Aspergillosis by cryptic Aspergillus species: A case series and review of the literature

BackgroundThe cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis.AimsWe aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital.MethodsWe retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel.ResultsA total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B.ConclusionsThe frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%.     

Fungal infections following treatment with monoclonal antibodies and other immunomodulatory therapies

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in a wide range of important physiologic processes and has a pathologic role in some diseases. TNF antagonists (infliximab, adalimumab, etanercept) are effective in treating inflammatory conditions. Antilymphocyte biological agents (rituximab, alemtuzumab), integrin antagonists (natalizumab, etrolizumab and vedolizumab), interleukin (IL)-17A blockers (secukinumab, ixekizumab) and IL-2 antagonists (daclizumab, basiliximab) are widely used after transplantation and for gastroenterological, rheumatological, dermatological, neurological and hematological disorders. Given the putative role of these host defense elements against bacterial, viral and fungal agents, the risk of infection during a treatment with these antagonists is a concern. Fungal infections, both opportunistic and endemic, have been associated with these biological therapies, but the causative relationship is unclear, especially among patients with poor control of their underlying disease or who are undergoing steroid therapy. Potential recipients of these drugs should be screened for latent endemic fungal infections. Cotrimoxazole prophylaxis could be useful for preventing Pneumocystis jirovecii infection in patients over 65 years of age who are taking TNF antagonists, antilymphocyte biological agents or who have lymphopenia and are undergoing concomitant steroid therapy. As with other immunosuppressant drugs, TNF antagonists and antilymphocyte antibodies should be discontinued for patients with active infectious disease.     

Eosinophil-mediated killing of schistosomula of Schistosoma mansoni: Oxidative requirement for enhancement by eosinophil colony stimulating factor (CSF-α) and supernatants with eosinophil cytotoxicity enhancing activity (E-CEA)

Factors which enhance eosinophil-mediated killing of antibody-coated schistosomula of Schistosoma mansoni include semipurified eosinophil colony stimulating factor (CSF-α) and eosinophil cytotoxicity enhancing activity (E-CEA) present in supernatants from cultured mononuclear cells. We have examined the mechanism of enhancement. Both actions require oxygen in order to enhance killing and do not enhance killing under anaerobic conditions (P ? 0.005). E-CEA had no detectable effect upon oxidative metabolism. In contrast to CSF-α which, in our previous studies, increased Superoxide anion productions and quantitative leukocyte iodination, E-CEA had no detectable effect upon oxidative metabolism. In order to test whether active oxygen products might mediate enhancement of killing, the effects of the addition of Superoxide dismutase and catalase were tested. Neither enzyme showed inhibition of CSF-α or E-CEA enhancement of eosinophil-mediated killing. The effects of CSF-α and E-CEA were not additive. These studies suggest that both CSF-α and E-CEA exert enhancement of killing by means of an as yet unidentified oxygen requiring process.     

Genetically determined differences in antibacterial activity of macrophages are expressed in the environment in which the macrophage precursors mature

Genetically determined enhanced resistance of C57BL-derived mouse strains to infection with Listeria monocytogenes can be attributed to a superior antibacterial activity of effector macrophages, regulated by a single, autosomal, dominant, gene. The present experiments investigated the phenotypic expression of this gene in the macrophage response. Radiation bone marrow chimeras between H-2 compatible B10.A/SgSn (Listeria-resistant) and A/J (Listeria-sensitive) mouse strains were infected with Listeria and their anti-listerial resistance measured. B10.A/SgSn hosts showed enhanced resistance as compared to A/J hosts, regardless of the genotype of the donor bone marrow used to reconstitute the chimeric hosts. The level of enhanced antibacterial activity of macrophages in the resistant strain is therefore determined by the genotype of the host, not of the macrophage precursor. Thus, the macrophage response to Listeria is expressed phenotypically at the level of environmental factors in the host that regulate monocyte/macrophage proliferation and/or differentiation rather than being expressed as an inherent property of the macrophage per se.     

Mechanism of effector cell blockade. III. The increased sensitivity of neonatal PFC to effector cell blockade

The response to staphylococcal protein A (SPA) of unfractionated, T-cell-enriched (TCE), and T-cell-depleted (TCD) populations of both adult mononuclear cells (AMC) and cord blood mononuclear cells (CBMC) was studied. Adult unfractionated and TCE populations formed more T-lymphocyte colonies than did similar populations of CBMC. However, TCD populations of CBMC formed B-lymphocyte colonies at least as well as did the TCD population of AMC. These results suggest that B cells from CBMC may be more mature than CBMC T-cell populations.     

Adenosine deaminase and immunodeficiency: An in vitro model

We have examined the effect of adenosine and EHNA, a competitive inhibitor of adenosine deaminase (ADA), upon the ability of human peripheral blood lymphocytes to respond to mitogen. Addition of adenosine at concentrations greater than 10 μm (10^?5m) resulted in inhibition of lymphocyte proliferation at 48 hr of culture, provided that the culture medium was relatively free of ADA activity. The actual concentrations of adenosine remaining in inhibited cultures at the time of harvest were considerably lower than those added initially. EHNA alone also inhibited PHA response (and to a lesser extent PWM and Con A responses), but only at high concentrations. Noninhibitory concentrations of EHNA and adenosine together acted synergistically to produce profound inhibition of lymphocyte proliferation. This may provide an in vitro model to explore further the mechanism of the immunodeficiency associated with deficiency of ADA. Adenosine deaminase activity in stimulated cultures did not differ significantly from that found in unstimulated cultures, and the activity per protein or per DNA actually decreased in stimulated versus unstimulated cultures.     

Gluconeogenesis in the rat renal cortex after warm ischemia and hypothermic storage

Rat kidney cortex slices were tested for their gluconeogenic capacity after the kidney has been either subjected to warm ischemia or flushed with and stored in cold hyperosmotic media. Kidneys damaged by warm ischemia for up to 60 min did not lose their ability to convert pyruvate to glucose. However, they then rapidly lost this capacity so that after 2 hr of ischemia they were devoid of activity. This observation closely corresponded to survival of partially nephrectomized rats whose remaining kidney had been treated in a similar manner. Cortex slices obtained from kidneys flushed and stored in cold hyperosmotic media were found to lose most of their gluconeogenic capacity after 3 days of storage.