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1.
Article in German | MEDLINE | ID: mdl-38925137

ABSTRACT

A 2-year-old Norwegian Forest cat was presented for evaluation of bilateral purulent nasal discharge and stertorous breathing. A computed tomography (CT) scan of the head revealed an intranasal mass of the left nasal cavity extending behind the tube openings and completely obstructing the nasopharynx. Rhinoscopy confirmed a pinkish, shiny mass. CT scan showed both compartments of the right middle ear filled with abnormal soft tissue attenuating material. There was no change in the bony outline of the middle ear. In the endoscopic examination, after endoscopically assisted tympanocentesis, this material in the accessible dorsolateral compartment proved to be classic polypous tissue in addition to highly viscous glue-like secretions. A secondary otitis media due to a drainage disorder was suspected.Using an endoscopic-interventional approach through the nostril, the nasopharyngeal mass was removed for histopathological examination, in order to restore the nasal airway, and to allow tube drainage. In contrast to cats with classical malignant nasal cavity masses, the cat showed several attachment points of the mass and multiple undulating elevations bilaterally in the nasopharyngeal mucosa.Cytological and histopathological examination identified the mass as a fungal granuloma in the context of a cryptococcus infection only rarely observed in Germany. Molecular genetic analysis confirmed an infection with Cryptococcus neoformans var. grubii.A single intranasal and nasopharyngeal endoscopic debridement resulted in a significant improvement of the clinical signs and a complete healing of the right middle ear (including the tympanic membrane) within 14 days, but not in a complete cure of the disease. The cat was therefore treated with oral itraconazole solution for several weeks.The case report shows that nasal cryptococcosis can also affect cats in Germany. Rhinoscopy reveals a nasopharyngeal mass with multiple attachment points, which is unusual for a neoplasia. In addition to the recommended removal of the mass, oral administration of systemic antimycotics is strongly advised.


Subject(s)
Cat Diseases , Cryptococcosis , Animals , Cats , Cat Diseases/diagnosis , Cat Diseases/microbiology , Cat Diseases/pathology , Cryptococcosis/veterinary , Cryptococcosis/diagnosis , Cryptococcosis/microbiology , Cryptococcosis/pathology , Cryptococcosis/drug therapy , Diagnosis, Differential , Nasopharyngeal Neoplasms/veterinary , Nasopharyngeal Neoplasms/diagnosis , Germany , Tomography, X-Ray Computed/veterinary , Nasopharyngeal Diseases/veterinary , Nasopharyngeal Diseases/diagnosis , Nasopharyngeal Diseases/microbiology , Nasopharyngeal Diseases/pathology
2.
Med Mycol ; 62(6)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935902

ABSTRACT

Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization's first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%-61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16-32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%-33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%-23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%-27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25-0.5 mg/l), 5-flucytosine (MIC range: 0.5-2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06-0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden.


Subject(s)
Antifungal Agents , Cryptococcosis , Cryptococcus gattii , Cryptococcus neoformans , Drug Resistance, Fungal , World Health Organization , Humans , Cryptococcosis/epidemiology , Cryptococcosis/microbiology , Cryptococcosis/mortality , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Cryptococcus gattii/drug effects , Cryptococcus neoformans/drug effects , Cryptococcus neoformans/isolation & purification , Microbial Sensitivity Tests
3.
Med Mycol ; 62(6)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935903

ABSTRACT

Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4-32 mg/l), while resistance to amphotericin B (MIC: 0.125-0.16 mg/l), itraconazole (MICs: 0.004-0.125 mg/l), and voriconazole (MICs: 0.004-0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat.


Subject(s)
Antifungal Agents , Drug Resistance, Fungal , Histoplasma , Histoplasmosis , World Health Organization , Humans , Histoplasmosis/epidemiology , Histoplasmosis/microbiology , Histoplasmosis/drug therapy , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Histoplasma/drug effects , Histoplasma/isolation & purification , Prevalence , Immunocompromised Host
4.
Med Mycol ; 62(6)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935907

ABSTRACT

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.


