Biomedical subjects

M B Krockenberger

Publications and source records attributed to M B Krockenberger.

15 recordsLinked to original sources

PubMed2006

Recrudescent cryptococcosis, caused by Cryptococcus gattii (molecular type VGII), over a 13-year period in a Birman cat.

A 17-year-old desexed male Birman cat presented with a fleshy mass protruding from the left ear canal. A culture from the mass revealed a heavy growth of Cryptococcus gattii (molecular type VGII, serotype B). The lesion resolved with antifungal therapy over 8 weeks. Itraconazole was continued indefinitely due to persistent high serum cryptococcal antigen titres. The cat was euthanased 12 months later due to the acute development of hindlimb ataxia and collapse which may or may not have been attributable to cryptococcosis. This cat had first presented when 4 years of age with a 3-week history of inappetance, sneezing and serous nasal discharge. Culture of swabs from both nostrils were positive for C. gattii (VGII). Fluconazole therapy produced steady improvement over a 6 month period, at which time therapy was discontinued. The cat presented 9 months later for sneezing, again with a positive culture of C. gattii from the nasal cavity. Antifungal therapy was continued for 8 months, after which time cultures were negative and symptoms resolved. Three episodes of cryptococcosis in a cat over a 13-year period were thus documented. Importantly, the two C. gattii isolates, obtained 13 years apart, were identical using DNA fingerprinting and random amplification of polymorphic DNA (RAPD) analysis.

Animals↗

PubMed2006

Nocardia infections in cats: a retrospective multi-institutional study of 17 cases.

OBJECTIVE: To record 17 cases of nocardiosis in cats from eastern Australia and to compare this series with cases previously reported. DESIGN: Retrospective/prospective study. RESULTS: Nocardia spp infections were diagnosed in 17 cats over 14 years from the three eastern states of Australia. There were no isolates from dogs during this period, but one isolate from a koala and two from dairy cows. The majority of cats presented with spreading lesions of the subcutis and skin associated with draining sinus tract(s). Early cutaneous lesions consisted of circumscribed abscesses. Infections spread at a variable rate, generally by extension to adjacent tissues. Lesions were generally located in regions subjected to cat bite or scratch injuries, including limbs, body wall, inguinal panniculus and nasal bridge. In some other cases, lesions were situated on distal extremities. The clinical course was variable, from chronic, indolent, initially localised infections to acute fulminating disease. Of the 17 cats, 14 were domestic crossbreds and three were purebreds. There was a preponderance of male cats (12 castrated, 1 entire young adult, 1 entire kitten). Nine of 17 cats were 10 years or older. Interestingly, the majority of infections were attributable to N nova. Immediate and/or predisposing causes could be identified in all cases, and included: renal transplantation [one cat]; chronic corticosteroid administration [three cats]; catabolic state following chylothorax surgery [one cat]; fight injuries [seven cats]; FIV infections [three of seven cats tested]. Of the 17 cats, three were apparently cured. Four were thought to be cured, but infection recurred after several months. Three cats responded partially but were euthanased, while another was improving when it died of unrelated complications. Two died despite treatment and two were euthanased without an attempt at therapy. For two cats there were either insufficient records or the patient was lost to follow up. CONCLUSION: Nocardiosis is a rare, serious disease. Currently it is more common in cats than dogs. Nocardial panniculitis may be clinically indistinguishable from the syndrome caused by rapidly growing mycobacteria. Although the prognosis is guarded, patients with localised infections caused by N nova often respond to appropriate therapy. If definitive treatment is delayed because of misdiagnosis, the disease tends to become chronic, extensive and refractory. Insufficient duration of therapy leads to disease recurrence.

Animals↗

PubMed2006

Long-term outcome of therapy for 59 cats and 11 dogs with cryptococcosis.

