View clinical trials related to Mycobacterium Ulcerans Disease.
Filter by:Buruli ulcer is a neglected tropical disease caused by infection with Mycobacterium ulcerans (Mu) in rural parts of West Africa. It causes large skin ulcers mainly in children aged 5 to 15 years. Access to treatment is limited and many cases present late. There have been major advances in understanding the mechanism of disease together with improved diagnosis and management. The aim of the proposed studies is to identify markers predictive of a rapid response to antibiotic treatment and to investigate the pathogenesis of paradoxical reactions and oedematous lesions in Mu disease. Infection with Mu results in a nodule under the skin which enlarges and breaks down to form an ulcer. This is because Mu produces a toxin that spreads outwards and damages subcutaneous tissue. In recent years it has been found that antibiotic treatment for 8 weeks with daily tablets and intramuscular injections heals ulcers. This is unpleasant and it would be better if the treatment could be shortened. Our previous studies suggest this may be possible. Therefore a wide range of tests will be investigated in order to identify markers for people in whom the infection is at an early stage with low numbers of Mu bacteria and low levels of toxin in the skin. During antibiotic treatment the rate of healing will be measured to find out which markers are the most reliable. In some patients new areas of inflammation develop despite treatment and this is called a paradoxical reaction. The immune response to Mu will be investigated serially during antibiotic treatment to investigate the cause of paradoxical reactions. About 15% of patients have oedematous disease, the most severe form of Buruli ulcer. We will study the amount of Mu toxin produced by the strain of Mu cultured from patients with this form of the disease. Hypothesis - Buruli ulcer patients that heal rapidly/slowly or develop paradoxical reactions with treatment will have associated predictive viability or serum biomarkers. - Buruli ulcer patients with oedematous disease are associated with larger amounts of mycolactone and viable organisms
SUMMARY Rationale: Buruli ulcer, caused by Mycobacterium ulcerans, is an ulcerative disease endemic in West Africa. It often leads to functional limitations. Treatment was by extensive surgery, until in 2005 gradually antibiotic treatment for eight weeks with rifampicin and streptomycin was added. Observation of Buruli ulcer lesions of limited size during antibiotic treatment showed that during treatment there is a paradoxical increase of the lesion, with a decrease of the lesion after week 14. Current WHO protocols advise to decide whether surgery is needed four weeks after the start of antibiotics. This might be too early in the healing process. The investigators hypothesize that delay in surgery is safe, and that it results in a reduction of the number of surgical interventions. Objectives: Primary Objective of this study is to compare the need for surgical treatment in standard timing of surgery at the end of eight weeks antimicrobial treatment with a policy to postpone surgical treatment until week 14. Secondary Objectives are to study whether postponing surgery leads to less extensive surgery and a change in frequency of functional limitations; Study design: Patients will be randomized for surgery at week 8 after start of antibiotic treatment and week 14 after start of treatment. Reasons for treating doctors to decide to intervene with surgery will be according to current clinical practice and will be clearly defined in this protocol. Standard care of eight weeks of rifampicin and streptomycin will be given. All patients will be followed and lesional size using acetate sheet recordings will be used during follow-up. Study population: Patients with a clinical picture of Buruli ulcer disease confirmed by diagnostic tests in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin. Patients who are pregnant, have a contraindication for general anaesthesia and children below three years old will be excluded. 130 Patients in each treatment arm will be included to detect a difference in percentage of patients needing surgery of 20 percent. Main study parameters/endpoints: Primary outcome measure is the number of patients healed without surgery. Secondary outcome measures are the extent of surgery by measurement of lesional size, functional limitations after the end of treatment and one year after the start of treatment and the duration of admission.