Subject(s)
Antifungal Agents , Aspergillosis , Aspergillus fumigatus , Drug Resistance, Fungal , World Health Organization , Humans , Aspergillus fumigatus/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Aspergillosis/epidemiology , Aspergillosis/microbiology , Aspergillosis/mortality , Voriconazole/pharmacology , Voriconazole/therapeutic use , Incidence , Microbial Sensitivity Tests , Invasive Fungal Infections/epidemiology , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/mortality , Invasive Fungal Infections/drug therapy , Risk Factors
5.
Med Mycol ; 62(6)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935914

ABSTRACT

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.


Subject(s)
Antifungal Agents , Fusarium , Microbial Sensitivity Tests , Scedosporium , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Fusarium/drug effects , Fusarium/isolation & purification , Scedosporium/drug effects , Scedosporium/isolation & purification , Scedosporium/classification , World Health Organization , Mycoses/epidemiology , Mycoses/microbiology , Fusariosis/microbiology , Fusariosis/epidemiology , Ascomycota/drug effects , Invasive Fungal Infections
6.
Med Mycol ; 62(6)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935911

ABSTRACT

In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.


Subject(s)
Antifungal Agents , Drug Resistance, Fungal , Pichia , World Health Organization , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Pichia/isolation & purification , Pichia/drug effects , Incidence , Risk Factors , Candidiasis/epidemiology , Candidiasis/microbiology , Candidiasis/prevention & control
7.
Int J Med Microbiol ; 314: 151614, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38368645

ABSTRACT

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis.


Subject(s)
Cryptococcosis , Cryptococcus neoformans , HIV Infections , Humans , HIV Infections/complications , HIV Infections/epidemiology , Multilocus Sequence Typing , Cohort Studies , Cryptococcosis/diagnosis , Cryptococcosis/epidemiology , Cryptococcosis/microbiology , Germany/epidemiology , Retrospective Studies
9.
J Health Monit ; 8(Suppl 3): 62-77, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37342430

ABSTRACT

Progressive climate change holds the potential for increasing human health risks from waterborne infections and intoxications, e. g. through an increase in pathogen concentrations in water bodies, through the establishment of new pathogens or through possible changes in pathogen properties. This paper presents some examples of potential impacts of climate change in Germany. Non-cholera Vibrio occur naturally in seawater, but can proliferate significantly in shallow water at elevated temperatures. In the case of Legionella, climate change could lead to temporary or longer-term increased incidences of legionellosis due to the combination of warm and wet weather. Higher temperatures in piped cold water or lower temperatures in piped hot water may also create conditions conducive to higher Legionella concentrations. In nutrient-rich water bodies, increased concentrations of toxigenic cyanobacteria may occur as temperatures rise. Heavy rainfall following storms or prolonged periods of heat and drought can lead to increased levels of human pathogenic viruses being washed into water bodies. Rising temperatures also pose a potential threat to human health through pathogens causing mycoses and facultatively pathogenic micro-organisms: increased infection rates with non-tuberculous mycobacteria or fungi have been documented after extreme weather events.

10.
Mycoses ; 66(9): 774-786, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37169736

ABSTRACT

BACKGROUND: In-house real-time PCR (qPCR) is increasingly used to diagnose the so-called endemic mycoses as commercial assays are not widely available. OBJECTIVES: To compare the performance of different molecular diagnostic assays for detecting Histoplasma capsulatum and Coccidioides spp. in five European reference laboratories. METHODS: Two blinded external quality assessment (EQA) panels were sent to each laboratory that performed the analysis with their in-house assays. Both panels included a range of concentrations of H. capsulatum (n = 7) and Coccidioides spp. (n = 6), negative control and DNA from other fungi. Four laboratories used specific qPCRs, and one laboratory a broad-range fungal conventional PCR (cPCR) and a specific cPCR for H. capsulatum with subsequent sequencing. RESULTS: qPCR assays were the most sensitive for the detection of H. capsulatum DNA. The lowest amount of H. capsulatum DNA detected was 1-4 fg, 0.1 pg and 10 pg for qPCRs, specific cPCR and broad-range cPCR, respectively. False positive results occurred with high concentrations of Blastomyces dermatitidis DNA in two laboratories and with Emergomyces spp. in one laboratory. For the Coccidioides panel, the lowest amount of DNA detected was 1-16 fg by qPCRs and 10 pg with the broad-range cPCR. One laboratory reported a false positive result by qPCR with high load of Uncinocarpus DNA. CONCLUSION: All five laboratories were able to correctly detect H. capsulatum and Coccidioides spp. DNA and qPCRs had a better performance than specific cPCR and broad-range cPCR. EQAs may help standardise in-house molecular tests for the so-called endemic mycoses improving patient management.


