Lancet Microbe最新文献

Controlled human infection models (CHIMs) can accelerate vaccine development for infectious diseases. Mycobacterium tuberculosis is a human-adapted pathogen that is the leading infectious cause of death worldwide. M tuberculosis infection results in a spectrum of clinical outcomes that are incompletely modelled in animals. To date, the risks of infection, prolonged treatment, and sequelae related to CHIMs with M tuberculosis have been considered ethically unacceptable. However, recent advances in bacterial engineering have resulted in safe strains that could permit M tuberculosis CHIM studies with reduced risks. In this Personal View, we address the practical considerations for conducting a pulmonary M tuberculosis CHIM study. We summarise the ethical issues of M tuberculosis CHIM studies in tuberculosis-endemic and non-endemic settings; describe safety considerations, such as optimising the challenge dose and minimising risks to third parties; and outline and prioritise clinical, microbiological, immunological, and radiological endpoints that would render such a model useful for vaccine development.

Antimicrobial resistance (AMR) remains a major global health threat. Despite increasing international attention, AMR governance has often neglected social and equity dimensions, and there is a crucial need to synthesise evidence from social sciences and humanities scholarship to devise more people-centred approaches. In this Personal View, we report a qualitative stocktake of the intended and unintended consequences of the most recent phase of global AMR governance that started around the year 2000 and reached a high point with the 2015 Global Action Plan (GAP) on AMR. Our interdisciplinary analysis was guided by the five key objectives of current AMR governance, as organised in the 2015 GAP, to reduce AMR through awareness, surveillance, infection reduction, antimicrobial use optimisation, and research and innovation. The resulting assessment indicated mixed outcomes. Although the past decade witnessed unprecedented AMR-related action and investment, empirical studies highlight negative consequences of the decontextualised export of high-income governance frameworks and the neglect of upstream antibiotic-sensitive reforms of production, care, and innovation systems. Not embedding AMR within more general developmental and environmental challenges has also undermined local buy-in and contributed to the siloed status of AMR policies. For the next GAP, we recommend foregrounding equitable interventions; adopting a bottom-up, integrated perspective to incorporate local realities and solutions; and creating robust social sciences and humanities feedback loops for global AMR frameworks.

Antibacterial research and development (R&D) increasingly relies on public and philanthropic investments over private investments and on academia and small businesses over large pharmaceutical companies. To complement scientific reviews of the antibacterial pipeline, we examined global public and philanthropic funding for R&D of antibacterial therapeutics from 2017 to 2023 using data obtained from the Global AMR R&D Hub's Dynamic Dashboard. Projects were analysed considering funders and recipients, geographical location, R&D stage, mechanism of action, antibacterial class, clinical novelty, spectrum of activity, and alignment with the WHO bacterial priority pathogen list 2024. A total of US$2·51 billion was invested in antibacterial R&D by 130 funders, with a marked concentration among a small number of major sources. Funding peaked at $445 million in 2020 but declined by 18% to $363 million in 2023. Universities received the most awards, yet more than half of the total funding volume went to industry recipients. Investment broadly followed the WHO bacterial priority pathogens list, with Mycobacterium tuberculosis accounting for a fifth of the total. While the funding for clinical development remained stable, that for discovery and preclinical research declined. In this environment, public-private partnerships, such as Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator and the Global Antibiotic Research and Development Partnership, are crucial for attracting, channelling, and targeting funding; however, these partnerships alone will be insufficient. Enhanced strategic alignment in funding priorities and continued public and private investment will be essential for ensuring the discovery and development of effective new antibacterials meeting priority public health needs.