Treatment of Buruli Ulcer

BU has long been treated by surgical resection. During the last two decades, it has become increasingly clear that antimicrobial treatment, first, using a combination of streptomycin 15 mg/kg i.m. and rifampin 10 mg/kg p.o. for 8 weeks, results in relapse-free cure in lesions &lt;10 cm cross-sectional diameter. Recently, a large clinical trial from Ghana and Benin showed that fully oral treatment—rifampin 10 mg/kg combined with clarithromycin—extended release, 15 mg/kg, also for 8 weeks, was equally effective but less toxic; none of the close to 300 study participants needed surgical resection, and only four had split skin grafts; sequelae were negligible. The use of other antimicrobials including fluoroquinolones has been shown to be effective in cohort studies from Australia. The role of resection surgery was studied in Benin in patients with larger lesions. Compared to patients that were operated on at week 8, a delayed decision on surgery at week 14 appeared beneficial; delay resulted in significantly less patients being operated, with reduced in-hospital treatment, and no difference in healing rate or sequelae. Sequelae such as contractures due to scar formation around joints may need specialized care in dedicated centers. General medical care with adequate nutrition and proper wound care are critical; wound saline rinsing and cleaning, dressings with non-adhesive cover, and absorptive material with short-stretch compression are all important for speedy healing. Other topical treatments (nitric oxide crème; traditional herbal remedies; clay; phenytoin) have been little studied; heat treatment might be an option for those that cannot tolerate antimicrobial treatment, such as during pregnancy. Active, early case finding has been shown to be highly efficacious.</p

Treatment of Buruli Ulcer

BU has long been treated by surgical resection. During the last two decades, it has become increasingly clear that antimicrobial treatment, first, using a combination of streptomycin 15 mg/kg i.m. and rifampin 10 mg/kg p.o. for 8 weeks, results in relapse-free cure in lesions &lt;10 cm cross-sectional diameter. Recently, a large clinical trial from Ghana and Benin showed that fully oral treatment—rifampin 10 mg/kg combined with clarithromycin—extended release, 15 mg/kg, also for 8 weeks, was equally effective but less toxic; none of the close to 300 study participants needed surgical resection, and only four had split skin grafts; sequelae were negligible. The use of other antimicrobials including fluoroquinolones has been shown to be effective in cohort studies from Australia. The role of resection surgery was studied in Benin in patients with larger lesions. Compared to patients that were operated on at week 8, a delayed decision on surgery at week 14 appeared beneficial; delay resulted in significantly less patients being operated, with reduced in-hospital treatment, and no difference in healing rate or sequelae. Sequelae such as contractures due to scar formation around joints may need specialized care in dedicated centers. General medical care with adequate nutrition and proper wound care are critical; wound saline rinsing and cleaning, dressings with non-adhesive cover, and absorptive material with short-stretch compression are all important for speedy healing. Other topical treatments (nitric oxide crème; traditional herbal remedies; clay; phenytoin) have been little studied; heat treatment might be an option for those that cannot tolerate antimicrobial treatment, such as during pregnancy. Active, early case finding has been shown to be highly efficacious.</p

Pharmacologic management of Mycobacterium ulcerans infection

Introduction: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. Areas covered: We review BU drug treatment–in vitro, in vivo and clinical trials (PubMed: ‘(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).’ We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. Expert opinion: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer

Buruli ulcer treatment:Rate of surgical intervention differs highly between treatment centers in West Africa

BACKGROUND: Antibiotic treatment proved itself as the mainstay of treatment for Buruli ulcer disease. This neglected tropical disease is caused by Mycobacterium ulcerans. Surgery persists as an adjunct therapy intended to reduce the mycobacterial load. In an earlier clinical trial, patients benefited from delaying the decision to operate. Nevertheless, the rate of surgical interventions differs highly per clinic. METHODS: A retrospective study was conducted in six different Buruli ulcer (BU) treatment centers in Benin and Ghana. BU patients clinically diagnosed between January 2012 and December 2016 were included and surgical interventions during the follow-up period, at least one year after diagnosis, were recorded. Logistic regression analysis was carried out to estimate the effect of the treatment center on the decision to perform surgery, while controlling for interaction and confounders. RESULTS: A total of 1193 patients, 612 from Benin and 581 from Ghana, were included. In Benin, lesions were most frequently (42%) categorized as the most severe lesions (WHO criteria, category III), whereas in Ghana lesions were most frequently (44%) categorized as small lesions (WHO criteria, category I). In total 344 (29%) patients received surgical intervention. The percentage of patients receiving surgical intervention varied between hospitals from 1.5% to 72%. Patients treated in one of the centers in Benin were much more likely to have surgery compared to the clinic in Ghana with the lowest rate of surgical intervention (RR = 46.7 CI 95% [17.5-124.8]). Even after adjusting for confounders (severity of disease, age, sex, limitation of movement at joint at time of diagnosis, ulcer and critical sites), rates of surgical interventions varied highly. CONCLUSION: The decision to perform surgery to reduce the mycobacterial load in BU varies highly per clinic. Evidence based guidelines are needed to guide the role of surgery in the treatment of BU

