Xanthinuria in a familial group of Munchkin cats and an unrelated domestic shorthair cat.

CASE SERIES SUMMARY: Four confirmed cases of xanthinuria in cats, and one suspected case based on pedigree analysis, were identified. Clinical presentations varied and included haematuria, pollakiuria, dysuria, and urethral and ureteral obstruction. All cats had upper urinary tract uroliths. Diagnosis was obtained through infrared mass spectrometry of uroliths or urine. Clinical signs commenced at 3-8 months of age and reduced in all cats in the medium to long term after the introduction of a protein-restricted diet. Four cats were castrated males and one was a spayed female. Cases consisted of four Munchkin pedigree cats and one unrelated domestic shorthair cat. All four affected Munchkin pedigree cats were related, with three cases full siblings and the fourth case a half-sibling. No connection to the Munchkin pedigree could be established for the domestic shorthair cat. A candidate causative genetic variant (XDH p.A681V) proposed for this cat was excluded in the Munchkin family. RELEVANCE AND NOVEL INFORMATION: All affected cats presented diagnostic challenges and routine urinalysis was insufficient to obtain a diagnosis. Cases of feline xanthinuria may be underdiagnosed due to situations where uroliths cannot be retrieved for analysis and there is an inability to make a diagnosis using crystal morphology alone on routine urinalysis. Metabolic screening of urine may provide an effective mechanism to confirm xanthinuria in suspected cases where uroliths are inaccessible or absent. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs and urethral obstruction developing secondary to xanthine urolithiasis. A protein-restricted diet appears to reduce clinical signs as part of long-term management. PLAIN LANGUAGE SUMMARY: Four closely related Munchkin cats and one domestic shorthair cat were found with a suspected genetic disease causing high levels of xanthine in their urine. The case series looks at similarities and differences in their clinical signs, as well as difficulties experienced in obtaining a correct diagnosis. All cats had upper urinary tract stones and required metabolic testing of the stones or urine to diagnose. All cats were young when their clinical signs started and were on a high-protein diet. Four cats were desexed males and one was a desexed female. A genetic variant that may have caused the disease in the domestic shorthair cat was ruled out in the Munchkin family. Cases of high xanthine levels in feline urine may be underdiagnosed as the stones may not be accessed for testing. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs. A protein-restricted diet appears to reduce clinical signs as part of long-term management.

Retrospective study and outcome of 307 cats with feline infectious peritonitis treated with legally sourced veterinary compounded preparations of remdesivir and GS-441524 (2020-2022).

OBJECTIVES: Feline infectious peritonitis (FIP) is a serious disease that arises due to feline coronavirus infection. The nucleoside analogues remdesivir and GS-441524 can be effective in its treatment, but most studies have used unregulated products of unknown composition. The aim of the present study was to describe the treatment of FIP using legally sourced veterinary-prescribed regulated veterinary compounded products containing known amounts of remdesivir (injectable) or GS-441524 (oral tablets). METHODS: Cats were recruited via email advice services, product sales contacts and study publicity. Cats were excluded if they were deemed unlikely to have FIP, were not treated exclusively with the veterinary compounded products, or if there was a lack of cat and/or treatment (including response) data. Extensive cat and treatment data were collected. RESULTS: Among the 307 cats recruited, the predominant type of FIP was most commonly abdominal effusive (49.5%) and then neurological (14.3%). Three treatment protocols were used; remdesivir alone (33.9%), remdesivir followed by GS-441524 (55.7%) and GS-441524 alone (10.4%). The median (range) initial treatment period duration and longest follow-up time point after starting treatment were 84 (1-330) days and 248 (1-814) days, respectively. The most common side effect was injection pain (in 47.8% of those given subcutaneous remdesivir). Of the 307 cats, 33 (10.8%) relapsed, 15 (45.5%) during and 18 (54.5%) after the initial treatment period. At the longest follow-up time point after completion of the initial treatment period, 84.4% of cats were alive. The cats achieving a complete response within 30 days of starting treatment were significantly more likely to be alive at the end of the initial treatment period than those cats that did not. CONCLUSIONS AND RELEVANCE: Legally sourced remdesivir and GS-441524 products, either alone or used sequentially, were very effective in the treatment of FIP in this group of cats. Variable protocols precluded statistical comparison of treatment regimens.

