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Idiopathic CD4+ T-lymphocytopenia in a child with disseminated cryptococcosis

Menon BS, Shuaib IL, Zamari M, Haq JA, Aiyar S, Noh LM

Ann Trop Paediatr, 1998 Mar;18(1):45-8.
PMID: 9692001

We describe a Malay girl with disseminated cryptococcosis affecting the lungs, liver, lymph nodes and bones. The diagnosis was made by culture of the bone marrow. Tests of immune function showed that she was HIV-negative but the CD4 percentage was persistently low. Idiopathic CD4+ T-lymphocytopenia was diagnosed. The child died despite two courses of anti-fungal therapy.

Matched MeSH terms: Cryptococcosis/complications*; Cryptococcosis/drug therapy; Cryptococcosis/immunology
Fulltext Large Solitary Pulmonary Cryptococcoma Mimicking Lung Carcinoma in an Immunocompetent Patient

Anandpara KM, Aswani Y, Hira P

Malays J Med Sci, 2018 Feb;25(1):114-118.
PMID: 29599641 DOI: 10.21315/mjms2018.25.1.13

Cryptococcosis is a life-threatening mycosis typically seen in immunocompromised patients. Pulmonary cryptococcosis generally presents as multiple or solitary nodular opacities. Cryptococcal infection presenting as a destructing cavernoma (cryptococcoma) without diffuse infiltration of the lung is an extremely rare presentation, even in immunocompromised patients. This report presents a healthy, HIV negative, immunocompetent patient who presented with a large solitary lung mass provisionally diagnosed as a lung malignancy on radiological imaging that proved to be a large cryptococcoma after biopsy. The patient was treated with liposomal Amphotericin B and fluconazole, and the lesion showed regression on serial imaging. This case report thus highlights an unconventional presentation of pulmonary cryptococcosis in an immunocompetent individual.

Matched MeSH terms: Cryptococcosis
MRI and CT findings of cryptococcal vaginitis

Ranganathan S, Moosa F, Kamarulzaman A, Looi LM

Br J Radiol, 2005 Apr;78(928):353-4.
PMID: 15774599

Cryptococcus neoformans is a yeast like fungus, which is commonly found in bird droppings, especially pigeons. Most cases of cryptococcal infections occur in immunocompromised patients or in those who are on long term immunosuppressant therapies. Cryptococcal infection usually presents as a meningoencephalitis or a pulmonary infection. Skin, bone and genital infections are very rare. We report the second case of vaginal cryptococcossis to be reported in English literature and the first to be imaged with CT and MRI.

Matched MeSH terms: Cryptococcosis/diagnosis*
Intracranial hypertension causing visual failure in cryptococcus meningitis

Tan CT

J Neurol Neurosurg Psychiatry, 1988 Jul;51(7):944-6.
PMID: 3204403

Thirty four patients with cryptococcal meningitis seen in the University of Malaya medical centre since 1980 were reviewed. Eleven patients had bilateral papilloedema and visual impairment but eventually survived. Seven patients had intensive aggressive measures, including shunting to reduce intracranial hypertension irrespective of ventricular size shown in CT scan, and showed substantial improvement in vision. It is concluded that papilloedema and visual failure in cryptococcal meningitis reflects raised intracranial pressure and that this should be treated vigorously.

Matched MeSH terms: Cryptococcosis/physiopathology*
Tuberculosis in living related donor renal transplant recipients

Suleiman AB, Musa Z, Morad Z

Ann Acad Med Singap, 1988 Jul;17(3):454-6.
PMID: 3064705

Ten out of 237 patients who underwent renal transplantation between 1975 and October 1986 developed tuberculosis. Most patients presented with vague symptoms, and typical symptoms commonly associated with tuberculosis were not common. Six had positive urine cultures. One patient had positive sputum and urine cultures and one had positive sputum and cerebrospinal fluid cultures for tuberculosis. In this last patient cryptococcus was also cultured from the sputum and CSF. Nine of the 10 patients responded well to antituberculosis therapy and was cured of the infection. The patient with associated cryptococcal infection died 2 months after presentation. Side effects of antituberculous therapy was minimal and easily resolved on stopping the offending drug.

