Peer-led recovery groups for people with psychosis in South Africa (PRIZE): Results of a randomized controlled feasibility trial.

AIMS: The aims of this feasibility trial were to assess the acceptability and feasibility of peer-led recovery groups for people with psychosis in a low-resource South African setting, to assess the feasibility of trial methods, and to determine key parameters in preparation for a definitive trial. METHODS: The design was an individually randomised feasibility trial comparing recovery groups in addition to treatment as usual (TAU) with TAU alone. Ninety-two isiXhosa-speaking people with psychosis and forty-seven linked caregivers were recruited from primary care clinics and randomly allocated to trial arms in a 1:1 allocation ratio. TAU comprised anti-psychotic medication delivered in primary care. The intervention arm comprised six recovery groups including service users and caregivers. Two-hour recovery group sessions were delivered weekly in a 2-month auxiliary social worker (ASW)-led phase, then a 3-month peer-led phase. To explore acceptability and feasibility, a mixed methods process evaluation included 25 in-depth interviews and 2 focus group discussions at 5 months with service users, caregivers and implementers, and quantitative data collection including attendance and facilitator competence. To explore potential effectiveness, quantitative outcome data (functioning, relapse, unmet needs, personal recovery, stigma, health service use, medication adherence and caregiver burden) were collected at baseline, 2 months and 5 months post randomisation. Trial registration: PACTR202202482587686. RESULTS: Qualitative interviews revealed that recovery groups were broadly acceptable with most participants finding groups to be an enjoyable opportunity for social interaction, and joint problem-solving. Peer facilitation was a positive experience; however a minority of participants did not value expertise by lived experience to the same degree as expertise of professional facilitators. Attendance was moderate in the ASW-led phase (participants attended 59% sessions on average) and decreased in the peer-led phase (41% on average). Participants desired a greater focus on productive activities and financial security. Recovery groups appeared to positively impact on relapse. Relapse occurred in 1 (2.2%) of 46 participants in the recovery group arm compared to 8 (17.4%) of 46 participants in the control arm (risk difference -0.15 [95% CI: -0.26; -0.05]). Recovery groups also impacted on the number of days in the last month totally unable to work (mean 1.4 days recovery groups vs 7.7 days control; adjusted mean difference -6.3 [95%CI: -12.2; -0.3]). There were no effects on other outcomes. CONCLUSION: Peer-led recovery groups for people with psychosis in South Africa are potentially acceptable, feasible and effective. A larger trial, incorporating amendments such as increased support for peer facilitators, is needed to demonstrate intervention effectiveness definitively.

Impact of age on antimicrobial prescriptions in hospitalized children at three academic centres in South Africa: a point prevalence survey.

Antimicrobial resistance is a global threat in children, and the emergence of multi-drug-resistant organisms is of concern. This secondary analysis of an antimicrobial point prevalence survey (PPS) in children evaluates the impact of age on antimicrobial use. The mean antimicrobial prescriptions were assessed in neonates, infants, young children (1-5 years), school-going children (6-12 years), and adolescents (13-15 years) from a cross-sectional PPS at three academic hospitals between September 2021 and January 2022. Primary and secondary diagnoses, antibiotic type (World Health Organization AWaRe and Anatomical Therapeutic Chemical classifications), and the incidence of healthcare-associated infections (HAI) were evaluated per age category. Multiple regression models were used to analyse age-related risk factors for HAI. The number of antimicrobials per child (1.7-1.9 per patient) was higher in neonates and infants compared to children 6-12 years old (1.4 per patient). Watch antibiotics, especially carbapenems, were commonly prescribed in neonates (32.5%) and infants (42.2%). Reserve antimicrobial use was notable in neonates (4.7%) and infants (4.1%). The incidence risk ratio (IRR) of HAI was higher in neonates and infants (IRR 2.13; 95% CI 1.23-3.70, IRR 2.20; 95% CI 1.40-3.45, respectively) compared to 6- to 12-year-olds. On multivariate analysis of participants according to age, being HIV infected, length of stay >6 days, high McCabe severity score, having surgery and receipt of blood transfusion were associated with an increased risk of HAI (P < .001 for all) while on univariate analysis only, being premature and/or underweight was associated with an increased risk of HAI in infants (P < .001 for both). Infants with risk factors for HAI significantly influenced antimicrobial prescribing, underscoring the necessity for tailored antimicrobial stewardship and enhanced surveillance. The increased use of Watch antibiotics, particularly carbapenems, in infants warrants closer scrutiny. Further research is required to identify inappropriate antimicrobial use in high-risk hospitalized young children.

Geospatial correlations and variations in child mortality and stunting in South Africa: Evaluating distal vs structural determinants.

South Africa has one of the highest child mortality and stunting rates in the world. Flexible geoadditive models were used to investigate the geospatial variations in child mortality and stunting in South Africa. We used consecutive rounds of national surveys (2008-2017). The child mortality declined from 31 % to 24 % over time. Lack of medical insurance, black ethnicity, low-socioeconomic conditions, and poor housing conditions were identified as the most significant correlates of child mortality. The model predicted degrees of freedom which was estimated as 19.55 (p < 0.001), provided compelling evidence for sub-geographical level variations in child mortality which ranged from 6 % to 35 % across the country. Population level impact of the distal characteristics on child mortality and stunting exceeded that of other risk factors. Geospatial analysis can help in monitoring trends in child mortality over time and in evaluating the impact of health interventions.

Safety and pharmacokinetics of subcutaneous administration of broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed, uninfected neonates and infants: study protocol for a phase I trial.

BACKGROUND: The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV. METHODS: Two bNAbs, CAP256V2LS and VRC07-523LS, will be assessed in a sequential and randomized phase I, single-site, single-blind, dose-finding trial. We aim to investigate the 28-day safety and pharmacokinetics (PK) profile of incrementally higher doses of these bNAbs in breastfeeding HIV-1 exposed born without HIV neonates alongside standard of care antiretroviral (ARV) medication to prevent (infants) or treat (mothers) HIV infection. The trial design includes 3 steps and 7 arms (1, 2, 3, 4, 5, 6 and 6b) with 8 infants in each arm. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single subcutaneous (SC) administration at increasing mg/kg body weight doses within 96 h of birth: arms 1, 2 and 3 at doses of 5, 10, and 20 mg/kg of CAP256V2LS, respectively; arms 4 and 5 at doses of 20 and 30 mg/kg of VRC07-523LS, respectively. Step two will evaluate the safety and PK profile of a combination of the two bNAbs administered SC at fixed doses within 96 h of birth. Step three will evaluate the safety and PK profile of the two bNAbs administered SC in combination at fixed doses, after 3 months. Arms 1 and 6 will follow sequential recruitment, whereas randomization will occur sequentially between arms (a) 2 & 4 and (b) 3 & 5. Before each randomization, a safety pause will allow review of safety data of the preceding arms. DISCUSSION: The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV. PROTOCOL VERSION: Version 4.0 dated 15 March 2024. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR): PACTR202205715278722, 21 April 2022; South African National Clinical Trial Registry (SANCTR): DOH-27-062022-6058.

Understanding the impact of women's correct risk perception on human immunodeficiency virus diagnosis: Insights from South Africa.

BACKGROUND: South African women have the highest burden of HIV infections globally. We investigated the temporal trends and the impact of key factors associated with HIV diagnosis among a nationally representative cohort of South African women. METHODS: Total of 24,657 women who participated in the National HIV, Behaviour and Health Surveys conducted from 2002-to-2017. RESULTS: Despite decades-long prevention efforts, we observed a significant increase in HIV prevalence over time (22% in 2002 to 21% in 2005-2008 and 29% in 2012-2017). Overall, 46% of the women living with HIV were not aware of their risk of HIV with age-specific disparities. Our findings revealed compelling evidence between HIV seropositivity and high HIV risk-perception (adjusted Odds Ratio (aOR):1.47 to 3.29) which increased overtime and exceeded the other factors. At a population-level, 45% of the HIV diagnoses were exclusively associated with women who believed they were at risk of HIV in 2012-2017. Women who reported using condoms at last sexual act were also at increased risk of HIV infection, with a population attributable risk of 18% (2002) to 21% (2012-2017). CONCLUSION: There is an urgent need for culturally, socially, and linguistically appropriate prevention and awareness campaigns with realistic, non-confrontational messages.

Preventing Stunting in South African Children Under 5: Evaluating the Combined Impacts of Maternal Characteristics and Low Socioeconomic Conditions.

