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Background: Buruli ulcer has been increasing in incidence in southeastern Australia with unclear transmission mechanisms. We aimed to investigate the link between rainfall and case numbers in two endemic areas of the state of Victoria; the Bellarine and Mornington Peninsulas. Methodology: We created yearly and monthly graphs comparing rainfall with local Buruli ulcer incidence for the period 2004–2016 by endemic region and then considered a range of time lag intervals of 0–24 months to investigate patterns of correlation. Conclusions: Optimal positive correlation for the Bellarine Peninsula occurred with a 12-month prior rainfall lag, however, no significant correlation was observed on the Mornington Peninsula for any time lag. These results provide an update in evidence to further explore transmission mechanisms which may differ between these geographically proximate endemic regions. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a geographically-restricted infection caused by Mycobacterium ulcerans; contact with an endemic region is the primary risk factor for disease acquisition. Globally, efforts to estimate the incubation period of BU are often hindered as most patients reside permanently in endemic areas. However, in the south-eastern Australian state of Victoria, a significant proportion of people who acquire BU are visitors to endemic regions. During a sustained outbreak of BU on the Bellarine peninsula we estimated a mean incubation period of 4.5 months. Since then cases on the Bellarine peninsula have declined but a new endemic area has developed centred on the Mornington peninsula. Method: Retrospective review of 443 cases of BU notified in Victoria between 2013 and 2016. Telephone interviews were performed to identify all cases with a single visit to an endemic region, or multiple visits within a one month period. The incubation period was defined as the time between exposure to an endemic region and symptom onset. Data were subsequently combined with those from our earlier study incorporating cases from 2002 to 2012. Results: Among the 20 new cases identified in short-term visitors, the mean incubation period was 143 days (4.8 months), very similar to the previous estimate of 135 days (4.5 months). This was despite the predominant exposure location shifting from the Bellarine peninsula to the Mornington peninsula. We found no association between incubation period and age, sex, location of exposure, duration of exposure to an endemic region or location of BU lesion. Conclusions: Our study confirms the mean incubation period of BU in Victoria to be between 4 and 5 months. This knowledge can guide clinicians and suggests that the mode of transmission of BU is similar in different geographic regions in Victoria. [ABSTRACT FROM AUTHOR]

Background: The origin and spread of tuberculosis (TB) in Tasmania and the types of strains of Mycobacterium tuberculosis complex (MTBC) present in the population are largely unknown. Objective: The aim of this study was to perform the first genomic analysis of MTBC isolates from Tasmania to better understand the epidemiology of TB in the state. Methods: Whole-genome sequencing was performed on cultured isolates of MTBC collected from 2014–2016. Single-locus variant analysis was applied to determine the phylogeny of the isolates and the presence of drug-resistance mutations. The genomic data were then cross-referenced against public health surveillance records on each of the cases. Results: We determined that 83.3% of TB cases in Tasmania from 2014–2016 occurred in non-Australian born individuals. Two possible TB clusters were identified based on single locus variant analysis, one from November-December 2014 (n = 2), with the second from May-August 2015 (n = 4). We report here the first known isolate of multi-drug resistant (MDR) M. tuberculosis in Tasmania from 2016 for which we established its drug resistance mutations and potential overseas origin. In addition, we characterised a case of M. bovis TB in a Tasmanian-born person who presented in 2014, approximately 40 years after the last confirmed case in the state’s bovids. Conclusions: TB in Tasmania is predominantly of overseas origin with genotypically-unique drug-susceptible isolates of M. tuberculosis. However, the state also exhibits features of TB that are observed in other jurisdictions, namely, the clustering of cases, and drug resistance. Early detection of TB and contact tracing, particularly of overseas-born cases, coordinated with rapid laboratory drug-susceptibility testing and molecular typing, will be essential for Tasmania to reach the World Health Organisation’s TB eradication goals for low-incidence settings. [ABSTRACT FROM AUTHOR]

