Clinical, Microbiological and Pathological Findings of Mycobacterium ulcerans Infection in Three Australian Possum Species

Abstract

BackgroundBuruli 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 FindingsTwenty-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/SignificanceThere 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.

Mycobacterium ulcerans Disease (Buruli Ulcer): Potential Reservoirs and Vectors

“…Classical M. ulcerans strains-defined as lineage 3-were represented by human isolates from Africa as well as human and animal isolates from Australia. In areas of south-eastern Australia known to be endemic for human BU, M. ulcerans infections have not only been described in different wild possum species [42], but also in other native wildlife and domestic mammals, including koalas [43], horses [17], dogs [18], alpacas [20], and a cat [16]. However, possums appear to be particularly susceptible to M. ulcerans.…”

“…However, possums appear to be particularly susceptible to M. ulcerans. Common ringtail possums were shown to develop single or multiple ulcerative cutaneous lesions and can become systemically and potentially fatally infected with M. ulcerans [42].…”

TranslocatingMycobacterium ulcerans: an experimental model

“…indeed M. ulcerans DNA has also been detected in some animals including Thryonomys swinderianus (here designed agoutis, the word commonly used in West Africa) [7–8] rabbits and rats, which have all in common to be rodent mammals [9]. Moreover, two isolates of M. ulcerans have been reported from possum feces collected in Melbourne, region, Australia although characterization and repository reference were not provided [10]. These observations led to suggest that possums and Pseudocheirus peregrinus may play a role in the epidemiology of Buruli ulcer in endemic Australian regions [11].…”

“…These observations suggested that T. swinderianus , an herbivorous mammal rodent may contaminate its digestive tract by the oral route after eating M. ulcerans -contaminated food; possibly acting as a secondary source of infection for populations as it is catched as brush meat and eaten after unprotected, manual evisceration [7] Likewise, it has been suggested that the small terrestrial mammals Mastomys natalensis can play a potential role in the natural history of M. ulcerans [12]. Also, we recently observed the PCR-based detection of the ketoreductase B gene (KR-b) and the IS 2404 and IS 2606 insertion sequences in one tenth of spleen specimens collected from T. swinderianus in the area of Yamoussoukro area, Côte d’Ivoire, and in spleen of common ringtail possums in some areas of Victoria endemic for M. ulcerans disease [7–10].…”

Epidemiology and disease burden of Buruli ulcer: a review

“…27,34 A detailed analysis of M. ulcerans human isolates of diverse geographical origin based on comparative genomic hybridization analysis revealed extensive large sequence polymorphisms, enabling a differentiation of M. ulcerans clinical isolates into two principal lineages. These lineages were designated "ancestral" in reference to M. ulcerans strains from Asia (People's Republic of China and Japan) and the Americas (Mexico, French Guiana, and Suriname) being closely related to M. marinum, and "classical", with most BU [35][36][37][38][39] and ectotherms, the different lineages appear to have adapted to distinct niche environments and may be considered as ecovars.…”