Matched MeSH terms: Cryptococcosis/etiology
Fulltext Bruton's agammaglobulinaemia in a child presenting with cryptococcal empyema thoracis and periauricular pyogenic abscess

Wahab JA, Hanifah MJ, Choo KE

Singapore Med J, 1995 Dec;36(6):686-9.
PMID: 8781652

We describe here a case of cryptococcal empyema thoracis and periauricular pyogenic abscess in a child with Bruton's agammaglobulinaemia. The cryptococcal empyema thoracis was treated with intravenous amphotericin B and intravenous fluconazole for six weeks followed by oral fluconazole. The pyogenic periauricular abscess was surgically drained and treated with intravenous ceftazidime and cloxacillin for two weeks. He also received monthly intravenous immunoglobulin.

Matched MeSH terms: Cryptococcosis/diagnosis*; Cryptococcosis/therapy
The role of host microfilaments and microtubules during opsonin-independent interactions of Cryptococcus neoformans with mammalian lung cells

Choo KK, Chong PP, Ho AS, Yong PV

Eur J Clin Microbiol Infect Dis, 2015 Dec;34(12):2421-7.
PMID: 26463450 DOI: 10.1007/s10096-015-2497-4

The purpose of this investigation was to characterise the interactions of Cryptococcus neoformans with mammalian host alveolar epithelial cells and alveolar macrophages, with emphasis on the roles of the cryptococcal capsule and the host cell cytoskeletons. The adherence and internalisation of C. neoformans into mammalian lung cells and the roles of host cell cytoskeletons in host-pathogen interactions were studied using in vitro models coupled with a differential fluorescence assay, fluorescence staining, immunofluorescence and drug inhibition of actin and microtubule polymerisation. Under conditions devoid of opsonin and macrophage activation, C. neoformans has a high affinity towards MH-S alveolar macrophages, yet associated poorly to A549 alveolar epithelial cells. Acapsular C. neoformans adhered to and internalised into the mammalian cells more effectively compared to encapsulated cryptococci. Acapsular C. neoformans induced prominent actin reorganisation at the host-pathogen interface in MH-S alveolar macrophages, but minimally affected actin reorganisation in A549 alveolar epithelial cells. Acapsular C. neoformans also induced localisation of microtubules to internalised cryptococci in MH-S cells. Drug inhibition of actin and microtubule polymerisation both reduced the association of acapsular C. neoformans to alveolar macrophages. The current study visualises and confirms the interactions of C. neoformans with mammalian alveolar cells during the establishment of infection in the lungs. The acapsular form of C. neoformans effectively adhered to and internalised into alveolar macrophages by inducing localised actin reorganisation, relying on the host's actin and microtubule activities.

Matched MeSH terms: Cryptococcosis
Fulltext Epidemiology of fungal infections at an infectious disease reference centre in Malaysia

Tzar, M.N., Suhaila, B., Shamsul, A.S., Azizah, M.

International Medical Journal Malaysia, 2013;12(1):39-42.
MyJurnal

Introduction: Epidemiology of fungal infections in an infectious disease reference centre is different from other institutions. This study aimed to look at the scenario of fungal infections at an infectious disease reference centre in Malaysia. Methods: All positive fungal cultures from an infectious disease reference centre were identified by routine mycology laboratory methods. Patient demographic, laboratory and clinical data were collected and analyzed. Duplicate data were excluded. Results: Middle-aged Malay males were the most common group. However, increased proportions of Chinese, Myanmar and Indonesians reduced the Malay predominance in HIV-positive group. In all patients, Candida species represented 64.1% isolates, followed by Cryptococcus neoformans (14.7%) and Penicillium marneffei (14.7%). Among HIVpositive individuals, C. neoformans (37.9%) was the most common species, followed by P. marneffei (35.6%) and all Candida species (17.2%). In contrast to other non-infectious disease reference centres, common causes of fungaemia included P. marneffei (43.5%), Candida species (25.8%), C. neoformans (24.2%) and H. capsulatum (6.5%). Conclusion: The prevalence of fungal infection at an infectious disease reference centre is different from other non-infectious disease reference centres. This may have an impact on current antifungal practice especially empiric antifungal therapy, patient morbidity and mortality.

Matched MeSH terms: Cryptococcosis
Fulltext Cell surface proteins of cryptococcus neoformans mediate adherence and internalisation into mammalian cells

Choo, K.K., Chin, V.K., Chong, P.P., Ho, S.H., Yong, V.C.

