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BackgroundSince there are currently no specific SARS-CoV-2 prognostic viral biomarkers for predicting disease severity, there has been interest in using SARS-CoV-2 polymerase chain reaction (PCR) cycle-threshold (Ct) values to predict disease progression.ObjectiveThis study assessed the association between in-hospital mortality of hospitalized COVID-19 cases and Ct-values of gene targets specific to SARS-CoV-2.MethodsClinical data of hospitalized COVID-19 cases from Gauteng Province from April 2020-July 2022 were obtained from a national surveillance system and linked to laboratory data. The study period was divided into pandemic waves: Asp614Gly/wave1 (7 June–22 Aug 2020); beta/wave2 (15 Nov 2020–6 Feb 2021); delta/wave3 (9 May–18 Sept 2021) and omicron/wave4 (21 Nov 2021–22 Jan 2022). Ct-value data of genes specific to SARS-CoV-2 according to testing platforms (Roche-ORF gene; GeneXpert-N2 gene; Abbott-RdRp gene) were categorized as low (Ct 30).ResultsThere were 1205 recorded cases: 836(69.4%; wave1), 122(10.1%;wave2) 21(1.7%; wave3) and 11(0.9%;in wave4). The cases' mean age(±SD) was 49 years(±18), and 662(54.9%) were female. There were 296(24.6%) deaths recorded: 241(81.4%;wave1), 27 (9.1%;wave2), 6 (2%;wave3), and 2 (0.7%;wave4) (p 30.ConclusionAlthough odds of COVID19-related death were high amongst cases with Ct-values

Original article: https://doi.org/10.17159/sajs.2022/13323 The following terminology was erroneously reported: “non-white race” should be “people of colour”, or “black African, coloured and people of Indian descent”. The error appears in the following instances: Page 1, abstract, line 1 and 14 Page 1, under Introduction, paragraph 2, line 6 Page 11, under ‘Higher risk of mortality among non-white patients’, column 1, sub-heading Page 11, under ‘Higher risk of mortality among non-white patients’, column 1, paragraph 1, lines 2, 5 and 9 Page 11, under ‘Higher risk of mortality among non-white patients’, column 2, paragraph 1, line 2 Page 12, under ‘Higher risk of mortality among non-white patients’, column 1, paragraph 3, line 10 Page 12, under ‘Socio-economic status’, column 1, paragraph 1, lines 1, 3, 6, 16 and 21 Page 12, under ‘Healthcare access’, column 2, paragraph 4, lines 3 and 13

Older age, male sex, and non-white race have been reported to be risk factors for COVID-19 mortality. Few studies have explored how these intersecting factors contribute to COVID-19 outcomes. This study aimed to compare demographic characteristics and trends in SARS-CoV-2 admissions and the health care they received. Hospital admission data were collected through DATCOV, an active national COVID-19 surveillance programme. Descriptive analysis was used to compare admissions and deaths by age, sex, race, and health sector as a proxy for socio-economic status. COVID-19 mortality and healthcare utilisation were compared by race using random effect multivariable logistic regression models. On multivariable analysis, black African patients (adjusted OR [aOR] 1.3, 95% confidence interval [CI] 1.2, 1.3), coloured patients (aOR 1.2, 95% CI 1.1, 1.3), and patients of Indian descent (aOR 1.2, 95% CI 1.2, 1.3) had increased risk of in-hospital COVID-19 mortality compared to white patients; and admission in the public health sector (aOR 1.5, 95% CI 1.5, 1.6) was associated with increased risk of mortality compared to those in the private sector. There were higher percentages of COVID-19 hospitalised individuals treated in ICU, ventilated, and treated with supplemental oxygen in the private compared to the public sector. There were increased odds of non-white patients being treated in ICU or ventilated in the private sector, but decreased odds of black African patients being treated in ICU (aOR 0.5; 95% CI 0.4, 0.5) or ventilated (aOR 0.5; 95% CI 0.4, 0.6) compared to white patients in the public sector. These findings demonstrate the importance of collecting and analysing data on race and socio-economic status to ensure that disease control measures address the most vulnerable populations affected by COVID-19. Significance: • These findings demonstrate the importance of collecting data on socio-economic status and race alongside age and sex, to identify the populations most vulnerable to COVID-19. • This study allows a better understanding of the pre-existing inequalities that predispose some groups to poor disease outcomes and yet more limited access to health interventions. • Interventions adapted for the most vulnerable populations are likely to be more effective. • The national government must provide efficient and inclusive non-discriminatory health services, and urgently improve access to ICU, ventilation and oxygen in the public sector. • Transformation of the healthcare system is long overdue, including narrowing the gap in resources between the private and public sectors.