Assessment and Treatment of Pain during Treatment of Buruli Ulcer

BACKGROUND:Buruli ulcer (BU) is described as a relatively painless condition; however clinical observations reveal that patients do experience pain during their treatment. Knowledge on current pain assessment and treatment in BU is necessary to develop and implement a future guideline on pain management in BU. METHODOLOGY:A mixed methods approach was used, consisting of information retrieved from medical records on prescribed pain medication from Ghana and Benin, and semi-structured interviews with health care personnel (HCP) from Ghana on pain perceptions, assessment and treatment. Medical records (n = 149) of patients treated between 2008 and 2012 were collected between November 2012 and August 2013. Interviews (n = 11) were audio-taped, transcribed verbatim and qualitatively analyzed. PRINCIPAL FINDINGS:In 113 (84%) of the 135 included records, pain medication, mostly simple analgesics, was prescribed. In 48% of the prescriptions, an indication was not documented. HCP reported that advanced BU could be painful, especially after wound care and after a skin graft. They reported not be trained in the assessment of mild pain. Pain recognition was perceived as difficult, as patients were said to suppress or to exaggerate pain, and to have different expectations regarding acceptable pain levels. HCP reported a fear of side effects of pain medication, shortage and irregularities in the supply of pain medication, and time constraints among medical doctors for pain management. CONCLUSIONS:Professionals perceived BU disease as potentially painful, and predominantly focused on severe pain. Our study suggests that pain in BU deserves attention and should be integrated in current treatment

Family Relationship, Water Contact and Occurrence of Buruli Ulcer in Benin

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This case control study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). The study involved 416 participants, of which 104 BU-confirmed cases and 312 age, gender and village of residence matched controls (persons who had no signs or symptoms of active or inactive BU). The results confirmed that contact with natural water sources is a risk factor. Furthermore, it suggests that a combination of genetic factors may constitute risk factors for the development of BU, possibly by influencing the type of immune response in the individual, and, consequently, the development of BU infection per se and its different clinical forms. These findings may be of major therapeutic interest

Pharmacologic management of Mycobacterium ulcerans infection

Introduction: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. Areas covered: We review BU drug treatment–in vitro, in vivo and clinical trials (PubMed: ‘(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).’ We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. Expert opinion: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer.</p

Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin:a randomised controlled trial

BACKGROUND: Surgical intervention was once the mainstay of treatment for Buruli ulcer disease, a neglected tropical disease caused by Mycobacterium ulcerans. Since the introduction of streptomycin and rifampicin for 8 weeks as standard care, surgery has persisted as an adjunct therapy, but its role is uncertain. We investigated the effect of delaying the decision to operate to 14 weeks on rates of healing without surgery. METHODS: In this randomised controlled trial, we enrolled patients aged 3 years or older with confirmed disease at one hospital in Lalo, Benin. Patients were randomly assigned (1:1) to groups assessing the need for excision surgery 8 weeks (standard care) or 14 weeks after initiation of antimicrobial treatment. The primary endpoint was the number of patients healed without the need for surgery (not including skin grafting), assessed in all patients in follow-up at 50 weeks (or last observation for those healed for >10 weeks). A doctor masked to treatment assignment checked the indications for surgery according to predefined criteria. This study is registered with ClinicalTrials.gov, number NCT01432925. FINDINGS: Between July 1, 2011, and Jan 15, 2015, 119 patients were enrolled, with two patients per group lost to follow-up. 55 (96%) of 57 participants in the delayed-decision group and 52 (90%) of 58 participants in the standard-care group had healed lesions 1 year after start of antimicrobial treatment (relative risk [RR] 1·08, 95% CI 0·97-1·19). 37 (67%) of 55 patients in the delayed-decision group had their lesions healed without surgical intervention, as did 25 (48%) of 52 in the standard-care group (RR 1·40, 95% CI 1·00-1·96). The time to heal and residual functional limitations did not differ between the two groups (median time to heal 21 weeks [IQR 10-27] in the delayed-decision group and 21 weeks [10-39] in the standard-care group; functional limitations in six [11%] of 57 and three [5%] of 58 patients; p=0·32). Postponing the decision to operate resulted in reduced median duration of hospitalisation (5 days [IQR 0-187] vs 131 days [0-224]; p=0·024) and wound care (153 days [IQR 56-224] vs 182 days [94-307]; p=0·036). INTERPRETATION: In our study, patients treated for Buruli ulcer benefited from delaying the decision to operate. Even large ulcers can heal with antibiotics alone, without delaying healing rate and without an increase in residual functional limitations. FUNDING: NWO-VENI grant 241500, BUG Foundation, and UBS OPTIMUS

Assessment and Treatment of Pain during Treatment of Buruli Ulcer Citation for published version (APA): Assessment and Treatment of Pain during Treatment of Buruli Ulcer

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