SARS-CoV-2 spike protein diversity at an intra-host level, among SARS-CoV-2 infected individuals in South Africa, 2020 to 2022.

Intra-host diversity studies are used to characterise the mutational heterogeneity of SARS-CoV-2 infections in order to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. The study included SARS-CoV-2 respiratory samples, from individuals of all ages, received at the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic hospital, Gauteng, South Africa, from June 2020 to May 2022. Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on a random selection of SARS-CoV-2 positive samples. The allele frequency (AF) was determined using TaqMan Genotyper software for SNP PCR analysis and galaxy.eu for analysis of FASTQ reads from sequencing. The SNP assays identified 5.3% (50/948) of Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50), however only heterogeneity for E484Q and delY144 were confirmed by sequencing. From sequencing we identified 9% (210/2381) of cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages that had heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2-0.7), 371 (92.3%) with S371FP (AF 0.1-1.0), and 484 (1.9%) with E484AK (0.2-0.7), E484AQ (AF 0.4-0.5) and E484KQ (AF 0.1-0.4). Mutations at heterozygous amino acid positions 19, 371 and 484 are known antibody escape mutations, however the impact of the combination of multiple substitutions identified at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host's natural and vaccine-induced immune responses.

Protocol for the OCAY study: a cohort study of orphanhood and caregiver loss in the COVID-19 era to explore the impact on children and adolescents.

INTRODUCTION: Globally, no person has been untouched by the COVID-19 pandemic. Yet, little attention has been given to children and adolescents in policy, provision and services. Moreover, there is a dearth of knowledge regarding the impact of COVID-19-associated orphanhood and caregiver loss on children. This study aims to provide early insights into the mental health and well-being of children and adolescents experiencing orphanhood or caregiver loss in South Africa. METHODS AND ANALYSIS: Data will be drawn from a quantitative longitudinal study in Cape Town, South Africa. A sample of children and adolescents between the ages of 9 and 18 years, experiencing parental or caregiver loss from COVID-19, will be recruited together with a comparison group of children in similar environments who did not experience loss. The study aims to recruit 500 children in both groups. Mental health and well-being among children will be explored through the use of validated and study-specific measures. Participants will be interviewed at two time points, with follow-up data being collected 12-18 months after baseline. A combination of analytical techniques (including descriptive statistics, regression modelling and structural equation modelling) will be used to understand the experience and inform future policy and service provision. ETHICS AND DISSEMINATION: This study received ethical approval from the Health Research Ethics Committee at Stellenbosch University (N 22/04/040). Results will be disseminated via academic and policy publications, as well as national and international presentations including high-level meetings with technical experts. Findings will also be disseminated at a community level via various platforms.

The added value of molecular-based diagnostics in the African forensic medical setting.

Sudden unexpected infant death (SUDI) is reported to be an extraordinarily high burden in sub-Saharan Africa, with the incidence rate in South Africa among the highest in the world. It is common for the cause of many such infant deaths to remain unexplained even after a full medico-legal death investigation, and then to be categorised as a sudden unexplained infant death (SUID). Fortunately, advances in molecular-based diagnostics allow researchers to identify numerous underlying inherited cardiac arrhythmogenic disorders in many SUDI cases, with a predominance of variants identified in the SCN5A gene. Such cardiac arrhythmogenic-related sudden deaths generally present with no structural alterations of the heart that are macroscopically identifiable at autopsy, therefore highlighting the importance of post mortem genetic testing. We report on a significant genetic finding that was made on a SUDI case in which the cause was ascribed to an acute bacterial pneumonia but it was still subjected to post mortem genetic testing of the SCN5A gene. The literature shows that many SUDI cases diagnosed with inherited cardiac arrhythmogenic disorders have demonstrated a viral prodrome within days of their death. It is therefore not uncommon for these cardiac disorders in infants to be mistaken for flu, viral upper respiratory tract infection or pneumonia, and without the incorporation of post mortem genetic testing, any other contributory causes of these deaths are often disregarded. This study highlights the need for research reporting on the genetics of inherited cardiac disorders in Africa.

