Cryptococcal meningitis has become the largest cause for the death of infectious diseases in the central nervous system infectious disease worldwide. Most patients with cryptococcal meningitis have AIDS, autoimmune diseases, hematologic malignancies, and some other relevant diseases. It is mainly caused by infection with
Antiphospholipid Syndrome/complications* ; Cryptococcus neoformans ; Female ; HIV Infections ; Humans ; Meningitis, Cryptococcal/complications* ; Middle Aged ; Stroke

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.
AIDS-Related Opportunistic Infections ; CD4 Lymphocyte Count ; China ; Cryptococcosis/epidemiology* ; Cryptococcus ; HIV Infections/complications* ; Humans ; Meningitis, Cryptococcal

Cryptococcal meningitis is a central nervous system infection cause by Cryptococcus neoformans. Although Cryptococcus is found in bird droppings, it has never been reported for those ranchers involved in the niche swiftlet ranching industry despite having close proximity with the bird droppings. We present here a case of a 41-year-old healthy swiftlet rancher who presents with a history of prolonged fever, headache and altered behaviour of a month duration. Cerebral spinal fluid analysis revealed the presence of Cryptococcus. He was treated with intravenous amphotericin B and flucytosine and discharged well with fluconazole consolidation therapy for 8 weeks, followed by maintenance therapy for 1 year. We believe this is the first reported case of Cryptococcal meningitis (CM) occurring in an immunocompetent swiftlet rancher. This case should highlight the needs to wear a proper personal protective equipment inside a swiftlet ranch due to the constant exposure to the potential cryptococcal-rich environment. A high index of suspicion, careful history taking and physical examination focusing on neurologic assessment is key to early diagnosis and timely management of CM.
Cryptococcus meningitis

Ventriculoperitoneal (VP) shunt insertion is the standard treatment for hydrocephalus; shunt-associated infection is the most common complication after surgery. However, fungal infections are unusual. We present a case of cryptococcal meningitis complicated by a brain abscess and an infected intra-abdominal pseudocyst that developed 14 weeks after VP shunt insertion to treat hydrocephalus in a 74-year-old patient. Cryptococcal central nervous system (CNS) infection has a high mortality rate; however, diagnosis is challenging. Therefore, prompt diagnosis and treatment are required when a cryptococcal CNS infection is suspected in patients with VP shunts.
Aged ; Brain Abscess ; Brain ; Central Nervous System ; Cryptococcus ; Diagnosis ; Humans ; Hydrocephalus ; Meningitis, Cryptococcal ; Mortality ; Ventriculoperitoneal Shunt

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.
Anti-Infective Agents ; Betaine ; Cell Membrane ; Cryptococcus ; Cryptococcus neoformans ; Dandruff ; Ergosterol ; Fungi ; Gene Deletion ; Genetic Testing ; Genomics ; Humans ; Malassezia ; Methods ; Skin ; Transcriptome

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.
Autophagy ; Cell Wall ; Cryptococcus neoformans* ; Cryptococcus* ; Endoplasmic Reticulum Stress ; Fluconazole ; GTP Phosphohydrolases ; Guanine Nucleotide Exchange Factors ; Humans ; Hypersensitivity ; Inhalation ; Insects ; Saccharomyces cerevisiae ; Vacuoles ; Virulence*

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.
Aged ; Capsules ; Cerebrospinal Fluid ; Cryptococcosis ; Cryptococcus neoformans ; Female ; Fever ; Humans ; Hyphae ; Immunocompromised Host ; Lymphoma, B-Cell ; Meningitis, Cryptococcal ; Methenamine ; Methods

OBJECTIVE: To compare the sensitivity and specificity of real-time fluorescent quanttative PCR(FQ-PCR), blood culture and serum capsular antigen test for the detection of blood flow infection with cryptococcus reoformans, so as to provide the experimental evidence for use of FQ-PCR to detect the blood flow infection with cryptococcus neoformans. METHODS: Sixty male Sprague-Dawley (SD) rats were randomly divided into group A (immune suppression plus infection), group B (immune normal plus infection), group C (immune suppression plus non infection) and group D (normal control). The rats in group A were injected intraperitoneally with cyclophosphamide at D1 of experiment and were injected with suspension of cryptococcus neoformans by tail vein at D4 of experiment; the rats in group B were injected intraperitoneally with saline at D1 and were injected with suspension of cryprococcus neoformans by tail vein at D4; the rats in group C were injected intraperitoneally with cyclophosphamide at D1 and were injected with saline by tail vein at D4; the rats in group D were injected intaperitoneally with saline at D1 and were injected with saline by tail vein at D4.At D 4 after successful extablishment of rat model with infection, the blood samples were collected from ocular veneous plexus at 0, 6, 12, 24, 48 and 72 hours by parity number respectively, then the plasma was extracted, and the blood samples infected at different time were detected by FQ-PCR, and at the same time, the blood culture and serum capsular antigen test were performed. The detected results obtained from above-mentioned 3 kinds of detection methods were compared. RESULTS: The FQ-PCR detection of cryptococcus neoformoms showed that the positive rate detected after 12 hours in A group significantly increased (P<0.05), as compared with B, C and D groups. For the blood samples, the positive rate detected by FQ-PCR was significantly higher than that detected by the blood culture and serum capsular antigen test, moreover the detected results could be quantified, and difference was statistically significant (P<0.05). CONCLUSION The FQ-PCR system for detection of cryptococcus neoformant can detect the pathogens in blood of infected rats, and its sensitivity is superior to the blood culture and serum capsular antigen test; the FQ-PCR can detect the pathogens in blood of infected rats much more early, as compared with the blood culture and serum capsular antigen test.
Animals ; Cryptococcus neoformans ; Female ; Male ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity

BACKGROUND: A new shampoo with anti-Malassezia properties obtained from various plants is required to provide seborrheic dermatitis patients with a wider range of treatment options. OBJECTIVE: The aim of this study was to obtain in vitro susceptibility profiles of Malassezia restricta and M. globosa, the most important pathogenic organisms in the development of seborrheic dermatitis, to the plant extracts used in commercial anti-dandruff shampoos. METHODS: Minimal inhibitory concentrations (MICs) were determined for eight candidate plant extracts and two plant-derived natural products diluted with Leeming and Notman medium to final concentrations of 0.016 to 1 mg/ml. RESULTS: Castanea crenata shell, Camellia sinensis leaf, and oil-soluble Glycyrrhiza extracts presented relatively low MIC values (≤0.5 mg/ml) against both strains. The C. crenata shell and oil-soluble Glycyrrhiza extracts demonstrated especially high anti-Malassezia activity, suggesting their potential use in the treatment of seborrheic dermatitis. The extracts also showed fungistatic activity against other common facultative pathogenic yeasts, Cryptococcus and Candida. CONCLUSION: C. crenata shell and oil-soluble Glycyrrhiza extracts could potentially be used as active ingredients in anti-seborrheic and anti-dandruff shampoo formulations. They could be helpful for repeated treatments and regular prophylaxis of scalp seborrheic dermatitis.
Biological Products ; Camellia sinensis ; Candida ; Cryptococcus ; Dermatitis, Seborrheic ; Glycyrrhiza* ; Humans ; In Vitro Techniques* ; Malassezia ; Plant Extracts ; Scalp ; Yeasts

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows rapid and accurate identification of clinical yeast isolates. In-tube formic acid/acetonitrile (FA/ACN) extraction is recommended prior to the analysis with MALDI Biotyper, but the direct on-plate FA extraction is simpler. We compared the Biotyper with the VITEK MS for the identification of various clinically relevant yeast species, focusing on the use of the FA extraction method. METHODS: We analyzed 309 clinical isolates of 42 yeast species (four common Candida species, Cryptococcus neoformans, and 37 uncommon yeast species) using the Biotyper and VITEK MS systems. FA extraction was used initially for all isolates. If ‘no identification' result was obtained following the initial FA extraction, these samples were then retested by using FA (both systems, additive FA) or FA/ACN (Biotyper only, additive FA/ACN) extraction. These results were compared with those obtained by sequence-based identification. RESULTS: Both systems correctly identified all 158 isolates of the four common Candida species after the initial FA extraction. The Biotyper correctly identified 8.7%, 30.4%, and 100% of 23 C. neoformans isolates after performing initial FA, additive FA, and FA/ACN extractions, respectively, while VITEK MS identified all C. neoformans isolates after the initial FA extraction. Both systems had comparable identification rates of 37 uncommon yeast species (128 isolates), following the initial FA (Biotyper, 74.2%; VITEK MS, 73.4%) or additive FA (Biotyper, 82.0%; VITEK MS, 73.4%). CONCLUSIONS: The identification rate of most common and uncommon yeast isolates is comparable between simple FA extraction/Biotyper method and VITEK MS methods, but FA/ACN extraction is necessary for C. neoformans identification by Biotyper.
Candida ; Cryptococcus neoformans ; Mass Spectrometry* ; Methods* ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Yeasts*