Systemic aspergillosis associated with acute enterocolitis in foals.

Aspergillosis is an uncommon disease in horses, but it can be fatal. We report two cases of systemic aspergillosis in foals that occurred in a short period in the same region of southern Brazil. In addition, a literature review of similar cases was also performed. Risk factors were attributed to an immunodepression by primary enterocolitis and corticosteroid treatment, the damage in the epithelium, and multiple antibacterial treatments, which allowed local fungal proliferation, tissue invasion and spread of infection, leading to death. Since the antemortem diagnosis of aspergillosis in foals is difficult, our report alerts equine veterinarians regarding the importance of suspecting and investigating fungal co-infections in complicated cases of enterocolitis.

Nikkomycin Z for the treatment of experimental sporotrichosis caused by Sporothrix brasiliensis.

Sporotrichosis caused by Sporothrix brasiliensis is a global emergent infectious disease. Due to the scarcity of therapeutic options for fungal diseases, new antifungals are urgently needed. Nikkomycin Z (NikZ) is a future option as an agent against dimorphic fungi. We evaluated NikZ monotherapy and in combination with itraconazole (ITZ; the conventional therapy) in the treatment of experimental sporotrichosis caused by S. brasiliensis in a murine model. Animals were subcutaneously infected, and treated orally for 30 days. The study groups were as follows control (untreated), ITZ group (50 mg/kg/day), and three groups treated with NikZ, two by monotherapy (200 or 400 mg/kg/day), and one combining NikZ (400 mg/kg/day) and ITZ. Efficacy of treatments was evaluated via body weight gain, mortality and fungal burden in tissues. Efficacy was noted in all treatment groups, and the group receiving the drug combination showed even better results than those with monotherapy. Our study shows for the first time the high potential of NikZ to be used in the treatment of sporotrichosis caused by S. brasiliensis.

Effectiveness of diphenyl diselenide against experimental sporotrichosis caused by Sporothrix brasiliensis.

Diphenyl diselenide (PhSe)2 is a stable organoselenium compound with promising in vitro antifungal activity against several fungi, including Sporothrix brasiliensis. This species is associated with feline and zoonotic sporotrichosis, an emergent mycosis in Latin America. We evaluated the activity of (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. Sixty mice were subcutaneously infected with S. brasiliensis in the footpad and treated by gavage for 30 consecutive days. The six treatment groups received: no active treatment, itraconazole (50 mg/kg), (PhSe)2 at 1, 5, and 10 mg/kg dosages, or itraconazole (50 mg/kg) + (PhSe)2 1 mg/kg, once a day, starting seven days post-inoculation. A significant reduction in the fungal burden of internal organs was achieved in the groups treated with (PhSe)2 1 mg/kg or itraconazole alone in comparison with the untreated group. Higher dosages (5 and 10 mg/kg) of (PhSe)2 increased the clinical manifestation of sporotrichosis and mortality rate. Treatment with both itraconazole and (PhSe)2 1 mg/kg was better than their activities alone (P < .001). This is the first demonstration of the potential use of (PhSe)2, alone or with the present drug of choice, in the treatment of sporotrichosis.

We evaluated the activity of diphenyl diselenide (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. This is the first demonstration of the potential use of (PhSe)2, alone or in an association against sporotrichosis.

Aspergillosis in free-ranging Magellanic penguins.

We evaluated the mortality due to aspergillosis in free-ranging Magellanic penguins during their migration and the reproductive season. A total of 98 carcasses of penguins were collected along 370 km of coastline in Southern Brazil, between June 2017 and October 2019, and from reproductive colonies in Patagonian Argentina, in January 2019. All animals were necropsied, and only proven cases were computed. Aspergillosis was diagnosed in 2.5% of the penguins evaluated during their migration route. Our study, of the Southern coast of Brazil, is the first to demonstrate that aspergillosis is an important cause of mortality in free-ranging penguins. The implications of these findings in the One Health context are discussed.

We evaluated the mortality due to aspergillosis in free-ranging Magellanic penguins during their migration and the reproductive season. The mortality rate of penguins was 2.5% during their migration route. Our study is the first to demonstrate aspergillosis as an important cause of mortality in free-ranging penguins.

Anti-Aspergillus fumigatus IgG in patients with bronchiectasis and its relationship with clinical outcome.

Aspergillosis is a mycosis, most commonly affecting the airways. This mycosis can worsen the clinical condition of patients with concurrent lung diseases. We assayed for the presence of serum anti-A. fumigatus IgG in bronchiectasis patients from a tertiary hospital in south Brazil and evaluated the relationship with clinical outcome. Thirty-one patients with bronchiectasis, without cystic fibrosis, were included. Clinical and epidemiological data were collected from all participants. Positive serological tests were detected in 13% (4/31) of the patients. The mortality rate for the year following the assay was, in the seropositive group, 75% (3/4), whereas in the seronegative group, 15% (4/27). An illustrative case is also shown and discussed. Our study highlights the diagnostic challenge and the possible impact of Aspergillus infection on these patients, indicating the necessity of more and larger investigations in the field.