BackgroundSome mother-to-child transmission (MTCT) studies suggest that allelic variations of Fc gamma receptors (FcγR) play a role in infant HIV-1 acquisition, but findings are inconsistent. To address the limitations of previous studies, the present study investigates the association between perinatal HIV-1 transmission and FcγR variability in three cohorts of South African infants born to women living with HIV-1.MethodsThis nested case-control study combines FCGR genotypic data from three perinatal cohorts at two hospitals in Johannesburg, South Africa. Children with perinatally-acquired HIV-1 (cases, n = 395) were compared to HIV-1-exposed uninfected children (controls, n = 312). All study participants were black South Africans and received nevirapine for prevention of MTCT. Functional variants were genotyped using a multiplex ligation-dependent probe amplification assay, and their representation compared between groups using logistic regression analyses.ResultsFCGR3A gene duplication associated with HIV-1 acquisition (OR = 10.27; 95% CI 2.00-52.65; P = 0.005) as did the FcγRIIb-232TT genotype even after adjusting for FCGR3A copy number and FCGR3B genotype (AOR = 1.72; 95%CI 1.07-2.76; P = 0.024). The association between FcγRIIb-232TT genotype and HIV-1 acquisition was further strengthened (AOR = 2.28; 95%CI 1.11-4.69; P = 0.024) if adjusted separately for FCGR2C c.134-96C>T. Homozygous FcγRIIIb-HNA1a did not significantly associate with HIV-1 acquisition in a univariate model (OR = 1.42; 95%CI 0.94-2.16; P = 0.098) but attained significance after adjustment for FCGR3A copy number and FCGR2B genotype (AOR = 1.55; 95%CI 1.01-2.38; P = 0.044). Both FcγRIIb-232TT (AOR = 1.83; 95%CI 1.13-2.97; P = 0.014) and homozygous FcγRIIIb-HNA1a (AOR = 1.66; 95%CI 1.07-2.57; P = 0.025) retained significance when birthweight and breastfeeding were added to the model. The common FCGR2A and FCGR3A polymorphisms did not associate with HIV-1 acquisition.ConclusionsCollectively, our findings suggest that the FcγRIIb-232TT genotype exerts a controlling influence on infant susceptibility to HIV-1 infection. We also show a role for less studied variants-FCGR3A duplication and homozygous HNA1a. These findings provide additional insight into a role for FcγRs in HIV-1 infection in children.