JUMMEC, 2019;22(2):24-30.
MyJurnal

Cryptococcus neoformans is an encapsulated fungal pathogen that causes severe disease primarily in
immunocompromised patients. Adherence and internalisation of microbial pathogens into host cells often
begin with engagement of microbes to the surface receptors of host. However, the mechanisms involved
remain poorly understood. In this study, we investigated the association of cell surface determinants of C.
neoformans with mammalian cells. Our results showed that treatment with trypsin, but not paraformaldehyde
or heat killing, could reduce host-cryptococci interaction, suggesting the involvement of cell surface proteins
(CSPs) of C. neoformans in the interaction. We extended our investigations to determine the roles of CSPs
during cryptococci-host cells interaction by extracting and conjugating CSPs of C. neoformans to latex beads.
Conjugation of CSPs with both encapsulated and acapsular C. neoformans increased the association of latex
beads with mammalian alveolar epithelial cells, alveolar macrophages and monocyte-derived macrophages.
Further examination on the actin organisation of the host cells implied the involvement of actin-dependent
phagocytosis in the internalisation of C. neoformans in CSP-conjugated latex beads. We hypothesised that
CSPs present on the cell wall of C. neoformans mediate the adherence and actin-dependent phagocytosis
of cryptococci by mammalian cells. Our results warrant further studies on the exact role of CSPs in the
pathogenesis of cryptococcosis.

Matched MeSH terms: Cryptococcosis
Enzymatic characterisation of clinical isolates of Cryptococcus neoformans, Cryptococcus gattii and other environmental Cryptococcus spp

Chan MY, Tay ST

Mycoses, 2010 Jan;53(1):26-31.
PMID: 19389064 DOI: 10.1111/j.1439-0507.2008.01654.x

This study compared the enzymatic activity of clinical isolates of Cryptococcus neoformans, Cryptococcus gattii, environmental isolates of C. neoformans and non-neoformans Cryptococcus. Most of the cryptococcal isolates investigated in this study exhibited proteinase and phospholipase activities. Laccase activity was detected from all the C. neoformans and C. gattii isolates, but not from the non-neoformans Cryptococcus isolates. There was no significant difference in the proteinase, phospholipase and laccase activities of C. neoformans and C. gattii. However, significant difference in the enzymatic activities of beta-glucuronidase, alpha-glucosidase, beta-glucosidase and N-acetyl-beta-glucosaminidase between C. neoformans and C. gattii isolates was observed in this study. Environmental isolates of C. neoformans exhibited similar enzymatic profiles as the clinical isolates of C. neoformans, except for lower proteinase and laccase activities.

Matched MeSH terms: Cryptococcosis/microbiology*
Fulltext Genome-Wide Transcription Study of Cryptococcus neoformans H99 Clinical Strain versus Environmental Strains

Movahed E, Munusamy K, Tan GM, Looi CY, Tay ST, Wong WF

PLoS One, 2015;10(9):e0137457.
PMID: 26360021 DOI: 10.1371/journal.pone.0137457

The infection of Cryptococcus neoformans is acquired through the inhalation of desiccated yeast cells and basidiospores originated from the environment, particularly from bird's droppings and decaying wood. Three environmental strains of C. neoformans originated from bird droppings (H4, S48B and S68B) and C. neoformans reference clinical strain (H99) were used for intranasal infection in C57BL/6 mice. We showed that the H99 strain demonstrated higher virulence compared to H4, S48B and S68B strains. To examine if gene expression contributed to the different degree of virulence among these strains, a genome-wide microarray study was performed to inspect the transcriptomic profiles of all four strains. Our results revealed that out of 7,419 genes (22,257 probes) examined, 65 genes were significantly up-or down-regulated in H99 versus H4, S48B and S68B strains. The up-regulated genes in H99 strain include Hydroxymethylglutaryl-CoA synthase (MVA1), Mitochondrial matrix factor 1 (MMF1), Bud-site-selection protein 8 (BUD8), High affinity glucose transporter 3 (SNF3) and Rho GTPase-activating protein 2 (RGA2). Pathway annotation using DAVID bioinformatics resource showed that metal ion binding and sugar transmembrane transporter activity pathways were highly expressed in the H99 strain. We suggest that the genes and pathways identified may possibly play crucial roles in the fungal pathogenesis.