Introduction: Mycobacterium ulcerans (M. ulcerans) is a necrotizing skin infection endemic to the Bellarine Peninsula, Australia. Current treatment recommendations include 8 weeks of combination antibiotics, with adjuvant surgery if necessary. However, antibiotic toxicity often results in early treatment cessation and local experience suggests that shorter antibiotic courses may be effective with concurrent surgery. We report the outcomes of patients in the Barwon Health M. ulcerans cohort who received shorter courses of antibiotic therapy than 8 weeks. Methodology / Principal findings: A retrospective analysis was performed of all M. ulcerans infections treated at Barwon Health from March 1, 1998 to July 31, 2013. Sixty-two patients, with a median age of 65 years, received < 56 days of antibiotics and 51 (82%) of these patients underwent concurrent surgical excision. Most received a two-drug regimen of rifampicin combined with either ciprofloxacin or clarithromycin for a median 29 days (IQR 21–41days). Cessation rates were 55% for adverse events and 36% based on clinician decision. The overall success rate was 95% (98% with concurrent surgery; 82% with antibiotics alone) with a 50% success rate for those who received < 14 days of antibiotics increasing to 94% if they received 14–27 days and 100% for 28–55 days (p<0.01). A 100% success rate was seen for concurrent surgery and 14–27 days of antibiotics versus 67% for concurrent surgery and < 14 days of antibiotics (p = 0.12). No previously identified risk factors for treatment failure with surgery alone were associated with reduced treatment success rates with < 56 days of antibiotics. Conclusion: In selected patients, antibiotic treatment durations for M. ulcerans shorter than the current WHO recommended 8 weeks duration may be associated with successful outcomes. Author Summary: Buruli ulcer is a necrotizing skin and subcutaneous tissue infection caused by Mycobacterium ulcerans and is the third most common mycobacterial infection, behind tuberculosis and leprosy, world-wide. In recent years, the World Health Organisation has modified its guidelines for M. ulcerans treatment, moving from predominantly surgical to predominantly medical based management. It now recommends the combination of oral rifampicin and intramuscular streptomycin for a period of eight weeks as first-line therapy, with surgery as adjunctive therapy if necessary. The Barwon Health experience from south-eastern Australia has demonstrated that the entirely oral combination of rifampicin with either ciprofloxacin or clarithromycin for eight weeks can be an effective treatment option. However, these antibiotics are often toxic leading to early cessation, especially in the elderly. In addition, clinicians have been using a shorter duration of therapy for smaller lesions that have also been surgically managed. This study reviews our experience treating M. ulcerans with antibiotic durations of less than 8 weeks and demonstrates that successful outcomes can be achieved in selected patients, with success rates influenced by the duration of treatment and the use of surgical excision. This finding needs confirmation in further studies, but could have significant benefits in terms of reducing toxicity and improving adherence associated with Buruli ulcer antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a necrotizing disease of the skin, soft tissue and bone. PCR is increasingly used in the diagnosis of BU and in research on the mode of transmission and environmental reservoir of M. ulcerans. Methodology/Principal Findings: The aim of this study was to evaluate the performance of laboratories in detecting M. ulcerans using molecular tests in clinical and environmental samples by implementing sequential multicenter external quality assessment (EQA) programs. The second round of the clinical EQA program revealed somewhat improved performance. Conclusions/Significance: Ongoing EQA programs remain essential and continued participation in future EQA programs by laboratories involved in the molecular testing of clinical and environmental samples for M. ulcerans for diagnostic and research purposes is strongly encouraged. Broad participation in such EQA programs also benefits the harmonization of quality in the BU research community and enhances the credibility of advances made in solving the transmission enigma of M. ulcerans. [ABSTRACT FROM AUTHOR]

The last 20 years has seen a significant series of outbreaks of Buruli/Bairnsdale Ulcer (BU), caused by Mycobacterium ulcerans, in temperate south-eastern Australia (state of Victoria). Here, the prevailing view of M. ulcerans as an aquatic pathogen has been questioned by recent research identifying native wildlife as potential terrestrial reservoirs of infection; specifically, tree-dwelling common ringtail and brushtail possums. In that previous work, sampling of environmental possum faeces detected a high prevalence of M. ulcerans DNA in established endemic areas for human BU on the Bellarine Peninsula, compared with non-endemic areas. Here, we report research from an emergent BU focus recently identified on the Mornington Peninsula, confirming associations between human BU and the presence of the aetiological agent in possum faeces, detected by real-time PCR targeting M. ulcerans IS2404, IS2606 and KR. Mycobacterium ulcerans DNA was detected in 20/216 (9.3%) ground collected ringtail possum faecal samples and 4/6 (66.6%) brushtail possum faecal samples. The distribution of the PCR positive possum faecal samples and human BU cases was highly