Understanding the impact of the COVID­19 pandemic on healthcare services for adults during three waves of COVID­19 infections: A South African private sector experience.

BACKGROUND: Since the onset of the COVID­19 pandemic, healthcare resources have been repurposed to focus on COVID­19. Resource reallocation and restrictions to movement that affected general access to care may have inadvertently resulted in undue disruptions in the continuum of care for patients requiring non-COVID­19 healthcare services. OBJECTIVES: To describe the change in pattern of health service use in the South African (SA) private sector. METHODS: We conducted a retrospective study of a nationwide cohort of privately insured individuals. An analysis of claims data was performed for non-COVID­19 related healthcare services provided from April 2020 to December 2020 (year 1 of COVID­19) and April 2021 to December 2021 (year 2 of COVID­19) relative to the same period in 2019 prior to the COVID­19 pandemic in SA. Over and above plotting the monthly trends, we tested for statistical significance of the changes using a Wilcoxon test given the non-normality of all the outcomes. RESULTS: Between April and December 2020, relative to the same period in 2021, and also relative to the same period in 2019, we found a 31.9% (p<0.01) and a 16.6% (p<0.01) reduction in emergency room visits, respectively; a 35.9% (p<0.01) and 20.5% (p<0.01) reduction in medical hospital admissions; a 27.4% (p=0.01) and 13.0% (p=0.03) reduction in surgical hospital admissions; a 14.5% (p<0.01) and 4.1% (p=0.16) reduction in face-to-face general practitioner consultations for chronic members; a 24.9% (p=0.06) and 5.2% (p=0.54) reduction in mammography for female members; a 23.4% (p=0.03) and 10.8% (p=0.09) reduction in Pap smear screenings for female members; a 16.5% (p=0.08) and 12.1% (p=0.27) reduction in colorectal cancer registrations and an 18.2% (p=0.08) and 8.9% (p=0.07) decrease in all oncology diagnoses. Uptake of telehealth services throughout the healthcare delivery system increased by 5 708% in 2020 compared with 2019, and 36.1% for 2021 compared with 2020. CONCLUSION: A significant reduction in emergency room visits, hospital admissions and utilisation of primary care services was observed since the start of the pandemic. Further research is required to understand if there are long-term consequences of delayed care. An increase in the use of digital consultations was observed. Research on their acceptability and effectiveness may open new modalities of care, which may have cost- and time-saving benefits.

Burden of disease and barriers to comprehensive care for rheumatic heart disease in South Africa: an updated systematic review protocol.

INTRODUCTION: Rheumatic heart disease (RHD) is responsible for a significant burden of cardiovascular morbidity and mortality, and remains the most common cause of acquired heart disease among children and young adults in low-income and middle-income countries. Additionally, the global COVID-19 pandemic has forced the emergency restructuring of many health systems, which has had a broad impact on health in general, including cardiovascular disease. Despite significant cost to the health system and estimates from 2015 indicating both high incidence and prevalence of RHD in South Africa, no cohesive national strategy exists. An updated review of national burden of disease estimates, as well as literature on barriers to care for patients with RHD, will provide crucial information to assist in the development of a national RHD programme. METHODS AND ANALYSIS: Using predefined search terms that capture relevant disease processes from Group A Streptococcal (GAS) infection through to the sequelae of RHD, a search of PubMed, Scopus, ISI Web of Science, Sabinet African Journals, SA Heart and Current and Completed Research databases will be performed. All eligible studies on RHD, acute rheumatic fever and GAS infection published from April 2014 to December 2022 will be included. Vital registration data for the same period from Statistics South Africa will also be collected. A standardised data extraction form will be used to capture results for both quantitative and qualitative analyses. All studies included in burden of disease estimates will undergo quality assessment using standardised tools. Updated estimates on mortality and morbidity as well as a synthesis of work on primary, secondary and tertiary prevention of RHD will be reported. ETHICS AND DISSEMINATION: No ethics clearance is required for this study. Findings will be disseminated in a peer-reviewed journal and submitted to national stakeholders in RHD. PROSPERO REGISTRATION NUMBER: CRD42023392782.