More than 140 million children under five suffered from stunting in 2020. This highlights the ongoing challenge of addressing childhood malnutrition globally. We utilized data from a nationally representative sample of children under five years of age (n = 14,151) who participated in five cycles of the South African National Income Dynamics Study (SA-NIDS) (2008-2017). We estimated the proportion of stunted children attributed to the mothers' anthropometric characteristics and socioeconomic conditions. We also quantified the population-level burden of low-socioeconomic conditions on hunger/food insecurity among pregnant women (n = 22,814) who participated in the nine rounds of the South African General Household Surveys (GHS) (2008-2021). Results from weighted-multivariate logistic regression were incorporated into the population-level impacts of correlates of stunting and low-socioeconomic conditions. The prevalence of stunting declined from 25% in 2008 to 23% in 2017. Mothers' anthropometric measures (underweight/height < 160 cm), marital status, low education, absence of medical insurance and low-socioeconomic conditions were all identified as the most influential risk factors for stunting. Their population-level impacts on stunting increased substantially from 34% (in 2008) to 65% (in 2017). Comprehensive strategies emphasizing enhanced food security, extended breastfeeding, appropriate nutrition, and access to adequate healthcare and education are urgently needed to reduce the burden of food insecurity low-socioeconomic, malnutrition, and its long-term consequences.

Antibiotic and antifungal use in paediatric departments at three academic hospitals in South Africa.

Objectives: South Africa implemented a National Strategic Framework to optimise antimicrobial stewardship in 2014; however, there is limited data on how this has affected prescribing, especially to children treated in academic centres. Methods: We conducted a point prevalence survey using the World Health Organization (WHO) methodology to evaluate antibiotic and antifungal prescribing practices in paediatric departments at three academic hospitals in South Africa. Results: We recorded 1946 antimicrobial prescriptions in 1191 children, with 55.2% and 39.2% of the antibiotics classified as WHO AWaRe Access and Watch drugs, respectively. There were significant differences in prescription of Reserve antibiotics and antifungals between institutions. Receipt of WHO Watch and Reserve antibiotics was independently associated with infancy (<12 months) and adolescents (13-17 years) (adjusted relative risk [aRR]: 2.09-9.95); prolonged hospitalisation (aRR: 3.29-30.08); rapidly or ultimately fatal illness (aRR: 1.94 to 5.52); and blood transfusion (aRR: 3.28-5.70). Antifungal prescribing was associated with treatment of hospital-associated infection (aRR: 2.90), medical prophylaxis (aRR: 3.30), and treatment in intensive care units (aRR: 2.15-2.27). Conclusions: Guidance on optimisation of infection prevention and control practice and strengthening of antimicrobial stewardship would impact positively on the care of sick children in our setting.

Safety of a second homologous Ad26.COV2.S vaccine among healthcare workers in the phase 3b implementation Sisonke study in South Africa.

The Sisonke 2 study provided a homologous boost at least 6 months after administration of the priming dose of Ad26.COV2.S for healthcare workers enrolled on the Sisonke phase 3b implementation study. Safety monitoring was via five reporting sources: (i.) self-report through a web-link; (ii.) paper-based case report forms; (iii.) a toll-free telephonic reporting line; (iv.) healthcare professionals-initiated reports; and (v.) active linkage with National Disease Databases. A total of 2350 adverse events were reported by 2117 of the 240 888 (0.88%) participants enrolled; 1625 of the 2350 reported events are reactogenicity events and 28 adverse events met seriousness criteria. No cases of thrombosis with thrombocytopaenia syndrome were reported; all adverse events including thromboembolic disorders occurred at a rate below the expected population rates apart from one case of Guillain Barre Syndrome and one case of portal vein thrombosis. The Sisonke 2 study demonstrates that two doses of Ad26.COV2.S is safe and well tolerated; and provides a feasible model for national pharmacovigilance strategies for low- and middle-income settings.

Using prevention cascades to investigate coverage of contraception services among young women enrolled in a large-scale combination HIV prevention program in South Africa.

