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Mycobacterium ulcerans , the causative agent of Buruli ulcer, is an emerging pathogen in southeastern Australia. Disease typically presents as a single cutaneous lesion although atypical and multi-focal infection does occur, and in these cases a lack of clinical suspicion may delay the diagnosis. With increased exposure of older and medically immunosuppressed populations to M. ulcerans transmission, we need a clearer understanding of how age and underlying immune dysfunction may alter both the risk of acquisition and the clinical presentation of the infection. We present the first known case of M. ulcerans infection involving a prosthetic joint. A 68-year-old female with rheumatoid arthritis immunosuppressed with methotrexate and prednisolone presented with an acutely painful, erythematous prosthetic metacarpophalangeal joint. She also reported multiple cutaneous ulcers, developing over the preceding year. Laboratory investigations revealed raised inflammatory markers, and a complex peri-prosthetic collection was seen on imaging. Swabs from the cutaneous ulcers and joint washout for M. ulcerans PCR and culture positive. PET-CT demonstrated the presence of further sub-clinical cutaneous lesions. The infection was successfully managed with a surgical washout, implant retention and 12 weeks of oral antimicrobials. This case highlights an atypical presentation of Buruli ulcer in an immunosuppressed patient, and the management considerations involved. The broadening geographical distribution of M. ulcerans will place a growing population of immunosuppressed patients at risk; thus awareness amongst clinicians is crucial to ensure prompt diagnosis and treatment.

The development of an oropharyngeal gonorrhoea controlled human infection model (CHIM) could result in important translational outcomes, including accelerated development of new drugs and vaccines. Ethical study design for such a model requires community consultation, including assessment of the acceptability of the proposed CHIM among key stakeholders. This qualitative study involved: (i) semi-structured interviews and focus groups with individuals who would be eligible for participation in the proposed oropharyngeal gonorrhoea CHIM, defined as healthy men who have sex with men (MSM) aged 18–50 years living in Victoria (Australia); and, (ii) semi-structured interviews with gonorrhoea experts. Data were analysed using inductive thematic analysis supported by NVivo. Twenty-seven semi-structured interviews and one focus group were undertaken with 32 individuals between July and November, 2024, comprising 22 potential CHIM participants, and 10 experts. Overall, an oropharyngeal gonorrhoea CHIM was acceptable to most participants. Financial compensation and including only MSM who do not have sex with women were highlighted as key areas of debate. Participants highlighted that recruitment strategies should be sensitive to the stigma associated with gonorrhoea and history of stigma experienced by MSM. An oropharyngeal gonorrhoea CHIM is acceptable to key stakeholders but must be carefully designed to avoid exacerbation of stigma.

Human adipose-derived mesenchymal stromal cells (ASC) are showing clinical promise for the treatment of a range of inflammatory and degenerative conditions. These lipoaspirate-derived cells are part of the abundant and accessible source of heterogeneous stromal vascular fraction (SVF). They are typically isolated and expanded from the SVF adherent cell culture for at least 2 weeks and as such represent a relatively undefined population of cells. We isolated ASC directly from lipoaspirate using a cocktail of antibodies combined with immunomagnetic bead sorting. This method allowed for the rapid enrichment of a defined and untouched ASC population (referred to as MACS-derived ASC) that were then compared to culture-derived ASC. This comparison found that MACS-derived ASC contain a greater proportion of cells with activity in differentiation assays. There were also significant differences in the secretion levels of some key paracrine molecules. Moreover, when the MACS-derived ASC were subjected to adherent tissue culture, rapid changes in gene expression were observed. This indicates that culturing cells may alter the clinical utility of these cells. Although MACS-derived ASC are more defined compared to culture-derived ASC, further investigations using a comprehensive multicolor flow cytometry panel revealed that this cell population is more heterogeneous than previously appreciated. Additional studies are therefore required to more precisely delineate phenotypically distinct ASC subsets with the most therapeutic potential. This research highlights the disparity between MACS-derived and culture-derived ASC and the need for further characterization.

