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|Title: ||Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease|
|Authors: ||Sarfo, Fred S|
Phillips, Richard O.
Abass, Mohammed K
|Keywords: ||Mycobacterium ulcerans, Mycolactone, Biomarker, Antibiotic therapy, Prognosis, Treatment response|
|Issue Date: ||2014|
|Publisher: ||BMC Infectious Diseases|
|Citation: ||BMC Infectious Diseases 14:202|
|Abstract: ||Background: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading
to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule
with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive
biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of
patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical
and bacteriological response to therapy.
Methods: Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after
antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass
spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy.
Results: Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete
healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with
antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end
of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were
detected in a proportion of these slowly healing lesions during and after treatment.
Conclusions: Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with
antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic
treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in
optimising antibiotic therapy.|
|Description: ||An article published by BMC Infectious Diseases|
|Appears in Collections:||College of Health Sciences|
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