OBJECTIVES: We investigated the coverage of contraception services (excluding condoms) to prevent unintended pregnancy among young women and girls aged 15 to 24 years who were beneficiaries of one of the two largest combination HIV and pregnancy prevention program in South Africa. STUDY DESIGN: We invited 2160 randomly sampled beneficiaries who were living in six of the 12 program districts across six provinces to participate in a telephone survey. We created pregnancy prevention coverage cascades and conducted univariate and multivariable analyses to identify key barriers and facilitators associated with each step of the cascade. RESULTS: We achieved a response rate of 23.8%, resulting in 515 respondents, of whom 303 had sex in the 6 months before the survey. Of this subsample, 80.4% had access to contraception services, 60.6% had access and motivation to use contraceptives, and 21.9% had access to, motivation to use, and effectively used contraceptives. Distance to travel to services and not ever being offered contraceptives by health workers were access barriers, while low pregnancy risk perception was a barrier to motivation. CONCLUSIONS: Most respondents had access to and were motivated to use contraceptives other than condoms but were not effectively using them. Having been offered contraceptives facilitated better access, while distance to the services was a barrier, suggesting the importance of improving supply-side interventions, such as increasing the number and accessibility of spaces where Sexual and Reproductive Health (SRH) services are offered. We recommend longitudinal behavioral counseling for young people, especially adolescents, as well as risk reduction and information-tailored interventions. IMPLICATIONS: Pregnancy prevention cascades are a promising tool to monitor progress toward universal access to contraception services and to identify barriers that need to be addressed to achieve the effective use of contraceptives.

Applying the HIV Prevention Cascade to an Evaluation of a Large-Scale Combination HIV Prevention Programme for Adolescent Girls and Young Women in South Africa.

Adolescent girls and young women (AGYW) in South Africa are at a three times higher risk of acquiring HIV than their male counterparts. The HIV prevention cascade is a tool which can be used to measure coverage of HIV prevention services, although there is limited empirical evidence to demonstrate its application in low-resourced settings. The unifying framework is a conceptualisation of the HIV prevention cascade which theorises that both motivation and access are required for an individual to effectively use an HIV prevention method. We applied this framework to data from a random sample of 127,951 beneficiaries of a combination HIV prevention programme for AGYW aged 15-24 in South Africa to measure the steps to, and identify key barriers to, effective use of male condoms and oral pre-exposure prophylaxis (PrEP) among this vulnerable population. Barriers to each step were analysed using univariate and multivariable logistic regression. Among self-reported HIV-negative AGYW who had sex in the past 6 months, effective use of condoms (15.2%), access to PrEP (39.1%) and use of PrEP (3.8%) were low. AGYW were: less likely to be motivated to use condoms if they believed that they had a faithful partner (aOR 0.44, 95% CI 0.22-0.90) or disliked condoms (aOR 0.26, 95% CI 0.11-0.57), less likely to access condoms if the place where AGYW accessed them was far away (aOR 0.25, 95% CI 0.10-0.64), more likely to effectively use condoms if they received counselling on how to use them (aOR 2.24, 95% CI 1.05-4.76), less likely to be motivated to use PrEP if they did not believe PrEP was efficacious (aOR 0.35, 95% CI 0.17-0.72), more likely to be motivated if they felt confident that they could use PrEP, and more likely to have access to PrEP if they had ever been offered PrEP (aOR 2.94, 95% CI 1.19-7.22). This combination HIV prevention programme and similar programmes should focus on risk-reduction counselling interventions for AGYW and their male partners to improve effective use of condoms and ensure easy access to condoms and PrEP by making them available in youth-friendly spaces. Our findings demonstrate that the application of HIV prevention cascades can inform AGYW HIV prevention programming in low-resourced settings.

Factors Associated with COVID-19 Vaccine Uptake among Schoolgoing Adolescent Girls and Young Women in South Africa.

