Setshaba Research Centre

Limited studies have been conducted on the safety and effectiveness of heterologous COVID-19 vaccine boosting in lower income settings, especially those with high-HIV prevalence., The Sisonke Heterologous mRNA-1273 boost after prime with Ad26.COV2.S (SHERPA) trial evaluated a mRNA-1273 boost after Ad26.COV2.S priming in South Africa. SHERPA was a single-arm, open-label, phase 3 study nested in the Sisonke implementation trial of 500000 healthcare workers (HCWs). Sisonke participants were offered mRNA-1273 boosters between May and November 2022, when Omicron sub-lineages were circulating. Adverse events (AE) were self-reported, and co-primary endpoints (SARS-CoV-2 infections and COVID-19 hospitalizations or deaths) were collected through national databases. We used Cox regression models with booster status as a time-varying covariate to determine the relative vaccine effectiveness (rVE) of the mRNA-1273 booster among SHERPA versus unboosted Sisonke participants. Of 11248 SHERPA participants in the rVE analysis cohort (79.3% female, median age 41), 45.4% had received one and 54.6% two Ad26.COV2.S doses. Self-reported comorbidities included HIV (18.7%), hypertension (12.9%) and diabetes (4.6%). In multivariable analysis including 413161 unboosted Sisonke participants, rVE of the booster was 59% (95%CI 29-76%) against SARS-CoV-2 infection: 77% (95%CI 9-94%) in the one-Ad26.COV2.S dose group and 52% (95%CI 13-73%) in the two-dose group. Severe COVID-19 was identified in 148 unboosted Sisonke participants, and only one SHERPA participant with severe HIV-related immunosuppression. Of 11798 participants in the safety analysis, 228 (1.9%) participants reported 575 reactogenicity events within 7 days of the booster (most commonly injection site pain, malaise, myalgia, swelling, induration and fever). More reactogenicity events were reported among those with prior SARS-CoV-2 infections (adjusted odds ratio [aOR] 2.03, 95%CI 1.59-2.59) and less among people living with HIV (PLWH) (aOR 0.49, 95%CI 0.34-0.69). There were 115 unsolicited adverse events (AEs) within 28 days of vaccination. No related serious AEs were reported. In an immunogenicity sub-study, mRNA-1273 increased binding and neutralizing antibody titres and spike-specific T-cell responses 4 weeks after boosting regardless of the number of prior Ad26.COV2.S doses, or HIV status, and generated Omicron spike-specific cross-reactive responses. mRNA-1273 boosters after one or two Ad26.COV2.S doses were well-tolerated, safe and effective against Omicron SARS-CoV-2 infections among HCWs and PLWH. Trial registration: The SHERPA study is registered in the Pan African Clinical Trials Registry (PACTR): PACTR202310615330649 and the South African National Clinical Trial Registry (SANCTR): DOH-27-052022-5778.

Background:Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, although false (both negative and positive) results are expected to occur.Setting:We assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using 3 contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia.Methods:HIV serologic testing was conducted quarterly using 2 parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and RNA.Results:A total of 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (ie, 1 negative and 1 positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing, but 6 (9.7%) had dually positive rapid results, and 4 (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%.Conclusions:Although most rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low.Trial registration:ClinicalTrials.gov number NCT02550067.

BackgroundReactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products. MethodsHVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18–35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18. Using multivariate logistic regression, we evaluated associations between reactogenicity with clinical, sociodemographic and laboratory variables. ResultsMore vaccine than placebo-recipients reported local symptoms (all p < 0.001), arthralgia (p = 0.008), chills (p = 0.012) and myalgia (p < 0.001). Reactogenicity was associated with female sex at birth (ORv = 2.50, ORp = 1.81, both p < 0.001) and geographic region. Amongst vaccine-recipients, each year of age was associated with 3 % increase in reactogenicity (OR = 1.03, p = 0.002). ConclusionVaccine receipt, female sex at birth, older age, and region may affect reactogenicity.