Subject(s)
Coccidioidomycosis , Histoplasmosis , Mycoses , Humans , Histoplasmosis/diagnosis , Coccidioidomycosis/diagnosis , Histoplasma/genetics , Real-Time Polymerase Chain Reaction/methods , Coccidioides/genetics , Multicenter Studies as Topic
11.
J Fungi (Basel) ; 9(2)2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36836272

ABSTRACT

The detection of Scedosporium/Lomentospora is still based on non-standardized low-sensitivity culture procedures. This fact is particularly worrying in patients with cystic fibrosis (CF), where these fungi are the second most common filamentous fungi isolated, because a poor and delayed diagnosis can worsen the prognosis of the disease. To contribute to the discovery of new diagnostic strategies, a rapid serological dot immunobinding assay (DIA) that allows the detection of serum IgG against Scedosporium/Lomentospora in less than 15 min was developed. A crude protein extract from the conidia and hyphae of Scedosporium boydii was employed as a fungal antigen. The DIA was evaluated using 303 CF serum samples (162 patients) grouped according to the detection of Scedosporium/Lomentospora in the respiratory sample by culture, obtaining a sensitivity and specificity of 90.48% and 79.30%, respectively; positive and negative predictive values of 54.81% and 96.77%, and an efficiency of 81.72%. The clinical factors associated with the results were also studied using a univariate and a multivariate analysis, which showed that Scedosporium/Lomentospora positive sputum, elevated anti-Aspergillus serum IgG and chronic Pseudomonas aeruginosa infection were significantly associated with a positive result in DIA, while Staphylococcus aureus positive sputum showed a negative association. In conclusion, the test developed can offer a complementary, rapid, simple and sensitive method to contribute to the diagnosis of Scedosporium/Lomentospora in patients with CF.

12.
Front Pediatr ; 10: 1060663, 2022.
Article in English | MEDLINE | ID: mdl-36533236

ABSTRACT

Background: Invasive mold infections are a well-known and life-threatening condition after allogeneic hematopoietic stem cell transplantation (HSCT). While Aspergillus species are recognized as predominant pathogens, Fusarium species should also be considered due to their broad environmental distribution and the expected poor outcome of invasive fusariosis. Particularly, splenic rupture as a complication of disseminated disease has not been reported yet. Case presentation: Two weeks after allogeneic HSCT for severe aplastic anemia, a 16-year-old boy presented with painful, erythematous skin nodules affecting the entire integument. As disseminated mycosis was considered, treatment with liposomal amphotericin B and voriconazole (VCZ) was initiated. Invasive fusariosis was diagnosed after histological and previously unpublished polymerase chain reaction-based examination of skin biopsies. Microbiological tests revealed Fusarium solani species. Despite stable neutrophil engraftment and uninterrupted treatment with VCZ, he developed mold disease-associated splenic rupture with hypovolemic shock and fungal endocarditis. The latter induced a cardiac thrombus and subsequent embolic cerebral infarctions with unilateral hemiparesis. Following cardiac surgery, the patient did not regain consciousness because of diffuse cerebral ischemia, and he died on day +92 after HSCT. Conclusion: Invasive fusariosis in immunocompromised patients is a life-threatening condition. Despite antimycotic treatment adapted to antifungal susceptibility testing, the patient reported here developed uncommon manifestations such as splenic rupture and fungal endocarditis.

13.
J Fungi (Basel) ; 8(8)2022 Aug 09.
Article in English | MEDLINE | ID: mdl-36012821

ABSTRACT

Histoplasmosis has been previously diagnosed in animals from Europe. The aim of this study is to review the literature on these reports, to analyze cases diagnosed at our laboratory (2000-2022) and to improve molecular typing of Histoplasma capsulatum directly from tissue to study the molecular epidemiology of Histoplasma capsulatum causing animal infections in Europe. Including 15 cases studied in our laboratory, we identified 39 cases of animal histoplasmosis between 1968 and 2022. They were diagnosed mostly in superficial tissue biopsies from cats and badgers from Central Europe. Using phylogenetic analyses of six partial genes, we were able to classify eight of the etiological agents as belonging to a highly supported lineage within the Eurasian clade. This study confirms the occurrence of autochthonous histoplasmosis in animals in Central Europe and proposes the addition of new loci to the MLST scheme to study the molecular epidemiology of histoplasmosis using either formalin-fixed paraffin-embedded tissue and fresh or cadaveric biopsies.