2022 ISFM Consensus Guidelines on Management of the Inappetent Hospitalised Cat.

PRACTICAL RELEVANCE: Inappetence may have many origins and, as a presenting sign or observation in the hospitalised patient, is common in feline practice. Nutritional assessment of every patient is encouraged, to identify the need for, and appropriate type of, intervention indicated. The impact of malnutrition may be significant on the feline patient, perpetuating illness, delaying recovery, slowing wound healing and negatively impacting gut health and immunity. Delayed intervention may result in the cat's deterioration; hence prompt control of contributing factors such as the underlying illness, pain, nausea, ileus and stress is vital to optimise voluntary food intake. Management is multimodal, comprising reduction of stress, medications and assisted nutrition in the form of tube feeding or parenteral nutrition. Use of antiemetic, analgesic, prokinetic and appetite stimulant medications may restore appetite, but placement of feeding tubes should not be delayed. Feeding tubes are generally well tolerated and allow provision of food, water and medication with minimal stress, although clinicians must be aware of complications such as stoma site infections and refeeding syndrome. CLINICAL CHALLENGES: Cats are vulnerable to malnutrition owing to their unique metabolism and specific nutritional requirements. Moreover, their nature as a species means they are susceptible to stress in the hospital environment, which may result in reduced food intake; previous negative experiences may compound the problem. In particular, an inappropriate clinic environment and/or handling may cause or exacerbate inappetence in hospitalised patients, with negative impacts on recovery. Postponing interventions such as feeding tube placement to await improvement, owing to clinician or caregiver apprehension, may hinder recovery and worsen nutritional deficits. EVIDENCE BASE: The 2022 ISFM Consensus Guidelines on Management of the Inappetent Hospitalised Cat have been created by a panel of experts brought together by the International Society of Feline Medicine (ISFM). Information is based on the available literature, expert opinion and the panel members' experience.

Use of liquefied petroleum gas in Puno, Peru: Fuel needs under conditions of free fuel and near-exclusive use.

Reducing the burden of household air pollution could be achieved with exclusive adoption of cleaner fuels such as liquefied petroleum gas (LPG). However, we lack understanding of how much LPG is required to support exclusive use and how household characteristics affect this quantity. This paper used data from 90 participants in the Cardiopulmonary outcomes and Household Air Pollution (CHAP) trial in Puno, Peru who received free LPG deliveries for one year. Households with a mean of four members that cooked nearly exclusively (>98%) with LPG used an average of 19.1 kg (95% CI 18.5 to 19.6) of LPG per month for tasks similar to those done with the traditional biomass stove. LPG use per month was 0.5 kg higher for each additional pig or dog owned (p=0.003), 0.7 kg higher for each additional household member (p<0.001), 0.3 kg higher for households in the second-lowest compared to the lowest wealth quintile (p=0.01), and 1.1 kg higher if the household had previously received subsidized LPG (p=0.05). LPG use per month was 1.1 kg lower during the rainy season (p<0.001) and 1.7 kg lower during the planting season (p<0.001) compared to the cold and harvest seasons, despite the fact that LPG was not typically used for space heating. LPG use decreased by 0.05 kg per month over the course of one year after receiving the LPG stove (p=0.02). These results suggest that achieving exclusive LPG use in Puno, Peru requires that rural residents have affordable access to an average of two 10 kg LPG tanks per month. Conducting similar investigations in other countries could help policymakers set and target LPG subsidies to ensure that households have access to enough LPG to achieve exclusive LPG use and the potential health benefits.

An evaluation of the Fondo de Inclusión Social Energético program to promote access to liquefied petroleum gas in Peru.