Factors associated with COVID-19 inpatient mortality cases within 24-hours South Africa.

BACKGROUND: African countries with limited healthcare capacity are particularly vulnerable to the novel coronavirus. The pandemic has left health systems short on resources to safely manage patients and protect health care workers. South Africa is still battling the epidemic of HIV/AIDS and tuberculosis which have had their programme/services interrupted due to the effects of the pandemic. Lessons learned from the HIV/AIDS and TB programme have shown that South Africans delay seeking health services when a new disease presents itself. OBJECTIVE: The study sought to investigate the risk factors for COVID-19 inpatients' mortality within 24-hours of hospital admission in Public health facilities in Limpopo Province, South Africa. METHODS: The study used retrospective secondary data obtained from the 1 067 clinical records of patients admitted between March 2020 and June 2021 by the Limpopo Department of Health (LDoH). A multivariable logistic regression model, both adjusted and unadjusted, was used to assess the risk factors associated with COVID-19 mortality within 24 hours of admission. RESULTS: This study, which was conducted in Limpopo public hospitals, discovered that 411 (40%) of COVID-19 patients died within 24-hours of admission. The majority of the patients were 60 years or older, mostly of female gender and had co-morbidities. In terms of vital signs, most had body temperatures less than 38°C. Our study findings revealed that COVID-19 patients who present with fever and shortness of breath are 1.8 and 2.5 times more likely to die within 24-hours of admission to the hospital, than patients without fever and normal respiratory rate . Hypertension was independently associated with mortality in COVID-19 patients within 24-hours of admission, with a high odds ratio for hypertensive patients (OR = 1.451; 95% CI = 1.013; 2.078) compared to non-hypertensive patients. CONCLUSION: Assessing demographic and clinical risk factors for COVID-19 mortality within 24-hours of admission aids in understanding and prioritising patients with severe COVID-19 and hypertension. Finally, this will provide guidelines for planning and optimising the use of LDoH healthcare resources and also aid in public awareness endeavours.

Investigating blood alcohol concentrations in injury-related deaths before and during the COVID-19 National lockdown in Western Cape, South Africa: A cross-sectional retrospective review.

BACKGROUND: Alcohol is a significant contributor to injury-related morbidity and mortality in South Africa (SA).  During the COVID-19 global pandemic, restrictions to movement and to the legal access of alcohol* were introduced in SA.  This study aimed to investigate the effect of alcohol bans during the COVID-19 lockdown periods on injury-related mortality and the blood alcohol concentrations (BAC) in these deaths. METHODS: A retrospective, cross-sectional analysis of injury-related deaths in Western Cape (WC) province, SA, between 1 January 2019 to 31 December 2020 was conducted. Cases where BAC testing was performed were further examined according to the periods of lockdown (AL5-1) and alcohol restrictions. RESULTS: A total of 16,027 injury-related cases were admitted to Forensic Pathology Service mortuaries in the WC over the two-year period.  An average decrease of 15.7% injury-related deaths in 2020 compared to 2019 was noted, as well as a 47.7% decrease in injury-related deaths during hard lockdown (April -May 2020) compared to the same period in 2019. In the injury-related deaths, 12,077 (75.4%) had blood specimens collected for BAC testing. In 5,078 (42.0%) of submitted cases, a positive BAC (≥0.01g/100 mL) was reported. No significant difference was observed in the mean positive BAC between 2019 and 2020, however in April and May 2020, the mean BACs observed (0.13 g/100 mL) was less than that in 2019 (0.18 g/100 mL). A high number of positive BACs in the 12-17-year age group (±23.4%) was observed. CONCLUSION: There was a clear decrease in injury-related deaths in the WC during the COVID-19-related lockdown periods that coincided with the alcohol ban and restriction of movement and an increase following relaxation of restrictions on alcohol sales and movement. The data illustrated that mean BACs were similar between all periods of alcohol restriction compared to 2019, apart from hard lockdown in April-May, 2020.  This coincided with a smaller mortuary intake during the level 5 and 4 lockdown periods.   Keywords: Alcohol; blood alcohol concentration; COVID-19; injury; lockdown; South Africa; violent death; Western Cape   * Alcohol refers to ethanol.