Matched MeSH terms: Cryptococcosis/microbiology*
Massive pleural effusions in cryptococcal meningitis

Wong CM, Lim KH, Liam CK

Postgrad Med J, 1999 May;75(883):297-8.
PMID: 10533638

Cryptococcal infection uncommonly presents with pulmonary manifestations and even more rarely so as massive bilateral effusions. Pleural involvement is usually associated with underlying pulmonary parenchymal lesions and is unusual while on antifungal therapy. We report a patient with cryptococcal meningitis who, while on intravenous 5-flucytosine and amphotericin B, developed life-threatening bilateral massive pleural effusions with evidence of spontaneous resolution, consistent with prior hypothesis of antigenic stimulation as the cause of pleural involvement.

Matched MeSH terms: Cryptococcosis
Fulltext Cryptococcal Meningitis in an immunocompetent Swiftlet Rancher – first reported case

Tan, Sin Nee, Lim, Thiam Seong Christopher

Malaysian Journal of Medicine and Health Sciences, 2019;15(1):82-84.
MyJurnal

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.

Matched MeSH terms: Cryptococcosis
Fulltext Lung-infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection

Movahed E, Cheok YY, Tan GMY, Lee CYQ, Cheong HC, Velayuthan RD, et al.

BMC Immunol, 2018 Nov 08;19(1):32.
PMID: 30409128 DOI: 10.1186/s12865-018-0269-5

BACKGROUND: IL-17A has emerged as a key player in the pathologies of inflammation, autoimmune disease, and immunity to microbes since its discovery two decades ago. In this study, we aim to elucidate the activity of IL-17A in the protection against Cryptococcus neoformans, an opportunistic fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we examined if C. neoformans infection triggers IL-17A secretion in vivo using wildtype C57BL/6 mice. In addition, an enhanced green fluorescence protein (EGFP) reporter and a knockout (KO) mouse models were used to track the source of IL-17A secretion and explore the protective function of IL-17A, respectively.
RESULTS: Our findings showed that in vivo model of C. neoformans infection demonstrated induction of abundant IL-17A secretion. By examining the lung bronchoalveolar lavage fluid (BALF), mediastinal lymph node (mLN) and spleen of the IL-17A-EGFP reporter mice, we showed that intranasal inoculation with C. neoformans promoted leukocytes lung infiltration. A large proportion (~ 50%) of the infiltrated CD4+ helper T cell population secreted EGFP, indicating vigorous TH17 activity in the C. neoformans-infected lung. The infection study in IL-17A-KO mice, on the other hand, revealed that absence of IL-17A marginally boosted fungal burden in the lung and accelerated the mouse death.
CONCLUSION: Therefore, our data suggest that IL-17A is released predominantly from TH17 cells in vivo, which plays a supporting role in the protective immunity against C. neoformans infection.

Matched MeSH terms: Cryptococcosis
A linking bridge between histopathological analysis and molecular assay in microbiology

Okubo Y

Malays J Pathol, 2017 08;39(2):207-208.
PMID: 28866707

No abstract available.

Matched MeSH terms: Cryptococcosis
Spectrum of opportunistic infections related to the central nervous system among AIDS patients in Hospital Kuala Lumpur

Nissapatorn V, Lee C, Khairul Anuar A

JUMMEC, 2000;5:89-92.

A relTospective study was conducted in Hospital Kuala Lumpur, May, 2001.49 (12.1%) of 406 AIDS patients were diagnosed as opportunistic infections related to the central nervous system. The sex ratio (M:F) was 7.2. The median age was 34 years. The predominant age group for male as same as female was 25-34 years.The majority of the study subjects were Chinese (79.6%), married (49%), unemployed (42.9%) and heterosexuals (95.9%) as the risk behavior related to HlV infection. The most frequent clinical manifestations was headache (71.4%). At the time of diagnosis, the greater number of patients 39 (79.6%) had CD4 count < 200 celVcumm. Outcome of acute therapy the patients had a complete (85.7%), treatment continued (10.3%), and transfer to other hospital (2.00/0). Toxoplasmic encephalitis (7.6%) and cryptococcosis (3.9%) were the frequent cause of focal intracerebral lesions and meningitis in these patients respectively. Oral candidiasis (32.7%) was the most common among other opportunistic infections in this study. KEYWORDS: AIDS, Opportunistic infections. central nervous system, clinical manifestations, outcome.

Matched MeSH terms: Cryptococcosis

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