focal: there was a significant non-random cluster of 16 M. ulcerans positive possum faecal sample points detected by spatial scan statistics (P<0.0001) within a circle of radius 0.42 km, within which were located the addresses of 6/12 human cases reported from the area to date; moreover, the highest sample PCR signal strength (equivalent to ≥106 organisms per gram of faeces) was found in a sample point located within this cluster radius. Corresponding faecal samples collected from closely adjacent BU-free areas were predominantly negative. Possums may be useful sentinels to predict endemic spread of human BU in Victoria, for public health planning. Further research is needed to establish whether spatial associations represent evidence of direct or indirect transmission between possums and humans, and the mechanism by which this may occur. Author Summary: Mycobacterium ulcerans causes the disfiguring human skin disease Buruli ulcer (BU). The mechanism of transmission and reservoir for human infection remain unknown. In previous research, we reported the detection of M. ulcerans DNA in the faeces of possums (small tree-dwelling marsupials) in an area of South-East Australia (the Bellarine peninsula) where the largest recorded outbreak of human BU has been in progress for the last decade. The current study was carried out in a new outbreak area (the Mornington peninsula), and describes the detection of M. ulcerans DNA in possum faeces collected from the ground, in locations which correspond closely with the addresses of human BU cases. The association of new human BU cases with areas where M. ulcerans positive possum faeces are found contributes further evidence to the possible role of possums as an environmental reservoir of infection. Possums may be useful sentinel animals to monitor the spread of BU in Australia. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans, with endemicity predominantly in sub-Saharan Africa and south-eastern Australia. The mode of transmission and the environmental reservoir(s) of the bacterium and remain elusive. Real-time PCR investigations have detected M. ulcerans DNA in a variety of Australian environmental samples, including the faeces of native possums with and without clinical evidence of infection. This report seeks to expand on previously published findings by the authors' investigative group with regards to clinical and subclinical disease in selected wild possum species in BU-endemic areas of Victoria, Australia. Methodology/Principal Findings: Twenty-seven clinical cases of M. ulcerans infection in free-ranging possums from southeastern Australia were identified retrospectively and prospectively between 1998–2011. Common ringtail possums (Pseudocheirus peregrinus), a common brushtail possum (Trichosurus vulpecula) and a mountain brushtail possum (Trichosurus cunninghami) were included in the clinically affected cohort. Most clinically apparent cases were adults with solitary or multiple ulcerative cutaneous lesions, generally confined to the face, limbs and/or tail. The disease was minor and self-limiting in the case of both Trichosurus spp. possums. In contrast, many of the common ringtail possums had cutaneous disease involving disparate anatomical sites, and in four cases there was evidence of systemic disease at post mortem examination. Where tested using real-time PCR targeted at IS2404, animals typically had significant levels of M. ulcerans DNA throughout the gut and/or faeces. A further 12 possums without cutaneous lesions were found to have PCR-positive gut contents and/or faeces (subclinical cases), and in one of these the organism was cultured from liver tissue. Comparisons were made between clinically and subclinically affected possums, and 61 PCR-negative, non-affected individuals, with regards to disease category and the categorical variables of species (common ringtail possums v others) and sex. Animals with clinical lesions were significantly more likely to be male common ringtail possums. Conclusions/Significance: There is significant disease burden in common ringtail possums (especially males) in some areas of Victoria endemic for M. ulcerans disease. The natural history of the disease generally remains unknown, however it appears that some mildly affected common brushtail and mountain brushtail possums can spontaneously overcome the infection, whereas some severely affected animals, especially common ringtail possums, may become systemically, and potentially fatally affected. Subclinical gut carriage of M. ulcerans DNA in possums is quite common and in some common brushtail and mountain brushtail possums this is transient. Further work is required to determine whether M. ulcerans infection poses a potential threat to possum populations, and whether these animals are acting as environmental reservoirs in certain geographical areas. Author Summary: Mycobacterium ulcerans causes skin disease predominantly in sub-Saharan Africa and southeastern Australia. The mode of transmission and the environmental reservoir(s) of the bacterium are unknown. Investigations have detected M. ulcerans DNA in a variety of Australian environmental samples, including