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Background: Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data. Methods and findings: In this open-label phase 3b implementation study among all eligible HCWs in South Africa registered in the national Electronic Vaccination Data System (EVDS), we monitored adverse events (AEs) at vaccination sites through self-reporting triggered by text messages after vaccination, healthcare provider reports, and active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from the day of first vaccination (17 February 2021) until 28 days after the final vaccination in the study (15 June 2021). COVID-19 breakthrough infections, hospitalisations, and deaths were ascertained via linkage of the electronic vaccination register with existing national databases. Among 477,234 participants, 10,279 AEs were reported, of which 138 (1.3%) were serious AEs (SAEs) or AEs of special interest. Women reported more AEs than men (2.3% versus 1.6%). AE reports decreased with increasing age (3.2% for age 18–30 years, 2.1% for age 31–45 years, 1.8% for age 46–55 years, and 1.5% for age > 55 years). Participants with previous COVID-19 infection reported slightly more AEs (2.6% versus 2.1%). The most common reactogenicity events were headache (n = 4,923) and body aches (n = 4,483), followed by injection site pain (n = 2,767) and fever (n = 2,731), and most occurred within 48 hours of vaccination. Two cases of thrombosis with thrombocytopenia syndrome and 4 cases of Guillain-Barré Syndrome were reported post-vaccination. Most SAEs and AEs of special interest (n = 138) occurred at lower than the expected population rates. Vascular (n = 37; 39.1/100,000 person-years) and nervous system disorders (n = 31; 31.7/100,000 person-years), immune system disorders (n = 24; 24.3/100,000 person-years), and infections and infestations (n = 19; 20.1/100,000 person-years) were the most common reported SAE categories. A limitation of the study was the single-arm design, with limited routinely collected morbidity comparator data in the study setting. Conclusions: We observed similar patterns of AEs as in phase 3 trials. AEs were mostly expected reactogenicity signs and symptoms. Furthermore, most SAEs occurred below expected rates. The single-dose Ad26.COV2.S vaccine demonstrated an acceptable safety profile, supporting the continued use of this vaccine in this setting. Trial registration: ClinicalTrials.gov NCT04838795; Pan African Clinical Trials Registry PACTR202102855526180. Saimbarashe Takuva, Azwi Takalani, and colleagues investigate the frequency and incidence of adverse events reported after receipt of a single dose of the Ad26.COV2.S COVID-19 vaccine among health care workers in South Africa. Author summary: Why was this study done?: While the safety of the Ad26.COV2.S vaccine was established in phase 3 clinical trials, continuous evaluation of safety in expanded populations is crucial. The Sisonke phase 3b implementation study enrolled almost half a million healthcare workers, providing an opportunity to further evaluate the safety of the single-dose Ad26.COV2.S vaccine. What did the researchers do and find?: A total of 477,234 healthcare workers across all South African provinces received the Ad26.COV2.S vaccine between 17 February 2021 and 17 May 2021. Through self-reports and active case finding, adverse events, serious adverse events, and adverse events of special interest were identified. Overall occurrence of adverse events was low. The majority of adverse events reported were common reactogenicity signs and symptoms. Most serious adverse events and adverse events of special interest, including vascular events, immune system disorders, and deaths, occurred at lower than the expected population rates. What do these findings mean?: The single-dose Ad26.COV2.S vaccine had an acceptable safety profile. This supports continued use of this vaccine in large rollout programmes. [ABSTRACT FROM AUTHOR]

To assess i) whether there is an independent association between HIV-prevalence and settlement types (urban formal, urban informal, rural formal, rural informal), and, ii) whether this changes over time, in South Africa. We draw on four (2002; 2005; 2008; 2012) cross-sectional South African household surveys. Data is analysed by sex (male/female), and for women by age categories (15–49; and 15–24; 25–49) at all-time points, for men in 2012 data is analysed by age categories (15–24; 25–49). By settlement type and sex/age combinations, we descriptively assess the association between socio-demographic and HIV-risk factors; HIV-prevalence; and trends in HIV-prevalence by time. Relative risk ratios assess unadjusted and adjusted risk for HIV-prevalence by settlement type. All estimates are weighted, and account for survey design. In all survey years, and combinations of sex/age categorisations, HIV-prevalence is highest in urban informal settlements. For men (15–49) an increasing HIV-prevalence over time in rural informal settlements was seen (p = 0.001). For women (15–49) HIV-prevalence increases over time for urban informal, rural informal, rural formal, and women (15–24) decreases in urban formal and urban informal, and women (25–49) increases urban informal and rural informal settlements. In analyses adjusting for potential socio-demographic and risk factors, compared to urban formal settlements, urban informal settlements had consistently higher relative risk of HIV for women, in all age categorisations, for instance in 2012 this was RR1.89 (1.50, 2.40) for all women (15–49), for 15–24 (RR1.79, 1.17–2.73), and women 25–49 (RR1.91, 1.47–2.48). For men, in the overall age categorization, urban informal settlements had a higher relative risk for HIV in all years. In 2012, when this was disaggregated by age, for men 15–24 rural informal (IRR2.69, 1.28–5.67), and rural formal (RR3.59, 1.49–8.64), and for men 25–49 it was urban informal settlements with the highest (RR1.68, 1.11–2.54). In 2012, rural informal settlements also had higher adjusted relative risk for HIV-prevalence for men (15–49) and women (15–49; 15–24; 25–49). In South Africa, HIV-prevalence is patterned geographically, with urban informal settlements having a particularly high burden. Geographical targeting of responses is critical for the HIV-response. [ABSTRACT FROM AUTHOR]

