Mycobacterium ulcerans Controlled Human Infection Model (MuCHIM) project

What is Buruli ulcer?

Buruli ulcer is a skin infection caused by a slow-growing bacterium called Mycobacterium ulcerans. It typically starts painlessly, presenting as a small area of redness or swelling on the skin. While Buruli ulcer is curable with antibiotics, if it’s not diagnosed and treated early, it can lead to large ulcers and long-term problems, including disability and cosmetic deformity.

This infection is considered a neglected tropical disease, meaning it affects vulnerable populations and hasn’t received as much research attention as other diseases. Buruli ulcer is now endemic in parts of Australia and during the last two decades there has been an exponential increase in reported cases in Victoria, escalating from 12 in 2003 to 363 in 2023. There are still critical gaps in our understanding of how M. ulcerans interacts with the human body, which has made it difficult to develop effective therapeutics to prevent it, like vaccines.

Introducing the MuCHIM project

The Mycobacterium ulcerans Controlled Human Infection Model (MuCHIM) project led by the Doherty Institute (University of Melbourne, Australia), is a research initiative designed to help us learn more about Buruli ulcer in a safe and controlled way, and eventually to test vaccines and other prevention tools.

In the MuCHIM study, participants will receive a tiny, precisely measured dose of an isolated strain of Buruli ulcer bacterium (Mycobacterium ulcerans JKD8049), which has been chosen for its suitability and safety for this kind of research, especially at ultra-low doses. The infection is given via an injection just under the skin on the forearm.

Identifying the challenge isolate, M. ulcerans JKD8049, was a critical step in the MuCHIM research pipeline. It was selected following a rigorous screening process to ensure it met key criteria: susceptibility to all clinically relevant antibiotics, ease of preservation, genetic stability, and suitability for administration in ultra-low doses. Learn more about the study published in PLOS Neglected Tropical Diseases.

The main goals of this initial pilot study are:

• To confirm that it is safe and acceptable for healthy adult volunteers to be given a tiny, precisely measured dose of the Buruli ulcer bacteria, and that any resulting infection can be reliably cured with standard treatment.
• To determine the rate of infection by monitoring the small, localised infection in healthy volunteers.

We also aim to:

• Test less invasive ways to diagnose Buruli ulcer lesions.
• Study how the human immune system responds to the infection, especially in its early stages.
• Explore the specific characteristics of the M. ulcerans bacteria when it infects humans.

If this pilot study is successful, the long-term vision is to use this MuCHIM model as a platform to speed up the development and testing of much-needed therapeutics, like vaccines,  for the prevention and treatment of Buruli ulcer. This could help people in Australia, where cases continue to rise and in other affected communities around the world.

The MuCHIM project is built on a foundation of thorough research and planning. These publications highlight our commitment to transparency and rigorous scientific and ethical practice. Sharing our research openly is crucial for advancing knowledge and building public trust. Here are some of the key publications related to our work:

Muhi S, Marshall JL, O’Brien DP, et al. (2025) Perceptions of a Buruli ulcer controlled human infection model: How, who, and why? PLoS Neglected Tropical Diseases, 19(2): e0012593.

This paper explores the views of community members and other stakeholders on the proposed MuCHIM study, helping to ensure the project is designed and communicated in a way that is transparent and addresses public values and concerns.

Muhi S, Marshall JL, O’Brien DP, et al. (2024) A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study. Wellcome Open Research, 9:488.

This publication details the initial plan and design for the MuCHIM clinical study, outlining the procedures, safety measures, and research questions.

Muhi S, Buultjens AH, Porter JL, et al. (2024) Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model. PLoS Neglected Tropical Diseases, 18(5): e0011979.

This research describes the careful process of selecting the specific strain of Mycobacterium ulcerans (JKD8049) that is most suitable and safe for use in the MuCHIM study.

Muhi S, Stinear TP. (2023) A human model of Buruli ulcer: The case for controlled human infection and considerations for selecting a Mycobacterium ulcerans challenge strain. PLoS Neglected Tropical Diseases, 17(6): e0011394.

This paper reviews the scientific basis and rationale for developing a CHIM for Buruli ulcer and discusses the important factors in choosing an appropriate bacterial strain for the model.

Muhi S, Stinear TP. (2021) Systematic review of M. bovis BCG and other candidate vaccines for Buruli ulcer prophylaxis. Vaccine, 39(32): 4439-4449.

This review examines the existing research on vaccines, particularly the BCG vaccine, for preventing Buruli ulcer and identifies promising future candidates. It also highlights the bottleneck from identifying promising vaccines to translating them into human clinical trials.