Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa: A randomized crossover phase 2a/2b trial.

COVID-19 remains a global public health issue and an improved understanding of vaccine performance in immunocompromised individuals, including people living with HIV (PLWH), is needed. Initial data from the present study's pre-crossover/booster phase were previously reported. This phase 2a/b clinical trial in South Africa (2019nCoV-501/NCT04533399) revisits 1:1 randomly assigned HIV-negative adults (18-84 years) and medically stable PLWH (18-64 years) who previously received two NVX-CoV2373 doses (5 μg recombinant Spike protein with 50 μg Matrix-M™ adjuvant) or placebo.

High recent PrEP adherence with point-of-care urine tenofovir testing and adherence counselling among young African women: results from the INSIGHT cohort.

Introduction: Adolescent girls and young women (AGYW) account for two-thirds of new HIV infections in Africa. African AGYW have had high uptake of oral HIV pre-exposure prophylaxis (PrEP) but low adherence, which might be improved by point-of-care adherence monitoring with tailored counselling.

Methods: From August 2022 to July 2023, we conducted a PrEP demonstration project with sexually active AGYW ages 16-30 years from 20 sites in South Africa, Eswatini, Kenya, Malawi, Uganda and Zambia.

Immunogenicity and safety of SARS-CoV-2 recombinant spike protein vaccine in South African people living with and without HIV-1 infection: A phase 2 randomised trial.

Background: Response data for COVID-19 vaccines in immunosuppressed individuals are typically limited to standard dosing in small populations. Adjusting number or interval of doses may impact immune responses based on HIV status.

Methods: This phase 2 randomised, observer-blinded, placebo-controlled South African study (2019nCoV-505/NCT05112848) enrolled medically stable people living with HIV (PLWH) and HIV-uninfected participants aged 18-65 years.

Open Data-Driven Decision Making: Observations from COVID-19 Minimal Essential Data, Canton Zürich, Switzerland.

This research delves into the relationship between open data and decision making, drawing insights from the utilization of Minimal Essential Data (MED) during the COVID-19 pandemic in Canton Zürich, Switzerland. It examines observations and lessons learned, emphasizing the pivotal role of open data in response to an emergency. Through a case study approach, this article sheds light on the practical implications and observed strategies in publishing open data from digital public health surveillance software.

Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

Background: There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women.

Methods: We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo.

Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial.

Background: The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to shorten TB therapy by exerting a bactericidal effect on non-replicating bacilli. Based on results from preclinical and early clinical studies, a four-drug combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) regimen was identified with treatment-shortening potential for both drug-susceptible (DS) and drug-resistant (DR) TB. This trial aimed to determine the safety and efficacy of BPaMZ.

Efficient Electrochemiluminescence Sensing in Microfluidic Biosensors: A Review.

Microfluidic devices are capable of handling 10-9 L to 10-18 L of fluids by incorporating tiny channels with dimensions of ten to hundreds of micrometers, and they can be fabricated using a wide range of materials including glass, silicon, polymers, paper, and cloth for tailored sensing applications. Microfluidic biosensors integrated with detection methods such as electrochemiluminescence (ECL) can be used for the diagnosis and prognosis of diseases. Coupled with ECL, these tandem devices are capable of sensing biomarkers at nanomolar to picomolar concentrations, reproducibly.

Digital Public Health Solutions in Response to the COVID-19 Pandemic: Comparative Analysis of Contact Tracing Solutions Deployed in Japan and Germany.

Background: In response to the COVID-19 pandemic, numerous countries, including the likes of Japan and Germany, initiated, developed, and deployed digital contact tracing solutions in an effort to detect and interrupt COVID-19 transmission chains. These initiatives indicated the willingness of both the Japanese and German governments to support eHealth solution development for public health; however, end user acceptance, trust, and willingness to make use of the solutions delivered through these initiatives are critical to their success. Through a case-based analysis of contact tracing solutions deployed in Japan and Germany during the COVID-19 pandemic we may gain valuable perspectives on the transnational role of digital technologies in crises, while also projecting possible directions for future pandemic technologies.

Quantifying community-wide antibiotic usage via urban water fingerprinting: Focus on contrasting resource settings in South Africa.

There has been a significant increase in antimicrobial agents (AAs) usage, globally - however the relative consumption is unevenly distributed between nations. Inappropriate use of antibiotics can harbour inherent antimicrobial resistance (AMR); therefore, it is important to understand and monitor community-wide prescribing and consumption behaviours throughout different communities around the world. Wastewater-Based Epidemiology (WBE) is a novel tool enabling low cost and large scale studies focussed on AA usage patterns.