Background: South Africa has a high burden of MDR-TB, and to provide accessible treatment the government has introduced different models of care. We report the most cost-effective model after comparing cost per patient successfully treated across 5 models of care: centralized hospital, district hospitals (2), and community-based care through clinics or mobile injection teams. Methods: In an observational study five cohorts were followed prospectively. The cost analysis adopted a provider perspective and economic cost per patient successfully treated was calculated based on country protocols and length of treatment per patient per model of care. Logistic regression was used to calculate propensity score weights, to compare pairs of treatment groups, whilst adjusting for baseline imbalances between groups. Propensity score weighted costs and treatment success rates were used in the ICER analysis. Sensitivity analysis focused on varying treatment success and length of hospitalization within each model. Results: In 1,038 MDR-TB patients 75% were HIV-infected and 56% were successfully treated. The cost per successfully treated patient was 3 to 4.5 times lower in the community-based models with no hospitalization. Overall, the Mobile model was the most cost-effective. Conclusion: Reducing the length of hospitalization and following community-based models of care improves the affordability of MDR-TB treatment without compromising its effectiveness. [ABSTRACT FROM AUTHOR]

Objective: Couples’ voluntary HIV counseling and testing (CVCT) significantly decreases HIV transmission within couples, the largest risk group in sub-Saharan Africa, but it is not currently offered in most HIV testing facilities. To roll out such an intervention, understanding locale-specific knowledge barriers is critical. In this study, we measured knowledge of HIV serodiscordance, transmission, and prevention before and after receipt of CVCT services in Durban. Design: Pre- and post-CVCT knowledge surveys were administered to a selection of individuals seeking CVCT services. Methods: Changes in knowledge scores were assessed with McNemar Chi-square tests for balanced data and generalized estimating equation methods for unbalanced data. Results: The survey included 317 heterosexual black couples (634 individuals) who were primarily Zulu (87%), unemployed (47%), and had at least a secondary level education (78%). 28% of couples proved to be discordant. Only 30% of individuals thought serodiscordance between couples was possible pre‐CVCT compared to 95% post-CVCT. One-third thought there was at least one benefit of CVCT pre‐CVCT, increasing to 96% post‐CVCT. Overall, there were positive changes in knowledge about HIV transmission and prevention. However, many respondents thought all HIV positive mothers give birth to babies with AIDS (64% pre-CVCT, 59% post-CVCT) and that male circumcision does not protect negative men against HIV (70% pre-CVCT, 67% post-CVCT). Conclusions: CVCT was well received and was followed by improvements in understanding of discordance, the benefits of joint testing, and HIV transmission. Country-level health messaging would benefit from targeting gaps in knowledge about serodiscordance, vertical transmission, and male circumcision. [ABSTRACT FROM AUTHOR]

In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses. [ABSTRACT FROM AUTHOR]

Background: Nosocomial transmission has been implicated as a key factor in the outbreak of extensively drug resistant (XDR) and multidrug-resistant (MDR-TB) tuberculosis at Church of Scotland Hospital (CoSH), in KwaZulu-Natal (KZN), South Africa. The aim of this study was to quantify the burden of potentially infectious tuberculosis and the proportion of drug resistance among hospital inpatients throughout the province of KZN. Methods: Inpatients with current cough, capable of producing sputum were selected from 19 public hospitals in KZN. After informed consent, demographic and clinical data, and sputum samples were collected. Samples were processed for fluorescent microscopy, liquid culture and first and second-line anti-tuberculosis drug susceptibility testing. Results: There were a total of 2,964 inpatients where sampling was done. About 1,585 inpatients (53%) had a current cough and sufficient microbiological and clinical data for inclusion. Mycobacterium tuberculosis was isolated from 543 inpatients (34% of those tested and 18% of all inpatients). Eighty-four (15%) inpatients with TB were found to be MDR-TB infected and 16 (3%) had XDR-TB. There was no association between the prevalence of MDR-TB and proximity to CoSH. Among patients with microbiologically confirmed TB, MDR/XDR-TB was associated with male sex, a longer length of stay between hospital admission and date of sample collection, and current or previous TB treatment. Conclusions: One in five inpatients had potentially infectious TB. This is an underestimate since patients without current cough were not tested. MDR-TB was frequently observed and was found in nearly one in six active TB inpatients. While present at lower levels than the original outbreak report at CoSH, XDR-TB was detected in hospitals throughout KZN. The high burden of potentially infectious TB and confirmed MDR-TB, much of it undiagnosed, indicates a serious risk for nosocomial transmission and the need for intensified infection control within the inpatient setting. [ABSTRACT FROM AUTHOR]

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests. All authors were Funded by the Solidarity Fund and the Human Sciences Research Council. The National Institute for Communicable Diseases, South Africa, funded testing with the Roche assay Sizulu Moyo, Leickness C.S. Simbayi, Khangelani Zuma, Nompumelelo Zungu, Edmore Marinda E, Sean Jooste, Whadi-ah Parker, Shandir Ramlagan, Inbarani Naidoo, Musawenkosi Mabaso designed and led the study and were and are still employed by the Human Sciences Research Council. Mirriam Fortuin Beverley Singh, Adrian Puren led and conducted the laboratory testing and were and are still employed by the National Institute for Communicable Diseases, South Africa., (Copyright: © 2023 Moyo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)