Background Some mother-to-child transmission (MTCT) studies suggest that allelic variations of Fc gamma receptors (FcγR) play a role in infant HIV-1 acquisition, but findings are inconsistent. To address the limitations of previous studies, the present study investigates the association between perinatal HIV-1 transmission and FcγR variability in three cohorts of South African infants born to women living with HIV-1. Methods This nested case-control study combines FCGR genotypic data from three perinatal cohorts at two hospitals in Johannesburg, South Africa. Children with perinatally-acquired HIV-1 (cases, n = 395) were compared to HIV-1-exposed uninfected children (controls, n = 312). All study participants were black South Africans and received nevirapine for prevention of MTCT. Functional variants were genotyped using a multiplex ligation-dependent probe amplification assay, and their representation compared between groups using logistic regression analyses. Results FCGR3A gene duplication associated with HIV-1 acquisition (OR = 10.27; 95% CI 2.00–52.65; P = 0.005) as did the FcγRIIb-232TT genotype even after adjusting for FCGR3A copy number and FCGR3B genotype (AOR = 1.72; 95%CI 1.07–2.76; P = 0.024). The association between FcγRIIb-232TT genotype and HIV-1 acquisition was further strengthened (AOR = 2.28; 95%CI 1.11–4.69; P = 0.024) if adjusted separately for FCGR2C c.134-96C>T. Homozygous FcγRIIIb-HNA1a did not significantly associate with HIV-1 acquisition in a univariate model (OR = 1.42; 95%CI 0.94–2.16; P = 0.098) but attained significance after adjustment for FCGR3A copy number and FCGR2B genotype (AOR = 1.55; 95%CI 1.01–2.38; P = 0.044). Both FcγRIIb-232TT (AOR = 1.83; 95%CI 1.13–2.97; P = 0.014) and homozygous FcγRIIIb-HNA1a (AOR = 1.66; 95%CI 1.07–2.57; P = 0.025) retained significance when birthweight and breastfeeding were added to the model. The common FCGR2A and FCGR3A polymorphisms did not associate with HIV-1 acquisition. Conclusions Collectively, our findings suggest that the FcγRIIb-232TT genotype exerts a controlling influence on infant susceptibility to HIV-1 infection. We also show a role for less studied variants–FCGR3A duplication and homozygous HNA1a. These findings provide additional insight into a role for FcγRs in HIV-1 infection in children.

In the Thai RV144 HIV-1 vaccine trial, a three-variant haplotype within the Fc gamma receptor 2C gene (FCGR2C) reduced the risk of HIV-1 acquisition. A follow-on trial, HVTN702, of a similar vaccine candidate found no efficacy in South Africa, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T (rs114945036). To investigate a role for this variant in HIV-1 acquisition in South Africans, we used the model of maternal-infant HIV-1 transmission. A nested case-control study was conducted of infants born to mothers living with HIV-1, comparing children with perinatally-acquired HIV-1 (cases, n = 176) to HIV-1-exposed uninfected children (controls, n = 349). All had received nevirapine for prevention of mother-to-child transmission. The FCGR2C copy number and expression variants (c.−386G>C, c.−120A>T c.169T>C, and c.798+1A>G) were determined using a multiplex ligation-dependent probe amplification assay and the c.134-96C>T genotype with Sanger sequencing. The copy number, genotype and allele carriage were compared between groups using univariate and multivariate logistic regression. The FCGR2C c.134-96C>T genotype distribution and copy number differed significantly between HIV-1 cases and exposed-uninfected controls (P = 0.002, PBonf = 0.032 and P = 0.010, PBonf = > 0.05, respectively). The FCGR2C c.134-96T allele was overrepresented in the cases compared to the controls (58% vs 42%; P = 0.001, PBonf = 0.016). Adjusting for birthweight and FCGR2C copy number, perinatal HIV-1 acquisition was associated with the c.134-96C>T (AOR = 1.89; 95% CI 1.25-2.87; P = 0.003, PBonf = 0.048) and c.169C>T (AOR = 2.39; 95% CI 1.45-3.95; P = 0.001, PBonf = 0.016) minor alleles but not the promoter variant at position c.−386G>C. The c.134-96C>T variant was in strong linkage disequilibrium with the c.169C>T variant, but remained significantly associated with perinatal acquisition when adjusted for c.169C>T in multivariate analysis. In contrast to the protective effect observed in the Thai RV144 trial, we found the FCGR2C variant c.134-96T-allele associated with increased odds of perinatal HIV-1 acquisition in South African children. These findings, taken together with a similar deleterious association found with HIV-1 disease progression in South African adults, highlight the importance of elucidating the functional relevance of this variant in different populations and vaccination/disease contexts.

