We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci,from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient.Ou...We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci,from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient.Our review of literature identified this coinfection as unusual presentation.Opportunistic infections associated with HIV infection are increasingly recognized.It may occur at an early stage of HIV-infection.Whereas concurrent opportunistic infections may occur,coexisting Pneumocystis jiroveci pneumonia(PCP)and disseminated cryptococcosis with cryptococcal pneumonia is uncommon.The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease.Pneumonia is the leading HIV-associated infection.We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV.Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid.In patients with<200/microliter CD4-lymphocytes,a bronchoalveolar lavage should be performed.This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole.After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.展开更多
In this study,microcomputer image processing and pattern recognition technology,and the knowledge of morphology and optical characteristics of Cryptococcus neoformans were used for identification of Cryptococcus neofo...In this study,microcomputer image processing and pattern recognition technology,and the knowledge of morphology and optical characteristics of Cryptococcus neoformans were used for identification of Cryptococcus neoformans.Four groups of mice were lethally infected with standard strain,Wuhan strain,American B-2643 strain and Var.Shanghainesis of the Cryptococcus neoformans.The samplescollected included mice brain,lung,kidney,liver,small intestine tissue and were observed under a light microscope.More than 600 images of the fungus were input into a microcomputer.A system of computer for automatic identification of the Cryptoccocus neoformans was developed. The technique involved image preprocessing,imagesegmenting,coding of line-length on the edge,curve fitting,extracting of image feature,building of image library and feature data bank etc..And then,768 images of the clinical samples and other fungus samples whose morphological features tend to be confused with Cryptococcus neoformans were input into microcomputer and subjected to automatic identification.The Cryptococcus neoformans was accurately identified within 15 min,and the consistence rate with results of routine culture was 98%.展开更多
Identification of Cryptococcus neoformans(C neoformans) has been considered depends on the phenotype and biochemical characteristics, especially on its urease positive characteristics During ...Identification of Cryptococcus neoformans(C neoformans) has been considered depends on the phenotype and biochemical characteristics, especially on its urease positive characteristics During the last ten years, there are 4 strains of urease negative C neoformans strains have been discovered, of which 2 were isolated from AIDS patients, 1 from pigeon dropping and another 1 from preserved cultures of 286 strains of C neoformans So far, from medlines, there was none of urease negative strain isolated clinically from non AIDS patient was report Recently, we isolated a strain of urease negative strain of C neoformans from neither AIDS nor immunocompromised patients for the first time展开更多
Cryptococcus neoformans is an encapsulated yeast causing mainly opportunistic infections. DNA molecular typing techniques divided C. neoformans into four major molecular types (AFLP1/VNI, AFLP1A/VNB/VNII, AFLP1B/ VNII...Cryptococcus neoformans is an encapsulated yeast causing mainly opportunistic infections. DNA molecular typing techniques divided C. neoformans into four major molecular types (AFLP1/VNI, AFLP1A/VNB/VNII, AFLP1B/ VNII, AFLP3/VNIII, AFLP2/VNIV) characterized by different pathogenicity, geographical distribution and susceptibility to antifungal treatments. In this study 170 Italian C. neoformans clinical isolates (CI) and 32 environmental isolates (EI), collected and serotyped during a ten-year period (1985 to 1995), were genotyped using [GACA]4 microsatellite PCR fingerprinting. The molecular types were compared to their geographic distribution, specimen sources and patient’s risk factors. All four molecular types were described among the CI and only VNI and VNIV among the EI. VNIV molecular type was isolated with significant prevalence among the CI and VNI among the EI. A different geographical distribution of molecular types was detected: VNIV was the most prevalent in the North and Center of Italy;VNIII was isolated almost exclusively in the Center. No significant correlation among molecular types versus predisposing diseases or isolation sources was detected. The strains isolated from different body sites of the same patient (17 cases) were of the same genotype. Five out 9 cases relapsed with a different molecular type. This preliminary investigation shows a high intraspecies variability and reveals a nonhomogeneous distribution of C. neoformans molecular types in Italy.展开更多
A retrospective cross-sectional study for patients with confirmed Cryptococcus neoformans meningitis(CM)in non-HIV-infected and non-transplant hosts in two class-A tertiary hospitals in Guangzhou,China is reported.181...A retrospective cross-sectional study for patients with confirmed Cryptococcus neoformans meningitis(CM)in non-HIV-infected and non-transplant hosts in two class-A tertiary hospitals in Guangzhou,China is reported.181 CM patients were enrolled during the study period,48%(87/181)of which died.Underlying diseases were risk factor associated with higher mortality,among which diabetes mellitus ranked first for the incidence of CM.The mortality was not related to antifungal drug susceptibility.All strains were considered susceptible to amphotericin B,although interpretative breakpoints for amphotericin B have not yet been established.According to the CLSI guidelines,most of the strains in our study were susceptible to voriconazole,fluconazole,fluorocytosine and dose-dependently susceptible to itraconazle.展开更多
Background Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal...Background Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL,Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections.Methods We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keywordCryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance ofC. neoformans to approved antifungal drugs.Results There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden.Conclusions The rising threat ofC. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.展开更多
The CLC chloride channel gene CLC-A of the pathogen yeast Cryptococcus neoformans was previously reported to be critical for multicopper laccase activity and growth at an elevated pH.This study reports that copper hom...The CLC chloride channel gene CLC-A of the pathogen yeast Cryptococcus neoformans was previously reported to be critical for multicopper laccase activity and growth at an elevated pH.This study reports that copper homeostasis was impaired in the clc-a mutant.This was demonstrated by the substantial decrease of the intracellular quantity of copper under copper-limited growth as determined by flame atomic absorption spectrometry.CLC-A is a critical factor in copper homeostasis which is required for copper acquisition of laccase in C.neoformans.展开更多
Objective To study the epidemiological features of Cryptococcus neoformans and Cryptococcus gattii isolated from clinical samples in Shenzhen and to elucidate the distribution of species,varieties,genotypes and mating...Objective To study the epidemiological features of Cryptococcus neoformans and Cryptococcus gattii isolated from clinical samples in Shenzhen and to elucidate the distribution of species,varieties,genotypes and mating types within the strains tested.Methods The strains involved in this study were 55 cryptococcal strains isolated from our clinical samples.The canavanine-glycine bromthymolblue(CGB)culture was performed to distinguish Cryptococcus neoformans from Cryptococcus gattii.展开更多
Cryptococcosis,a serious systemic fungal infection caused by Cryptococcus neoformans(C.neoformans)and its variants,poses a significant clinical challenge due to its poor prognosis and severe health implications.The tr...Cryptococcosis,a serious systemic fungal infection caused by Cryptococcus neoformans(C.neoformans)and its variants,poses a significant clinical challenge due to its poor prognosis and severe health implications.The treatment of cryptococcal infections is complicated by several unique factors,stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit.These include the fungi’s protective capsule,their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain,in particular their strategic positioning within the brain,protected by the blood-brain barrier(BBB).To overcome these obstacles,precise active targeting emerges as a pivotal strategy.Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems.However,research on the methodology for selecting such shared targets remains sparse.In our investigation,we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways.We identified the mannoprotein Cig1,prominently expressed on the surfaces of infected macrophages,lungs,and brains,as a viable shared target.On this basis,we utilized Hemin,a ligand for Cig1,to design liposomes(Hemin Lip)tailored for addressing complex fungal infections.By leveraging the interaction with the secreted protein Cig1,Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections,thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus.Moreover,we have extended this targeting mechanism to other nanomedicinal platforms,including albumin nanoparticles.This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment,offering a streamlined formulation with the potential for effective therapy against complex infections.展开更多
BACKGROUND Worldwide,there has been a steady increase in the number of cases of pulmonary cryptococcosis diagnosed in immunocompetent patients,where symptoms can range from mild to severe.Clinical and radiological dis...BACKGROUND Worldwide,there has been a steady increase in the number of cases of pulmonary cryptococcosis diagnosed in immunocompetent patients,where symptoms can range from mild to severe.Clinical and radiological distinction of disease may be made when compared with immunodeficient cases and in those presenting with primary lung carcinoma.In the latter case confusion can lead to initial misdiagnosis and delayed treatment.We report a case of disseminated cryptococcosis in an immunocompetent patient which mimicked a primary lung carcinoma with brain metastases.CASE SUMMARY A 51-year-old male farmer with a 30-year smoking history presented with a twoweek history of productive cough,streaky hemoptysis,and low-grade fever.He had no history of immunosuppression,tuberculosis,or specific risk factors.Chest computed tomography revealed a posterior basal left lower lobe mass,but tumor markers and transbronchial tests were negative.Brain magnetic resonance imaging showed an enhancing left frontal lobe lesion,raising suspicion for metastatic lung cancer.However,computed tomography-guided biopsy confirmed fungal pneumonia with“titan”cells,and a positive serum cryptococcal antigen test confirmed Cryptococcus neoformans infection.Bronchoscopy and lavage detected fungal spores,while cerebrospinal fluid cytology and culture were negative.Fluconazole(0.4 mg/day)was initiated,but progressive central nervous system lesions required amphotericin B.A six-week combination of fluconazole(600 mg/day)and flucytosine led to resolution.At 24-month follow-up,he remained asymptomatic with no recurrence.CONCLUSION Cryptococcosis is increasing in immunocompetent individuals in China and should be considered in pneumonia and lung or brain lesions.展开更多
Objective:To study disseminated cryptococcal infection in a tertiary care hospital in Southern India.Methods:The clinical profile of 12 disseminated cryptococcosis patients with the age group of 28-52 years was retros...Objective:To study disseminated cryptococcal infection in a tertiary care hospital in Southern India.Methods:The clinical profile of 12 disseminated cryptococcosis patients with the age group of 28-52 years was retrospectively analyzed.Results:7(58.3%) presented with fever 【 30 days and 3(25%) 】 30 days whereas 2(16.7%) did not have fever.All the 12(100%) had headache. 2(16.7%) had altered sensorium,one(8%) seizure.5(41.7%) had diarrhea and vomiting.6(50%) had oral candidiasis,and anemia.9(75%) had elevated erythrocyte sedimentation rate(ESR).6(50%) had neck stiffness.Cerebrospinal fluid(CSF) pressure was elevated in all 12(100%) patients. Blood culture positive for Cryptococcus neqformans(C.neoformans) in 11(91.7%) and CSF culture positive in all 12(100%),one(8%) had urine culture positive.India ink preparation was positive in 10(83.3%).CD4 count was less than 50/microl in 4(33.3%),between 50-100 in 6(50%) and 2(16.7%) in the range of 100-200.6(50%) were treated with parenteral amphotericin B(0.7 mg/kg/d) during intensive phase followed by oral fluconazole 400 mg/d for 8 weeks then maintenance oral fluconazole 200 mg/d.5(41.6%) were treated with fluconazole alone.8(66.7%) improved and 4(33.3%) patients died.Among those who succumbed to the illness,2(16.7%) received amphotericin and fluconazole,2(16.7%) patients received fluconazole alone.Conclusions:Disseminated cryptococcosis can cause considerable mortality in HIV patients and immunocompromised non- HIV individuals.At times,its presentation closely mimics that of Tuberculosis.Early diagnosis and appropriate treatment should be started as early as possible.展开更多
BACKGROUND Cryptococcal osteomyelitis is a bone infection caused by cryptococcus.As an opportunistic infection,bone cryptococcosis usually occurs in patients with immunodeficiency diseases or in those undergoing immun...BACKGROUND Cryptococcal osteomyelitis is a bone infection caused by cryptococcus.As an opportunistic infection,bone cryptococcosis usually occurs in patients with immunodeficiency diseases or in those undergoing immunosuppressive therapy and often displays characteristics of disseminated disease.Isolated cryptococcal osteomyelitis is extremely unusual in immunocompetent person.The pathogenic fungus often invades vertebrae,femur,tibia,rib,clavicle,pelvis,and humerus,but the ulna is a rare target.CASE SUMMARY A 79-year-old woman complaining of chronic pain,skin ulceration and a sinus on her right forearm was admitted,and soon after was diagnosed with cryptococcal osteomyelitis in the right ulna.Unexpectedly,she was also found to have apparently normal immunity.After treatment with antifungal therapy combined with surgery debridement,the patient’s osteomyelitis healed with a satisfactory outcome.CONCLUSION Although rare,cryptococcal osteomyelitis should be considered in the differential diagnosis of osteolytic lesions even in immunocompetent patients,and good outcomes can be expected if early definitive diagnosis and etiological treatment are established.展开更多
Pleural involvement of cryptococcal infection is uncommon and is more commonly observed in immunocompromised hosts than in immunocompetent ones.Pleural involvement in cryptococcal infections can manifest with or witho...Pleural involvement of cryptococcal infection is uncommon and is more commonly observed in immunocompromised hosts than in immunocompetent ones.Pleural involvement in cryptococcal infections can manifest with or without pleural effusion.The presence of Cryptococcus spp.in the effusion or pleura is required for the diagnosis of cryptococcal pleural infection,which is commonly determined by pleural biopsy,fluid culture,and/or detection of cryptococcal antigen in the pleura or pleural fluid.展开更多
BACKGROUND Cryptococcosis is a fungal infection caused by the yeast-like encapsulated basidiomycetous fungus of the Cryptococcus neoformans(C.neoformans)species complex.These fungi are ubiquitous in soil and bird drop...BACKGROUND Cryptococcosis is a fungal infection caused by the yeast-like encapsulated basidiomycetous fungus of the Cryptococcus neoformans(C.neoformans)species complex.These fungi are ubiquitous in soil and bird droppings,and infection by them is an important global health concern,particularly in immunosuppressed patients,such as organ transplant recipients and those infected by the human immunodeficiency virus.The fungus usually enters the body through the respiratory tract,but extremely rare cases of infection acquired by transplantation of solid organs have been reported.CASE SUMMARY We report a case of disseminated cryptococcosis in a liver transplant recipient,diagnosed 2 wk after the procedure.The patient initially presented with fever,hyponatremia and elevated transaminase levels,manifesting intense headache after a few days.Blood cultures were positive for C.neoformans.Liver biopsy showed numerous fungal elements surrounded by gelatinous matrix and sparse granulomatous formations.Magnetic resonance imaging of the brain showed multiple small lesions with low signal in T2,peripheric enhancement and edematous halo,diffuse through the parenchyma but more concentrated in the subcortical regions.Treatment with amphotericin B for 3 wk,followed by maintenance therapy with fluconazole,led to complete resolution of the symptoms.The recipients of both kidneys from the same donor also developed disseminated cryptococcosis,confirming the transplant as the source of infection.The organ donor lived in a rural area,surrounded by tropical rainforest,and had negative blood cultures prior to organ procurement.CONCLUSION This case highlights the risk of transmission of fungal diseases,specifically of C.neoformans,through liver graft during liver transplantation.展开更多
This work was aimed to study of fungicidal activity and mechanism of action of the killer toxin of Cryptococcus pinus VKM Y-2958. A killer-toxin preparation was obtained and partly purified from the culture liquid of ...This work was aimed to study of fungicidal activity and mechanism of action of the killer toxin of Cryptococcus pinus VKM Y-2958. A killer-toxin preparation was obtained and partly purified from the culture liquid of the yeast Cryptococcus pinus. Its fungicidal activity against the pathogenic yeast Filobasidiella neoformans was assessed by assay of target cells growth inhibition and propidium iodide staining. The preparation contained three peptides with molecular masses of about 11 - 13 kDa, which did not show similarities in the mass spectrometric analysis. When frozen, the killer-toxin preparation remained active for several years. The killer toxin of Cr. pinus exhibits the high fungicidal activity against the known pathogen F. neoformans, is stable during long-term storage, and its mechanism of action is based on damaging target cell membranes. The killer toxin was obtained by a simple procedure and is of interest for the development of novel fungicidal preparations.展开更多
Outbreak of autoimmune diseases by pathogenic yeasts has led to a serious medical threat. As these organisms evolve resistance to existing antifungal drugs, the concern could be further compounded. The realm of plant ...Outbreak of autoimmune diseases by pathogenic yeasts has led to a serious medical threat. As these organisms evolve resistance to existing antifungal drugs, the concern could be further compounded. The realm of plant derived products offers a wide spectrum of potentially valuable alternatives to the existing synthetic fungicides. Essential oils from sev-eral medicinal plants have been shown to exhibit pharmacological attributes. In the present study, anti-yeast properties of Oregano essential oil (OEO) were examined in vitro against four human patho-genic yeasts i.e., Candida albicans, Cryptococcus al-bidus, Cryptococcus neoformans and Rhodotorula ru-brum. OEO concentration of 200 μg/mL was found to be growth inhibitory against all four yeasts examined, thereby showing its potential to function as a natural anti-yeast agent.展开更多
Background: Yeasts from the genus Cryptococcus (species C. neoformans and C. gattii) are opportunistic pathogens that afflict humans with low immunity caused by diseases such as AIDS or by the usage of immunosuppressi...Background: Yeasts from the genus Cryptococcus (species C. neoformans and C. gattii) are opportunistic pathogens that afflict humans with low immunity caused by diseases such as AIDS or by the usage of immunosuppressive drugs. It is a fatal disease that has been studied around the whole world and its most fatal form is the brain cryptococcosis. Purpose: The present review describes the disease from pathogen isolation, the various clinical presentations of the disease, the most important virulence factors of yeast in human and animal model and their clinical issues. Methods: On this review, several published studies about the disease are presented. Results: Numerous researches have been done worldwide in order to find a kind of therapy that is more effective against the disease. Amphotericin B, in all forms is still the drug of choice in the treatment of the cryptococcosis. Fluconazole, as well as voriconazole in combination with amphotericin B, is recommended in the cases of treatment failure. Conclusion: This study presented has elucidated a little more about the disease. Further studies should be conducted to find more diagnoses that are accurate as well as more effective treatments for eradicating the disease. In this study, the bibliographic survey makes reference to the world literature;with regard to ecology, taxonomy, mains factors related to virulence, the clinical manifestations, the action of antifungal drugs and histopathological analysis used in an animal model, were the objectives deleterious aspects of this study, thus informing, in a simple way, the importance of this microorganism for research and researchers working with this global disease, called Cryptococcosis.展开更多