the faeces of native possums. This report expands on these studies by detailing the clinical, pathological and microbiological findings in affected wild possum species in endemic areas. Twenty-seven clinically and 12 subclinically affected individuals were identified. Most clinical cases were adults with skin ulcers of the face, limbs and/or tail. The disease was mild and self-limiting in both Trichosurus spp. possums. In contrast, many of the common ringtail possums had multiple skin ulcers and in some there was evidence of internal disease. There were also significant levels of M. ulcerans DNA throughout the gut. Comparisons were made with regards to disease category, species and sex; with clinical cases more likely to be male common ringtail possums. Asymptomatic gut carriage of M. ulcerans DNA is quite common and may be transient in some individuals. Further work is needed to determine whether M. ulcerans infection poses a potential threat to possum populations, and whether these animals are acting as reservoirs in some areas. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans, with endemicity predominantly in sub-Saharan Africa and south-eastern Australia. The mode of transmission and the environmental reservoir(s) of the bacterium and remain elusive. Real-time PCR investigations have detected M. ulcerans DNA in a variety of Australian environmental samples, including the faeces of native possums with and without clinical evidence of infection. This report seeks to expand on previously published findings by the authors' investigative group with regards to clinical and subclinical disease in selected wild possum species in BU-endemic areas of Victoria, Australia. Methodology/Principal Findings: Twenty-seven clinical cases of M. ulcerans infection in free-ranging possums from southeastern Australia were identified retrospectively and prospectively between 1998–2011. Common ringtail possums (Pseudocheirus peregrinus), a common brushtail possum (Trichosurus vulpecula) and a mountain brushtail possum (Trichosurus cunninghami) were included in the clinically affected cohort. Most clinically apparent cases were adults with solitary or multiple ulcerative cutaneous lesions, generally confined to the face, limbs and/or tail. The disease was minor and self-limiting in the case of both Trichosurus spp. possums. In contrast, many of the common ringtail possums had cutaneous disease involving disparate anatomical sites, and in four cases there was evidence of systemic disease at post mortem examination. Where tested using real-time PCR targeted at IS2404, animals typically had significant levels of M. ulcerans DNA throughout the gut and/or faeces. A further 12 possums without cutaneous lesions were found to have PCR-positive gut contents and/or faeces (subclinical cases), and in one of these the organism was cultured from liver tissue. Comparisons were made between clinically and subclinically affected possums, and 61 PCR-negative, non-affected individuals, with regards to disease category and the categorical variables of species (common ringtail possums v others) and sex. Animals with clinical lesions were significantly more likely to be male common ringtail possums. Conclusions/Significance: There is significant disease burden in common ringtail possums (especially males) in some areas of Victoria endemic for M. ulcerans disease. The natural history of the disease generally remains unknown, however it appears that some mildly affected common brushtail and mountain brushtail possums can spontaneously overcome the infection, whereas some severely affected animals, especially common ringtail possums, may become systemically, and potentially fatally affected. Subclinical gut carriage of M. ulcerans DNA in possums is quite common and in some common brushtail and mountain brushtail possums this is transient. Further work is required to determine whether M. ulcerans infection poses a potential threat to possum populations, and whether these animals are acting as environmental reservoirs in certain geographical areas. [ABSTRACT FROM AUTHOR]

Introduction: Buruli Ulcer (BU) is caused by the environmental microbe Mycobacterium ulcerans. Despite unclear transmission, contact with a BU endemic region is the key known risk factor. In Victoria, Australia, where endemic areas have been carefully mapped, we aimed to estimate the Incubation Period (IP) of BU by interviewing patients who reported defined periods of contact with an endemic area prior to BU diagnosis. Method: A retrospective review was undertaken of 408 notifications of BU in Victoria from 2002 to 2012. Telephone interviews using a structured questionnaire and review of notification records were performed. Patients with a single visit exposure to a defined endemic area were included and the period from exposure to disease onset determined (IP). Results: We identified 111 of 408 notified patients (27%) who had a residential address outside a known endemic area, of whom 23 (6%) reported a single visit exposure within the previous 24 months. The median age of included patients was 30 years (range: 6 to 73) and 65% were male. 61% had visited the Bellarine