INTRODUCTION: Over 80% of rural households in Peru use solid fuels as their primary source of domestic energy, which contributes to several health problems. In 2016, 6.7 million Peruvians were living in rural areas. The Fondo de Inclusión Social Energético (FISE) LPG Promotion Program, which began in 2012 and is housed under the Ministry of Energy and Mining, is a government-sponsored initiative aimed at reducing use of solid fuels by increasing access to clean fuel for cooking to poor Peruvian households. METHODS: We conducted a mixed methods study incorporating data from publicly available records and reports, a community survey of 375 households in Puno (the province with the largest number of FISE beneficiary households), and in-depth interviews with community members and key stakeholders. We used the Reach, Effectiveness - Adoption, Implementation, Maintenance (RE-AIM) framework to guide our data collection and analysis efforts. In a sample of 95 households, we also measured 48-hour area concentrations and personal exposures to fine particulate matter (PM2.5). RESULTS: The FISE LPG promotion program has achieved high geographical reach; the program is currently serving households in 100% of districts in Peru. Households with access to electricity may be participating at a higher level than households without electricity because the program is implemented primarily by electricity distributors. In a sample of 95 households, FISE beneficiaries experienced a reduction in kitchen concentrations of PM2.5; however, there were no differences in personal exposures, and both kitchen and personal exposures were above the WHO intermediate target for indoor air quality. Among the 375 households surveyed, stove stacking with biomass fuels was reported in more than 95% of both beneficiary and non-beneficiary households, with fewer than 5% reporting exclusive use. In-depth interviews suggest that the complexity of enrollment process and access to LPG distribution points may be key barriers to participating in FISE. CONCLUSION: The FISE LPG Program has achieved high reach and its targeted subsidy and surcharge-based financing structure represent a potentially feasible and sustainable model for other government programs. However, the prevalence of stove stacking among FISE beneficiaries remains high. There is a need for improved communication channels between program implementers and beneficiaries. FISE should also consider expanding the mobile LPG network and community delivery service to reduce physical barriers and indirect costs of LPG acquisition. Finally, increasing the value of LPG vouchers to completely cover one or two tanks a month, or alternatively, introducing behavior change strategies to reduce monthly LPG usage, may facilitate the transition to exclusive LPG use.

Feline leprosy due to Candidatus 'Mycobacterium lepraefelis': Further clinical and molecular characterisation of eight previously reported cases and an additional 30 cases.

OBJECTIVES: This paper, the last in a series of three on 'feline leprosy', provides a detailed description of disease referable to the previously unnamed species, Candidatus 'Mycobacterium lepraefelis', a close relative of the human pathogens Mycobacterium leprae and Mycobacterium lepromatosis. METHODS: Cases were sourced retrospectively and prospectively for this observational study, describing clinical, geographical and molecular microbiological data for cats definitively diagnosed with Candidatus 'M lepraefelis' infection. RESULTS: A total of 145 cases of feline leprosy were scrutinised; 114 'new' cases were sourced from the Victorian Infectious Diseases Reference Laboratory (VIDRL) records, veterinary pathology laboratories or veterinarians, and 31 cases were derived from six published studies. Thirty-eight cats were definitively diagnosed with Candidatus 'M lepraefelis' infection. Typically, cats tended to be middle-aged or older when first infected, with a male predilection. Affected cats typically had widespread cutaneous lesions, in some cases after initially localised disease. Advanced cases were often systemically unwell. All cats had outdoor access. The histological picture was lepromatous in the majority of patients, although two cases had tuberculoid disease. In one case that underwent necropsy, lesions were evident in the liver, spleen and lungs. Treatment was varied, although most cats received a combination of oral clarithromycin and rifampicin. Prognosis for recovery was variable, but typically poor. CONCLUSIONS AND RELEVANCE: Candidatus 'M lepraefelis' typically causes high bacterial index (lepromatous) feline leprosy that in some cases progresses to systemic mycobacteriosis. The disease has a variable clinical course and prognosis. Many cases either died or were euthanased due to the infection. Multilocus sequence analysis reveals a heterogeneous picture and further analysis of draft genome sequencing may give clues to the taxonomy and epidemiology of this organism. Prospective treatment trials and/or additional drug susceptibility testing in specialised systems would further inform treatment recommendations. Comparative aspects: This paper finishes with a discussion of comparative aspects of infection caused by the three feline leproid disease agents that have been the subject of this series: Candidatus 'Mycobacterium tarwinense', Mycobacterium lepraemurium and Candidatus 'M lepraefelis'.

Feline leprosy due to Mycobacterium lepraemurium.