(1) Background: By October 2022, vaccination rates with at least one dose of a COVID-19 vaccine were low among adolescent girls aged 12-17 (38%) and young women aged 18-34 (45%) in South Africa. This study aimed to measure and identify barriers to and facilitators of motivation to take up, access to, and uptake of COVID-19 vaccines among schoolgoing adolescent girls and young women in two districts in South Africa. (2) Methods: Using the theory of the HIV prevention cascade, we conceptualised the relationship between motivation, access, and uptake of COVID-19 vaccines, and associated barriers. Potential barriers and facilitators were identified using bivariate and multivariable Poisson regression. (3) Results: Among all 2375 participants, access was high (69%), but motivation (49%) and vaccination with at least one COVID-19 vaccine (45%) were lower. Fear of injections was a barrier to vaccine uptake (aRR 0.85 95% CI 0.82-0.88), while being tested for COVID-19 (aRR 2.10 95% CI 1.85-2.38) and believing that the COVID-19 vaccine was safe (aRR 1.31 95% CI 1.18-1.44) and would prevent you from getting very sick (aRR 1.11 95% CI 1.04-1.19) were facilitators. (4) Conclusions: The controversy about the value of vaccinating adolescents and the delay in vaccine rollout for adolescents and young adults may have contributed to fears about the safety and efficacy of COVID-19 vaccines, as well as a lack of motivation to get vaccinated.

Seroprevalence survey of anti-SARS-CoV-2 antibody and associated factors in South Africa: Findings of the 2020-2021 population-based household survey.

Population-based serological testing is important to understand the epidemiology and estimate the true cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to inform public health interventions. This study reports findings of a national household population SARS-CoV-2 serosurvey in people 12 years and older in South Africa. This cross-sectional multi-stage random stratified cluster survey undertaken from November 2020 to June 2021 collected sociodemographic data, medical history, behavioural data, and blood samples from consenting participants. The samples were tested for SARS-CoV-2 antibodies using the Roche ElecsysAnti-SARS-CoV-2 chemiluminescence immunoassay (CLIA) Total Antibody Test. The survey data were weighted by age, race, sex, and province with final individual weights benchmarked against the 2020 mid-year population estimates and accounted for clustering. Descriptive statistics summarize the characteristics of participants and seroprevalence. Logistic regression analyses were used to identify factors associated with seropositivity. From 13290 survey participants (median age 33 years, interquartile range (IQR) 23-46 years), SARS-CoV-2 seroprevalence was 37.8% [95% Confidence Interval (CI) 35.4-40.4] and varied substantially across the country's nine provinces, and by sex, age and locality type. In the final adjusted model, the odds of seropositivity were higher in women than in men [aOR = 1.3 (95% CI: 1.0-1.6), p = 0.027], and those living with HIV (self-report) [aOR = 1.6 (95% CI: 1.0-2.4), p = 0.031]. The odds were lower among those 50 years and older compared to adolescents 12-19 years old [aOR = 0.6 (95% CI: 0.5-0.8), p<0.001] and in those who did not attend events or gatherings [aOR = 0.7 (95% CI: 0.6-1.0), p = 0.020]. The findings help us understand the epidemiology of SARS-CoV-2 within different regions in a low-middle-income country. The survey highlights the higher risk of infection in women in South Africa likely driven by their home and workplace roles and also highlighted a need to actively target and include younger people in the COVID-19 response.

Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial.

Aim: The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study. Methods: Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5 days of symptom onset were assigned to the intervention (n = 77) or placebo (n = 79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11-13 days post-symptom onset. Results: One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11-13 days post-symptom onset (p = 0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed. Conclusion: The intervention reduced symptoms of mild/moderate COVID-19. Clinical Trial Registration: DOH-27-062021-9191 (South African National Clinical Trials Register).

Natural proteins found in milk (lactoferrin) and egg white (ovotransferrin and lysozyme) could have therapeutic value in COVID-19 through their effects on the immune system. We identified bovine colostrum and hen egg white powders containing adequate quantities of these proteins. We investigated whether short-term daily consumption of a hen egg white and bovine colostrum mixture (reconstituted with glycerin and water) could reduce the risk of progression to severe disease and assist in the recovery of patients with mild or moderate COVID-19. Adults with mild or moderate COVID-19 who were within 5 days of symptom onset and had risk factors for severe disease were enrolled, and randomly assigned to take a hen egg white and bovine colostrum mixture or placebo mixture twice daily for 5 days, and then followed up telephonically for 6 weeks. The main findings were that consumption of the hen egg white and bovine colostrum mixture was associated with fewer protocol-defined severe-type symptoms overall, and in particular lower frequencies of joint pain/malaise, chest pain, fever/chills, and sore throat. Only one individual developed severe COVID-19 and therefore the effect of the intervention on reducing the risk of progression to severe disease could not be assessed. The results of this study suggest that consumption of the hen egg white bovine colostrum mixture within a few days of symptom onset lessens symptoms in people with mild or moderate COVID-19.