Peninsula, currently the most active endemic area. The median time from symptom onset to diagnosis was 71 days (range: 34–204 days). The midpoint of the reported IP range was utilized to calculate a point estimate of the IP for each case. Subsequently, the mean IP for the cohort was calculated at 135 days (IQR: 109–160; CI 95%: 113.9–156), corresponding to 4.5 months or 19.2 weeks. The shortest IP recorded was 32 days and longest 264 days (Figure 1 & 2). IP did not vary for variables investigated. Conclusions: The estimated mean IP of BU in Victoria is 135 days (IQR: 109–160 days), 4.5 months. The shortest recorded was IP 34 days and longest 264 days. A greater understanding of BU IP will aid clinical risk assessment and future research. Author Summary: Buruli Ulcer (BU) is a necrotizing skin infection caused by the environmental organism Mycobacterium ulcerans. Despite an unknown mode of transmission, contact with a BU endemic region is the known key risk factor. In Victoria, Australia, endemic areas have been carefully mapped and patients are known to report single visits or defined exposures to these areas. From a retrospective review, we identified 23 patients with a single visit exposure to BU endemic regions from a total of 408 notifications of BU in Victoria (2002–2012). We were able to estimate the time from exposure to disease onset, incubation period (IP), via notification record review and telephone questionnaire. The IP of the cohort was subsequently estimated at 4.5 months (Range 1–9 months). An understanding of the IP of BU will be of value to communities, clinicians and government health bodies via aiding clinical risk assessment, epidemiological studies and public health investigations in the future. [ABSTRACT FROM AUTHOR]

Introduction: Buruli Ulcer (BU) is caused by the environmental microbe Mycobacterium ulcerans. Despite unclear transmission, contact with a BU endemic region is the key known risk factor. In Victoria, Australia, where endemic areas have been carefully mapped, we aimed to estimate the Incubation Period (IP) of BU by interviewing patients who reported defined periods of contact with an endemic area prior to BU diagnosis. Method: A retrospective review was undertaken of 408 notifications of BU in Victoria from 2002 to 2012. Telephone interviews using a structured questionnaire and review of notification records were performed. Patients with a single visit exposure to a defined endemic area were included and the period from exposure to disease onset determined (IP). Results: We identified 111 of 408 notified patients (27%) who had a residential address outside a known endemic area, of whom 23 (6%) reported a single visit exposure within the previous 24 months. The median age of included patients was 30 years (range: 6 to 73) and 65% were male. 61% had visited the Bellarine Peninsula, currently the most active endemic area. The median time from symptom onset to diagnosis was 71 days (range: 34–204 days). The midpoint of the reported IP range was utilized to calculate a point estimate of the IP for each case. Subsequently, the mean IP for the cohort was calculated at 135 days (IQR: 109–160; CI 95%: 113.9–156), corresponding to 4.5 months or 19.2 weeks. The shortest IP recorded was 32 days and longest 264 days (Figure 1 & 2). IP did not vary for variables investigated. Conclusions: The estimated mean IP of BU in Victoria is 135 days (IQR: 109–160 days), 4.5 months. The shortest recorded was IP 34 days and longest 264 days. A greater understanding of BU IP will aid clinical risk assessment and future research. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans (M. ulcerans), is a necrotizing skin disease found in more than 30 countries worldwide. BU incidence is highest in West Africa; however, cases have substantially increased in coastal regions of southern Australia over the past 30 years. Although the mode of transmission remains uncertain, the spatial pattern of BU emergence in recent years seems to suggest that there is an environmental niche for M. ulcerans and BU prevalence. Methodology/Principal Findings: Network analysis was applied to BU cases in Victoria, Australia, from 1981-2008. Results revealed a non-random spatio-temporal pattern at the regional scale as well as a stable and efficient BU disease network, indicating that deterministic factors influence the occurrence of this disease. Monthly BU incidence reported by locality was analyzed with landscape and climate data using a multilevel Poisson regression approach. The results suggest the highest BU risk areas occur at low elevations with forested land cover, similar to previous studies of BU risk in West Africa. Additionally, climate conditions as far as 1.5 years in advance appear to impact disease incidence. Warmer and wetter conditions 18-19 months prior to case emergence, followed by a dry period approximately 5 months prior to case emergence seem to favor the occurrence of BU. Conclusions/Significance: The BU network structure in Victoria, Australia, suggests external environmental factors favor M. ulcerans transmission and, therefore, BU incidence. A unique combination of environmental conditions, including land cover type, temperature and a wet-dry sequence, may produce habitat characteristics that support M. ulcerans transmission and BU prevalence. These findings imply that future BU research efforts on transmission mechanisms should focus on potential vectors/reservoirs found in those environmental niches. Further, this study is the first to quantitatively estimate environmental lag times associated with BU outbreaks, providing insights for future transmission investigations. [ABSTRACT FROM AUTHOR]

