Vitamin D and experimental invasive aspergillosis.

Immune cells express the vitamin D receptor and vitamin D metabolizing enzymes. Favorable vitamin D effects have been indicated in tuberculosis. Vitamin D deficiency increases T helper (Th) 2 responses to Aspergillus, and it suppresses Th2 responses in cystic fibrosis-allergic bronchopulmonary aspergillosis. Can vitamin D modulate the proinflammatory effects of amphotericin B (AmB) therapy in aspergillosis? Groups of mice were infected intravenously (IV) with 3-8 × 10(6) Aspergillus fumigatus conidia. In six experiments, doses of 0.08, 2, or 4 µg/kg calcitriol (active form of vitamin D) were given intraperitoneally +/- AmB-deoxycholate (AmBd) at 0.4, 0.8, 1.2, 1.8, 3.3, or 4.5 mg/kg or 0.8 or 1.2 mg/kg IV. Calcitriol doses were selected to range from doses used in humans to those just below doses shown to decalcify murine bones. In most experiments, doses of calcitriol and AmBd (or control diluents) were given five times, on alternate days, to minimize drug-drug interactions. Calcitriol treatment began on the day of challenge, and survival assessed for 10 days. In no experiments did calcitriol alone significantly worsen or enhance survival or affect residual infection in survivors. Calcitriol also did not affect the efficacy of AmBd. In a representative experiment, AmBd at 0.8 or 1.2 mg/kg IV alone +/- calcitriol at 2 µg/kg enhanced survival (P ≤ 0.01). However, the AmBd regimens with calcitriol were not different than those without, and calcitriol alone was identical to controls. In disseminated invasive aspergillosis, calcitriol did not affect outcome nor influence antifungal efficacy.

Protective role of host complement system in Aspergillus fumigatus infection.

Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms. Herein we have examined the in vivo role of various complement pathways as well as the complement receptors C3aR and C5aR1 during experimental systemic infection by Aspergillus fumigatus, the main species responsible for IA. We show that C3 knockout (C3-/-) mice are highly susceptible to systemic infection of A. fumigatus. Intriguingly, C4-/- and factor B (FB)-/- mice showed susceptibility similar to the wild-type mice, suggesting that either the complement pathways display functional redundancy during infection (i.e., one pathway compensates for the loss of the other), or complement is activated non-canonically by A. fumigatus protease. Our in vitro study substantiates the presence of C3 and C5 cleaving proteases in A. fumigatus. Examination of the importance of the terminal complement pathway employing C5-/- and C5aR1-/- mice reveals that it plays a vital role in the conidial clearance. This, in part, is due to the increased conidial uptake by phagocytes. Together, our data suggest that the complement deficiency enhances the susceptibility to systemic infection by A. fumigatus.

Systemic Aspergillosis: Radiological Findings in a Case With Diffuse Large B Cell Lymphoma Treated by Ibrutinib.

Herein, we present a case of systemic aspergillosis with a fatal outcome in a case with diffuse large B cell lymphoma (DLBCL) treated by ibrutinib. Aspergillosis was suspected clinically and proven microbiologically. Radiological findings were compatible with aspergillosis. We aim to review radiological findings in a case with DLBCL treated with ibrutinib, which is an important tyrosine kinase inhibitor used in lymphoid neoplasias.

Presentación sistémica de Aspergillus spp con semiología neurológica en un Pastor Alemán: informe de un caso clínico / Systemic presentation of Aspergillus spp with neurological involvement in a German Shepherd: clinical case report

Infections of the central nervous system are uncommon in dogs. Pathogenic fungi such as Aspergillus, Cryptococcus spp, Blastomyces dermatitidis and Coccidioides immitis have been reported. An Aspergillus infection is mainly a respiratory event and very seldom it may become disseminated, the German shepherd seems to be the more prone to this type of aspergillosis specially if an immunological deficiency is present. A 1.5 year old female German Shepherd from Cancun, Quintana Roo, State, in the southeast of Mexico was presented to the small animal hospital, she showed tetraparesis, hiporeflex and deep retarded sensitivity in all four members, loss of sensitivity in the left side of the face, absence of pupil reflex and menace reflex as well as absence of muscular tone of the vulva and anal sphincter. The third day after presentation, she died. At necropsy polyencephalomalace, mielitis and diffuse leucomielitis piogranomalotosus were found. In the cytology of lymph node and other tissues aspergilli like hiphae were observed, this was confirmed by using the highly specific double diffusion test. Then, a PCR test was carried out with tissue fixed in 10% formaldehyde, but it failed probably due to destruction of the DNA.

La infección del sistema nervioso en el perro es poco común; posibles causas son Aspergillus spp, Cryptococcus neoformans, Blastomyces dermatidis y Coccidioides immitis. La infección por Aspergillus spp afecta al aparato respiratorio y en pocas ocasiones se presenta de manera diseminada. Sin embargo, en el Pastor Alemán hay mayor incidencia de éste, pues dicha infección se asocia con una deficiencia inmunológica. Se describe el caso de una perra de raza Pastor Alemán, de 1.5 años de edad, referida de Cancún, Quintana Roo, México, con tetraparesis, hiporreflexia y sensibilidad profunda retardada en los cuatro miembros, disminución de sensibilidad en el lado derecho de la cara y ausencia de reflejo pupilar y de amenaza en ojo derecho; además de ausencia de tono vulvar y de esfínter anal. A los tres días después del ingreso la perra falleció. A la necropsia se encontró polioencefalomalacia, mielitis y leucomielitis piogranulomatosa difusa. En la citología de linfonodo y en la histopatología de diferentes tejidos se identificaron hifas compatibles con Aspergillus spp. Con el fin de dar certeza al diagnóstico, se realizó prueba de doble inmunodifusión, que es altamente específica, la cual confirmó el diagnóstico de Aspergillus spp. Posteriormente se corrió PCR a partir de una muestra de tejido en formalina al 10%, para identificar la especie, en donde no se lograron resultados, probablemente debido a la destrucción del ADN por el formaldehído.