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Background: Infection with Mycobacterium ulcerans causes slowly progressive skin lesions known as Buruli ulcer. An M. ulcerans controlled human infection model (MuCHIM) is likely to accelerate our understanding of this otherwise neglected disease, and may be an efficient platform for testing vaccines and other interventions. The aim of this study was to understand perceptions of this model across a range of key stakeholders in an endemic Australian community setting. Methods: We recruited young adults who live near an Australian BU endemic area but without a personal history of BU, clinicians involved in the management of BU, young adults with a personal history of a small, treated BU, and participants of any age with a demonstrated interest in public advocacy related to their personal BU lived experience. Participants reviewed an abridged version of the provisional protocol. A series of three focus groups were then conducted by video, and the transcribed text was analysed using reflexive thematic analysis to generate themes for exploration. Results: Participants universally valued the outcomes that MuCHIM might deliver. The predominant theme was that informed consent required fully transparent communication with potential participants regarding what their participation would involve, how it would impact their lives, and both the expected outcome and 'worst-case scenario'. They also offered actionable recommendations on how best to communicate the tension between the expected outcome and the 'worst-case scenario' of disease associated with delayed diagnosis and comorbidity, as typically portrayed by the media. Participants recommended including images and testimonials from people who have had BU to support the conditions for informed consent. Focus groups also gave a clear sense of who they believed would volunteer for this type of research. Conclusions: This study offers valuable guidance regarding the content and presentation of information to inform potential participants, with focus group participants suggesting a multimodal approach of communication, including lived experience testimonials and clinical images of the expected outcome. This information will inform development of materials for enrolment to adequately communicate risks and expectations to potential study participants. Author summary: Buruli ulcer (BU) is a slow-growing skin infection caused by the bacterium Mycobacterium ulcerans. A new type of research study, called the Mycobacterium ulcerans Controlled Human Infection Model (MuCHIM), involves deliberately infecting consenting adult volunteers and treating them quickly. This approach could help us learn more about BU and test vaccines (or other preventative measures) and treatments. This study asked for the opinions of people connected to BU in Victoria, Australia. We invited adults living near BU-affected areas (but who had not had BU themselves), doctors who treat patients with BU, young adults who have had a small, treated BU, and advocates who have publicly shared their own personal BU experience. Participants reviewed a summary of the MuCHIM research plan and then joined focus groups on Zoom. We analysed and summarised their discussions. Participants saw the research as valuable but emphasised the need for clear, honest communication. They wanted potential volunteers to fully understand what the study involves, how it might affect their lives, and the possible risks, including the 'worst-case' scenario. Suggestions included using images and stories from real BU patients to help understand the study. Participants also shared their thoughts on who might volunteer for such research. This feedback will guide how we explain risks and expectations to future MuCHIM study participants. [ABSTRACT FROM AUTHOR]

We describe two locally acquired cases of Mycobacterium ulcerans infection (Buruli ulcer) in the town of Batemans Bay on the east coast of New South Wales (NSW), Australia, 150 km north of Eden, the only other place in NSW where Buruli ulcer has likely been locally acquired. Genomic analysis showed that the bacterial isolates from the cases were identical but belonged to a phylogenetically distinct M. ulcerans clade that was most closely related to the isolate from the earlier case in Eden to the south. It is proposed that Batemans Bay is a new endemic focus of human Buruli ulcer transmission. Author summary: Mycobacterium ulcerans causes Buruli ulcer, a progressive infection affecting skin and subcutaneous soft tissues. Although predominantly reported in central and west Africa, Australia, and Japan, new endemic regions for Buruli ulcer continue to be discovered. In Australia, the state of Victoria has seen a significant public health challenge with Buruli ulcer, where evidence points to zoonotic transmission from native possums to humans via mosquitoes. Recently, a new location of locally acquired Buruli ulcer has been identified in Batemans Bay, New South Wales (NSW), Australia. Genome sequencing of cases in this area has revealed a distinct M. ulcerans genotype, suggesting the pathogen is extant in NSW similar to the situation in Victoria. Surveys of possum excreta in Batemans Bay have confirmed the presence of M. ulcerans, indicating its establishment in a local wildlife reservoir in a new endemic region. [ABSTRACT FROM AUTHOR]

Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017–2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans. [ABSTRACT FROM AUTHOR]

Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection. Non-technical author summary: In this paper, we progress our research towards establishing a controlled human infection model (CHIM) of Buruli ulcer, caused by Mycobacterium ulcerans. It is crucial that the challenge agent used for such experiments is thoroughly characterised; not only is this important to ensure standardisation between participants, but also to reinforce their safety. Using established criteria, we systematically demonstrate why the isolate M. ulcerans JKD8049 may be a suitable challenge strain. This strain is non-genetically modified, susceptible to antibiotics, can be cultured in relatively simple media, and can be filtered and preserved as individual bacteria to ensure accurate dosing of participants. Even after repeatedly culturing the organism for months, it remains genetically stable, so significant mutations are not expected to develop during manufacture. After preserving the isolate at -80°C, it can be revived and diluted for human inoculation at very low doses. Importantly, it produces the toxin mycolactone, so it is expected to recreate typical Buruli ulcer disease in participants, which will be important to properly test vaccines and other therapeutics. We also demonstrate a set of principles to ensure the produced batch is free from contamination. [ABSTRACT FROM AUTHOR]

Background Aims Methods Results Conclusions Antimicrobial stewardship (AMS) guidelines now recommend antifungal stewardship (AFS) interventions to improve the management of invasive fungal diseases (IFDs). AFS programmes have not been reported in Australia.To determine the monitoring of antifungal use, AFS strategies and targets, and barriers to AFS implementation in Australian hospitals.An electronic quantitative cross‐sectional survey was developed and distributed to public and private hospitals in Australia in February 2018. Descriptive statistics were used to summarise the findings.Eighty‐three Australian hospitals completed the survey with an overall response rate of 58% (83/143). Most hospitals monitored antifungal use (62/83, 75%). Frequently used AFS metrics included costs (48/60, 80%) and yearly point prevalence surveys (45/60, 75%). Core AFS strategies were commonly in place, including preauthorisation requirements (71/80, 89%) and expert antifungal post‐prescription review and feedback (PPRF) (63/80, 79%). Both these strategies were more strictly applied to high‐cost, intravenous agents. Formal education (44/79, 56%) and hospital‐endorsed guidelines (35/79, 44%) were modestly used. Fungal diagnostics and antifungal therapeutic drug monitoring (TDM) were utilised, largely off site. IFD surveillance was infrequently performed (9/77, 12%). Barriers to AFS identified included lack of staff time, prioritisation of AFS, and access to rapid diagnostics and TDM.AFS strategies utilised in Australian hospitals have focused on high‐cost, intravenous agents. Although expert oversight of antifungals is evident, many sites omit potentially important targets for AFS, including fluconazole and oral posaconazole. Identifying these gaps and barriers to AFS will guide the development of an AFS model for hospitals. [ABSTRACT FROM AUTHOR]