Pain Neuroscience Education in Elementary and Middle Schools.

Purpose: The purpose of this study was to deliver pain neuroscience education (PNE) to participants in grades 3 to 8 to determine whether participants in these grades had positive shifts in pain knowledge and beliefs.

Methods: Three hundred twenty participants, grades 3 to 8, received a 1-time, 30-minute PNE lecture. The Neurophysiology of Pain Questionnaire and the Health Care Provider's Pain and Impairment Relationship Scale were administered before and after the PNE lecture.

A comparison of interaural asymmetry, audiogram slope, and psychometric measures of tinnitus, hyperacusis, anxiety and depression for patients with unilateral and bilateral tinnitus.

Objective: To evaluate differences in tinnitus impact, hyperacusis and hearing threshold level (HTL) between patients with unilateral and bilateral tinnitus. For patients with unilateral tinnitus, to compare audiological variables for the tinnitus ear and the non-tinnitus ear. To assess whether the presence of unilateral tinnitus increases the likelihood of interaural hearing asymmetry (relative to bilateral tinnitus) that warrants referral for an MRI scan.

High Levels of Pretreatment HIV-1 Drug Resistance Mutations Among South African Women Who Acquired HIV During a Prospective Study.

Background: Pretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

Background: HIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Methods: ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptives.

The influence of a manipulation of threat on experimentally-induced secondary hyperalgesia.

Pain is thought to be influenced by the threat value of the particular context in which it occurs. However, the mechanisms by which a threat achieves this influence on pain are unclear. Here, we explore how threat influences experimentally-induced secondary hyperalgesia, which is thought to be a manifestation of central sensitization.

Global Good Open Source Software Development in Response to the COVID-19 Pandemic - Perspectives from SORMAS Implementation in Europe.

In recent years, software has evolved from being static, closed source, proprietary products to being dynamic, open source, ecosystems contributing to the global good. To this end, the open source software (OSS) solution and global good, Surveillance Outbreak Response Management and Analysis System (SORMAS), rapidly adjusted to the demands of the Coronavirus disease 2019 (COVID-19) outbreak by introducing a COVID-19 module. This allowed countries that were already making use of the software as part of their public health surveillance infrastructure to make use of the new module in order to respond to the pandemic.

Immunogenicity and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine in people living with and without HIV-1 infection: a randomised, controlled, phase 2A/2B trial.

Background: There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373; Novavax) in HIV-negative people and people living with HIV-1.

Methods: In this randomised, observer-blinded, multicentre, placebo-controlled phase 2A/B trial in South Africa, participants aged 18-84 years, with and without underlying HIV-1, were enrolled from 16 sites and randomly assigned (1:1) to receive two intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.

Dynamic mathematical model development and validation of in vitro Mycobacterium smegmatis growth under nutrient- and pH-stress.

Mycobacterium tuberculosis can exist within a host for lengthy periods, tolerating even antibiotic challenge. This non-heritable, antibiotic tolerant "persister" state, is thought to underlie latent Tuberculosis (TB) infection and a deeper understanding thereof could inform treatment strategies. In addition to experimental studies, mathematical and computational modelling approaches are widely employed to study persistence from both an in vivo and in vitro perspective.

Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant.

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.

A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB.

Treatment for TB is lengthy and toxic, and new regimens are needed. Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6PaMZ) or 4 months (4PaMZ); 100 mg pretomanid daily for 4 months in the same combination (4PaMZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation.

Computational modelling of the Δ4 and Δ5 adrenal steroidogenic pathways provides insight into hypocortisolism.

This study demonstrates the application of a mathematical steroidogenic model, constructed with individual in vitro enzyme characterisations, to simulate in vivo steroidogenesis in a diseased state. This modelling approach was applied to the South African Angora goat, that suffers from hypocortisolism caused by altered adrenal function. These animals are extremely vulnerable to cold stress, leading to substantial monetary loss in the mohair industry.

Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study.

Background: The Ring Study, a phase 3 trial in 1959 sexually active women (randomised 2:1), showed a favourable safety profile and a 31% HIV-1 infection risk reduction for a vaginal ring containing 25 mg of dapivirine, compared with a placebo ring. We report here the DREAM study, which aimed to evaluate safety, adherence, and HIV-1 incidence in those using the dapivirine vaginal ring (DVR) in open-label use.

Methods: The DREAM study is an open-label extension of The Ring Study, done at five research centres in South Africa and one research centre in Uganda.