14.
J Fungi (Basel) ; 8(3)2022 Mar 11.
Article in English | MEDLINE | ID: mdl-35330291

ABSTRACT

Mucormycosis is an invasive fungal infection associated with high mortality, partly due to delayed diagnosis and inadequate empiric therapy. As fungal cultures often fail to grow Mucorales, identification of respective hyphae in tissue is frequently needed for diagnosis but may be challenging. We studied fluorescence in situ hybridization (FISH) targeting specific regions of the fungal ribosomal RNA (rRNA) of Mucorales to improve diagnosis of mucormycosis from tissue samples. We generated a probe combination specifically targeting Mucorales. Probe specificity was verified in silico and using cultivated fungi. Mucorales hyphae in tissue of a mouse model demonstrated a bright cytoplasmatic hybridization signal. In tissue samples of patients with mucormycosis, a positive signal was seen in 7 of 12 (58.3%) samples. However, autofluorescence in 3 of 7 (42.9%) samples impaired the diagnostic yield. Subsequent experiments suggested that availability of nutrients and antifungal therapy may impact on the FISH signal obtained with Mucorales hyphae. Diagnosis of mucormycosis from tissue might be improved by rRNA FISH in a limited number of cases only. FISH signals may reflect different physiological states of fungi in tissue. Further studies are needed to define the value of FISH to diagnose mucormycosis from other clinical samples.

15.
J Fungi (Basel) ; 8(3)2022 Mar 16.
Article in English | MEDLINE | ID: mdl-35330308

ABSTRACT

Invasive fungal infections are associated with increased mortality in hematological patients. Despite considerable advances in antifungal therapy, the evaluation of suspected treatment failure is a common clinical challenge requiring extensive diagnostic testing to rule out potential causes, such as mixed infections. We present a 64-year-old patient with secondary AML, diabetes mellitus, febrile neutropenia, and sinusitis. While cultures from nasal tissue grew Aspergillus flavus, a microscopic examination of the tissue was suggestive of concomitant mucormycosis. However, fluorescence in situ hybridization (FISH) using specific probes targeting Aspergillus and Mucorales species ruled out mixed infection. This was confirmed by specific qPCR assays amplifying the DNA of Aspergillus, but not of Mucorales. These results provided a rational basis for step-down targeted therapy, i.e., the patient received posaconazole after seven days of calculated dual therapy with liposomal amphotericin B and posaconazole. Despite clinical response to the antifungal therapy, he died due to the progression of the underlying disease within two weeks after diagnosis of fungal infection. Molecular diagnostics applied to tissue blocks may reveal useful information on the etiology of invasive fungal infections, including challenging situations, such as with mixed infections. A thorough understanding of fungal etiology facilitates targeted therapy that may improve therapeutic success while limiting side effects.

16.
Microorganisms ; 10(2)2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35208777

ABSTRACT

Cryptococcus neoformans var. neoformans is the second most prevalent agent of cryptococcosis in central Europe. Infections mostly present with localized skin and disseminated infections. Previous studies did not find these presentations to be determined by the fungal genotype as detected by multilocus sequence typing (MLST). However, phenotypic fungal traits may impact clinical presentation. Here, we studied the growth and virulence factors of C. neoformans var. neoformans isolates from disseminated and localized infections and an environmental isolate. We used coincubation with Acanthamoeba castellanii and the Galleria mellonella infection model to identify phenotypic characteristics potentially associated with clinical presentation. Clinical isolates of C. neoformans var. neoformans present a substantial phenotypic variability. Median survival of G. mellonella varied between 6 and 14 days. C. neoformans var. neoformans isolates from disseminated infections showed stronger melanization and larger capsules. They demonstrated superior uptake into an amoeba and increased cytotoxicity for the amoeba. Differences of strains from localized and disseminated infections in coincubation with amoeba are in line with the importance of phagocytes in the pathogenesis of disseminated cryptococcosis. Phenotypic traits and non-vertebrate infection models may help understand the virulence potential of C. neoformans var. neoformans isolates.