OBJECTIVE: To determine the outcome of therapy in cats and dogs with naturally occurring cryptococcosis. Design Retrospective study of 59 cats and 11 dogs at the University Veterinary Centre Sydney from 1986 to 2004. METHOD: Following detailed analysis of case notes potential associations between patient characteristics, cryptococcal species, retroviral status (cats), disease severity and type of therapy were examined in relation to duration and success of therapy. Treatment protocols based on amphotericin B, fluconazole and itraconazole were compared. RESULTS: Seventy-six percent of feline patients were successfully treated. For cats, the presence of central nervous system disease was the only factor found to influence outcome. Cats with neurological involvement, disseminated disease or refractory disease treated with amphotericin B containing protocols did as well, on average, as cats with less severe disease treated with azole monotherapy. Amphotericin B was thus an effective agent for treating severe cases of cryptococcosis. The median cumulative dose of amphotericin B for cats cured at the first attempt was 16 mg/kg (range 7 to 23 mg/kg). The median duration of treatment required to effect a cure at first attempt was significantly shorter for fluconazole (4 months; range 1 to 8 months) than for itraconazole (9 months; range 3 to 24 months; P = 0. 0191; Mann Whitney U test). The success rate for treatment of canine cases was 55%. No factor appeared to influence disease outcome in dogs. Large cumulative doses of amphotericin B could be administered via the subcutaneous route in both species and generally with minimal nephrotoxicity. Recrudescence occurred in a significant proportion of animals, in some cases despite a reduction of serum latex cryptococcal antigen agglutination test to zero. CONCLUSION: Although the prognosis of cryptococcosis should be described as guarded, a majority of the canine and especially feline patients can be expected to be cured, although treatment is protracted and expensive.

Amphotericin B↗

PubMed2004

Concurrent Fusarium chlamydosporum and Microsphaeropsis arundinis infections in a cat.

A 7-year-old cat was presented initially with multiple draining sinuses on the metatarsal region of its right hindlimb. Another lesion had appeared at the same time on the fifth proximal interphalangeal joint of the left forelimb. Histopathological examination of a biopsy from the right hindlimb lesion revealed chronic pyogranulomatous inflammation associated with yeast-like bodies and septate mycelia; a fungus was cultured on conventional media but not identified further. Culture of a swab collected from the left forelimb lesion demonstrated a pigmented fungus, also not characterised further. Although there was initially a favourable response to ketoconazole (Nizoral, Janssen-Cilag Pty. Ltd) and beta-lactam therapy, the infection in the hind limb relapsed subsequently, and Fusarium chlamydosporum was cultured from deep biopsy specimens. Clinical improvement followed debridement and itraconazole (Sporanox, Janssen-Cilag Pty. Ltd; 100 mg orally once daily), however amputation of the limb represented the best chance for a cure. The cat made an uncomplicated recovery following surgery and remained well for five months until the lesion on the left forelimb recurred. Amputation of the distal fourth digit was then performed, and the resected tissue submitted for culture. The dematiaceous fungus Microsphaeropsis arundinis was subsequently cultured. The cat remained well for several months, until a further F. chlamydosporum infection developed on the body wall. This was excised 7 months ago, and no lesions have recurred in this area. Importantly, this is the first reported case of M. arundinis infection in a mammalian host.

Animals↗

PubMed2004

Retrospective study of feline and canine cryptococcosis in Australia from 1981 to 2001: 195 cases.

A retrospective study of 155 cats and 40 dogs diagnosed with cryptococcosis between 1981 and 2001 was undertaken. Age, sex, breed, clinical findings, feline immunodeficiency virus and feline leukaemia virus status (in cats), species of Cryptococcus causing disease and region of domicile were recorded. Associations between variables were tested. Male and female cats were affected equally. Age ranged from 1 to 16 years, with a preponderance of cats aged between 2 and 3 years. Siamese, Himalayan and Ragdoll breeds were over-represented. Rural cats were more frequently infected with Cryptococcus gattii. Retroviral infection was not identified as a predisposing condition and was not correlated with either species of Cryptococcus or physical findings. Most cats had signs of nasal cavity infection, which was typically localised for a substantial period before invasion of adjacent structures or dissemination. Male and female dogs were affected equally. A marked preponderance of young, large breed dogs was noted. Border Collies, Boxers, Dalmatians, Dobermann Pinschers, Great Danes and German Shepherds were over-represented. Cryptococcus species involved was not affected by place of domicile. Although nasal cavity involvement was important, the canine cohort had a greater propensity to develop secondary central nervous system involvement and disseminated disease than feline cases. There were no clinical findings in either cats or dogs which could be reliably used to distinguish disease caused by Cryptococcus neoformans variety grubii from disease caused by Cryptococcus gattii. Both Cryptococcus species appear to be primary pathogens of cats and dogs, with the upper respiratory tract presumed to be the predominant primary site of inoculation in most but not all cases.

Animals↗

PubMed2004

Successful treatment of cryptococcal pneumonia in a pony mare.

A 20-year-old Welsh Mountain Pony (212 kg) mare was initially presented for a chronic cough, fever, weight loss and low grade abdominal pain. She later developed dyspnoea, tachypnoea and exercise intolerance. The presence of multiple masses (up to 17 cm diameter) in the pulmonary parenchyma was established using lateral thoracic radiography and transthoracic ultrasonography. Encapsulated, budding yeasts were observed in smears made from transtracheal washings and needle aspirates of the pulmonary lesions. Cryptococcus gattii (synonym: Cryptococcus neoformans variety gattii; Cryptococcus bacillisporus) was cultured from the transtracheal washings and aspirates of the lung masses. The pony was successfully treated using daily intravenous infusions of amphotericin B (typically 0.5 mg/kg in 1 L 5% dextrose in water over 1 h, following premedication with 50 mg flunixin intravenously) over a 1 month period, until a cumulative dose of 3 g had been administered. Treatment was considered to be successful on the basis of progressive improvement in clinical signs, reduction in the size of pulmonary cryptococcomas, 48 kg weight gain and a reduction in the cryptococcal antigen titre from 4096 to 256, 1 year after cessation of treatment.

Amphotericin B↗

PubMed2003

Disseminated melioidosis in two cats.

Melioidosis was diagnosed in two cats at necropsy. The first cat presented with jaundice and anaemia but died of overwhelming sepsis soon after admission, despite blood transfusion and other supportive measures. The second cat died several days after developing neurological signs; an infected digital wound may have been the primary focus of infection in this patient. The cats had presumably acquired the infection in Malaysia and northern Australia, respectively, and in both cases disease may have represented reactivation of a latent infection brought on by the stress of relocation. The epidemiology, clinical presentation, diagnosis and treatment of melioidosis are discussed from a feline perspective.

Animals↗

PubMed2003

Cryptococcus neoformans var. gattii in the koala (Phascolarctos cinereus): a review of 43 cases of cryptococcosis.

Details of 11 previously reported cases and 32 new cases of cryptococcosis in captive and wild koalas were analysed. Cryptococcus neoformans var. gattii accounted for all 29 cases in which varietal status was determined. No age or sex predisposition was observed. The respiratory tract was the primary focus of disease in 77% of cases. Although the lower respiratory tract was affected most commonly (60% of cases), 30% of cases had upper respiratory tract lesions and 14% had both. Dissemination was common, especially to the central nervous system (37% cases). Local extension to surrounding tissues was a feature of upper respiratory tract disease. Other tissues showing cryptococcal invasion included lymph nodes (19%), gastrointestinal tract (12%), kidneys (12%), spleen (9%) and skin (7%). Only three cases (7%) had no respiratory tract or central nervous system involvement, two cases of primary skin inoculation and one case of primary lymphadenopathy. Late presentation was a likely factor in the high proportion of cases with disseminated disease (40%). The proportion of koala cases with involvement of the central nervous system, lower respiratory tract and skin, parallels what has been reported for immunocompetent people. Cryptococcosis in the koala appears to be an excellent naturally occurring model for examination of the cryptococcal host-parasite relationship in all species.

Animals↗

PubMed2003

Avian cryptococcosis.

Clinical and laboratory findings in 15 unreported cases of avian cryptococcosis from Australia were collated and contrasted with 11 cases recorded in the literature. Cryptococcus species produced localized invasive disease of the upper respiratory tract of captive parrots living in Australia. This resulted in signs referable to mycotic rhinitis or to involvement of structures contiguous with the nasal cavity, such as the beak, sinuses, choana, retrobulbar space and palate. Parrots of widely differing ages were affected and of the seven birds for which sex was determinable, six were male. Cryptococcus bacillisporus (formerly C. neoformans var. gattii) accounted for four of five infections in which the species or variety was determinable, suggesting that exposure to eucalyptus material may be a predisposing factor. In these cases, Cryptococcus appeared to behave as a primary pathogen of immunocompetent hosts. One tissue specimen was available from an Australian racing pigeon with minimally invasive subcutaneous disease; immunohistology demonstrated a C. neoformans var. grubii (formerly C. neoformans var. neoformans serotype A) infection, presumably subsequent to traumatic inoculation of yeast cells into the subcutis. Two similar cases had been reported previously in pigeons domiciled in America. Data for parrots, one pigeon and other birds studied principally in America and Europe (and likely infected with C. neoformans) suggested a different pattern of disease, more suggestive of opportunistic infection of immunodeficient hosts. In this cohort of patients, the organism was not restricted to cool superficial sites such as the upper respiratory tract or subcutis. Instead, infections typically penetrated the lower respiratory tract or disseminated widely to a variety of internal organs. Finally, three captive North Island brown kiwis, one residing in Australia, the other two in New Zealand, died as a result of severe diffuse cryptococcal pneumonia (two cases) or widely disseminated disease (one case). C. bacillisporus strains were isolated from all three cases, as reported previously for another kiwi with disseminated disease in New Zealand.

Animals↗

PubMed2002

Central nervous system cryptococcoma in a cat.

This report describes the gross, histopathological, immunohistochemical and electron microscopic findings in a 4-year-old cat with systemic Cryptococcus neoformans infection. A 1-cm diameter pontine mass, pinpoint lesions in the cerebellum and in the right kidney were the main macroscopic findings. A presumptive diagnosis of cerebral neoplasia with metastasis was formulated. Light microscopy revealed a huge number of yeasts surrounded by a pyogranulomatous inflammatory reaction in the cerebral parenchyma and, to a lesser extent, in the kidney, while the meninges were not involved. The positive mucicarmine stain that coloured the capsule of the yeasts was indicative of cryptococcal infection. Immunohistochemistry confirmed the presence of C. neoformans var. grubii (C. neoformans serotype A). Electron microscopy revealed yeasts with a massive fibrillar capsule and lamellar cell wall free in the cerebral tissue and within macrophages.

Animals↗

PubMed2002

Cryptococcus neoformans in the koala (Phascolarctos cinereus): colonization by C n. var. gattii and investigation of environmental sources.

This study is the one in a series looking at the relationship among Cryptococcus neoformans var. gattii, koalas and the environment. The koala was used as a natural biological sampler in an attempt to understand the dynamics of C. neoformans var. gattii in Australian environments. Evidence of asymptomatic nasal and skin colonization for extended periods by large numbers of C. n. var. gattii was obtained and geographical factors assessed. The key finding was the ability of koalas to amplify numbers of C. n. var. gattii in certain environments. Koalas were not found to be obligatory for the survival of the organism in all environments. Geographical factors alone could not explain differing rates of nasal and skin colonization in koalas in different environments. A strong association between healthy koalas and C. n. var. gattii was confirmed and C n. var. gattii was isolated from novel sources, including the turpentine gum tree (Syncarpia glomulifera), tallowwood (Eucalyptus microcorys) and flooded gum (E. grandis). It seems likely that as yet undiscovered environmental sources of C. n. var. gattii exist in eastern Australia. Further investigation of host, environmental and organism factors integral to the hostpathogen relationship will assist an understanding of the progression from colonization to tissue invasion and cryptococcosis in all species.

Animals↗

PubMed2002

Cryptococcus neoformans var. gattii in the koala (Phascolarctos cinereus): serological evidence for subclinical cryptococcosis.

Cryptococcus neoformans var. gattii has been shown to have a strong association with eucalypts frequently used by koalas and, not surprisingly, it has been shown to colonize the nasal cavities of koalas. The progression from nasal colonization to tissue invasion is critical to understanding the pathogenesis of cryptococcosis in this species and provides a model for pathogenesis of cryptococcosis in other species. Cryptococcal antigenaemia was detected in twenty-eight healthy koalas from three different regions. This was interpreted as representing limited subclinical disease. One koala developed cryptococcal pneumonia 6 months after leaving the study, whereas another developed cryptococcal meningoencephalitis during the course of the study. Opportunistic necropsies on ten antigen-positive koalas resulted in discovery of small cryptococcal lesions in two (paranasal sinus and lung, respectively). Our data suggest that cryptococcal antigenaemia occurs commonly in koalas, especially in areas with a high environmental presence of C n. var. gattii. Subclinical disease appears most likely to manifest as a small focal lesion in the respiratory tract. Possible outcomes include elimination by an effective immune response, quiescence with possibility of later re-activation or direct progression to overt disease. Symptomatic and subclinical cases showed differences in levels of antigenaemia. The data presented have significant implications for koalas in captivity.

Agglutination Tests↗

PubMed2002

Cryptococcosis in ferrets: a diverse spectrum of clinical disease.

Cryptococcosis was diagnosed in seven ferrets (five from Australia; two from western Canada) displaying a wide range of clinical signs. Two of the ferrets lived together. One (5-years-old) had cryptococcal rhinitis and presented when the infection spread to the nasal bridge. Its sibling developed cryptococcal abscessation of the right retropharyngeal lymph node 12 months later, soon after developing a severe skin condition. DNA fingerprinting and microsatellite analysis demonstrated that the two strains isolated from these siblings were indistinguishable. Two ferrets (2- to 3-years-old) developed generalised cryptococcosis: one had primary lower respiratory tract disease with pneumonia, pleurisy and mediastinal lymph node involvement, while in the other a segment of intestine was the primary focus of infection with subsequent spread to mesenteric lymph nodes, liver and lung. The remaining three ferrets (1.75 to 4-years-old) had localised disease of a distal limb, in one case with spread to the regional lymph node. Cryptococcus bacillisporus (formerly C. neoformans var gattii) accounted for three of the four infections in Australian ferrets where the biotype could be determined. The Australian ferret with intestinal involvement and the two ferrets from Vancouver had C. neoformans var grubii infections.

Animals↗

PubMed2001

An immunohistochemical method that differentiates Cryptococcus neoformans varieties and serotypes in formalin-fixed paraffin-embedded tissues.

An immunohistochemical method for determining the variety of Cryptococcus neoformans in formalin-fixed paraffin-embedded tissues was developed using mAbs 471, 302 and CRND8. The method was validated primarily using veterinary patients for which both formalin-fixed lesions and a cultured isolate were available. L-Canavanine glycine bromothymol blue (CGB) agar and the 'Crypto-Check' kit were used to determine the variety and serotype, respectively, of cultured isolates. Immunohistochemistry accurately predicted the C. neoformans variety in all tissue specimens. The CGB agar method of determining C. neoformans variety gave the same result as immunohistochemistry for 30/31 specimens. For the single discordant isolate, the serotype, random amplification of polymorphic DNA profile, microscopic and colony morphology all supported the immunohistochemical staining pattern in suggesting C. neoformans var. gattii; however, the CGB agar result was at variance. Of the C. neoformans var. neoformans cases, immunohistochemistry was congruent with variety for 13/13 cases and with serotyping for 10/13 cases. The three discordant cases were classified as having some serotype D reactivity by immunohistochemistry, but were considered to be serotype A using the Crypto-Check kit. This new method should prove a valuable epidemiological tool in studies of cryptococcosis, especially in the veterinary setting where archival tissue specimens may exist but corresponding mycological data is typically absent. The versatility of this method will expand in the future as other monoclonal antibodies with different specificities are developed.

Antibodies, Monoclonal↗

PubMed1999

Asymptomatic carriage of Cryptococcus neoformans in the nasal cavity of the koala (Phascolarctos cinereus).

Over a 22-month period, sequential nasal and skin swabs were obtained from 52 healthy captive koalas (Phascolarctos cinereus) from the Sydney region. Cryptococcus neoformans was isolated in 17 koalas from 64 of 262 (24%) nasal swabs and from nine of 262 (3%) skin swabs. Prevalence of nasal colonization varied seasonally from 12% (3/25) to 38% (10/26). Cryptococcus neoformans var. gattii alone was cultured from 37, var. neoformans alone from 22 and both varieties from five nasal swabs. Of 33 koalas sampled on three or more occasions, organisms were isolated persistently from six, occasionally from eight and never from 19. Two koalas were persistently and heavily (>/=100 colonies/plate) colonized by C. neoformans var. gattii and two with var. neoformans. Isolation of C. neoformans var. gattii from the skin was low grade and sporadic. No koalas from which C. neoformans was persistently isolated showed clinical signs of cryptococcosis and all except one had a negative latex cryptococcal antigen test, therefore the nasal cavity was presumed to be colonized by, rather than infected with, C. neoformans. Preliminary observations of koalas from Coffs Harbour indicated a much higher prevalence of colonization by C. neoformans, suggesting that environmental factors influenced the extent of carriage by C. neoformans.

Animals↗