Background: Previous analyses of sera from a limited number of Ghanaian Buruli ulcer (BU) patients, their household contacts, individuals living in BU non-endemic regions as well as European controls have indicated that antibody responses to the M. ulcerans 18 kDa small heat shock protein (shsp) reflect exposure to this pathogen. Here, we have investigated to what extent inhabitants of regions in Ghana regarded as non-endemic for BU develop anti-18 kDa shsp antibody titers. Methodology/Principal Findings: For this purpose we determined anti-18 kDa shsp IgG titers in sera collected from healthy inhabitants of the BU endemic Densu River Valley and the Volta Region, which was so far regarded as BU non-endemic. Significantly more sera from the Densu River Valley contained anti-18 kDa shsp IgG (32% versus 12%, respectively). However, some sera from the Volta Region also showed high titers. When interviewing these sero-responders, it was revealed that the person with the highest titer had a chronic wound, which was clinically diagnosed and laboratory reconfirmed as active BU. After identification of this BU index case, further BU cases were clinically diagnosed by the Volta Region local health authorities and laboratory reconfirmed. Interestingly, there was neither a difference in sero-prevalence nor in IS2404 PCR positivity of environmental samples between BU endemic and non-endemic communities located in the Densu River Valley. Conclusions: These data indicate that the intensity of exposure to M. ulcerans in endemic and non-endemic communities along the Densu River is comparable and that currently unknown host and/or pathogen factors may determine how frequently exposure is leading to clinical disease. While even high serum titers of anti-18 kDa shsp IgG do not indicate active disease, sero-epidemiological studies can be used to identify new BU endemic areas. Author Summary: Sero-epidemiological analyses revealed that a higher proportion of sera from individuals living in the Buruli ulcer (BU) endemic Densu River Valley of Ghana contain Mycobacterium ulcerans 18 kDa small heat shock protein (shsp)-specific IgG than sera from inhabitants of the Volta Region, which was regarded so far as BU non-endemic. However, follow-up studies in the Volta Region showed that the individual with the highest anti-18 kDa shsp-specific serum IgG titer of all participants from the Volta Region had a BU lesion. Identification of more BU patients in the Volta Region by subsequent active case search demonstrated that sero-epidemiology can help identify low endemicity areas. Endemic and non-endemic communities along the Densu River Valley differed neither in sero-prevalence nor in positivity of environmental samples in PCR targeting M. ulcerans genomic and plasmid DNA sequences. A lower risk of developing M. ulcerans disease in the non-endemic communities may either be related to host factors or a lower virulence of local M. ulcerans strains. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a destructive skin condition caused by infection with the environmental bacterium, Mycobacterium ulcerans. The mode of transmission of M. ulcerans is not completely understood, but several studies have explored the role of biting insects. In this study, we tested for an association between the detection of M. ulcerans in mosquitoes and the risk of BU disease in humans in an endemic area of southeastern Australia. Methodology/Principal Findings: Adult mosquitoes were trapped in seven towns on the Bellarine Peninsula in Victoria, Australia, from December 2004 to December 2009 and screened for M. ulcerans by real-time PCR. The number of laboratory-confirmed cases of BU in permanent residents of these towns diagnosed during the same period was tallied to determine the average cumulative incidence of BU in each location. Pearson's correlation coefficient (r) was calculated for the proportion of M. ulcerans-positive mosquitoes per town correlated with the incidence of BU per town. We found a strong dose-response relationship between the detection of M. ulcerans in mosquitoes and the risk of human disease (r, 0.99; 95% CI, 0.92–0.99; p<0.001). Conclusions/Significance: The results of this study strengthen the hypothesis that mosquitoes are involved in the transmission of M. ulcerans in southeastern Australia. This has implications for the development of intervention strategies to control and prevent BU. Author Summary: Buruli ulcer (BU) is a destructive skin condition caused by infection with the environmental bacterium, Mycobacterium ulcerans. BU has been reported in more than 30 countries in Africa, the Americas, Asia and the Western