Table 1. Questions that a BU CHIM may answer.

1	What is the natural history of natural infection?
2	What are the systemic and local immunological responses to low dose infection?
3	What are the immunological correlates of protection?
4	What proportion of people develop antibodies against M. ulcerans-specific antigens?
5	What kind of antibodies do people develop against M. ulcerans?
6	What is the immunological basis for paradoxical reactions?
7	Can paradoxical reactions be predicted based on systemic immunological parameters?
8	What are the immunological correlates of spontaneous healing?
9	Can M. bovis BCG protect people from low-dose M. ulcerans infection? [45]
10	Can candidate vaccines delay or prevent clinical disease?
11	Can clinical disease be prevented by using early, short courses of antibiotics prior to the onset of clinical disease? (i.e., chemoprophylaxis)
12	Can abbreviated antibiotic courses (e.g., 4 to 6 weeks of rifampicin and clarithromycin) be used to treat early disease?
13	Can ultra-short treatment with telacebac [52] successfully treat BU in humans?
14	Can M. ulcerans-targeted bacteriophages be used in the management of BU?
15	Can non-antibiotic options be useful in the treatment of early (pre-ulcerative or small) lesions? For example, local heat therapy (thermotherapy) [53]

BU, Buruli ulcer; CHIM, controlled human infection model.