There is increasing debate regarding the harms and benefits of frequent asymptomatic screening for Chlamydia trachomatis and Neisseria gonorrhoeae in men who have sex with men (MSM). One concern is that frequent asymptomatic screening could result in increased antimicrobial resistance in an array of sexually acquired infections and other pathogens, due to selection pressure exerted by frequent broad-spectrum antimicrobial usage within some sexual networks. Here, we outline the harms and benefits of frequent C trachomatis and N gonorrhoeae screening in MSM in high-income settings and propose that screening frequency be reduced. We describe the evidence gaps that should be further explored to better understand the implications of reducing the frequency of asymptomatic C trachomatis and N gonorrhoeae screening in MSM and the surveillance systems that should be in place to prepare for such changes.

Novel interventions are needed to tackle a public health crisis

There have been significant advances in the prevention and management of Ebola virus disease (EVD) caused by Zaire Ebola virus (ZEBOV), including the development of two effective vaccines, rVSV-ZEBOV and Ad26.ZEBOV/MVA-BN-Filo. In addition, ZEBOV monoclonal antibodies have become first-line therapy for EVD. However, the 2022–23 outbreak of Sudan Ebola virus (SUDV) in Uganda has highlighted the gap in current therapies and vaccines, whose efficacy is uncertain against non-ZEBOV species. Health-care and laboratory staff working in EVD treatment centres or Ebola virus diagnostic and research laboratories face unique risks relating to potential occupational exposure to Ebola viruses. Given the substantial morbidity and mortality associated with EVD, facilities should have strategies in place to manage occupational exposures, including consideration of post-exposure therapies. In this Review, we discuss currently available evidence for prevention and post-exposure prophylaxis of EVD, including therapies currently under evaluation for SUDV.

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is a highly effective biomedical intervention for the prevention of HIV acquisition. There is a strong interest among communities and policymakers for LAI-PrEP scale-up, accelerating the demand for clear guidance on testing approaches that balance accuracy with scalability. Unlike oral pre-exposure prophylaxis, LAI-PrEP may overcome adherence challenges, such as difficulty with frequent clinic visits. However, LAI-PrEP results in prolonged subtherapeutic drug levels after discontinuation, which can increase the risk of drug resistance among those who have an undetected HIV infection. This systematic review evaluates how different HIV testing strategies, including rapid diagnostic tests (RDTs), laboratory-based immunoassays and nucleic acid testing (NAT), affect clinical utility and programme delivery of LAI-PrEP. We searched databases and retrieved studies up to April 8, 2025, and supplemented findings with data collected through a World Health Organization (WHO) survey among ongoing and completed LAI-PrEP implementation studies. We included publications reporting original or primary data on clinical, diagnostic and resource-use outcomes of HIV testing for LAI-PrEP. Meta-analyses were conducted using random-effects models. Chi-square tests were used to examine differences between related outcomes. Certainty of evidence was determined using the GRADE methodology (Prospero: CRD42024605562). Risk Of Bias In Non-randomised Studies of Interventions, Version 2 (ROBINS-I V2) assessment tool was used to assess bias for non-randomised comparative studies. Of 7,698 records identified, 38 reports representing 22 studies (cabotegravir: 20, lenacapavir: 2) across 15 countries were included. The overall certainty of evidence was low. Most were observational cohorts (n = 13) or non-randomised comparator studies (n = 7). Among 8,171 LAI-PrEP users in four randomised controlled trials, HIV detection rates were similar across strategies (9/8171 (RDT) versus 14/8171 (NAT) (Odds ratio (OR) 0.66 (95% confidence interval: 0.29-1.50; P = 0.87)), with no difference in adverse events. Compared with laboratory-based tests, RDTs enabled faster turnaround (same-day versus up to 7 days), more rapid treatment initiation (1 day versus 6-9 days), and lower test costs (US$4 versus US$22). All tests had similar negative predictive value (~100%) at LAI-PrEP initiation and comparable positive predictive value (~55%) at continuation. There was little difference in delayed HIV detection (11/8171 (RDT) versus 0/8171 (NAT)). In the HPTN 083 trial, NAT use was occasionally associated with false-positive results, leading to unnecessary PrEP holds or discontinuation (7/2483). NAT might have detected HIV before resistance emerged, though no prospective or modelling evidence showed clinical benefit at a population level. There was limited evidence of HIV self-testing for LAI-PrEP delivery. We noted that our assessment of performance accuracy in different testing strategies may introduce selection bias. RDT-based testing strategies have comparable accuracy to laboratory-based strategies and are more accessible and scalable, which can ensure that testing does not become a barrier to accessing or continuing LAI-PrEP. As countries expand access to LAI-PrEP amid increasingly constrained resources, adoption of new WHO guidance supporting the use of RDTs can enable simpler, more affordable, and user-centred HIV testing approaches.