Pacific. How people become infected with M. ulcerans is not completely understood, but numerous studies have explored the role of biting insects. In 2007, it was discovered that M. ulcerans could be detected in association with mosquitoes trapped in one town in southeastern Australia during a large outbreak of BU. In the present study we investigated whether there was a relationship between the incidence of BU in humans in several towns and the likelihood of detecting M. ulcerans in mosquitoes trapped in those locations. We found a strong association between the proportion of M. ulcerans-positive mosquitoes and the incidence of human disease. The results of this study strengthen the hypothesis that mosquitoes are involved in the transmission of M. ulcerans in southeastern Australia. This has implications for the development of strategies to control and prevent BU. [ABSTRACT FROM AUTHOR]

It has recently been shown that in a Buruli ulcer (BU) endemic region of southeastern Australia, significant numbers of possums (native tree-dwelling marsupials) have clinical BU disease. Furthermore, based on quantitative PCR (qPCR) analysis, animals with BU lesions (and some without) shed M. ulcerans DNA in their faeces, indicative of bacterial loads of up to 108 organisms/gram. These findings led us to propose that humans might also harbour M. ulcerans in their gastrointestinal tract and shed the bacterium in their faeces. We conducted a pilot study and collected faecal swabs from 26 patients with confirmed BU and 31 healthy household controls. Faecal samples were also collected from 10 healthy controls from nonendemic regions in Ghana. All 67 specimens were negative when tested by IS2404 PCR. The detection sensitivity of this method was ≥104, bacteria per gram (wet-weight) of human faecal material. We conclude that the human gastrointestinal tract is unlikely to be a significant reservoir of M. ulcerans. [ABSTRACT FROM AUTHOR]

This article explores the treatment of Buruli ulcer (BU), a skin infection caused by Mycobacterium ulcerans. Traditionally, surgery has been the main treatment, but recent studies have shown the effectiveness of oral antibiotics. The article presents four cases where patients were treated with oral antibiotics, either followed by surgery or as the sole treatment. After several weeks of antibiotic therapy, three patients showed no signs of the bacteria. The article provides detailed information about the patients' characteristics, diagnosis, treatment, and histopathology. It suggests that using oral antibiotics before surgery may simplify management and prevent relapse. [Extracted from the article]

Background: Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a destructive skin disease found predominantly in sub-Saharan Africa and south-eastern Australia. The precise mode(s) of transmission and environmental reservoir(s) remain unknown, but several studies have explored the role of aquatic invertebrate species. The purpose of this study was to investigate the environmental distribution of M. ulcerans in south-eastern Australia. Methodology/Principal Findings: A range of environmental samples was collected from Point Lonsdale (a small coastal town southwest of Melbourne, Australia, endemic for BU) and from areas with fewer or no reported incident cases of BU. Mycobacterium ulcerans DNA was detected at low levels by real-time PCR in soil, sediment, water residue, aquatic plant biofilm and terrestrial vegetation collected in Point Lonsdale. Higher levels of M. ulcerans DNA were detected in the faeces of common ringtail (Pseudocheirus peregrinus) and common brushtail (Trichosurus vulpecula) possums. Systematic testing of possum faeces revealed that M. ulcerans DNA could be detected in 41% of faecal samples collected in Point Lonsdale compared with less than 1% of faecal samples collected from non-endemic areas (p<0.0001). Capture and clinical examination of live possums in Point Lonsdale validated the accuracy of the predictive value of the faecal surveys by revealing that 38% of ringtail possums and 24% of brushtail possums had laboratory-confirmed M. ulcerans skin lesions and/or M. ulcerans PCR positive faeces. Whole genome sequencing revealed an extremely close genetic relationship between human and possum M. ulcerans isolates. Conclusions/Significance: The prevailing wisdom is that M. ulcerans is an aquatic pathogen and that BU is acquired by contact with certain aquatic environments (swamps, slow-flowing water). Now, after 70 years of research, we propose a transmission model for BU in which terrestrial mammals are implicated as reservoirs for M. ulcerans. Author Summary: Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a destructive skin disease found predominantly in sub-Saharan Africa and south-eastern Australia. The mode of transmission and environmental reservoir remain unknown, but several studies have explored the role of aquatic insects, such as water bugs, and biting insects, such as mosquitoes. In the present study we investigated possible environmental source(s) of M. ulcerans in Victoria, Australia. Our results revealed that although M. ulcerans DNA could be detected at low levels in a variety of environmental samples, the highest concentrations of M. ulcerans DNA were found in the faeces of two species of possums, common ringtails and common brushtails. Possums are small arboreal marsupial mammals, native to Australia, and these particular species occur in both urban and rural areas. Examination and sampling of live captured possums in an area endemic for BU revealed that 38% of ringtail possums and 24% of brushtail possums, respectively, had laboratory-confirmed M. ulcerans lesions and/or M. ulcerans PCR-positive faeces. The finding that large numbers of possums in a BU-endemic area are infected with M. ulcerans raises the possibility that mammals are an environmental reservoir for M. ulcerans. [ABSTRACT FROM AUTHOR]