Initial Results of the International Efforts in Screening New Agents against Candida auris.

BACKGROUND: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. OBJECTIVE: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. METHODS: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. RESULTS: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. CONCLUSION: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study.

Monitoring of SARS-CoV-2 Specific Antibodies after Vaccination.

Vaccination is considered the most important measure to control the COVID-19 pandemic. Extensive follow-up studies with distinct vaccines and populations are able to promote robust and reliable data to better understand the effectiveness of this pharmacologic strategy. In this sense, we present data regarding binding and neutralizing (achieved by surrogate ELISA assay) antibodies throughout time, from vaccinated and previously infected (PI) health care workers (HCW) in Portugal. We analyzed serum samples of 132 HCW, who were vaccinated and with previous SARS-CoV-2 infection. Samples were collected before vaccination (baseline, M1), at second dose vaccine uptake (M2), and 25-70 days (M3) and 150-210 days (M4) after the second dose for vaccinated individuals. The IgG (anti-RBD/S) antibody geometric mean titers found on vaccinated HCW at M2 (GM = 116.1 BAU/mL; CI: 92.3-146.1) were significantly higher than those found on PI HCW at recruitment (M1) (GM = 35.9 BAU/mL; CI:15.4-83.4), and the neutralizing antibodies (nAb) were similar between these groups, of 93.2 UI/mL (95% CI 73.2-118.5) vs. 84.1 UI/mL (95% CI 40.4-155.9), respectively. We detected around 10-fold higher IgG (anti-RBD/S) antibodies titers in M3 when compared with M2, with a slight but significant decrease in titers from 36 days after the second dose vaccine uptake. The increase of nAb titers was correlated with IgG (anti-RBD/S) antibodies titers; however, in contrast to IgG (anti-RBD/S) antibodies titers, we did not detect a decrease in the nAb titer 36 days after a second vaccine dose uptake. At M4, a decrease of 8-fold in binding IgG (anti-RBD/S) and nAb was observed. No significant differences in antibody titers were observed by sex, age or chronic diseases. Our results suggest that IgG (anti-RBD/S) antibodies titers and nAb titers could be correlated, but an ongoing follow up of the cohort is required to better understand this correlation, and the duration of the immune response.

Molecular epidemiology of aspergillosis in Magellanic penguins and susceptibility patterns of clinical isolates.

Aspergillus section Fumigati is reported in up to 99% of aspergillosis cases in penguins. So far, no data regarding molecular epidemiology and azole resistance are available for A. fumigatus isolates collected from Magellanic penguins. The aim of this work was to perform molecular identification of Aspergillus section Fumigati at species level, to genotype those isolates using microsatellite markers, to evaluate the in vitro susceptibility patterns of A. fumigatus sensu stricto, and to characterize the cyp51A gene in clinical A. fumigatus strains isolated from Magellanic penguins with proven aspergillosis. All 34 isolates included in the study were identified as A. fumigatus sensu stricto. Analyzing the genetic diversity of the isolates of A. fumigatus sensu stricto, we identified two possible outbreaks in the rehabilitation center and we also observed the maintenance of clonal strains through the years. One A. fumigatus sensu stricto isolate was resistant to posaconazole, but the mutations found in the cyp51A gene of this isolate have not been described as conferring phenotypic resistance, suggesting that other mechanisms of resistance could be involved in the resistance of this isolate. With this study, we were able to understand the molecular diversity of Aspergillus fumigatus isolates collected from Magellanic penguins, to characterize them and to associate them with the described global population of Aspergillus fumigatus.

A. fumigatus sensu stricto is of great importance in penguins' aspergillosis. We could identify two outbreaks in the rehabilitation center and the maintenance of clonal strains through the years. Regarding antifungal prophylaxis, it may proceed, but preferably with surveillance for azole resistance.

Ebselen and diphenyl diselenide against fungal pathogens: A systematic review.

