Treating
            <i>Mycobacterium ulcerans</i>
            disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?

Converse, Paul J.; Nuermberger, Eric L.; Almeida, Deepak; Grosset, J

doi:10.2217/fmb.11.101

Cited by 55 publications

(53 citation statements)

References 94 publications

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“…Firstly, the mouse was too small to facilitate a proper clinical evaluation of the ulcers. Secondly, the ulcers were short-lived and progressed rapidly to necrosis, resulting in the destruction of the limb (Addo et al, 2005), as also observed later on by Converse et al (2011). These findings support the assertion that better BU animal models need to be found.…”

Section: The Mouse Footpad Modelsupporting

confidence: 61%

Methods used in preclinical assessment of anti-Buruli ulcer agents: A global perspective

Tsouh

Addo

Yeboah-Manu

et al. 2015

Journal of Pharmacological and Toxicological Methods

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Buruli ulcer (BU) caused by Mycobacterium ulcerans is the third most common chronic mycobacterial infection in humans. Approximately 5000 cases are reported annually from at least 33 countries around the globe, especially in rural African communities. Even though anti-mycobacterial therapy is often effective for early nodular or ulcerative lesions, surgery is sometimes employed for aiding wound healing and correction of deformities. The usefulness of the antibiotherapy nonetheless is challenged by huge restrictive factors such as high cost, surgical scars and loss of income due to loss of man-hours, and in some instances employment. For these reasons, more effective and safer drugs are urgently needed, and research programs into alternative therapeutics including investigation of natural products should be encouraged. There is the need for appropriate susceptibility testing methods for the evaluation of potency. A number of biological assay methodologies are in current use, ranging from the classical agar and broth dilution assay formats, to radiorespirometric, dye-based, and fluorescent/luminescence reporter assays. Mice, rats, armadillo, guinea pigs, monkeys, grass cutters and lizards have been suggested as animal models for Buruli ulcer. This review presents an overview of in vitro and in vivo susceptibility testing methods developed so far for the determination of anti-Buruli ulcer activity of natural products and derivatives.

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Section: The Mouse Footpad Modelsupporting

confidence: 61%

Methods used in preclinical assessment of anti-Buruli ulcer agents: A global perspective

Tsouh

Addo

Yeboah-Manu

et al. 2015

Journal of Pharmacological and Toxicological Methods

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“…1 The WHO recommended first-line treatment of BU is daily injection with streptomycin (SR) and oral rifampicin for 8 weeks, and if necessary, surgery either to improve healing and/or to correct deformities. 1,5,6 The efficacy of this treatment regimen has been confirmed in several studies. [7][8][9] Active lesions present with large focal clusters of extracellular acid-fast bacilli (AFB) and only minor leukocyte infiltration.…”

Section: Introductionmentioning

confidence: 81%

Challenges Associated with Management of Buruli Ulcer/Human Immunodeficiency Virus Coinfection in a Treatment Center in Ghana: A Case Series Study

Tuffour

Owusu-Mireku

Ruf

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. The synergy between Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome is well established but not so in Buruli ulcer (BU). We screened confirmed BU cases for HIV infection and followed seven BU/HIV-coinfected patients. Management of BU/HIV was based on the World Health Organization guidelines and patient condition. The HIV positivity among BU patients (8.2%; 11/134) was higher compared with that of general patients attending the facility (4.8%; 718/14,863; P = 0.07) and that of pregnant women alone (2.5%; 279/11,125; P = 0.001). All seven BU/HIV-coinfected cases enrolled in the study presented with very large (category III) lesions with four having multiple lesions compared with 54.5% of category III lesions among HIV-negative BU patients. During the recommended BU treatment with streptomycin and rifampicin (SR) all patients developed immune infiltrates including CD4 T cells in their lesions. However, one patient who received antiretroviral therapy (ART) 1 week after beginning SR treatment developed four additional lesions during antibiotic treatment, while two out of the four who did not receive ART died. Further evidence is required to ascertain the most appropriate time to commence ART in relation to SR treatment to minimize paradoxical reactions.

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“…Currently, Buruli ulcer is managed on a regimen of streptomycin and rifampicin for an eight-week period as recommended by the WHO [9, 10]. This was a shift from an initial wide surgical excision of the infected tissue, followed by skin grafting [11, 12]. In severe cases, patients are treated with antibiotics in addition to surgery.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Susceptibility ofMycobacterium ulceransIsolates to Selected Antimicrobials

Owusu

Newman

Addo

et al. 2017

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Background. The current definitive treatment of Buruli ulcer with antibiotics makes the issue of antimicrobial drug resistance an unavoidable one. This is as a result of drug misuse by health personnel and patients' noncompliance to treatment regimen. Monitoring of these factors and screening for new effective antimicrobials are crucial to effective management of Buruli ulcer disease. This study therefore investigated the inhibitory activity of some antibiotics against isolates of Mycobacterium ulcerans. Methods. Activity of eight antibiotics was tested against twelve M. ulcerans isolates (2 reference strains and 10 clinical isolates). The anti-M. ulcerans activities were determined by the agar dilution method and the minimum inhibitory concentrations (MICs) were determined by the agar proportion method. Results. All antimicrobials investigated had activity against M. ulcerans isolates tested. The MICs ranged from 0.16 μg/mL to 2.5 μg/mL. Azithromycin recorded the highest inhibitory activity at a mean MIC of 0.39 μg/mL, whilst clofazimine a second-line antileprosy drug, recorded the lowest at a mean MIC of 2.19 μg/mL. Among the four antituberculosis drugs, rifampicin had the highest activity with a mean MIC of 0.81 μg/mL. Conclusion. Azithromycin could be considered as a lucrative alternative to existing treatment methods for inhibiting M. ulcerans in Ghana.

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Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?

Cited by 55 publications

References 94 publications

Methods used in preclinical assessment of anti-Buruli ulcer agents: A global perspective

Methods used in preclinical assessment of anti-Buruli ulcer agents: A global perspective

Challenges Associated with Management of Buruli Ulcer/Human Immunodeficiency Virus Coinfection in a Treatment Center in Ghana: A Case Series Study

In Vitro Susceptibility ofMycobacterium ulceransIsolates to Selected Antimicrobials

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