Intervention effects and long-term changes in physical activity and cardiometabolic outcomes among children at risk of noncommunicable diseases in South Africa: a cluster-randomized controlled trial and follow-up analysis.

Introduction: Risk factors for noncommunicable diseases such as insufficient physical activity (PA), overweight or hypertension are becoming increasingly predominant among children globally. While school-based interventions are promising preventive strategies, evidence of their long-term effectiveness, especially among vulnerable populations, is scarce. We aim to assess the short-term effects of the physical and health KaziKidz intervention on cardiometabolic risk factors and the long-term, pre-and post-COVID-19 pandemic changes thereof in high-risk children from marginalized communities. Methods: The intervention was tested in a cluster-randomized controlled trial between January and October 2019 in eight primary schools near Gqeberha, South Africa. Children with overweight, elevated blood pressure, pre-diabetes, and/or borderline dyslipidemia were identified and re-assessed 2 years post-intervention. Study outcomes included accelerometry-measured PA (MVPA), body mass index (BMI), mean arterial pressure (MAP), glucose (HbA1c), and lipid levels (TC to HDL ratio). We conducted mixed regression analyses to assess intervention effects by cardiometabolic risk profile, and Wilcoxon signed-rank tests to evaluate longitudinal changes in the high-risk subpopulation. Results: We found a significant intervention effect on MVPA during school hours for physically inactive children, and among active as well as inactive girls. In contrast, the intervention lowered HbA1c and TC to HDL ratio only in children with glucose or lipid values within the norm, respectively. At follow-up, the intervention effects were not maintained in at-risk children, who showed a decline in MVPA, and an increase in BMI-for-age, MAP, HbA1c and TC to HDL ratio. Conclusion: We conclude that schools are key settings in which to promote PA and improve health; however, structural changes are necessary to ensure that effective interventions reach marginalized school populations and achieve sustainable impact.

The impact of COVID-19 on a South African pediatric cardiac service: implications and insights into service capacity.

Background and Objectives: The Western Cape public pediatric cardiac service is under-resourced. COVID-19 regulations are likely to have long-term effects on patient care but may provide insight into service capacity requirements. As such, we aimed to quantify the impact of COVID-19 regulations on this service. Methods: An uncontrolled retrospective pre-post study of all presenting patients over two, one-year periods; the pre-COVID-19 period (01/03/2019-29/02/2020) and the peri-COVID-19 period (01/03/2020-28/02/2021). Results: Admissions decreased by 39% (624 to 378) and cardiac surgeries decreased by 29% (293 to 208) in the peri-COVID-19 period, with an increase in urgent cases (PR:5.99, 95%CI:3.58-10.02, p < 0.001). Age at surgery was lower in the peri-COVID-19 period, 7.2 (2.4-20.4) vs. 10.8 (4.8-49.2) months (p < 0.05), likewise, age at surgery for transposition of the great arteries (TGA) was lower peri-COVID-19, 15 (IQR:11.2-25.5) vs. 46 (IQR:11-62.5) days (p < 0.05). Length of stay 6 (IQR:2-14) vs. 3 days (IQR:1-9) (p < 0.001), complications (PR:1.21, 95%CI:1.01-1.43, p < 0.05), and age-adjusted delayed-sternal-closure rates (PR:3.20, 95%CI:1.09-9.33, p < 0.05) increased peri-COVID-19. Conclusion: Cardiac procedures were significantly reduced in the peri-COVID-19 period which will have implications on an overburdened service and ultimately, patient outcomes. COVID-19 restrictions on elective procedures freed capacity for urgent cases, demonstrated by the absolute increase in urgent cases and significant decrease in age at TGA-surgery. This facilitated intervention at the point of physiological need, albeit at the expense of elective procedures, and also revealed insights into capacity requirements of the Western Cape. These data emphasize the need for an informed strategy to increase capacity and reduce backlog whilst ensuring minimal morbidity and mortality.Graphical Abstract.

Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).

BACKGROUND: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. METHODS AND FINDINGS: Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. CONCLUSIONS: Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. TRIAL REGISTRATION: South African National Clinical Trials Registry DOH-27-092021-4901.

Quality of routine health data at the onset of the COVID-19 pandemic in Ethiopia, Haiti, Laos, Nepal, and South Africa.

BACKGROUND: During the COVID-19 pandemic, governments and researchers have used routine health data to estimate potential declines in the delivery and uptake of essential health services. This research relies on the data being high quality and, crucially, on the data quality not changing because of the pandemic. In this paper, we investigated those assumptions and assessed data quality before and during COVID-19. METHODS: We obtained routine health data from the DHIS2 platforms in Ethiopia, Haiti, Lao People's Democratic Republic, Nepal, and South Africa (KwaZulu-Natal province) for a range of 40 indicators on essential health services and institutional deaths. We extracted data over 24 months (January 2019-December 2020) including pre-pandemic data and the first 9 months of the pandemic. We assessed four dimensions of data quality: reporting completeness, presence of outliers, internal consistency, and external consistency. RESULTS: We found high reporting completeness across countries and services and few declines in reporting at the onset of the pandemic. Positive outliers represented fewer than 1% of facility-month observations across services. Assessment of internal consistency across vaccine indicators found similar reporting of vaccines in all countries. Comparing cesarean section rates in the HMIS to those from population-representative surveys, we found high external consistency in all countries analyzed. CONCLUSIONS: While efforts remain to improve the quality of these data, our results show that several indicators in the HMIS can be reliably used to monitor service provision over time in these five countries.

HIV and AIDS prevention: knowledge, attitudes, practices and health literacy of older persons in the Western Cape and KwaZulu-Natal Provinces, South Africa and in Lesotho.

BACKGROUND: Population ageing and access to anti-retroviral therapies in South Africa have resulted in ageing of the HIV/AIDS epidemic, which has implications for policy, planning and practice. Impactful interventions on HIV/AIDS for older persons require knowledge on effects of the pandemic on this population. A study was undertaken to assess knowledge, attitudes, and practices (KAP) of HIV/AIDS, as well as health literacy (HL) level of a population aged ≥ 50 years. METHODS: A cross-sectional survey was conducted at three sites in South Africa and two sites in Lesotho with an educational intervention at the South African sites. At baseline, data were collected for assessment of KAP of HIV/AIDS and HL levels. The pre- and post-intervention comprised participants at South African sites being familiarised with the contents of a specially constructed HIV/AIDS educational booklet. Participants' KAP was reassessed six weeks later. A composite score of ≥ 75% was considered adequate KAP and an adequate HL level. RESULTS: The baseline survey comprised 1163 participants. The median age was 63 years (range 50-98 years); 70% were female, and 69% had ≤ 8 years' education. HL was inadequate in 56% and the KAP score was inadequate in 64%. A high KAP score was associated with female gender (AOR = 1.6, 95% CI = 1.2-2.1), age < 65 years (AOR = 1.9, 95% CI = 1.5-2.5) and education level (Primary school: AOR = 2.2; 95% CI = 1.4-3.4); (High school: AOR = 4.4; 95% CI = 2.7-7.0); (University/college: AOR = 9.6; 95% CI = 4.7-19.7). HL was positively associated with education but no association with age or gender. The educational intervention comprised 614 (69%) participants. KAP scores increased post intervention: 65.2% of participants had adequate knowledge, versus 36% pre-intervention. Overall, younger age, being female and higher education level were associated with having adequate knowledge about HIV/AIDS, both pre- and post-intervention. CONCLUSIONS: The study population had low HL, and KAP scores regarding HIV/AIDS were poor but improved following an educational intervention. A tailored educational programme can place older people centrally in the fight against the epidemic, even in the presence of low HL. Policy and educational programmes are indicated to meet the information needs of older persons, which are commensurate with the low HL level of a large section of that population.

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa.

We conducted a mixed-methods study to understand current drug use practices and access to healthcare services for people who use injection drugs in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who used injection drugs within the past 6 months from KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP. None of the participants ever tested for Hepatitis C.

