Increased Severity and Spread of<i>Mycobacterium ulcerans</i>, Southeastern Australia

Tai, Alex; Athan, Eugene; Friedman, N. Deborah; Hughes, Andrew; Walton, Aaron; O’Brien, D. P.

doi:10.3201/eid2401.171070

Cited by 52 publications

(71 citation statements)

References 34 publications

(35 reference statements)

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“…This process typically results in a painless nodule which erodes the overlying skin and ulcerates . BU most commonly occurs on the limbs, but is also occasionally seen on the face, and less commonly on non‐exposed areas of skin …”

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confidence: 99%

“…Classified as one of the neglected tropical diseases by the World Health Organization (WHO), BU is a major threat to public health in sub‐Saharan Africa and discrete non‐tropical settings in Australia, especially the Bellarine and Mornington Peninsulas of South‐Eastern Victoria . Australian BU cases are steadily increasing in number, severity and geographical location .…”

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confidence: 99%

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Paediatric Buruli ulcer in Australia

Walker

Friedman

O'Brien

et al. 2019

J Paediatrics Child Health

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Aim: This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients. Methods: Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age. Results: A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery. Conclusions: Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.

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confidence: 99%

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confidence: 99%

Paediatric Buruli ulcer in Australia

Walker

Friedman

O'Brien

et al. 2019

J Paediatrics Child Health

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“…Buruli ulcer is a chronic ulcerating disease of the skin and underlying tissues caused by Mycobacterium ulcerans . The disease is regaining importance in West Africa and South East Australia with increasing incidence and severity (1, 2). The current treatment strategy involves an eight-week regimen of rifampicin administered with streptomycin or clarithromycin (3, 4).…”

Section: Textmentioning

confidence: 99%

Toward a single dose cure for Buruli ulcer

Thomas

Kalia²,

Ruf

et al. 2020

Preprint

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25A single dose of TELACEBEC (Q203), a phase 2 clinical candidate for tuberculosis, eradicates 26 Mycobacterium ulcerans in a mouse model of Buruli ulcer infection without relapse up to 19 27 weeks post treatment. Clinical use of Q203 could dramatically simplify the clinical management 28 of Buruli ulcer, a neglected mycobacterial disease. 29 Text 30 Buruli ulcer is a chronic ulcerating disease of the skin and underlying tissues caused by 31 Mycobacterium ulcerans. The disease is regaining importance in West Africa and South East 32Australia with increasing incidence and severity (1, 2). The current treatment strategy involves 33 an eight-week regimen of rifampicin administered with streptomycin or clarithromycin (3, 4). 34Disease management is complicated by an underreporting, especially in rural Africa (5), social 35 stigmata, and lack of awareness that impede the deployment of medical treatment. Inadequate 36 therapy may drive a substantial number of permanent disabilities, especially in children. 37Compliance to an eight-week therapy is also a serious limitation. 38Telacebec (Q203) is an imidazopyridine amide drug targeting the mycobacterial cytochrome 39 bcc:aa 3 terminal oxidase. The drug candidate, currently in clinical trial phase 2 for tuberculosis 40 (6), has excellent activity against M. ulcerans in vitro and in vivo (7)(8)(9). In Mycobacterium 41 3 tuberculosis, the bactericidal potency of Q203 is limited by the presence of the cytochrome bd 42 oxidase, an alternate terminal oxidase. The exquisite sensitivity of M. ulcerans to Q203 is 43 explained by the absence of a functional cytochrome bd oxidase in this species (10, 11). 44Considering the distinct potency of Q203 coupled with a long half-life and favourable 45 toxicological profile (7, 10), we evaluated the potency of a single dose of Q203 to eradicate M. 46 ulcerans in an established mouse model of Buruli ulcer infection. BALB/c mice were infected in 47 97

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“…The bacterium and associated disease has subsequently been found in several other areas of Africa including Angola [71], Benin [72], the Democratic Republic of the Congo [71], Côte D'Ivoire [73], Ghana [74], Nigeria [75], and Togo [76]. The infection also has been identified in Australia [77], and most recently Jordan [78]. While the association between the bacterium and the symptoms are well established, the mode of transmission has yet to be elucidated.…”

Section: Mycobacterium Ulceransmentioning

confidence: 99%

From hidden outbreaks to epidemic emergencies: the threat associated with neglecting emerging pathogens

Tetro

2019

Microbes and Infection

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Not all infectious disease outbreaks undergo full epidemiological investigations. In certain situations, the resultant lack of knowledge has led to the development of epidemics and public health emergencies. This review will examine six emerging pathogens including their history, present status, and potential to expand to epidemics. Recommendations to improve our understanding of these hidden outbreaks and others also will be provided in the context of health systems policy.

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Increased Severity and Spread ofMycobacterium ulcerans, Southeastern Australia

Cited by 52 publications

References 34 publications

Paediatric Buruli ulcer in Australia

Paediatric Buruli ulcer in Australia

Toward a single dose cure for Buruli ulcer

From hidden outbreaks to epidemic emergencies: the threat associated with neglecting emerging pathogens

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