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Disorders of the nervous system represent a significant proportion of the global burden of non-communicable diseases, due to the trend towards ageing populations. The Department (now Division) of Human Genetics at the University of Cape Town (UCT) has been involved in pioneering research into these diseases since the appointment of Prof. Peter Beighton as Head of Department in 1972. Beighton's emphasis on understanding the genetic basis of disease laid the groundwork for investigations into several monogenic neurodegenerative conditions, including Huntington's disease and the polyglutamine spinocerebellar ataxias (SCAs). In particular, SCA7, which occurs at an unusually high frequency in the South African (SA) population, was identified as a target for further research and therapeutic development. Beginning with early epidemiological surveys, the SCA7 project progressed to molecular genetics-based investigations, leading to the identification of a founder effect in the SA SCA7 patient population in the mid-2000s. Capitalising on the founder haplotype shared by many SCA7 patients, UCT researchers went on to develop the first population-specific gene-silencing approach for the disease. More recently, efforts have shifted to the development of a more accurate model to decipher the precise mechanisms of neurodegeneration, using induced pluripotent stem cells derived from SA SCA7 patients. In many ways, the SA SCA7 journey reflects the legacy and vision of Prof. Peter Beighton, and his efforts to establish world-class, collaborative research into diseases affecting the African continent.

Background Engagement in protective behaviours relating to the COVID-19 pandemic has been proposed to be key to infection control. This is particularly the case for youths as key drivers of infections. A range of factors influencing adherence have been identified, including impulsivity and risk taking. We assessed the association between pre-COVID impulsivity levels and engagement in preventative measures during the COVID-19 pandemic in a longitudinal South African sample, in order to inform future pandemic planning. Methods Data were collected from N = 214 youths (mean age at baseline: M = 17.81 (SD = .71), 55.6% female) living in a South African peri-urban settlement characterised by high poverty and deprivation. Baseline assessments were taken in 2018/19 and the COVID follow-up was conducted in June–October 2020 via remote data collection. Impulsivity was assessed using the Balloon Analogue Task (BART), while hygiene and social distancing behaviours were captured through self-report. Stepwise hierarchical regression analyses were performed to estimate effects of impulsivity on measure adherence. Results Self-rated engagement in hygiene behaviours was high (67.1–86.1% “most of the time”, except for “coughing/sneezing into one’s elbow” at 33.3%), while engagement in social distancing behaviours varied (22.4–57.8% “most of the time”). Higher impulsivity predicted lower levels of hygiene (β = .14, p = .041) but not social distancing behaviours (β = −.02, p = .82). This association was retained when controlling for a range of demographic and COVID-related factors (β = .14, p = .047) and was slightly reduced when including the effects of a life-skills interventions on hygiene behaviour (β = −.13, p = .073). Conclusions Our data indicate that impulsivity may predict adolescent engagement in hygiene behaviours post COVID-19 pandemic onset in a high risk, sub-Saharan African setting, albeit with a small effect size. For future pandemics, it is important to understand predictors of engagement, particularly in the context of adversity, where adherence may be challenging. Limitations include a small sample size and potential measure shortcomings.

COVID-19 has a substantial and unexpected impact on individuals’ daily life around the world. Unprecedented public health restrictions such as lockdowns have the potential to affect multiple dimensions of individuals’ well-being, while the severity of such restrictions varies across countries. However, a holistic perspective comparing differences in and drivers of the different dimensions of well-being across countries differentially affected by COVID-19 is missing to date. We address this gap in the literature by examining the mental, social, functional, and financial well-being of 2,100 individuals across Australia, France, Germany, and South Africa by means of a survey administered during May of 2021. Supporting our holistic approach, we find that the different dimensions of well-being are correlated, with survey respondents from France reporting the lowest and those from Australia reporting the highest overall level of well-being. Respondents’ subjective and objective evaluations of their living conditions during lockdowns as well as positive health and financial behaviors are positively associated with their well-being during the pandemic.

Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa’s fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69–70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69–70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08–0.09) and 0.10 (95% CI: 0.09–0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.