Research topics surrounding the giraffe have been subject to recent disagreement, with work focusing on taxonomy over ecological phenomena such as behavioural thermoregulation. Much interest in taxonomy arises around the existence of distinct local populations of giraffes, often enclosed in small, fenced reserves, preventing natural gene flow. Targeted management of reserves may act as a buffer for declining populations, providing landscape that minimises requirements for thermoregulatory behaviours. Notable behaviours include shade-usage via trees and other giraffes, and positioning of the body towards the sun, employing an individual’s own neck as a shade source. Breeding programmes and translocation of individuals away from large communities on fenced reserves may increase giraffe population numbers across their range; however, the genetic diversity of large populations in enclosed spaces may be called into question. 55 of the 57 giraffes from the population on the Mogalakwena River Reserve (MRR) were observed over eight months, recording thermoregulatory behaviours such as body positioning in response to sun exposure, and shade usage; behaviours both noted in secondary works. These behaviours were compared across identities, such as sex and age, to assess how thermoregulation varies per individual. The population on the MRR spent more time facing the sun during high temperature days, with adults, sub-adults, males, and dark-coated individuals prioritising the behaviour beyond other individuals. Body positioning behaviours of individuals were also found to be more important in thermoregulation than shade-seeking, with shade usage decreasing on hotter days. Positional behaviour, disregarding identity, was also observed across wet and dry seasons, with a clear contrast; giraffes face the sun significantly more during the hotter wet season. The behaviours observed in this work provide an insight into the direction conservational strategies may take on closed reserves. However, further work is required on other reserves with varied population structures, to determine whether one strategy may be implemented across the giraffe&amp;#039;s range, or whether specialised strategies are required in individual locations.

ObjectiveDetermine the change in concussion incidence in collegiate rugby union following a lowering of the legal tackle height.DesignCohort study with existing tackle laws in 2018 (‘standard’) and a tackle height law variation in 2019 (‘lowered’).Setting2018 and 2019 collegiate rugby seasons.ParticipantsAll male rugby players participating in the 2018 and 2019 seasons. All injuries were reported by campus medical staff using standardised methods.Interventions (or Assessment of Risk Factors)Tackle law variation: maximum legal height was reduced from the shoulder to the armpit of the player being tackled.Outcome MeasuresDependent variable = concussion incidence (injury count/match exposure time) with 95% confidence intervals. Incidence rate ratios (IRR) were calculated by dividing ‘lowered’ by ‘standard’ rates. Concussion mechanism was also captured.Main ResultsThere were 27 concussions and 2,910 match hours and 21 concussions in 3,415 match hours in the ‘standard’ and ‘lowered’ seasons, respectively (IRR=0.66, 95%CI: 0.37–1.17). This incidence was significantly lower in the last third of the ‘lowered’ season (IRR=0.14, 95% CIs: 0.05–0.45). The most common concussion mechanisms in the ‘standard’ season were tackling (33%), accidental collisions (30%) and being tackled (11%); and tackling (43%), being tackled (24%) and the ruck (33%) in the ‘lowered’ season.ConclusionsConcussion incidence reduced by 34% after introducing a tackle height law variation. Although this reduction was not statistically significant, it can be considered clinically important. The unexpected increase in concussions to players being tackled warrants further investigation, but could be explained by misreported ‘accidental collisions’ in the ‘standard’ season.

BackgroundIncidence data of respiratory syncytial virus–associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions.MethodsThis prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV.ResultsAmong 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3–2.3), 0.8 (.3–1.5), and 1.6 (1.1–2.2) per 100 person-years for infants aged 0–2, 0–5, and 0–11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1–14.0), 11.7 (9.6–14.0), and 8.7 (7.5–10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0–8.3, all-cause LRTI: 0.0–49.6 per 100 person-years for 0- to 11-month-olds).ConclusionsRSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19–related nonpharmaceutical interventions.Clinical Trials RegistrationNCT03614676.

Adolescent girls and young women (AGYW) account for 25% of new HIV infections in South Africa. Pre-exposure prophylaxis (PrEP) is approved by the South African Government, but the factors that promote PrEP uptake among AGYW are not well understood. This study examines multilevel factors associated with PrEP uptake among AGYW in six clinic catchment areas in Tshwane (Pretoria), South Africa. After consent/assent, PrEP-eligible AGYW (n = 448) completed a questionnaire assessing factors at the individual, network/interpersonal, and community levels and were prescribed PrEP in study clinics, if interested. A multivariable model, adjusting for clustering, assessed factors associated with PrEP uptake over a 9-month period. At the individual level, multiple partners in the past 3 months (OR = 0.47), perceived risk of HIV (OR = 0.71), and PrEP-related shame (OR = 0.63) were correlated with lower odds of PrEP uptake (ps ≤ 0.05). The findings highlight modifiable factors that should be addressed to support PrEP uptake efforts.