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Antimicrobial treatment for buruli ulcer is effective in early, limited disease

Lancet

New research shows that two different antimicrobial regimens for treating buruli ulcer (MycobacteriuM ulcerans infection) are effective at treating early, limited disease. This is the conclusion of an Article published Online First (www.thelancet.com) and in an upcoming edition of The Lancet--written by Professor Tjip S van der Werf, University Medical Centre Groningen, Netherlands, and colleagues.

Buruli ulcer is classed a neglected tropical disease. The early stage of infection is characterised by a painless nodule, with lesions developing on the skin, and occasionally in adjacent bone, as the disease progresses. Surgery was the standard treatment for Buruli ulcer disease until WHO issued provisional guidelines in 2004 recommending treatment with antimicrobial drugs (streptomycin and rifampicin) in addition to surgery. In this study, the authors investigated the efficacy of two regimens of antimicrobial treatment in early-stage M ulcerans infection.

In this randomised trial undertaken in two sites in Ghana, patients were eligible for enrolment if they were aged five years or older and had early (duration <6 months), limited (cross-sectional diameter <10 cm), M ulcerans infection confirmed by dry-reagent-based PCR. Eligible patients were randomly assigned to receive intramuscular streptomycin (15 mg/kg once daily) and oral rifampicin (10 mg/kg once daily) for 8 weeks (8-week streptomycin group; n=76) or streptomycin and rifampicin for 4 weeks followed by rifampicin and clarithromycin (7•5 mg/kg once daily), both orally, for 4 weeks (4-week streptomycin plus 4-week clarithromycin group; n=75). The primary endpoint was lesion healing at 1 year after the start of treatment without lesion recurrence or extensive surgery.

The researchers found that 96% of patients in the 8-week streptomycin group and 91% of patients in the 4-week streptomycin plus 4-week clarithromycin group had healed lesions at 1 year. No patients had lesion recurrence at 1 year. Three participants experienced giddiness/dizziness as a result of the injected streptomycin (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, two). One participant developed an injection abscess and two participants developed an abscess close to the initial lesion, which was incised and drained (all three participants were in the 4-week streptomycin plus 4-week clarithromycin group).

The authors say: "Our study has shown that early, limited M ulcerans infection can be safely and effectively managed by antimicrobial treatment alone, without surgical debridement. The drug regimen proposed by WHO, consisting of 8 weeks of streptomycin and rifampicin, seemed effective and was not associated with deterioration requiring subsequent surgical debridement."

They conclude: "Antimycobacterial treatment for M ulcerans infection is effective in early, limited disease. 4 weeks of streptomycin and rifampicin followed by 4 weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of streptomycin and rifampicin; however, the number of injections of streptomycin can be reduced by switching to oral clarithromycin after 4 weeks."

In an accompanying Comment, Dr Paul Johnson, Infectious Diseases Department and Department of Medicine, Austin Health & University of Melbourne, and WHO Collaborating Centre for MycobacteriuM ulcerans (Western Pacific Region), Melbourne, VIC, Australia says: "Nienhuis and colleagues have established beyond reasonable doubt that early and limited Buruli can be effectively treated with antibiotics, without surgery. In so doing they have extended the excellent work of WHO, Etuaful and colleagues, and Chauty and co-workers, and established a benchmark for subsequent trials that could assess new antibiotic combinations. Skilled surgery and good rehabilitation will still be needed for some cases of Buruli disease, but the question of whether there a role for antibiotics in the treatment of Buruli ulcer has now been answered with a resounding yes."

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Professor Tjip S van der Werf, University Medical Centre Groningen, Netherlands. T) +31 50 3611501 / +31 6 23833846 E) t.s.van.der.werf@int.umcg.nl

Dr Paul Johnson, Infectious Diseases Department and Department of Medicine, Austin Health & University of Melbourne, and WHO Collaborating Centre for MycobacteriuM ulcerans (Western Pacific Region), Melbourne, VIC, Australia. T) +61 438 32 49 13 E) paul.johnson@austin.org.au

For full Article and Comment see: http://press.thelancet.com/buruli.pdf

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