.01 increase in frailty index: 1.06 [95% confidence interval 1.04-1.07]). The frailty index alone showed moderate discrimination for one-year mortality: c-statistic 0.68-0.76; combining the frailty index with age and sex improved performance (c-statistic 0.77-0.81). CONCLUSION: frailty measured by cumulative deficits is common and predicts mortality in a rural population of older South Africans. The number of measures needed may limit utility in resource-poor settings.

Older Adults Vastly Overestimate Both HIV Acquisition Risk and HIV Prevalence in Rural South Africa.

Perceptions of HIV acquisition risk and prevalence shape sexual behavior in sub-Saharan Africa (SSA). We used data from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa baseline survey. Data were collected through home-based interviews of 5059 people ≥ 40 years old. We elicited information on perceived risk of HIV acquisition and HIV prevalence among adults ≥ 15 and ≥ 50 years old. We first describe these perceptions in key subgroups and then compared them to actual estimates for this cohort. We then evaluated the relationship between sociodemographic characteristics and accurate perceptions of prevalence in regression models. Finally, we explored differences in behavioral characteristics among those who overestimated risk compared to those who underestimated or accurately estimated risk. Compared to the actual HIV acquisition risk of < 1%, respondents vastly overestimated this risk: 35% (95% CI: 32-37) and 34% (95% CI: 32-36) for men and women, respectively. Respondents overestimated HIV prevalence at 53% (95% CI: 52-53) for those ≥ 15 years old and 48% (95% CI: 48-49) for those ≥ 50 years old. True values were less than half of these estimates. There were few significant associations between demographic characteristics and accuracy. Finally, high overestimators of HIV prevalence tested themselves less for HIV compared to mild overestimators and accurate reporters. More than 30 years into the HIV epidemic, older people in a community with hyperendemic HIV in SSA vastly overestimate both HIV acquisition risk and prevalence. These misperceptions may lead to fatalism and reduced motivation for prevention efforts, possibly explaining the continued high HIV incidence in this community.