17.
Front Pharmacol ; 12: 723727, 2021.
Article in English | MEDLINE | ID: mdl-34489710

ABSTRACT

In this study, we describe a nano-carrier system for propolis that is able to cross an in vitro model of the blood-brain barrier (BBB) and effectively reduce the virulence of Cryptococcus neoformans in animal models. Antimicrobial properties of propolis have been widely studied. However, propolis applications are limited by its low water solubility and poor bioavailability. Therefore, we recently formulated novel poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NP) containing propolis. PBCA-NP are biocompatible, biodegradable and have been shown to effectively cross the BBB using apolipoprotein E (ApoE) as a ligand. Prepared nanoparticles were characterized for particle size, zeta potential, propolis entrapment efficiency and in vitro release. Additionally, the PBCA-NP were functionalized with polysorbate 80, which then specifically adsorbs ApoE. Using an in vitro BBB model of human brain microvascular endothelial cells hCMEC/D3, it was shown that fluorescence labelled ApoE-functionalized PBCA-NP were internalized by the cells and translocated across the cell monolayer. Propolis-loaded PBCA-NP had in vitro, antifungal activity against C. neoformans, which causes meningitis. To utilize the invertebrate model, Galleria mellonella larvae were infected with C. neoformans and treated with propolis-loaded PBCA-NP. The larvae exhibited normal behavior in toxicity testing, and treatment with propolis-loaded PBCA-NP increased survival in the C. neoformans-infected larvae group. In addition, following cryptococcal infection and then 7 days of treatment, the tissue fungal burden of mice treated with propolis-loaded PBCA-NP was significantly lower than control groups. Therefore, our ApoE-functionalized propolis-loaded PBCA-NP can be deemed as a potential targeted nanoparticle in the therapeutic treatment of cerebral cryptococcosis.

18.
Mycoses ; 64(10): 1177-1182, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34180098

ABSTRACT

BACKGROUND: Little is known about the infrastructure to translate advances in the management of patients at risk to develop invasive opportunistic fungal diseases. To assess the current state of Medical Mycology support in Germany, we conducted a survey among all 36 academic medical centres. METHODS: The survey consisted of a 3-pages questionnaire sent out in the first half of 2019. Information included details of infrastructure, education and teaching; consultation services and interdisciplinary conferences; research activities and participation in network groups; radiology, microbiology and pharmacology support; publication activity; and European Confederation for Medical Mycology (ECMM) Excellence Center designation, if assigned. RESULTS: Information was returned from 24 centres (67%). Thirteen institutions (54%) reported an independent infectious disease, and two a separate Medical Mycology department (8%); a Medical Mycology working group was reported for nine institutions (38%). An infectious disease consultation service was existent in 16 institutions (67%) and a multidisciplinary conference in 13 (54%). Fifteen institutions reported a separate study office with activities in infectious disease studies (63%). Laboratory capability for fungal identification and susceptibility testing was confirmed by all 24 institutions; testing of galactomannan by 23 (96%), cryptococcal antigen by 21 (88%), ß-D-Glucan by 9 (38%), and panfungal and Pneumocystis PCR by 21 and 22 (88% and 92%), respectively. Therapeutic drug monitoring of voriconazole was reported to be available in 15 (63%) institutions with a turnaround of ≤24 h during weekdays in 10 (42%). Two of the 24 University hospitals (8%) reported ECMM Diamond Excellence Status. CONCLUSIONS: The results of this survey document the continuing need to improve the availability of specialised Medical Mycology support in German academic medical centres.


Subject(s)
Invasive Fungal Infections , Mycology/education , Mycoses , Academic Medical Centers , Germany , Humans , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Mycoses/diagnosis , Mycoses/drug therapy , Surveys and Questionnaires
20.
J Fungi (Basel) ; 7(1)2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33467409

ABSTRACT

We describe a case of chronic meningoencephalitis with hydrocephalus caused by Cryptococcus bacillisporus (VGIII) in an immunocompetent patient from Santa Cruz, Bolivia. This first report of a member of the Cryptococcus gattii species complex from Bolivia suggests that C. bacillisporus (VGIII) is present in this tropical region of the country and complements our epidemiological and clinical knowledge of this group of emerging fungal pathogens in South America.

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