Companion restrictions in the emergency department during COVID-19: physician perceptions from the Western Cape, South Africa.

OBJECTIVES: To determine emergency department (ED) physicians' perceptions regarding hospital companions being prohibited from accompanying the patient during COVID-19. DESIGN: Two qualitative datasets were combined. Data collected included voice recordings, narrative interviewing and semistructured interviews. A reflexive thematic analysis was conducted and guided by the Normalisation Process Theory. SETTING: Six hospital EDs in the Western Cape, South Africa. PARTICIPANTS: Convenience sampling was used to recruit a total of eight physicians working full time in the ED during COVID-19. RESULTS: The lack of physical companions provided an opportunity for physicians to assess and reflect on a companion's role in efficient patient care. Physicians perceived that the COVID-19 restrictions illuminated that patient companions engaged in the ED as providers contributing to patient care by providing collateral information and patient support, while simultaneously engaging as consumers detracting physicians from their priorities and patient care. These restrictions prompted the physicians to consider how they understand their patients largely through the companions. When companions became virtual, the physicians were forced to shift how they perceive their patient, which included increased empathy. CONCLUSION: The reflections of providers can feed into discussions about values within the healthcare system and can help explore the balance between medical and social safety, especially with companion restrictions still being practised in some hospitals. These perceptions illuminate various tradeoffs physicians had to consider throughout the pandemic and may be used to improve companion policies when planning for the continuation of the COVID-19 pandemic and future disease outbreaks.

Modelling the economic burden of SARS-CoV-2 infection in health care workers in four countries.

Health care workers (HCWs) experienced greater risk of SARS-CoV-2 infection during the COVID-19 pandemic. This study applies a cost-of-illness (COI) approach to model the economic burden associated with SARS-CoV-2 infections among HCWs in five low- and middle-income sites (Kenya, Eswatini, Colombia, KwaZulu-Natal province, and Western Cape province of South Africa) during the first year of the pandemic. We find that not only did HCWs have a higher incidence of COVID-19 than the general population, but in all sites except Colombia, viral transmission from infected HCWs to close contacts resulted in substantial secondary SARS-CoV-2 infection and death. Disruption in health services as a result of HCW illness affected maternal and child deaths dramatically. Total economic losses attributable to SARS-CoV-2 infection among HCWs as a share of total health expenditure ranged from 1.51% in Colombia to 8.38% in Western Cape province, South Africa. This economic burden to society highlights the importance of adequate infection prevention and control measures to minimize the risk of SARS-CoV-2 infection in HCWs.

SARS-CoV-2 Transmission Risk in the School Environment: a pilot case-ascertained prospective study to inform future school-based surveillance.

BACKGROUND: There is no current active or passive disease surveillance programme focused on schools in South Africa. As such the country is missing an opportunity to rapidly and effectively flag and address pathogen outbreaks, for example SARS-CoV-2, in a key closed setting. Furthermore, the role of school transmission in the spread of the SARS-CoV-2 virus within communities is uncertain.  Objective. This pilot study, conducted during March 2022 in Cape Town, aimed to indicate the feasibility of conducting intense active contact-tracing in a school environment prior to a large national study to compare school versus community SARS-CoV-2 transmission risk.  Methods. We conducted a pilot school-level case-ascertained prospective study with a component of enhanced surveillance. Following study initiation, the first learner at a participating school who tested SARS-CoV-2 positive (via Polymerase Chain Reaction (PCR) or a Rapid Antigen Test (RAT)) was invited to join the study as the index case and all their school-based close contacts were followed up telephonically, monitored for symptoms for 14 days, and tested using a PCR if any symptoms were reported.  Results. On 8th March 2022, a student with RAT laboratory-confirmed COVID-19 was identified and they and their guardian consented to participate as the index case. Of the 11 eligible close contacts, six provided consent/assent and completed symptom monitoring calls until the end of the 14-day study period. The Secondary Attack Rate (SAR) was 2/11 (18.18%) of all close contacts who were at risk of infection, 2/4 (50.0%) of all those close contacts who developed symptoms, and 2/4 (50.0%) of all those close contacts who developed symptoms and were tested for SARS-CoV-2. During the same period, the school reported that nine of the 926 learner body tested COVID-19 positive (0.97%). Total hours spent conducting monitoring for 6 learners was 27 hours, with each learner requiring approximately 4.5 hours of contact time during the study period.  Conclusion. This is the first South African school-based COVID-19 transmission study, the results of which can inform national discussions regarding the role of schools and school-based active and passive surveillance in pathogen prevention and control.