Fungal infections are one of the most prevalent diseases in the world and there is a lack of new antifungal drug development for these diseases. We conducted a systematic review of the literature regarding the in vitro antifungal activity of the organoselenium compounds ebselen (Eb) and diphenyl diselenide [(PhSe)2]. A systematic review was carried out based on the search for articles with data concerning Minimal Inhibitory Concentration (MIC) values, indexed in international databases and published until August 2020. A total of 2337 articles were found, and, according to the inclusion and exclusion criteria used, 22 articles were included in the study. Inhibitory activity against 96% (200/208) and 95% (312/328) of the pathogenic fungi tested was described for Eb and [(PhSe)2], respectively. Including in these 536 fungal isolates tested, organoselenium activity was highlighted against Candida spp., Cryptococcus ssp., Trichosporon spp., Aspergillus spp., Fusarium spp., Pythium spp., and Sporothrix spp., with MIC values lower than 64 µg/mL. In conclusion, Eb and [(PhSe)2] have a broad spectrum of in vitro inhibitory antifungal activity. These data added with other pharmacological properties of these organoselenium compounds suggest that both compounds are potential future antifungal drugs. Whether MICs toward the upper end of the ranges described here are compatible with efficacious therapy, and whether they may achieve such end as a result of the favorable non-antimicrobial effects of selenium on the host, requires more in vivo testing.

Fungal infections require the investigation of new drugs. The study is a systematic review of organo-selenium compounds with potential antifungal action. In 22 articles included in this review, in a total of 536 isolates of pathogenic fungi tested, the compounds showed action in more than 90% of them.

Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance.

The One Health context considers health based on three pillars: humans, animals, and environment. This approach is a strong ally in the surveillance of infectious diseases and in the development of prevention strategies. Aspergillus spp. are fungi that fit substantially in this context, in view of their ubiquity, as well as their importance as plant pathogens, and potentially fatal pathogens for, particularly, humans and avian species. In addition, the emergence of azole resistance, mainly in Aspergillus fumigatus sensu stricto, and the proven role of fungicides widely used on crops, reinforces the need for a multidisciplinary approach to this problem. Avian species are involved in short and long distance travel between different types of landscapes, such as agricultural fields, natural environments and urban environments. Thus, birds can play an important role in the dispersion of Aspergillus, and of special concern, azole-resistant strains. In addition, some bird species are particularly susceptible to aspergillosis. Therefore, avian aspergillosis could be considered as an environmental health indicator. In this review, aspergillosis in humans and birds will be discussed, with focus on the presence of Aspergillus in the environment. We will relate these issues with the emergence of azole resistance on Aspergillus. These topics will be therefore considered and reviewed from the "One Health" perspective.

Disseminated sporotrichosis with immune reconstitution inflammatory syndrome in an HIV patient: Case report and review of the literature.

BACKGROUND: Sporotrichosis has been occurring as outbreaks in Brazil, reaching epidemic levels in some regions. Zoonotic transmission is the main route to acquire Sporothrix. CASE REPORT: We describe a case of disseminated sporotrichosis caused by Sporothrix brasiliensis in an HIV/AIDS patient, with the presentation of immune reconstitution inflammatory syndrome (IRIS). CONCLUSIONS: This case reinforces that sporotrichosis should always be suspected in patients with IRIS from endemic regions, even in patients without the typical cutaneous lesions of this mycosis.

Disseminated sporotrichosis with immune reconstitution inflammatory syndrome in an HIV patient: case report and review of the literature / Esporotricosis diseminada y síndrome inflamatorio de reconstitución inmune en un paciente con VIH: reporte de un caso y revisión de la literatura

BACKGROUND: Sporotrichosis has been occurring as outbreaks in Brazil, reaching epidemic levels in some regions. Zoonotic transmission is the main route to acquire Sporothrix. CASE REPORT: We describe a case of disseminated sporotrichosis caused by Sporothrix brasiliensis in an HIV/AIDS patient, with the presentation of immune reconstitution inflammatory syndrome (IRIS). CONCLUSIONS: This case reinforces that sporotrichosis should always be suspected in patients with IRIS from endemic regions, even in patients without the typical cutaneous lesions of this mycosis

ANTECEDENTES: La esporotricosis suele aparecer en Brasil en forma de brotes y alcanza tasas epidémicas en algunas regiones. La ruta principal de transmisión es la zoonótica. CASO CLÍNICO: Describimos un caso de esporotricosis diseminada causado por Sporothrix brasiliensis en una paciente con VIH/sida que presentó un síndrome inflamatorio de reconstitución inmune (SIRI). CONCLUSIONES: Este caso demuestra que en regiones endémicas de esporotricosis esta micosis siempre debe ser sospechada en casos de SIRI, incluso en pacientes sin las lesiones cutáneas típicas de esta enfermedad

Diphenyl diselenide and its interaction with antifungals against Aspergillus spp.