This report of a joint World Health Organization (WHO) and United Kingdom (UK) Health Research Authority (HRA) workshop discusses the ethics review of the first COVID-19 human challenge studies, undertaken in the midst of the pandemic. It reviews the early efforts of international and national institutions to define the ethical standards required for COVID-19 human challenge studies and create the frameworks to ensure rigorous and timely review of these studies. This report evaluates the utility of the WHO’s international guidance document Key criteria for the ethical acceptability of COVID-19 human challenge studies (WHO Key Criteria) as a practical resource for the ethics review of COVID-19 human challenge studies. It also assesses the UK HRA’s approach to these complex ethics reviews, including the formation of a Specialist Ad-Hoc Research Ethics Committee (REC) for COVID-19 Human Challenge Studies to review all current and future COVID-19 human challenge studies. In addition, the report outlines the reflections of REC members and researchers regarding the ethics review process of the first COVID-19 human challenge studies. Finally, it considers the potential ongoing scientific justification for COVID-19 human challenge studies, particularly in relation to next-generation vaccines and optimisation of vaccination schedules. Overall, there was broad agreement that the WHO Key Criteria represented an international consensus document that played a powerful role in setting norms and delineating the necessary conditions for the ethical acceptability of COVID-19 human challenge studies. Workshop members suggested that the WHO Key Criteria could be practically implemented to support researchers and ethics reviewers, including in the training of ethics committee members. In future, a wider audience may be engaged by the original document and potential additional materials, informed by the experiences of those involved in the first COVID-19 human challenge studies outlined in this document.

New HIV-1 infections are genotyped as part of standard of care testing to ensure that antiretroviral treatment will be efficacious against the virus. Historically this has been performed by sequencing the pol region of the HIV-1 genome only. The popularity of next-generation sequencing (NGS) methods during the SARS-CoV-2 pandemic has resulted in a shift towards using NGS in diagnostic sequencing, but there remain limited methodologies utilising the strengths of NGS for robust diagnostic sequencing of longer regions of the HIV-1 genome. Given the acceptance and success of tiling PCR methodologies during the SARS-CoV-2 pandemic, we aimed to design and verify a novel tiling PCR method for routine HIV-1 sequencing. A set of tiling PCR primers was designed to amplify the 5’ half of HIV-1 in six overlapping segments of 1,000 bp in only two PCR reactions. The assay can move from sample to sequencer in under a day. The tiling PCR was able to generate HIV-1 sequences from 90 (100%) samples in a comparison panel, and complete protease-reverse transcriptase and integrase regions were amplified in > 90% of samples with a viral load > 5000 copies/mL. Seven additional drug resistance mutations were identified when using this novel method. As such, this novel designer tiling PCR is a promising method for the routine NGS-based diagnostic sequencing of HIV-1.

There is clinical interest in using human adipose tissue-derived mesenchymal stromal cells (ASC) to treat a range of inflammatory and regenerative conditions. Aspects of ASC biology, including their regenerative potential and paracrine effect, are likely to be modulated, in part, by microRNAs, small RNA molecules that are embedded as regulators of gene-expression in most biological pathways. However, the effect of standard isolation and expansion protocols on microRNA expression in ASC is not well explored. Here, by using an untouched and enriched population of primary human ASC, we demonstrate that there are rapid and significant changes in microRNA expression when ASC are subjected to standard isolation and expansion methods. Functional studies focusing on miR-378 indicate that these changes in expression may have an impact on phenotype and function. Specifically, we found that increased levels of miR-378 significantly promoted adipogenesis in late passage ASC. These results are informative to maximizing the potential of ASC for use in various clinical applications, and they have implications for targeting microRNAs as a therapeutic strategy for obesity or metabolic disease.