Using generalized structured additive regression models to determine factors associated with and clusters for COVID-19 hospital deaths in South Africa.

BACKGROUND: The first case of COVID-19 in South Africa was reported in March 2020 and the country has since recorded over 3.6 million laboratory-confirmed cases and 100 000 deaths as of March 2022. Transmission and infection of SARS-CoV-2 virus and deaths in general due to COVID-19 have been shown to be spatially associated but spatial patterns in in-hospital deaths have not fully been investigated in South Africa. This study uses national COVID-19 hospitalization data to investigate the spatial effects on hospital deaths after adjusting for known mortality risk factors. METHODS: COVID-19 hospitalization data and deaths were obtained from the National Institute for Communicable Diseases (NICD). Generalized structured additive logistic regression model was used to assess spatial effects on COVID-19 in-hospital deaths adjusting for demographic and clinical covariates. Continuous covariates were modelled by assuming second-order random walk priors, while spatial autocorrelation was specified with Markov random field prior and fixed effects with vague priors respectively. The inference was fully Bayesian. RESULTS: The risk of COVID-19 in-hospital mortality increased with patient age, with admission to intensive care unit (ICU) (aOR = 4.16; 95% Credible Interval: 4.05-4.27), being on oxygen (aOR = 1.49; 95% Credible Interval: 1.46-1.51) and on invasive mechanical ventilation (aOR = 3.74; 95% Credible Interval: 3.61-3.87). Being admitted in a public hospital (aOR = 3.16; 95% Credible Interval: 3.10-3.21) was also significantly associated with mortality. Risk of in-hospital deaths increased in months following a surge in infections and dropped after months of successive low infections highlighting crest and troughs lagging the epidemic curve. After controlling for these factors, districts such as Vhembe, Capricorn and Mopani in Limpopo province, and Buffalo City, O.R. Tambo, Joe Gqabi and Chris Hani in Eastern Cape province remained with significantly higher odds of COVID-19 hospital deaths suggesting possible health systems challenges in those districts. CONCLUSION: The results show substantial COVID-19 in-hospital mortality variation across the 52 districts. Our analysis provides information that can be important for strengthening health policies and the public health system for the benefit of the whole South African population. Understanding differences in in-hospital COVID-19 mortality across space could guide interventions to achieve better health outcomes in affected districts.

Tracking the Trauma Epidemic in KwaZulu-Natal, South Africa.

BACKGROUND: Trauma remains an important cause of morbidity and mortality in South Africa, but attempts to track the epidemic are often based on mortality data, or derived from individual health facilities. This project is based on the routine collection of trauma data from all public health facilities in the province of KwaZulu-Natal (KZN), between 2012 and 2022. METHODS: Hospital level data on trauma over the past ten years was drawn from the district health information system (DHIS). Data relating to assaults, gunshots and motor vehicle collisions (MVCs) were recorded in the emergency rooms, whilst data on admissions are recorded in the wards and intensive care units. RESULTS: There were 1,263,847 emergency room visits for assaults, gunshots and MVCs over the ten-year period and trauma admissions ranged between four and five percent of the total number of hospital admissions annually. There was a dramatic decrease in trauma presentations and admissions over 2020/2021 as a result of the COVID lockdowns. Over the entire period, intentional injury was roughly twice as frequent as non-intentional injury. Intentional trauma had an almost equal ratio of blunt assault to penetrating assault. Gunshot-related assault increased dramatically over the 2021/2022 collecting period. CONCLUSIONS: The burden of trauma in KZN remains high. The unique feature of this burden is the excessively high rate of intentional trauma in the form of both blunt and penetrating mechanisms. Developing injury-prevention strategies to reduce the burden of interpersonal violence is more difficult than for unintentional trauma.