OBJECTIVES: This paper, the second in a series of three on 'feline leprosy', provides a detailed description of disease referable to Mycobacterium lepraemurium, the most common cause of feline leprosy worldwide. METHODS: Cases were sourced retrospectively and prospectively for this observational study, describing clinical, geographical and molecular microbiological data for cats definitively diagnosed with M lepraemurium infection. RESULTS: A total of 145 cases of feline leprosy were scrutinised; 114 'new' cases were sourced from the Victorian Infectious Diseases Reference Laboratory records, veterinary pathology laboratories or veterinarians, and 31 cases were derived from six published studies. Sixty-five cats were definitively diagnosed with M lepraemurium infection. Typically, cats were 1-3 years of age when first infected, with a male gender predilection. Affected cats were generally systemically well. All had outdoor access. Lesions tended to consist of one or more cutaneous/subcutaneous nodules, typically located on the head and/or forelimbs, possibly reflecting the most likely locations for a rodent bite as the site of inoculation for organisms. Nodules had the propensity to ulcerate at some stage in the clinical course. The cytological and histological picture varied from tuberculoid, with relatively low bacterial numbers, to lepromatous with moderate to high bacterial numbers. Treatment was varied, although most cats underwent surgical resection of lesions with adjunctive medical therapy, most often using a combination of oral clarithromycin and rifampicin. Prognosis for recovery was generally good, and in two cases there was spontaneous remission without the requirement for medical intervention. Untreated cats continued to enjoy an acceptable quality of life despite persistence of the disease, which extended locally but had no apparent tendency to disseminate to internal organs. CONCLUSIONS AND RELEVANCE: M lepraemurium causes high bacterial index (lepromatous) or low bacterial index (tuberculoid) feline leprosy. The infection typically causes nodules of the skin and/or subcutis (which tend towards ulceration) on the head and/or forelimbs. The disease usually has an indolent clinical course and infected cats have a generally favourable response to therapeutic interventions, with rare cases undergoing spontaneous resolution. Genomic analysis may yield clues as to the environmental niche and culture requirements of this elusive organism. Prospective treatment trials and/or additional drug susceptibility testing in specialised systems would further inform treatment recommendations.

Feline leprosy due to Candidatus 'Mycobacterium tarwinense':Further clinical and molecular characterisation of 15 previously reported cases and an additional 27 cases

OBJECTIVES: This paper, the first in a series of three on 'feline leprosy', provides a detailed description of disease referable to Candidatus 'Mycobacterium tarwinense', the most common cause of feline leprosy in Victoria, Australia. METHODS: Cases were sourced retrospectively and prospectively for this observational study, describing clinical, geographical and molecular microbiological data for cats definitively diagnosed with Candidatus 'M tarwinense' infection. RESULTS: A total of 145 cases of feline leprosy were scrutinised; 114 'new' cases were sourced from the Victorian Infectious Diseases Reference Laboratory records, veterinary pathology laboratories or veterinarians, and 31 cases were derived from six published studies. Forty-two cats were definitively diagnosed with Candidatus 'M tarwinense' infection. Typically, cats were between 3 and 11 years of age, with no gender predilection, and were generally systemically well. All had outdoor access. Most cats underwent surgical resection of lesions with adjunctive medical therapy, often utilising a combination of oral clarithromycin and rifampicin for at least 3 months. Prognosis for recovery was generally good. Resolution of lesions was not observed in the absence of treatment, but a number of untreated cats continued to enjoy an acceptable quality of life despite persistence of the disease, which extended locally but did not appear to disseminate to internal organs. Preliminary results of draft genome sequencing confirmed that the species is a member of the Mycobacterium simiae complex. CONCLUSIONS AND RELEVANCE: Candidatus 'M tarwinense', a fastidious member of the M simiae complex, is capable of causing feline leprosy with a tendency to produce lesions on the head, particularly involving the eyes and periocular skin. The disease has an indolent clinical course and generally responds favourably to therapy despite lesions often containing large numbers of organisms. Detailed genomic analysis may yield clues as to the environmental niche and culture requirement of this elusive organism. Prospective treatment trials and/or drug susceptibility testing in specialised systems would further inform treatment recommendations.

Case-based clinical reasoning in feline medicine: 3: Use of heuristics and illness scripts.

AIM: This is Article 3 of a three-part series on clinical reasoning that encourages practitioners to explore and understand how they think and make case-based decisions. It is hoped that, in the process, they will learn to trust their intuition but, at the same time, put in place safeguards to diminish the impact of bias and misguided logic on their diagnostic decision-making. SERIES OUTLINE: Article 1, published in the January 2016 issue of JFMS, discussed the relative merits and shortcomings of System 1 thinking (immediate and unconscious) and System 2 thinking (effortful and analytical). In Article 2, published in the March 2016 issue, ways of managing cognitive error, particularly the negative impact of bias, in making a diagnosis were examined. This final article explores the use of heuristics (mental short cuts) and illness scripts in diagnostic reasoning.

Case-based clinical reasoning in feline medicine: 2: Managing cognitive error.

AIM: This is Article 2 of a three-part series on clinical reasoning that encourages practitioners to explore and understand how they think and make case-based decisions. It is hoped that, in the process, they will learn to trust their intuition but, at the same time, put in place safeguards to diminish the impact of bias and misguided logic on their diagnostic decision-making. SERIES OUTLINE: Article 1, published in the January 2016 issue of JFMS, discussed the relative merits and shortcomings of System 1 thinking (immediate and unconscious) and System 2 thinking (effortful and analytical). This second article examines ways of managing cognitive error, particularly the negative impact of bias, when making a diagnosis. Article 3, to appear in the May 2016 issue, explores the use of heuristics (mental short cuts) and illness scripts in diagnostic reasoning.