Rickettsia spp. can be found across the globe and cause disease of varying clinical severity, ranging from life-threatening infections with widespread vasculitis to milder, more localized presentations. Vector and, to some degree, reservoir are hematophagous arthropods, with most species harboured by ticks. In Denmark, rickettsiae are known as a cause of imported travel-related infections, but are also found endemically in ticks across the country. Data are, however, lacking on the geographical origin and clinical features of diagnosed cases. In this study, we have examined the travel history and clinical features of two groups of patients; 1) hospital-patients diagnosed with rickettsioses in the years 2010–2015 and 2) patients from primary health care (PHC) centers in Denmark having demonstrated anti-rickettsia antibodies in the years 2012–2015. The patients were identified using the Danish National Patient Registry (DNPR) and through the serological database at the State Serum Institute, where the laboratory diagnosis of rickettsioses is currently centralized. Data were collected for 86 hospital patients and 26 PHC center patients by reviewing hospital medical records and performing telephone interviews with PHC centers. Of the hospital patients, 91% (78/86) had a history of international travel 14 days prior to symptom start, with most having imported their infection from southern Africa, South Africa in particular (65%), and presenting with a clinical picture most compatible with African tick-bite fever caused by R. africae. Only two patients presented with a CRP > 100 mg/L and no mortalities were reported. At the PHC centers, most patients presented with mild flu-like symptoms and had an unknown (50%) or no history (19%) of international travel, raising the possibility of endemic rickettsioses. In view of our findings, rickettsioses do not appear to constitute a major public health problem in Denmark, with most cases being imported infections and potential endemic cases presenting as mild infections.

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, andPrevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associatedStreptococcus, Prevotella, andVeillonellawere enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

Background Research on reproductive health effects on children from low-level, long-term exposure to pesticides currently used in the agricultural industry is limited and those on neurobehavioral effects have produced conflicting evidence. We aim at investigating the association between pesticide exposure on the reproductive health and neurobehavior of children in South Africa, by including potential relevant co-exposures from the use of electronic media and maternal alcohol consumption. Methods The design entails a prospective cohort study with a follow-up duration of 2 years starting in 2017, including 1000 school going children between the ages of 9 to 16 years old. Children are enrolled with equal distribution in sex and residence on farms and non-farms in three different agricultural areas (mainly apple, table grapes and wheat farming systems) in the Western Cape, South Africa. The neurobehavior primary health outcome of cognitive functioning was measured through the iPad-based CAmbridge Neuropsychological Test Automated Battery (CANTAB) including domains for attention, memory, and processing speed. The reproductive health outcomes include testicular size in boys and breast size in girls assessed in a physical examination, and blood samples to detect hormone levels and anthropometric measurements. Information on pesticide exposure, co-exposures and relevant confounders are obtained through structured questionnaire interviews with the children and their guardians. Environmental occurrence of pesticides will be determined while using a structured interview with farm owners and review of spraying records and collection of passive water and air samples in all three areas. Pesticide metabolites will be analysed in urine and hair samples collected from the study subjects every 4 months starting at baseline. Discussion The inclusion of three different agricultural areas will yield a wide range of pesticide exposure situations. The prospective longitudinal design is a further strength of this study to evaluate the reproductive and neurobehavioural effects of different pesticides on children. This research will inform relevant policies and regulatory bodies to improve the health, safety and learning environments for children and families in agricultural settings.

Item does not contain fulltext Objectives: Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with RA. We sought to externally validate risk calculators recommended for use in patients with RA including the EULAR 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for RA (ERS-RA) and QRISK2. Methods: Seven RA cohorts from UK, Norway, Netherlands, USA, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischaemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared with other risk calculators [American College of Cardiology/American Heart Association (ACC/AHA), Framingham Adult Treatment Panel III Framingham risk score-Adult Treatment Panel (FRS-ATP) and Reynolds Risk Score] using c-statistics and net reclassification index. Results: Among 1796 RA patients without prior CVD [mean ( s . d .) age: 54.0 (14.0) years, 74% female], 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA [mean ( s . d .) 8.8% (9.8%)] was comparable to FRS-ATP [mean ( s . d .) 9.1% (8.3%)] and Reynolds [mean ( s . d .) 9.2% (12.2%)], but lower than ACC/AHA [mean ( s . d .) 9.8% (12.1%)]. QRISK2 substantially overestimated risk [mean ( s . d .) 15.5% (13.9%)]. Discrimination was not improved for ERS-RA (c-statistic = 0.69), QRISK2 or EULAR multiplier applied to ACC/AHA compared with ACC/AHA (c-statistic = 0.72 for all) or for FRS-ATP (c-statistic = 0.75). The net reclassification index for ERS-RA was low (-0.8% vs ACC/AHA and 2.3% vs FRS-ATP). Conclusion: The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population.

