Pilot Randomized Double-Blind Trial of Treatment of Mycobacterium ulcerans Disease (Buruli Ulcer) with Topical Nitrogen Oxides
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Date
2004-08
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Publisher
Antimicrobial Agents and Chemotherapy
Abstract
Mycobacterium ulcerans disease (Buruli ulcer) is a serious ulcerating skin disease which is common in many
tropical countries. Standard treatment, by extensive excision and skin grafting, is not available in rural
communities where the disease is common. We evaluated the efficacy and safety of treatment with topical
nitrogen oxides. Thirty-seven patients with a clinical diagnosis of Buruli ulcer caused by M. ulcerans disease
were randomly assigned to one of two groups. In one group, two creams containing sodium nitrite (6%, wt/wt)
or citric acid monohydrate (9%, wt/wt) were applied daily for 6 weeks, while the other group received a placebo.
In the second 6 weeks, both groups received the nitrogen oxide-generating combination of creams. Treatment
was continued for another 4 weeks for patients whose ulcers were not healed after 12 weeks. The ulcer surface
area was monitored by weekly tracings made by assessors blinded to the treatment. In the first 6 weeks, patients
on sodium nitrite and citric acid monohydrate (group I, active treatment) showed a rapid decrease in ulcer size
from 28.6 5.6 cm2 (mean standard error) to 12.6 3.2 cm2, a decrease significantly greater than that in
group II (from 15.3 3.1 to 11.7 3.7 cm2; P 0.03). Five ulcers in the placebo group enlarged during this
period, compared with one in the active group. In the second 6 weeks (both groups on active treatment), the
rates of healing were similar for the two groups and there was a significant reduction in ulcer size in group II
(previously on placebo) compared to the first 6 weeks. Yellow pigmentation of the skin, which disappeared 3
days after treatment was stopped, was the only side effect to date. We conclude that creams releasing nitrogen
oxides increase the healing rate of ulcers caused by M. ulcerans infection with minimal adverse events. This is
the first controlled trial of any form of therapy which demonstrates efficacy in treating this disease.
Description
An article published by Antimicrobial Agents and Chemotherapy and is available at DOI: 10.1128/AAC.48.8.2866–2870.2004
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Citation
Antimicrobial Agents and Chemotherapy Vol. 48, No. 8