Given the few antifungal classes available to treat aspergillosis, this study aimed to evaluate the in vitro antifungal activity of diphenyl diselenide (PhSe)2 alone and in combination with classical antifungals against Aspergillus spp., and its in vivo activity in a systemic experimental aspergillosis model. We performed in vitro broth microdilution assay of (PhSe)2 against 32 Aspergillus isolates; and a checkboard assay to test the interaction of this compound with itraconazole (ITC), voriconazole (VRC), amphotericin B (AMB), and caspofungin (CAS), against nine Aspergillus isolates. An experimental model of invasive aspergillosis in mice was studied, and survival curves were compared between an untreated group and groups treated with 100 mg/kg ITC, or (PhSe)2 in different dosages (10 mg/kg, 50 mg/kg and 100 mg/kg). All Aspergillus non-fumigatus and 50% of A. fumigatus were inhibited by (PhSe)2 in concentrations ≤ 64 µg/ml, with significant differences in MICs between the sections. Synergism or additive effect in the in vitro (PhSe)2 interaction with VRC and CAS was observed against the majority of isolates, and with ITC against the non-fumigatus strains. In addition to the inhibitory interaction, (PhSe)2 was able to add a fungicidal effect to CAS. Survival curves from the systemic experimental aspergillosis model demonstrated that the inoculum caused an acute and lethal infection in mice, and no treatment applied significantly prolonged survival over that of the control group. The results highlight the promising activity of (PhSe)2 against Aspergillus species, but more in vivo studies are needed to determine its potential applicability in aspergillosis treatment. LAY SUMMARY: The activity of diphenyl diselenide (PhSe)2 alone and in combination with itraconazole, voriconazole, and caspofungin, is described against three of the most pathogenic Aspergillus sections. (PhSe)2 may prove useful in therapy of infection in future; further study is required.

Aspergillosis in free-ranging aquatic birds.

Due to the difficulty in the access to free-ranging birds, data regarding Aspergillus infections in wild avian species is rare compared to captive wild and domestic birds. OBJECTIVE: report three cases of Aspergillus section Fumigati causing fungal disease in free-ranging aquatic birds, with the identification of the causal agent to the species level. CASE REPORTS: The diagnosis of aspergillosis was performed by macroscopic lesions found during the necropsy and confirmed by culture. Molecular identification by partial sequencing of the calM and benA genes allowed to confirm Aspergillus fumigatus sensu stricto as the etiological agent of aspergillosis in Procellaria aequinoctialis (White-chinned petrel) (n = 1), Nannopterum brasilianus (Neotropical cormorant) (n = 1) and Chroicocephalus maculipennis (Brown-hooded gull) (n = 1). CONCLUSION: Larger studies regarding the importance of aspergillosis in free-ranging aquatic birds are necessary, as well as it potential role in the One Heath context.

Aspergillosis in albatrosses.

Aspergillosis is a respiratory fungal disease of importance in captive marine birds. The aim of this study was to describe the occurrence of aspergillosis in Thalassarche melanophris during rehabilitation events and to identify the etiological agent. All the albatrosses that were received for rehabilitation and died within a 2-year period were included in the study. The proportionate mortality rate caused by aspergillosis was 21.4% (3/14). One of the etiological agents was Aspergillus flavus/oryzae lineage, and the other was A. fumigatus sensu stricto. Our study suggests that aspergillosis can act as a limiting factor in the rehabilitation of albatrosses.

Can Aspergillus fumigatus conidia cause false-positive results in the galactomannan enzyme immunoassay test?

INTRODUCTION: Several factors can cause false-positive results in the galactomannan (GM) test; however, others remain unknown. Presently, the impact of airborne contamination by Aspergillus conidia during enzyme-linked immunosorbent assay (ELISA) remains uninvestigated. METHODS: We studied 12 A. fumigatus isolates. Fungal conidia were serially diluted and tested for GM detection using the Platelia® Aspergillus enzyme immunoassay (EIA). RESULTS: The conidia concentration required for an EIA-positive result was 4.8 × 103 (median). CONCLUSIONS: This is the first study to evaluate the impact of environmental contamination on the Platelia® Aspergillus EIA assay. Only massive contamination can interfere with GM optical readings, suggesting that environmental contamination does not cause false-positive test results.

Can Aspergillus fumigatus conidia cause false-positive results in the galactomannan enzyme immunoassay test?

Abstract INTRODUCTION: Several factors can cause false-positive results in the galactomannan (GM) test; however, others remain unknown. Presently, the impact of airborne contamination by Aspergillus conidia during enzyme-linked immunosorbent assay (ELISA) remains uninvestigated. METHODS: We studied 12 A. fumigatus isolates. Fungal conidia were serially diluted and tested for GM detection using the Platelia® Aspergillus enzyme immunoassay (EIA). RESULTS: The conidia concentration required for an EIA-positive result was 4.8 × 103 (median). CONCLUSIONS: This is the first study to evaluate the impact of environmental contamination on the Platelia® Aspergillus EIA assay. Only massive contamination can interfere with GM optical readings, suggesting that environmental contamination does not cause false-positive test results.