Detection of viability markers of mycobacterium ulcerans and their association with healing in buruli ulcer patients

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NOVEMBER, 2016
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Abstract
Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans (M. ulcerans), an infection common in rural parts of West Africa including Ghana. It affects predominantly children between the ages of 5-15 years. Treatment of BU has changed over the past 11 years with the introduction of antibiotics (rifampicin and streptomycin) as an alternative to surgery. The aim of antibiotic treatment is that each patient receives the minimum appropriate therapy needed to achieve recurrent free cure. The current duration of antibiotic therapy (8 weeks) was based on observations in patients with early M. ulcerans which were excised after treatment. Thus it is likely that a shorter course of antibiotic treatment may be successful in some patients. To characterise the viability of M. ulcerans in BU and to ascertain its association with time to/ rate of healing of lesions. Fine needle aspirates and swabs were obtained from patients confirmed with active BU using IS2404 PCR as a gold standard. Samples were obtained at baseline (week 0), during treatment (week 4), end of treatment (week8) and after treatment (weeks 12 and 16) for detection of viable M. ulcerans using combined assay 16S rRNA/IS2404 RT qPCR and culture. Patients were followed up 2 weekly with wound measurements using Silhouette required for determination of rate of healing. Of one hundred and twenty-nine patients, viable M ulcerans could be detected in 65% at baseline. By week 4, 20 (15.5%) of lesions had healed or 29 (22%) had undetectable viable organisms. At week 8 viable M. ulcerans were still detected in 43 (33%) lesions of unhealed, 15 (12%) of unhealed at week 12 and 3 (2%) of unhealed at week 16. Patients with detectable viable organisms after antibiotic treatment had significantly higher bacterial load, vii longer healing time and lower healing rate at week 4 compared with those with undetectable viable organisms at baseline or by week 4. We demonstrated that current antibiotic therapy for BU disease is highly successful in most patients but it may be possible to abbreviate the treatment to 4 weeks in patients with a low initial bacterial load. On the other hand, evidence has been presented that persistent infection with viable M. ulcerans contributes to slow healing in other patients, suggesting that those with a high bacterial load, may need antibiotics for longer than 8 weeks.
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A thesis submitted in fulfillment of the requirements for the degree of Master of Philosophy, Immunology in the Department of Molecular Medicine.
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