Healthcare-associated Infections Drive Antimicrobial Prescribing in Pediatric Departments at Three Academic Hospitals in South Africa.

BACKGROUND: The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals. METHODS: This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site. RESULTS: Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI. CONCLUSIONS: The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level.

Wastewater-based SARS-CoV-2 airport surveillance: key trends at the Cape Town International Airport.

Monitoring of SARS-CoV-2 RNA in wastewater has revealed the role of mobility in the transmission of coronavirus disease (COVID-19), and the surveillance of airport wastewater in cities across the world has demonstrated how travel entry points can give an indication of trends in transmission. This study undertook wastewater surveillance at the Cape Town International Airport (CTIA) to assess the use of a WBE approach to provide supplementary information on the presence of COVID-19 at a key air travel entry point in South Africa. Grab wastewater samples (n = 55) were collected from the CTIA wastewater pump station and analysed using quantitative real-time polymerase chain reaction (qRT-PCR) method. The study found a correlation between the wastewater data and clinical cases reported in the City of Cape Town during various time periods and during the peak of a COVID-19 wave. Highly elevated viral loads in the wastewater were observed at times there was increased mobility through the airport. The study also revealed elevated viral load levels at the airport despite the stricter restrictions and through the lower restrictions. The study findings indicate wastewater surveillance and airports can provide supplementary information to airport authorities to assess the impacts of imposed travel restrictions.

Heterogeneity in COVID-19 infection among older persons in South Africa: Evidence from national surveillance data.

Background: The 2021 World Health Organization study on the impact of COVID-19 on older people (≥60 years) in the African region highlighted the difficulties they faced as the virus spread across borders and dominated the way of life. These difficulties included disruptions to both essential health care services and social support, as well as disconnections from family and friends. Among those who contracted COVID-19, the risks of severe illness, complications, and mortality were highest among near-old and older persons. Objective: Recognizing that older persons are a diverse group including younger- and older-aged individuals, a study was conducted to track the epidemic among near-old (50-59 years) and older persons (≥60 years) in South Africa covering the 2 years since the epidemic emerged. Methods: Using a quantitative secondary research approach, data for near-old and older persons were extracted for comparative purposes. COVID-19 surveillance outcomes (confirmed cases, hospitalizations, and deaths) and vaccination data were compiled up to March 5th, 2022. COVID-19 surveillance outcomes were plotted by epidemiological week and epidemic waves to visualize the overall growth and trajectory of the epidemic. Means for each age-group and by COVID-19 waves, together with age-specific rates, were calculated. Results: Average numbers of new COVID-19 confirmed cases and hospitalizations were highest among people aged 50-59- and 60-69-years. However, average age-specific infection rates showed that people aged 50-59 years and ≥80 years were most vulnerable to contracting COVID-19. Age-specific hospitalization and death rates increased, with people aged ≥ 70 years most affected. The number of people vaccinated was slightly higher among people aged 50-59 years before Wave Three and during Wave Four, but higher among people aged ≥ 60 years during Wave Three. The findings suggest that uptake of vaccinations stagnated prior to and during Wave Four for both age groups. Discussion: Health promotion messages and COVID-19 epidemiological surveillance and monitoring are still needed, particularly for older persons living in congregate residential and care facilities. Prompt health-seeking should be encouraged, including testing and diagnosis as well as taking up vaccines and boosters, particularly for high-risk older persons.

HIV-1 subtype C Nef-mediated SERINC5 down-regulation significantly contributes to overall Nef activity.

BACKGROUND: Nef performs multiple cellular activities that enhance HIV-1 pathogenesis. The role of Nef-mediated down-regulation of the host restriction factor SERINC5 in HIV-1 pathogenesis is not well-defined. We aimed to investigate if SERINC5 down-regulation activity contributes to HIV-1 subtype C disease progression, to assess the relative contribution of this activity to overall Nef function, and to identify amino acids required for optimal activity. We measured the SERINC5 down-regulation activity of 106 subtype C Nef clones, isolated from individuals in early infection, for which the Nef activities of CD4 and HLA-I down-regulation as well as alteration of TCR signalling were previously measured. The relationship between SERINC5 down-regulation and markers of disease progression, and the relative contribution of SERINC5 down-regulation to a Nef fitness model-derived E value (a proxy for overall Nef fitness in vivo), were assessed. RESULTS: No overall relationship was found between SERINC5 down-regulation and viral load set point (p = 0.28) or rate of CD4+ T cell decline (p = 0.45). CD4 down-regulation (p = 0.02) and SERINC5 down-regulation (p = 0.003) were significant determinants of E values in univariate analyses, with the greatest relative contribution for SERINC5 down-regulation, and only SERINC5 down-regulation remained significant in the multivariate analysis (p = 0.003). Using a codon-by-codon analysis, several amino acids were significantly associated with increased (10I, 11V, 38D, 51T, 65D, 101V, 188H and, 191H) or decreased (10K, 38E, 65E, 135F, 173T, 176T and, 191R) SERINC5 down-regulation activity. Site-directed mutagenesis experiments of selected mutants confirmed a substantial reduction in SERINC5 down-regulation activity associated with the mutation 173T, while mutations 10K, 135F, and 176T were associated with more modest reductions in activity that were not statistically significant. CONCLUSIONS: These results suggest that SERINC5 down-regulation is a significant contributor to overall Nef function and identify potential genetic determinants of this Nef function that may have relevance for vaccines or therapeutics.

Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study).

Objective: To assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population. Design: Open label, single arm, phase 3B study. Setting: Sisonke study, South Africa, 17 February to 15 June 2021. Participants: The Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine. Main outcome measures: Observed rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software). Results: Most of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population. Conclusions: Vaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates. Trial registration: ClinicalTrials.gov NCT04838795.

Relations between personal exposure to elevated concentrations of arsenic in water and soil and blood arsenic levels amongst people living in rural areas in Limpopo, South Africa.

Exposure to arsenic even at low levels can lead to adverse health outcomes, however, there is a paucity of research from South Africa in relation to human exposure to arsenic. We investigated long-term exposure of residents in Limpopo province, South Africa, in a cross-sectional study by analysing water, soil and blood arsenic concentrations from two arsenic-exposed (high and medium-low exposure) villages and one non-exposed (control) village. There were statistically significant differences in the distribution of arsenic in water, soil and blood amongst the three sites. The median drinking water arsenic concentration in the high-exposure village was 1.75 µg/L (range = 0.02 to 81.30 µg/L), 0.45 µg/L (range = 0.100 to 6.00 µg/L) in the medium- / low-exposure village and 0.15 µg/L (range = < limit of detection (LOD) to 29.30 µg/L) in the control site. The median soil arsenic concentration in the high-exposure village was 23.91 mg/kg (range = < LOD to 92.10 mg/kg) whilst arsenic concentrations were below the limit of detection in all soil samples collected from the medium-/low-exposure and control villages. In the high-exposure village, the median blood arsenic concentration was 1.6 µg/L (range = 0.7 to 4.2 µg/L); 0.90 µg/L (range = < LOD to 2.5 µg/L) in the medium-/low-exposure village and 0.6 µg/L (range = < LOD to 3.3 µg/L) in the control village. Significant percentages of drinking water, soil and blood samples from the exposed sites were above the internationally recommended guidelines (namely, 10 µg/L, 20 mg/kg and 1 µg/L, respectively). Majority of participants (86%) relied on borehole water for drinking and there was a significant positive correlation between arsenic in blood and borehole water (p-value = 0.031). There was also a statistically significant correlation between arsenic concentrations in participants' blood and soil samples collected from gardens (p-value = 0.051). Univariate quantile regression found that blood arsenic concentrations increased by 0.034 µg/L (95% CI = 0.02-0.05) for each one unit increase in water arsenic concentrations (p < 0.001). After adjusting for age, water source and homegrown vegetable consumption in multivariate quantile regression, participants from the high-exposure site had significantly higher blood concentrations than those in the control site (coefficient: 1.00; 95% CI = 0.25-1.74; p-value = 0.009) demonstrating that blood arsenic is a good biomarker of arsenic exposure. Our findings also provide new evidence for South Africa on the association between drinking water and arsenic exposure, emphasising the need for the provision of potable water for human consumption in areas with high environmental arsenic concentrations.