Treatment of Buruli Ulcer

BU has long been treated by surgical resection. During the last two decades, it has become increasingly clear that antimicrobial treatment, first, using a combination of streptomycin 15 mg/kg i.m. and rifampin 10 mg/kg p.o. for 8 weeks, results in relapse-free cure in lesions &lt;10 cm cross-sectional diameter. Recently, a large clinical trial from Ghana and Benin showed that fully oral treatment—rifampin 10 mg/kg combined with clarithromycin—extended release, 15 mg/kg, also for 8 weeks, was equally effective but less toxic; none of the close to 300 study participants needed surgical resection, and only four had split skin grafts; sequelae were negligible. The use of other antimicrobials including fluoroquinolones has been shown to be effective in cohort studies from Australia. The role of resection surgery was studied in Benin in patients with larger lesions. Compared to patients that were operated on at week 8, a delayed decision on surgery at week 14 appeared beneficial; delay resulted in significantly less patients being operated, with reduced in-hospital treatment, and no difference in healing rate or sequelae. Sequelae such as contractures due to scar formation around joints may need specialized care in dedicated centers. General medical care with adequate nutrition and proper wound care are critical; wound saline rinsing and cleaning, dressings with non-adhesive cover, and absorptive material with short-stretch compression are all important for speedy healing. Other topical treatments (nitric oxide crème; traditional herbal remedies; clay; phenytoin) have been little studied; heat treatment might be an option for those that cannot tolerate antimicrobial treatment, such as during pregnancy. Active, early case finding has been shown to be highly efficacious.</p

Pharmacologic management of Mycobacterium ulcerans infection

Introduction: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. Areas covered: We review BU drug treatment–in vitro, in vivo and clinical trials (PubMed: ‘(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).’ We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. Expert opinion: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer