CRYPTOCOCCUS NEOFORMANS VAR. GRUBII-ASSOCIATED RENAL AMYLOIDOSIS CAUSING PROTEIN-LOSING NEPHROPATHY IN A RED KANGAROO (MACROPUS RUFUS).

A 10-year-old male castrated red kangaroo (Macropus rufus) presented with mandibular swelling. Examination findings included pitting edema with no dental disease evident on examination or radiographs. The results of blood work were moderate azotemia, hypoalbuminemia, and severely elevated urine protein:creatinine ratio (9.9). Radiographs showed an interstitial pattern of the caudal right lung, and an abdominal ultrasound demonstrated scant effusion. Symptomatic and empirical therapy with antibiotics, anti-inflammatory drugs, and an angiotensin-converting enzyme (ACE) inhibitor did not resolve clinical signs. Due to poor prognosis and declining quality of life, euthanasia was elected. Necropsy revealed chronic granulomatous pneumonia of the caudal right lung lobe with intralesional Cryptococcus, identified as C. neoformans var. grubii by DNA sequencing. Severe bilateral glomerular and tubulointerstitial amyloidosis induced protein-losing nephropathy, leading to tri-cavitary effusion, subcutaneous edema, and cachexia. The authors speculate that renal amyloidosis was associated with chronic cryptococcal pneumonia in this red kangaroo.

Scintigraphic imaging using 99mTc-labeled PEG liposomes allows early detection of experimental invasive pulmonary aspergillosis in neutropenic rats.

The value of scintigraphic imaging using 99mTc labeled poly(ethyleneglycol) (PEG) -liposomes for detecting invasive pulmonary aspergillosis at different stages of the disease was investigated in a rat model. At 24, 48, 72, 120 and 168 h after fungal inoculation scintigraphic images were obtained and biodistribution of the radiolabel was determined. Findings were compared with serum galactomannan detection and other parameters of progression of fungal infection. At 48 h liposomal uptake in the infected left lung was increased significantly and 82% of the scintigraphic images was assessed positive. Serum galactomannan was only detected at 72 h and later. Liposomal uptake in the infected left lung increased over time and was significantly correlated with both the size of the pulmonary hemorrhagic lesion and the levels of circulating galactomannan. It was concluded that scintigraphic imaging using 99mTc-PEG-liposomes allows early detection of invasive pulmonary aspergillosis in this model, and that liposomal uptake in the infected lung was strongly associated with the severity of the disease.

Leukotriene B4-loaded microspheres as a new approach to enhance antimicrobial responses in Histoplasma capsulatum-infected mice.

Histoplasmosis is a pulmonary disease characterised by chronic granulomatous and suppurative inflammatory reactions caused by Histoplasma capsulatum. Regarding new therapies to control fungal infections, the aim of this study was to investigate whether pulmonary administration of leukotriene B(4) (LTB(4))-loaded microspheres (MS) could confer protection to 5-lipoxygenase knockout (5-LO(-/-)) mice infected by H. capsulatum. In this study, MS containing LTB(4) were administered intranasally to mice infected by H. capsulatum. On Day 14 after the infection, fungal recovery from the lungs and histology were evaluated and inflammatory cytokines were measured. Pulmonary administration of LTB(4)-loaded MS was able to reduce fungal recovery from infected lungs. Production of important inflammatory cytokines related to host defence was augmented following MS administration to the lungs. Lung histology also showed that infected mice presented a clear reduction in the fungal burden following the pulmonary release of LTB(4) from MS. Our study provides evidence that the proposed biodegradable microparticulate system, which can release LTB(4) to the lungs, can be employed as therapy, enhancing the antimicrobial activity of host cells during histoplasmosis.

Clinical presentation of invasive aspergillosis.

Invasive aspergillosis has increasingly been recognised to cause significant morbidity and mortality in immunocompromised patients. Fever unresponsive to broad-spectrum antibiotics is the earliest and most common sign of an invasive fungal infection. As invasive Aspergillus infections are usually acquired by inhalation of Aspergillus conidia, symptoms of a pulmonary infection such as cough, rales and marked pleuritic chest pain can be noted early in the course, whereas hemoptysis typically comes late after neutrophil recovery. Aspergillus infections of the upper respiratory tract may also involve the nasal cavity or sinuses resulting in nasal obstruction, epistaxis, facial pain, periorbital swelling and even palate destruction. Primary cutaneous infections present as non-purulent ulcerations and may be seen in association with implantable intravenous devices. Other sites of infections, such as the central nervous system, originate from dissemination of molds and may be suspected when focal neurological findings or meningism develop. The recognition of symptoms associated with invasive aspergillosis in patients at risk should prompt further diagnostic procedures, as an early diagnosis and immediate institution of antifungal therapy might improve the treatment outcome in this life-threatening condition.

Successful use of liposome encapsulated amphotericin to treat invasive aspergillosis following failure of conventional amphotericin.

We describe a case of proven invasive pulmonary aspergillosis in a neutropenic patient in whom disease progression occurred during treatment with conventional amphotericin B despite neutrophil recovery. Treatment with liposomal encapsulated amphotericin B resulted in clinical and radiological improvement and the clearance of aspergillus spores from the sputum.

Fatal fungal infection complicating aortic dissection following coronary artery bypass grafting.

The case of a 52-year-old man with severe coronary atheroma/ischaemic heart disease, who underwent successful triple vessel coronary artery bypass grafting is described. One month later this was complicated by aortic dissection arising at the aortic cannulation site. An emergency resection and Dacron graft placement were performed. Five weeks later he represented with haemoptysis. Despite inconclusive investigations the patient went on to suffer a massive fatal haemoptysis. Autopsy revealed Candida infection of the graft with a secondary aortobronchial fistula.

Long-circulating immunoliposomal amphotericin B against invasive pulmonary aspergillosis in mice.

We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number of Aspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 microg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 microg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.