Background and aims Apelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA. Methods Apelin levels were measured in 235 (114 black, 121 white) RA patients. Associations between apelin concentrations and ultrasound determined carotid artery intima-media thickness (cIMT) and plaque, and levels of matrix metalloproteinase (MMP)-2 and -9 that mediate plaque stability and vulnerability respectively, were identified in confounder adjusted multivariate regression analysis. Results In all patients, apelin concentrations were directly associated with those of MMP-2 (β (SE) = 0.324 (0.112), p = 0.004) and inversely with those of MMP-9 (β (SE) = -0.239 (0.060), p = 0.000). Apelin concentration-subclinical CVD relations were influenced by population origin, RA disease activity, erythrocyte sedimentation rate (ESR) and interleukin (IL)-6 concentrations (interaction p = 0.001 to 0.04). Accordingly, the apelin-MMP-2 concentration relationship was reproduced in white (β (SE) = 0.367 (0.146), p = 0.01) but not black RA patients (β (SE) = 0.197 (0.220), p = 0.4), and only in those without (but not with) large erythrocyte sedimentation rates (β (SE) = 0.428 (0.143), p = 0.003) or interleukin-6 levels (β (SE) = 0.485 (0.288), p = 0.04). By contrast, the apelin-MMP-9 concentration relation was reproduced more consistently. Apelin levels were inversely related to cIMT in patients with RA remission or mild (β (SE) = -0.068 (0.033), p = 0.04) but not moderate or high disease activity (β (SE) = 0.015 (0.112), p = 0.7). Conclusions Apelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with RA. These relations are partially dependent on population origin and systemic inflammatory status.

Background Hypertension is the leading cause of cardiovascular disease and premature death worldwide. The prevalence of this public health problem is increasing in low- and middle-income countries (LMICs) in both urban and rural communities. Objective The aim of this study was to examine hypertension prevalence, awareness, treatment, and control in adults 35 to 74 years of age from urban and rural communities in LMICs in Africa, Asia, and South America. Methods The authors analyzed data from 7 population-based cross-sectional studies in selected communities in 9 LMICs that were conducted between 2008 and 2013. Age- and sex-standardized prevalence rates of pre-hypertension and hypertension were calculated. The prevalence rates of awareness, treatment, and control of hypertension were estimated overall and by subgroups of age, sex, and educational level. Results In selected communities, age- and sex-standardized prevalence rates of hypertension among men and women 35 to 74 years of age were 49.9% (95% confidence interval [CI]: 42.3% to 57.4%) in Kenya, 54.9% (95% CI: 51.3% to 58.4%) in South Africa, 52.5% (95% CI: 50.1% to 54.8%) in China, 32.5% (95% CI: 31.7% to 33.3%) in India, 42.3% (95% CI: 40.4% to 44.2%) in Pakistan, 45.4% (95% CI: 43.6% to 47.2%) in Argentina, 39.9% (95% CI: 37.8% to 42.1%) in Chile, 19.2% (95% CI: 17.8% to 20.5%) in Peru, and 44.1% (95% CI: 41.6% to 46.6%) in Uruguay. The proportion of awareness varied from 33.5% in India to 69.0% in Peru, the proportion of treatment among those who were aware of their hypertension varied from 70.8% in South Africa to 93.3% in Pakistan, and the proportion of blood pressure control varied from 5.3% in China to 45.9% in Peru. Conclusions The prevalence of hypertension varies widely in different communities. The rates of awareness, treatment, and control also differ in different settings. There is a clear need to focus on increasing hypertension awareness and control in LMICs. Fil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Gutierrez, Laura. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Bloomfield, Gerald. Duke Clinical Research Institute; Estados Unidos Fil: Carrillo-Larco, Rodrigo M.. Cronicas Centro de Excelencia En Enfermedades Crónicas; Perú Fil: Dorairaj, Prabhakaran. Public Health Foundation Of India; India. Centre For Chronic Disease Control; India Fil: Gaziano, Thomas. Harvard University. Harvard School of Public Health; Estados Unidos. Brigham And Women's Hospital; Estados Unidos Fil: Levitt, Naomi S.. University Of Cape Town; Sudáfrica Fil: Miranda, J. Jaime. Universidad Peruana Cayetano Heredia; Perú. Cronicas Centro de Excelencia En Enfermedades Crónicas; Perú Fil: Ortiz, Antonio Bernabe. Cronicas Centro de Excelencia En Enfermedades Crónicas; Perú Fil: Steyn, Krisela. University Of Cape Town; Sudáfrica Fil: Wu, Yangfeng. Peking University; China Fil: Xavier, Denis. St. John's Medical College; India Fil: Yan, Lijing L.. Peking University; China. Duke Kunshan University; China Fil: He, Jiang. University of Tulane; Estados Unidos Fil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina