Pulmonary coinfection by Pneumocystis jiroveci and Cryptococcus neoformans

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.

Microcomputer System for Automatic Identification of the Cryptococcus neoformans and Its Clinical Application

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%.

Molecular Typing of Clinical and Environmental <i>Cryptococcus neoformans</i>Strains Isolated in Italy

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.

STUDY OF UREASE NEGATIVE CRYPTOCOCCUS NEOFORMANS ISOLATED FROM NON-AIDS PATIENT IN CHINA

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

Characterization of Clinical and Environmental Isolates of <i>Cryptococcus neoformans</i>/<i>Cryptococcus gattii</i>Complex Maintained in Yeast Culture Collection in S&#227;o Paulo, Brazil

Objective: As isolates of Cryptococcus are frequently kept collection stocks in institutions, sometimes without proper characterization, we sought to determine the genotype profiles, protease and phospholipase activities “in vitro” and the susceptibility testing for azoles and amphotericin B. Methodology: 84 isolates from several regions of Brazil (40 samples from clinical origin and 44 isolates from environmental origin) were maintained at the microorganism’s bank of the Biomedical Science Institute (ICB-USP) of the S&#227;o Paulo University, in S&#227;o Paulo, Brazil. This isolates was submitted fungal strains determination, DNA extraction and purification, determination of genotype by URA5 gene RFLP of CGB-positive isolates, protease and phospholipase activity and susceptibility to antifungals. Results: Of six CGB positive isolates tested by RFLP-PCR, only four presented a genomic profile consistent C. gattii species (VGII), while two other were C. neoformans (VNI and VNIII), indicating the existence of canavanine-resistante C. neoformans isolates in the culture collections. The clinical isolates secreted higher levels of phospholipase and environmental isolates but no differences were observed for the protease levels. Almost all isolates were sensible to azoles and amphotericin B. Conclusion: We point out in this research the existence of C. neoformans strains resistant to canavanine and intrinsic characteristic of C. gatti. These results demonstrate the importance to perform a detailed characterization of isolates kept in culture collections.

Isolates of Cryptococcus Neoformans from Non-HIV and Non-Transplant Hospitalized Patients

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.

Pulmonary <i>Aspergillus fumigatus</i>and <i>Cryptococcus neoformans</i>Co-Infection on an Underlying Sarcoidosis Condition: Report of a Rare Case

Sarcoidosis is a systemic granulomatosis from an unknown etiology, particularly affecting the lungs and the lymphatic system. It is associated with an immune deficiency involving an excessive immune response mediated by TH1 lymphocytes. Its evolution can lead to serious complications such as pulmonary fibrosis, pulmonary hypertension, bronchial stenosis and opportunistic infections. Opportunistic infections rarely occur on an underlying sarcoidosis condition. We report a rare case of pulmonary aspergillary and cryptococcal co-infection, on a patient with sarcoidosis who was finally lost to follow up. It was about a 47 years old female patient, diagnosed in 2015 for mediastino-pulmonary and neurological sarcoidosis. She was in therapeutical rupture after a 3-month period of corticotherapy at a dosage of 20 mg daily. The patient has been lost of sight for 3 years and was seen again on November, 22nd, 2018 at the Internal Medicine/Rheumatology Department of DALAL JAMM Hospital. At his admission she presented: a low grade hemoptysia, a chronic cough, a shortness of breath on exertion CRD Stage 2. At the biological investigation, the CRP was at 71.9 mg/l. Calcium serum levels were at 102.6 mg/l. Sputum culture and AFBS were negative. The screening serology of aspergillary Ig G was positive at 12.4 UA/ml. Thoracic High Resonance CT pointed suggests a Stage 2 Sarcoidosis complicated with aspergillary graft. The bronchoscopy showed out a severe suppurated bronchopathy. Microscopic examination of the BAF found some Cryptococcus neoformans settlement. We concluded a diagnosis of pulmonary aspergilloma and cryptococcosis co-infection with an underlying condition of Stage 2 Sarcoidosis. We successfully treated our patient with an oral intake of Itraconazole at a dosage of 400 mg daily over a period of 10 days. This is a rare and life-threatening triple association. In our case, the patient was lost to follow up for a long period and this was considered as the first morbidity risk factor.

Cryptococcus curvatusO3酵母菌培养及产油脂特性

生物柴油的发展,导致全球油脂供求紧张。微生物油脂的甘三酯组成与植物油类似,发展微生物油脂可部分缓解植物油脂供应压力。本文研究了Cryptococcus curvatusO3酵母利用葡萄糖为碳源生长和积累油脂的特性。Cryptococcus curvatusO3酵母在培养过程中能适应间歇式碳源流加方式达到高密度培养的目的,但在相同培养条件下,不同氮源能影响其代谢过程中糖到油脂转化的脂肪系数。Cryptococcus curvatusO3酵母利用葡萄糖作为碳源在30°C下摇瓶发酵,菌体生物量为51.8g/L,油脂含量达65.1%。脂肪酸组成分析结果表明,菌油富含饱和及低度不饱和长链脂肪酸,其中饱和脂肪酸之和占总脂肪酸组成的64%左右,其脂肪酸组成类似于可可脂,这些结果对于利用产油微生物转化生物质获取如类可可脂等具有高附加值油脂的研究具有重要意义。

白地霉Cryytococcus neoformans脂肪酶的双水相萃取

研究不同无机盐的双水相体系对白地霉脂肪酶的萃取分离效果,对PEG/(NH4)2SO4成相系统进行了系统的研究,通过考察体系PEG分子量、不同的无机盐、PEG浓度、(NH4)2SO4浓度、离子强度、pH及(NH4)2SO4浓度对反萃取的影响,并通过正交实验进一步优化实验条件,初步确定在PEG浓度15%,(NH4)2SO4浓度22.5%,pH8.0,不加NaCl的条件下进行双水相萃取,脂肪酶分离系数和纯化倍数分别为6.8和7.5,比活力达到40.3U/mg蛋白。

白地霉Cryytococcus neoformans脂肪酶产酶条件与纯化

目的:获得白地霉脂肪酶发酵的最优条件。方法:采用摇床培养的方法对各种影响因素进行筛选,结果:最适产酶条件为:豆油作碳源,蛋白胨作氮源,PEG600为表面活性剂,添加MgSO4、FeSO4、ZnSO4,pH8.7培养48h。采用双水相萃取和凝胶过滤两步纯化得到电泳均一的脂肪酶,纯化倍数达到72.2倍,其相对分子量约为38±1kDa。结论:得出采用双水相萃取脂肪酶的方法比较理想,该研究为新疆天山一号冰川白地霉脂肪酶的研究奠定了理论基础。

Descriptions of Male and Immature Stages of Cryptococcus ulmi Tang et Hao (Homoptera: Coccoidea: Eriococcidae) with Brief Notes on Its Biology

In this paper, the crawler, second instar female and male, prepupa, pupa and adult male of Cryptococcus ulmi are described and illustrated for the first time; adult female is redescribed; a key to all stages is given and the biology is briefly repor ted.

Interaction Between Cryptococcus laurentii,Monilinia fructicola,and Sweet Cherry Fruit at Different Temperatures

The present study was performed mainly to investigate the antagonist-pathogen-host interaction in wounds of the sweet cherry fruits. The antagonistic yeast Cryptococcus laurentii could significantly reduce the brown rot of the sweet cherry fruit caused by Monilinia fructicola at 25 and 1 ℃. The populations of yeast increased faster in the presence of the pathogen initially, but then decreased rapidly. In the fruits inoculated with M. fructicola alone or combined with C. laurentii, an induction of lipid peroxidation as well as activities of the antioxidant enzymes, such as, superoxide dismutases （SOD）, catalase （CAT）, and peroxidase （POD）, was observed. The isoenzyme pattern of polypheno/oxidase （PPO） changed greatly after the symptoms appeared, with new PPO isoforms being induced. By contrast, the induction of lipid peroxidation and activities of SOD, CAT, and POD were low, although no significant changes were found in the PPO isoenzyms in the fruits inoculated with antagonist C. laurentii alone. The inhibition of brown rot during the antagonist- pathogen-host interaction in wounds of the sweet cherry fruits was mainly on account of the stimulated growth of C. laurentii as well as the induction of antioxidant enzymes of the fruits by M. fructicola.

Metastatic infection caused by hypervirulent Klebsiella pneumonia and co-infection with Cryptococcus meningitis: A case report

BACKGROUND Klebsiella pneumoniae(K.pneumoniae)used to affect mainly people with compromised immunity or weakened by other infections,but recent emergence of hypervirulent strains has increased infections even in healthy individuals.These infections include liver abscess,pneumonia,bacteremia,meningitis,necrotizing fasciitis,and endophthalmitis.Although metastatic infection by hypervirulent K.pneumoniae(hvKP)is increasingly recognized,co-infection with Cryptococcus neoformans(C.neoformans)meningitis in immunocompetent hosts is rare but fatal.So,it is necessary to determine the risk factors,complications,and comorbidity of this disease.CASE SUMMARY This report describes a 58-year-old man with hvKP pulmonary abscess,bacteremia,and meningitis,accompanied by fatal Cryptococcus meningitis.This patient presented with fever for 1 wk and drowsiness for 3 d.Laboratory findings revealed pulmonary abscess and bacteremia of K.pneumoniae.He was given intravenous antibiotic therapy,and the infection was under control for about 1 wk.However,his condition deteriorated rapidly because of metastatic purulent meningitis.Although hvKP and C.neoformans were isolated and confirmed,the patient died of spontaneous respiratory and cardiac arrest caused by cerebral hernia.CONCLUSION HvKP has emerged as a cause of metastatic infections in immunocompetent hosts.polymicrobial co-infections should be taken into consideration when metastatic infection is present.

Cryptococcus neoformans,a global threat to human health

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.

Cryptococcus infection with asymptomatic diffuse pulmonary disease in an immunocompetent patient:A case report

BACKGROUND Cryptococcus presenting as an opportunistic pathogen mainly affects immunocompromised patients,but the disseminated form of infection is rare among immunocompetent populations.The partial radiographic characteristics of pulmonary cryptococcosis mimic lung carcinoma,leading to unnecessary open chest exploratory surgery,and the lack of a gold-standard noninvasive diagnostic increases the risk of misdiagnosis.Positron emission tomography/computed tomography(PET/CT),a sensitive method for distinguishing malignant tumors,coupled with cryptococcal latex agglutination test showing a high positive rate may overcome these issues.CASE A 36-year-old man presented for general examination,without health complaints.Routine CT showed multiple pulmonary nodules and a mass with high maximum standardized uptake value.Initially,we suspected primary malignancy with hematogenous metastasis.Although his routine fungal analysis had been negative,subsequent CT-guided percutaneous core needle biopsy and histopathology examination indicated a diagnosis of pulmonary cryptococcosis.Fluconazole(200 mg/d)antifungal drug treatment was initiated,and 1 mo later the pulmonary mass had reduced in size markedly(on chest CT scan)without any complications.CONCLUSION Serologic and PET/CT examinations may not rule out cryptococcosis,and percutaneous lung puncture is critical under all circumstances.

Characteristics of Killer Toxin of the Yeast <i>Cryptococcus pinus</i>

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.

Analysis on Immune Tolerance and Resistance Mechanism of <i>Cryptococcus albidus</i>of AIDS Patients with Opportunistic Cryptococci Infection

Objective: To explore more about the immune tolerance and drug resistance of white Cryptococci albidus in AIDS patients with opportunistic Cryptococcus infection. Methods: To analyze drug resistance of the samples of white Cryptococcus albidus extracted from opportunistic infection AIDS patients in the certain infection area from October 2011 to December 2014. Results: After analyzing two samples of Cryptococcus albidus from 885 cases with opportunistic infection, we found that one of the samples do resist to ten common antibiotics. They were fluconazole, flu-cytosine, fluconazole, caspofungin, amphotericin B, MI miconazole, terbinafine, ketoconazole and itraconazole. The other one was sensitive to voriconazole, but resistant to the rest of the drug. Two strains of bacteria were inoculated into the animals in vivo and their DNA was extracted to carry out the genotyping analysis. The results showed that different degrees of resistance gene amplification bands were found in the 10 kinds of antibiotics. Conclusion: Although there were few opportunistic infection Cryptococcus albidus in AIDS patients, it was easy to show its resistance to drugs. Therefore, great attention should be paid to it for the medical workers.

Ophthalmic manifestations of Cryptococcus gattii species complex:a case series and review of the literature

AIM:To report 4 cases of Cryptococcus gattii(C.gattii)species complex infection with diverse ophthalmic manifestations,and to review the literature to examine pathobiology of disease,classical ophthalmic presentations and outcomes,and treatment modalities for this emerging pathogen.METHODS:Cases of C.gattii meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series.Additionally,a MEDLINE literature review was conducted to identify all reported cases of C.gattii with ophthalmic manifestations from 1990-2020.Cases were reviewed and tabulated,together with our series of patients,in this report.RESULTS:Four cases of C.gattii with ophthalmic manifestations are presented;three from Australia and one from the USA.A literature review identified a total of 331 cases of C.gattii with visual sequelae.The majority of cases occurred in immunocompetent individuals.Blurred vision and diplopia were the most common presenting symptoms,with papilloedema the most common sign,reported in 10%-50%of cases.Visual loss was reported in 10%-53%of cases,as compared to rates of visual loss of 1%-9%in C.neoformans infection.Elevated intracranial pressure,cerebrospinal fluid(CSF)fungal burden,and abnormal neurological exam at presentation correlated with poor visual outcomes.The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures.CSF diversion procedures should be considered for refractory cases.Acetazolamide and mannitol are associated with high complication rates,and adjuvant corticosteroids have demonstrated higher mortality rates;these treatments should be avoided.CONCLUSION:Permanent visual loss represents a devastating yet potentially preventable sequelae of C.gattii infection.Intracranial hypertension needs to be recognised early and aggressively managed.Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended.

Meningitis secondary to Cryptococcus gattii,an emerging pathogen affecting immunocompetent hosts

BACKGROUND:Meningitis continues to be one of the most important infections diagnosed and treated by emergency physicians.Despite the advent of anti-infective therapy,meningitis carries a mortality rate of 20%-40%.In this study,we describe the first reported emergency medicine case of meningitis associated with Cryptococcus gattii to alert providers of this insidious,emerging global pathogen infecting immunocompetent individuals.METHODS:We provided a case report and accompanying review of the literature.A MEDLINE search for the term Cryptoccocus gattii was performed to obtain background information on Cryptococcus gattii.RESULTS:After two months of hospitalization,the patient was eventually discharged neurologically intact except for a continued mild bilateral hearing deficit.CONCLUSION:Cryptococcus gattii is an emerging world pathogen,which affects otherwise healthy,immunocompetent patients and requires timely identification and treatment in order to prevent severe neurological sequelae.

Anti-Candida and anti-Cryptococcus evaluation of 15 non-alkaloidal compounds from Pterogyne nitens

Objective: To evaluate anti-Candida and anti-Cryptococcus activities of 15 nonalkaloidal compounds from Pterogyne nitens Tulasne(Leguminosae), a South American medicinal plant.Methods: Compounds were submitted to antifungal assays, using microdilution method described by Clinical and Laboratory Standards Institute document, with minor modifications. Five species of Candida and two species of Cryptococcus, including clinical isolates were screened. Antifungal activity was expressed by minimum inhibitory concentration(MIC). Amphotericin B and fluconazole were used as standard antifungal drugs.Results: Among tested compounds, six substances presented fungal growth inhibition(MIC < 31.2 mg/m L) [three flavone derivatives(1–3), a glycosylated flavonol derivative(5)and two phenolic acids(10 and 12)]. Sorbifolin(1), exhibited potent antifungal activity,demonstrating MIC value of 3.90 mg/m L against Candida glabrata ATCC 90030, Cryptococcus gattii 118 and fluconazole-resistant clinical isolate of Cryptococcus neoformans var. grubii. Pedalin(2) and nitensoside B(3), two glycosylated flavone derivatives, were active against Cryptococcus neoformans ATCC 90012(MIC = 7.80 mg/m L).Conclusions: Flavone derivatives from Pterogyne nitens can serve as prototypes for the design and development of innovative anti-Candida and anti-Cryptococcus hits.