Background Despite recent reports on the molecular epidemiology of cryptococcal infections in China,clinical isolates have been mostly reported from human immunodeficiency virus （HIV）-negative patients,and environme...Background Despite recent reports on the molecular epidemiology of cryptococcal infections in China,clinical isolates have been mostly reported from human immunodeficiency virus （HIV）-negative patients,and environmental isolates from China have rarely been included.The aim of this study was to investigate the ecological profile of Cryptococcus （C.）neoformans and C.gattii in China.Methods A survey was performed in 10 cities from 20°N （North latitude） to 50°N and in a Eucalyptus （E.） camaldulensis forestry farm at the Guixi forestry center,China.Results Six hundred and twenty samples of pigeon droppings from 10 cities and 819 E.camaldulensis tree samples were collected and inoculated on caffeic acid cornmeal agar （CACA）.The brown-colored colonies were recultured to observe their morphology,growth on canavanine-glycine-bromothymol-blue （CGB） medium,phenol oxidase and urease activities,serotype and mating type.There were obvious differences in the positive sample rates of C.neoformans in pigeon droppings collected from the different cities,ranging from 50% in the cities located at latitudes from 30°N-40°N,29% at 20°N-30°N and 13% at 40°N-50°N.Conclusions There were no differences in positive bevy rates （approximately 80%） among the three grouped cities.Mycological tests of 101 isolates purified from pigeon droppings revealed that they were C.neoformans var.grubii.We also observed variable capsular size around the C.neoformans cells in colonies with variable melanin production and the bio-adhesion of the natural C.neoformans cells with other microorganisms.One urease-negative C.neoformans isolatewas isolated from pigeon droppings in Jinan city.No C.gattiiwas isolated in this study.展开更多
基金Supported by the"Scientific Research Fund for Neglected Tropical Diseases"(Project Grant number J500798759)the Argentinian Institutes for Health System Improvement-a Public Health Agency.through a scholarship(Grant numbers300820891)
文摘We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci,from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient.Our review of literature identified this coinfection as unusual presentation.Opportunistic infections associated with HIV infection are increasingly recognized.It may occur at an early stage of HIV-infection.Whereas concurrent opportunistic infections may occur,coexisting Pneumocystis jiroveci pneumonia(PCP)and disseminated cryptococcosis with cryptococcal pneumonia is uncommon.The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease.Pneumonia is the leading HIV-associated infection.We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV.Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid.In patients with<200/microliter CD4-lymphocytes,a bronchoalveolar lavage should be performed.This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole.After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.
文摘In this study,microcomputer image processing and pattern recognition technology,and the knowledge of morphology and optical characteristics of Cryptococcus neoformans were used for identification of Cryptococcus neoformans.Four groups of mice were lethally infected with standard strain,Wuhan strain,American B-2643 strain and Var.Shanghainesis of the Cryptococcus neoformans.The samplescollected included mice brain,lung,kidney,liver,small intestine tissue and were observed under a light microscope.More than 600 images of the fungus were input into a microcomputer.A system of computer for automatic identification of the Cryptoccocus neoformans was developed. The technique involved image preprocessing,imagesegmenting,coding of line-length on the edge,curve fitting,extracting of image feature,building of image library and feature data bank etc..And then,768 images of the clinical samples and other fungus samples whose morphological features tend to be confused with Cryptococcus neoformans were input into microcomputer and subjected to automatic identification.The Cryptococcus neoformans was accurately identified within 15 min,and the consistence rate with results of routine culture was 98%.
文摘Identification of Cryptococcus neoformans(C neoformans) has been considered depends on the phenotype and biochemical characteristics, especially on its urease positive characteristics During the last ten years, there are 4 strains of urease negative C neoformans strains have been discovered, of which 2 were isolated from AIDS patients, 1 from pigeon dropping and another 1 from preserved cultures of 286 strains of C neoformans So far, from medlines, there was none of urease negative strain isolated clinically from non AIDS patient was report Recently, we isolated a strain of urease negative strain of C neoformans from neither AIDS nor immunocompromised patients for the first time
文摘Cryptococcus neoformans is an encapsulated yeast causing mainly opportunistic infections. DNA molecular typing techniques divided C. neoformans into four major molecular types (AFLP1/VNI, AFLP1A/VNB/VNII, AFLP1B/ VNII, AFLP3/VNIII, AFLP2/VNIV) characterized by different pathogenicity, geographical distribution and susceptibility to antifungal treatments. In this study 170 Italian C. neoformans clinical isolates (CI) and 32 environmental isolates (EI), collected and serotyped during a ten-year period (1985 to 1995), were genotyped using [GACA]4 microsatellite PCR fingerprinting. The molecular types were compared to their geographic distribution, specimen sources and patient’s risk factors. All four molecular types were described among the CI and only VNI and VNIV among the EI. VNIV molecular type was isolated with significant prevalence among the CI and VNI among the EI. A different geographical distribution of molecular types was detected: VNIV was the most prevalent in the North and Center of Italy;VNIII was isolated almost exclusively in the Center. No significant correlation among molecular types versus predisposing diseases or isolation sources was detected. The strains isolated from different body sites of the same patient (17 cases) were of the same genotype. Five out 9 cases relapsed with a different molecular type. This preliminary investigation shows a high intraspecies variability and reveals a nonhomogeneous distribution of C. neoformans molecular types in Italy.
文摘A retrospective cross-sectional study for patients with confirmed Cryptococcus neoformans meningitis(CM)in non-HIV-infected and non-transplant hosts in two class-A tertiary hospitals in Guangzhou,China is reported.181 CM patients were enrolled during the study period,48%(87/181)of which died.Underlying diseases were risk factor associated with higher mortality,among which diabetes mellitus ranked first for the incidence of CM.The mortality was not related to antifungal drug susceptibility.All strains were considered susceptible to amphotericin B,although interpretative breakpoints for amphotericin B have not yet been established.According to the CLSI guidelines,most of the strains in our study were susceptible to voriconazole,fluconazole,fluorocytosine and dose-dependently susceptible to itraconazle.
基金supported by the National Key Research and Development Program of China[2022YFC2303000(L.W.),2021YFC2300400(L.W.)]the CAS Interdisciplinary Innovation Team(L.W.),and Henan Agricultural University[30900880(Y.Z.),30500946(Y.Z.)].
文摘Background Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL,Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections.Methods We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keywordCryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance ofC. neoformans to approved antifungal drugs.Results There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden.Conclusions The rising threat ofC. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.
基金supported by the Natural Nature Science Foundation of China(Grant No 30770043)the National Basic Research Program of China(Grant No 2007CB707801)the Tianjin Science and Technology Development Plan(Grant No 06YFGSH00500)
文摘The CLC chloride channel gene CLC-A of the pathogen yeast Cryptococcus neoformans was previously reported to be critical for multicopper laccase activity and growth at an elevated pH.This study reports that copper homeostasis was impaired in the clc-a mutant.This was demonstrated by the substantial decrease of the intracellular quantity of copper under copper-limited growth as determined by flame atomic absorption spectrometry.CLC-A is a critical factor in copper homeostasis which is required for copper acquisition of laccase in C.neoformans.
文摘Objective To study the epidemiological features of Cryptococcus neoformans and Cryptococcus gattii isolated from clinical samples in Shenzhen and to elucidate the distribution of species,varieties,genotypes and mating types within the strains tested.Methods The strains involved in this study were 55 cryptococcal strains isolated from our clinical samples.The canavanine-glycine bromthymolblue(CGB)culture was performed to distinguish Cryptococcus neoformans from Cryptococcus gattii.
基金supported by the National Natural Science Foundation of China(NSFC No.82073789)Chongqing’Special Funding for Postdoctoral Research Projects(2212013362060154)+1 种基金the Fundamental Research Funds for the Central Universities(SWU120068)the Venture and Innovation Support Program for Chongqing Over-seas Returnees(cx2022025)。
文摘Cryptococcosis,a serious systemic fungal infection caused by Cryptococcus neoformans(C.neoformans)and its variants,poses a significant clinical challenge due to its poor prognosis and severe health implications.The treatment of cryptococcal infections is complicated by several unique factors,stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit.These include the fungi’s protective capsule,their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain,in particular their strategic positioning within the brain,protected by the blood-brain barrier(BBB).To overcome these obstacles,precise active targeting emerges as a pivotal strategy.Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems.However,research on the methodology for selecting such shared targets remains sparse.In our investigation,we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways.We identified the mannoprotein Cig1,prominently expressed on the surfaces of infected macrophages,lungs,and brains,as a viable shared target.On this basis,we utilized Hemin,a ligand for Cig1,to design liposomes(Hemin Lip)tailored for addressing complex fungal infections.By leveraging the interaction with the secreted protein Cig1,Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections,thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus.Moreover,we have extended this targeting mechanism to other nanomedicinal platforms,including albumin nanoparticles.This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment,offering a streamlined formulation with the potential for effective therapy against complex infections.
文摘BACKGROUND Worldwide,there has been a steady increase in the number of cases of pulmonary cryptococcosis diagnosed in immunocompetent patients,where symptoms can range from mild to severe.Clinical and radiological distinction of disease may be made when compared with immunodeficient cases and in those presenting with primary lung carcinoma.In the latter case confusion can lead to initial misdiagnosis and delayed treatment.We report a case of disseminated cryptococcosis in an immunocompetent patient which mimicked a primary lung carcinoma with brain metastases.CASE SUMMARY A 51-year-old male farmer with a 30-year smoking history presented with a twoweek history of productive cough,streaky hemoptysis,and low-grade fever.He had no history of immunosuppression,tuberculosis,or specific risk factors.Chest computed tomography revealed a posterior basal left lower lobe mass,but tumor markers and transbronchial tests were negative.Brain magnetic resonance imaging showed an enhancing left frontal lobe lesion,raising suspicion for metastatic lung cancer.However,computed tomography-guided biopsy confirmed fungal pneumonia with“titan”cells,and a positive serum cryptococcal antigen test confirmed Cryptococcus neoformans infection.Bronchoscopy and lavage detected fungal spores,while cerebrospinal fluid cytology and culture were negative.Fluconazole(0.4 mg/day)was initiated,but progressive central nervous system lesions required amphotericin B.A six-week combination of fluconazole(600 mg/day)and flucytosine led to resolution.At 24-month follow-up,he remained asymptomatic with no recurrence.CONCLUSION Cryptococcosis is increasing in immunocompetent individuals in China and should be considered in pneumonia and lung or brain lesions.
文摘Objective:To study disseminated cryptococcal infection in a tertiary care hospital in Southern India.Methods:The clinical profile of 12 disseminated cryptococcosis patients with the age group of 28-52 years was retrospectively analyzed.Results:7(58.3%) presented with fever 【 30 days and 3(25%) 】 30 days whereas 2(16.7%) did not have fever.All the 12(100%) had headache. 2(16.7%) had altered sensorium,one(8%) seizure.5(41.7%) had diarrhea and vomiting.6(50%) had oral candidiasis,and anemia.9(75%) had elevated erythrocyte sedimentation rate(ESR).6(50%) had neck stiffness.Cerebrospinal fluid(CSF) pressure was elevated in all 12(100%) patients. Blood culture positive for Cryptococcus neqformans(C.neoformans) in 11(91.7%) and CSF culture positive in all 12(100%),one(8%) had urine culture positive.India ink preparation was positive in 10(83.3%).CD4 count was less than 50/microl in 4(33.3%),between 50-100 in 6(50%) and 2(16.7%) in the range of 100-200.6(50%) were treated with parenteral amphotericin B(0.7 mg/kg/d) during intensive phase followed by oral fluconazole 400 mg/d for 8 weeks then maintenance oral fluconazole 200 mg/d.5(41.6%) were treated with fluconazole alone.8(66.7%) improved and 4(33.3%) patients died.Among those who succumbed to the illness,2(16.7%) received amphotericin and fluconazole,2(16.7%) patients received fluconazole alone.Conclusions:Disseminated cryptococcosis can cause considerable mortality in HIV patients and immunocompromised non- HIV individuals.At times,its presentation closely mimics that of Tuberculosis.Early diagnosis and appropriate treatment should be started as early as possible.
文摘BACKGROUND Cryptococcal osteomyelitis is a bone infection caused by cryptococcus.As an opportunistic infection,bone cryptococcosis usually occurs in patients with immunodeficiency diseases or in those undergoing immunosuppressive therapy and often displays characteristics of disseminated disease.Isolated cryptococcal osteomyelitis is extremely unusual in immunocompetent person.The pathogenic fungus often invades vertebrae,femur,tibia,rib,clavicle,pelvis,and humerus,but the ulna is a rare target.CASE SUMMARY A 79-year-old woman complaining of chronic pain,skin ulceration and a sinus on her right forearm was admitted,and soon after was diagnosed with cryptococcal osteomyelitis in the right ulna.Unexpectedly,she was also found to have apparently normal immunity.After treatment with antifungal therapy combined with surgery debridement,the patient’s osteomyelitis healed with a satisfactory outcome.CONCLUSION Although rare,cryptococcal osteomyelitis should be considered in the differential diagnosis of osteolytic lesions even in immunocompetent patients,and good outcomes can be expected if early definitive diagnosis and etiological treatment are established.
文摘Pleural involvement of cryptococcal infection is uncommon and is more commonly observed in immunocompromised hosts than in immunocompetent ones.Pleural involvement in cryptococcal infections can manifest with or without pleural effusion.The presence of Cryptococcus spp.in the effusion or pleura is required for the diagnosis of cryptococcal pleural infection,which is commonly determined by pleural biopsy,fluid culture,and/or detection of cryptococcal antigen in the pleura or pleural fluid.
文摘BACKGROUND Cryptococcosis is a fungal infection caused by the yeast-like encapsulated basidiomycetous fungus of the Cryptococcus neoformans(C.neoformans)species complex.These fungi are ubiquitous in soil and bird droppings,and infection by them is an important global health concern,particularly in immunosuppressed patients,such as organ transplant recipients and those infected by the human immunodeficiency virus.The fungus usually enters the body through the respiratory tract,but extremely rare cases of infection acquired by transplantation of solid organs have been reported.CASE SUMMARY We report a case of disseminated cryptococcosis in a liver transplant recipient,diagnosed 2 wk after the procedure.The patient initially presented with fever,hyponatremia and elevated transaminase levels,manifesting intense headache after a few days.Blood cultures were positive for C.neoformans.Liver biopsy showed numerous fungal elements surrounded by gelatinous matrix and sparse granulomatous formations.Magnetic resonance imaging of the brain showed multiple small lesions with low signal in T2,peripheric enhancement and edematous halo,diffuse through the parenchyma but more concentrated in the subcortical regions.Treatment with amphotericin B for 3 wk,followed by maintenance therapy with fluconazole,led to complete resolution of the symptoms.The recipients of both kidneys from the same donor also developed disseminated cryptococcosis,confirming the transplant as the source of infection.The organ donor lived in a rural area,surrounded by tropical rainforest,and had negative blood cultures prior to organ procurement.CONCLUSION This case highlights the risk of transmission of fungal diseases,specifically of C.neoformans,through liver graft during liver transplantation.
文摘This work was aimed to study of fungicidal activity and mechanism of action of the killer toxin of Cryptococcus pinus VKM Y-2958. A killer-toxin preparation was obtained and partly purified from the culture liquid of the yeast Cryptococcus pinus. Its fungicidal activity against the pathogenic yeast Filobasidiella neoformans was assessed by assay of target cells growth inhibition and propidium iodide staining. The preparation contained three peptides with molecular masses of about 11 - 13 kDa, which did not show similarities in the mass spectrometric analysis. When frozen, the killer-toxin preparation remained active for several years. The killer toxin of Cr. pinus exhibits the high fungicidal activity against the known pathogen F. neoformans, is stable during long-term storage, and its mechanism of action is based on damaging target cell membranes. The killer toxin was obtained by a simple procedure and is of interest for the development of novel fungicidal preparations.
文摘Outbreak of autoimmune diseases by pathogenic yeasts has led to a serious medical threat. As these organisms evolve resistance to existing antifungal drugs, the concern could be further compounded. The realm of plant derived products offers a wide spectrum of potentially valuable alternatives to the existing synthetic fungicides. Essential oils from sev-eral medicinal plants have been shown to exhibit pharmacological attributes. In the present study, anti-yeast properties of Oregano essential oil (OEO) were examined in vitro against four human patho-genic yeasts i.e., Candida albicans, Cryptococcus al-bidus, Cryptococcus neoformans and Rhodotorula ru-brum. OEO concentration of 200 μg/mL was found to be growth inhibitory against all four yeasts examined, thereby showing its potential to function as a natural anti-yeast agent.
文摘Background: Yeasts from the genus Cryptococcus (species C. neoformans and C. gattii) are opportunistic pathogens that afflict humans with low immunity caused by diseases such as AIDS or by the usage of immunosuppressive drugs. It is a fatal disease that has been studied around the whole world and its most fatal form is the brain cryptococcosis. Purpose: The present review describes the disease from pathogen isolation, the various clinical presentations of the disease, the most important virulence factors of yeast in human and animal model and their clinical issues. Methods: On this review, several published studies about the disease are presented. Results: Numerous researches have been done worldwide in order to find a kind of therapy that is more effective against the disease. Amphotericin B, in all forms is still the drug of choice in the treatment of the cryptococcosis. Fluconazole, as well as voriconazole in combination with amphotericin B, is recommended in the cases of treatment failure. Conclusion: This study presented has elucidated a little more about the disease. Further studies should be conducted to find more diagnoses that are accurate as well as more effective treatments for eradicating the disease. In this study, the bibliographic survey makes reference to the world literature;with regard to ecology, taxonomy, mains factors related to virulence, the clinical manifestations, the action of antifungal drugs and histopathological analysis used in an animal model, were the objectives deleterious aspects of this study, thus informing, in a simple way, the importance of this microorganism for research and researchers working with this global disease, called Cryptococcosis.
基金This study was supported by grants from the National Natural Science Foundation of China （No.80171335,No.30970130）,the PLA Clinical High-tech Major Projects Fund （No.2010gxjs063）,and Shanghai Science and Technology Commission Fund （No.10dz2220100）.
文摘Background Despite recent reports on the molecular epidemiology of cryptococcal infections in China,clinical isolates have been mostly reported from human immunodeficiency virus （HIV）-negative patients,and environmental isolates from China have rarely been included.The aim of this study was to investigate the ecological profile of Cryptococcus （C.）neoformans and C.gattii in China.Methods A survey was performed in 10 cities from 20°N （North latitude） to 50°N and in a Eucalyptus （E.） camaldulensis forestry farm at the Guixi forestry center,China.Results Six hundred and twenty samples of pigeon droppings from 10 cities and 819 E.camaldulensis tree samples were collected and inoculated on caffeic acid cornmeal agar （CACA）.The brown-colored colonies were recultured to observe their morphology,growth on canavanine-glycine-bromothymol-blue （CGB） medium,phenol oxidase and urease activities,serotype and mating type.There were obvious differences in the positive sample rates of C.neoformans in pigeon droppings collected from the different cities,ranging from 50% in the cities located at latitudes from 30°N-40°N,29% at 20°N-30°N and 13% at 40°N-50°N.Conclusions There were no differences in positive bevy rates （approximately 80%） among the three grouped cities.Mycological tests of 101 isolates purified from pigeon droppings revealed that they were C.neoformans var.grubii.We also observed variable capsular size around the C.neoformans cells in colonies with variable melanin production and the bio-adhesion of the natural C.neoformans cells with other microorganisms.One urease-negative C.neoformans isolatewas isolated from pigeon droppings in Jinan city.No C.gattiiwas isolated in this study.