This article discusses a case of spontaneous clearance of Mycobacterium ulcerans, the bacteria that causes Buruli ulcer. The patient, a 72-year-old man from Australia, had a slowly progressive lesion on his ankle. The diagnosis of Buruli ulcer was made through testing and confirmed by PCR and culture. The patient underwent excision of the lesion without antibiotics, and subsequent tests showed no presence of the bacteria. This case highlights the potential for spontaneous resolution of Buruli ulcer and the importance of understanding the immune response to develop effective treatments and vaccines. [Extracted from the article]

The article discusses the confusion surrounding the nomenclature of Mycobacterium ulcerans and other mycolactone-producing mycobacteria (MPM). These MPM have been given various species names, but the article argues that they should all be recognized as M. ulcerans due to their shared characteristics. The article also highlights the difficulty in defining bacterial species and the importance of genomic context in taxonomy. Reclassifying all MPM as M. ulcerans would help alleviate confusion and promote research and awareness of Buruli ulcer, a neglected tropical disease. [Extracted from the article]

Background: Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), a necrotizing disease of the skin, soft tissue and bone. PCR is increasingly used in the diagnosis of BU and in research on the mode of transmission and environmental reservoir of M. ulcerans., Methodology/principal Findings: The aim of this study was to evaluate the performance of laboratories in detecting M. ulcerans using molecular tests in clinical and environmental samples by implementing sequential multicenter external quality assessment (EQA) programs. The second round of the clinical EQA program revealed somewhat improved performance., Conclusions/significance: Ongoing EQA programs remain essential and continued participation in future EQA programs by laboratories involved in the molecular testing of clinical and environmental samples for M. ulcerans for diagnostic and research purposes is strongly encouraged. Broad participation in such EQA programs also benefits the harmonization of quality in the BU research community and enhances the credibility of advances made in solving the transmission enigma of M. ulcerans.

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans (M. ulcerans), is a necrotizing skin disease found in more than 30 countries worldwide. BU incidence is highest in West Africa; however, cases have substantially increased in coastal regions of southern Australia over the past 30 years. Although the mode of transmission remains uncertain, the spatial pattern of BU emergence in recent years seems to suggest that there is an environmental niche for M. ulcerans and BU prevalence., Methodology/principal Findings: Network analysis was applied to BU cases in Victoria, Australia, from 1981-2008. Results revealed a non-random spatio-temporal pattern at the regional scale as well as a stable and efficient BU disease network, indicating that deterministic factors influence the occurrence of this disease. Monthly BU incidence reported by locality was analyzed with landscape and climate data using a multilevel Poisson regression approach. The results suggest the highest BU risk areas occur at low elevations with forested land cover, similar to previous studies of BU risk in West Africa. Additionally, climate conditions as far as 1.5 years in advance appear to impact disease incidence. Warmer and wetter conditions 18-19 months prior to case emergence, followed by a dry period approximately 5 months prior to case emergence seem to favor the occurrence of BU., Conclusions/significance: The BU network structure in Victoria, Australia, suggests external environmental factors favor M. ulcerans transmission and, therefore, BU incidence. A unique combination of environmental conditions, including land cover type, temperature and a wet-dry sequence, may produce habitat characteristics that support M. ulcerans transmission and BU prevalence. These findings imply that future BU research efforts on transmission mechanisms should focus on potential vectors/reservoirs found in those environmental niches. Further, this study is the first to quantitatively estimate environmental lag times associated with BU outbreaks, providing insights for future transmission investigations.