Case-based clinical reasoning in feline medicine: 1: Intuitive and analytical systems.

AIM: This is Article 1 of a three-part series on clinical reasoning that encourages practitioners to explore and understand how they think and make case-based decisions. It is hoped that, in the process, they will learn to trust their intuition but, at the same time, put in place safeguards to diminish the impact of bias and misguided logic on their diagnostic decision-making. SERIES OUTLINE: This first article discusses the relative merits and shortcomings of System 1 thinking (immediate and unconscious) and System 2 thinking (effortful and analytical). Articles 2 and 3, to appear in the March and May 2016 issues of JFMS, respectively, will examine managing cognitive error, and use of heuristics (mental short cuts) and illness scripts in diagnostic reasoning.

Clinical, microbiological and pathological findings of Mycobacterium ulcerans infection in three Australian Possum species.

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.

Potential wildlife sentinels for monitoring the endemic spread of human buruli ulcer in South-East australia.

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 ≥10(6) 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.

Ulcerated and nonulcerated nontuberculous cutaneous mycobacterial granulomas in cats and dogs.

BACKGROUND: Mycobacterial granulomas of the skin and subcutis can be caused by one of a number of pathogens. This review concentrates on noncultivable species that cause diseases characterized by focal granuloma(s), namely leproid granuloma (in dogs) and feline leprosy (in cats). Clinically indistinguishable lesions can be caused by tuberculous organisms (Mycobacterium bovis and Mycobacterium microti) and members of the Mycobacterium avium complex. Rapidly growing mycobacterial species that cause infection of the subcutaneous panniculus associated with draining tracts are not discussed. Disease caused by Mycobacterium ulcerans is an important emerging differential diagnosis for ulcerated cutaneous nodules in certain localized regions. CLINICAL LESIONS: Lesions comprise one or multiple nodules in the skin/subcutis. These are generally firm and well circumscribed, and typically become denuded of hair. They may or may not ulcerate, depending on the virulence of the causal organisms and the immune response of the host. DIAGNOSIS: The most inexpensive, noninvasive means of diagnosis is by submission of methanol-fixed, Romanowsky-stained smears to a Mycobacterium Reference Laboratory after detecting negatively stained or acid-fast bacilli on cytological smears. Scrapings of material from slides usually provide sufficient mycobacterial DNA to enable identification of the causal organism using sequence analysis of amplicons after PCR using specific mycobacterial primers. THERAPY: Therapy relies upon a combination of marginal resection of easily accessible lesions and treatment using two or three drugs effective against slowly growing mycobacteria, choosing amongst rifampicin, clarithromycin, clofazimine and pradofloxacin/moxifloxacin.

A major role for mammals in the ecology of Mycobacterium ulcerans.

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.

Primary ocular melioidosis due to a single genotype of Burkholderia pseudomallei in two cats from Arnhem Land in the Northern Territory of Australia.

Melioidosis was diagnosed in two domestic crossbred cats presented for unilateral ocular disease. One patient was born and bred in Nhulunbuy, Arnhem Land, while the other had moved there 6 months previously from Townsville, Queensland. Both patients were presented with sudden onset of a 'red eye' and blepharospasm, which progressed to an enlarged, painful, firm globe with loss of pupillary light reflexes and vision. An obvious primary focus of infection outside the eye was not detected in either cat. In both patients, the affected eye was surgically removed and vitreal culture revealed a pure growth of Burkholderia pseudomallei. In each instance, the infection had penetrated the sclera to produce retrobulbar cellulitis, and in one case frank retrobulbar abscessation. Histologically, there was a pyogranulomatous uveitis with extensive destruction of intraocular structures. The first case was still alive approximately 1 year following enucleation and limited antimicrobial therapy using amoxicillin clavulanate and doxycycline. The second was euthanased when a localised abscess developed on the same side of the face as the healed surgical incision, despite appropriate antimicrobial therapy. Both cases were caused by the same multilocus sequence type of B pseudomallei (ST 116), which had only been isolated previously from two human patients, both living in the same isolated geographical area as the cats of this report. Apart from the geographical clustering, no epidemiological links were evident between the two cats and/or the two people. The presumptive pathogenesis of these infections is discussed in relation to current knowledge about melioidosis in northern Australia.