Comparison of two diagnostic intervention packages for community-based active case finding for tuberculosis: an open-label randomized controlled trial.

Two in every five patients with active tuberculosis (TB) remain undiagnosed or unreported. Therefore community-based, active case-finding strategies require urgent implementation. However, whether point-of-care (POC), portable battery-operated, molecular diagnostic tools deployed at a community level, compared with conventionally used POC smear microscopy, can shorten time-to-treatment initiation, thus potentially curtailing transmission, remains unclear. To clarify this issue, we performed an open-label, randomized controlled trial in periurban informal settlements of Cape Town, South Africa, where we TB symptom screened 5,274 individuals using a community-based scalable mobile clinic. Some 584 individuals with HIV infection or symptoms of TB underwent targeted diagnostic screening and were randomized (1:1) to same-day smear microscopy (n = 296) or on-site DNA-based molecular diagnosis (n = 288; GeneXpert). The primary aim was to compare time to TB treatment initiation between the arms. Secondary aims included feasibility and detection of probably infectious people. Of participants who underwent targeted screening, 9.9% (58 of 584) had culture-confirmed TB. Time-to-treatment initiation occurred significantly earlier in the Xpert versus the smear-microscopy arm (8 versus 41 d, P = 0.002). However, overall, Xpert detected only 52% of individuals with culture-positive TB. Notably, Xpert detected almost all of the probably infectious patients compared with smear microscopy (94.1% versus 23.5%, P = <0.001). Xpert was associated with a shorter median time to treatment of probably infectious patients (7 versus 24 d, P = 0.02) and a greater proportion of infectious patients were on treatment at 60 d compared with the probably noninfectious patients (76.5% versus 38.2%, P < 0.01). Overall, a greater proportion of POC Xpert-positive participants were on treatment at 60 d compared with all culture-positive participants (100% versus 46.5%, P < 0.01). These findings challenge the traditional paradigm of a passive case-finding, public health strategy and argues for the implementation of portable DNA-based diagnosis with linkage to care as a community-oriented, transmission-interruption strategy. The study was registered with the South African National Clinical Trials Registry (application ID 4367; DOH-27-0317-5367) and ClinicalTrials.gov (NCT03168945).

COVID­19 in pregnant women in South Africa: A retrospective review.

BACKGROUND: The majority of maternal deaths in South Africa (SA) occur as a result of non-pregnancy-related infections (NPRI). Pregnancy is a known risk factor in severe COVID­19, increasing the burden of NPRI in SA. In this study, we describe the prevalence, profile and clinical outcomes of pregnant women with COVID­19 admitted to a tertiary facility. OBJECTIVES: To describe the prevalence, profile and clinical outcomes of pregnant women with COVID­19 admitted to a tertiary facility in Gauteng, SA. METHODS: We performed a retrospective review of all pregnant women with COVID­19 admitted to Charlotte Maxeke Johannesburg Academic Hospital between 6 March and 30 August 2020. Data collected included demographics, medical history, obstetric history, clinical findings and laboratory variables. Outcomes assessed were mortality, admission to intensive care unit (ICU), symptomatic v. asymptomatic disease, maternal and fetal outcome and mode of delivery. RESULTS: A total of 204 pregnant women were included in the study. Of these, 33 (16.2%) women were critically ill, with 21 (10.3%) admitted to the ICU and 3 (1.5%) deaths related to COVID­19. The median gestational age was 37 weeks and median birthweight 2 940 g. Sixty-seven women (33%) were HIV-positive, in keeping with national statistics regarding HIV in pregnancy. Caesarean section was the most common mode of delivery (n=105, 60%). However, no women underwent caesarean section for indications related to COVID­19. CONCLUSION: COVID­19-related mortality in our cohort was higher than that seen internationally, likely due to differences in background maternal mortality rates and difficulty in accessing care.