Background: We describe the epidemiology of COVID-19 in South Africa following importation and during implementation of stringent lockdown measures. Methods: Using national surveillance data including demographics, laboratory test data, clinical presentation, risk exposures (travel history, contacts and occupation) and outcomes of persons undergoing COVID-19 testing or hospitalised with COVID-19 at sentinel surveillance sites, we generated and interpreted descriptive statistics, epidemic curves, and initial reproductive numbers (Rt). Findings: From 4 March to 30 April 2020, 271,670 SARS-CoV-2 PCR tests were performed (462 tests/100,000 persons). Of these, 7,892 (2.9%) persons tested positive (median age 37 years (interquartile range 28–49 years), 4,568 (58%) male, cumulative incidence of 13.4 cases/100,000 persons). Hospitalization records were found for 1,271 patients (692 females (54%)) of whom 186 (14.6%) died. Amongst 2,819 cases with data, 489/2819 (17.3%) travelled internationally within 14 days prior to diagnosis, mostly during March 2020 (466 (95%)). Cases diagnosed in April compared with March were younger (median age, 37 vs. 40 years), less likely female (38% vs. 53%) and resident in a more populous province (98% vs. 91%). The national initial Rt was 2.08 (95% confidence interval (CI): 1.71–2.51). Interpretation: The first eight weeks following COVID-19 importation were characterised by early predominance of imported cases and relatively low mortality and transmission rates. Despite stringent lockdown measures, the second month following importation was characterised by community transmission and increasing disease burden in more populous provinces. Funding: Surveillance for SARS-CoV-2 is conducted by the National Institute for Communicable Diseases, and South African national and provincial health departments with funding, resources and material provided by the South African government and other sources as detailed in declaration of interest.

Background: Typhoid fever remains a public health concern in South Africa, where the risk of transmission is high because of poor access to safe water and sanitation. This study describes the investigation of typhoid fever outbreak in Limpopo province. Methodology: Following notification of laboratory-confirmed cases, a descriptive study was conducted at Sekhukhune District, Limpopo province. A suspected case was defined as any person residing in Makhuduthamaga Municipality from November 2017 to January 2018, presenting with fever and gastrointestinal symptoms. Data were collected using case investigation forms. Whole-genome sequencing (WGS) was carried out on Salmonella Typhi isolates and polymerase chain reaction (PCR) test was done for Salmonella species from water samples. Location of cases and water sources were mapped using ArcGIS mapping tool. Results: Amongst 122 cases, 54% (n = 66) were female and 6% (n = 7) laboratory-confirmed. The median age of the cases was 11 years (range 2–83 years), with 79% (n = 102) being children under the age of 14 years. Salmonella species were detected in 37% (10/27) of water samples and geographic information system (GIS) mapping showed clustering of cases in Tswaing-Kgwaripe and Vlakplaas villages. Six isolates were available for WGS analysis, with resulting data showing that five of the six isolates were genetically related. Phylogenetic analysis showed that the five isolates clustered together were genetically related showing 22 single nucleotide polymorphisms when compared to each other. Conclusion: Molecular epidemiology of isolates suggests a common source outbreak, supported by the detection of Salmonella species from water sources. Consumption of water from contaminated open water sources, because of ongoing interruption of municipal water supply, was the likely cause of the outbreak. The investigation highlights the importance of consistent safe water supply and the ability of district surveillance systems to identify and contain outbreaks.

To investigate and compare determinates for delayed first presentation to antenatal care (ANC) services.A cross-sectional study was conducted amongst pregnant women attending their first ANC visit in rural Capricorn District and peri-urban Tlokwe sub-district communities in South Africa. Data collection included questionnaires and medical record abstraction. Bivariate and multivariate analyses assessed factors associated with late ANC presentation.We recruited 807 pregnant women. Of these, 51% of rural women and 28% of peri-urban women presented late for first ANC. Rural women were more likely to present late for first ANC (AOR = 2.65; 95% CI 1.98-3.55) and report barriers to accessing ANC services (P