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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 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
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
Fulltext Spinal cryptoccoma mimicking a spinal cord tumor complicated by cryptococcal meningitis in an immunocompetent patient

Carol L, Tai MS, Yusoff SM, Rose N, Rafia MH, Viswanathan S

Neurol India, 2018 7 25;66(4):1181-1183.
PMID: 30038119 DOI: 10.4103/0028-3886.237012
Matched MeSH terms: Cryptococcosis/complications*; Cryptococcosis/diagnosis*; Cryptococcosis/surgery
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
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
Fulltext Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and Induces Apoptosis-Like Cell Death in Cryptococcus neoformans

Movahed E, Tan GM, Munusamy K, Yeow TC, Tay ST, Wong WF, et al.

Front Microbiol, 2016;7:360.
PMID: 27047474 DOI: 10.3389/fmicb.2016.00360

Cryptococcus neoformans is an opportunistic fungus that causes fatal meningoencephalitis especially in AIDS patients. There is an increasing need for discovery of new anti-cryptococcal drugs due to emergence of resistance cases in recent years. In this study, we aim to elucidate the antifungal effect of triclosan against C. neoformans.

Matched MeSH terms: Cryptococcosis
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 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*
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 Cryptococcal osteomyelitis of the femur: a case report and review of literature

Zainal AI, Wong SL, Pan KL, Wong OL, Tzar MN

Trop Biomed, 2011 Aug;28(2):444-9.
PMID: 22041767 MyJurnal

Fungal osteomyelitis is a rare opportunistic infection. It exhibits some clinical and radiological similarities to several other bone pathologies. A diagnostic delay may result in significant increase in morbidity. We report a case of a 37-year-old man with underlying hypogammaglobulinaemia presented with isolated cryptococcal osteomyelitis of the femur.

Matched MeSH terms: Cryptococcosis/diagnosis*; Cryptococcosis/microbiology; Cryptococcosis/pathology*
Cryptococcocis: a rare fungal infection of the tongue

Mohamad I, Abdullah B, Salim R, Rajet KA, Naik VR

Southeast Asian J. Trop. Med. Public Health, 2010 Sep;41(5):1188-91.
PMID: 21073040

Fungal infection in the oral cavity is not uncommon. The site involved is usually species related. Cryptococcus rarely infects the oral cavity. We report an elderly patient who presented with a central lesion on the dorsum of the tongue. Biopsy revealed a fungal infection. Special stains confirmed cryptococcus. Being a rare location for cryptococcal infection, clinical suspicion should be correlated with histopathological examination. Once confirmed, the patient should be treated with an antifungal medication.

Matched MeSH terms: Cryptococcosis/diagnosis; Cryptococcosis/drug therapy; Cryptococcosis/microbiology*
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*
Detection of IgM and IgG antibodies to Cryptococcus neoformans proteins in blood donors and HIV patients with active cryptococcosis

Chai HC, Tay ST

Mycoses, 2009 Mar;52(2):166-70.
PMID: 18643920 DOI: 10.1111/j.1439-0507.2008.01549.x

The serological responses to Cryptococcus neoformans proteins of blood donors and HIV patients with active cryptococcosis from a tropical region were investigated in this study. Exposure to C. neoformans, an organism ubiquitous in the environment, contributes to the antibody responses observed in the blood donors. IgG responses to cryptococcal proteins were stronger than IgM responses in most sera tested in this study. A 53-kDa cryptococcal protein fragment was identified as the most immunoreactive protein on the IgM immunoblots of both blood donors and patients. Overall, there was no obvious difference in IgG responses of patients when compared with blood donors. Some immunogenic protein fragments (27.5, 76, 78 and 91.5 kDa) were detected at least two times more frequently on IgM immunoblots of patients compared with those of blood donors. It is yet to be investigated whether the proteins identified in this study may have any potential to be used as biomarker for cryptococcosis.

Matched MeSH terms: Cryptococcosis/immunology*; Cryptococcosis/microbiology
Fulltext An unusual cause of haemoptysis and headache: cryptococcosis

How SH, Kuan YC, Ng TH, Ramachandram K, Fauzi AR

Malays J Pathol, 2008 Dec;30(2):129-32.
PMID: 19291924 MyJurnal

Pulmonary cryptococcosis can be clinically silent in non-HIV infected patients but can also present as nodules and masses on the chest radiograph, which can be mistaken for tuberculosis or lung cancer. Common symptoms include fever and cough, and uncommonly haemoptysis. This report illustrates a non-HIV infected patient whose main complaint was haemoptysis and headache. He was diagnosed with pulmonary cryptococcosis from biopsy of an endobronchial mass found on flexible bronchoscopy. Disseminated cryptoccoccal infection should be considered as a differential diagnosis in non-HIV infected patients presenting with haemoptysis and headache. Early recognition and administration of appropriate therapy will improve clinical outcome in these patients.

Matched MeSH terms: Cryptococcosis/complications; Cryptococcosis/drug therapy; Cryptococcosis/pathology*
Determination of molecular types and genetic heterogeneity of Cryptococcus neoformans and C. gattii in Malaysia

Tay ST, Lim HC, Tajuddin TH, Rohani MY, Hamimah H, Thong KL

Med Mycol, 2006 Nov;44(7):617-22.
PMID: 17071555

The molecular types and genetic heterogeneity of Cryptococcus neoformans and C. gattii clinical isolates in Malaysia were determined in this study. Of 44 C. neoformans collected between 1980 and 2003, 42 (95.5%) were molecular type VNI, 2 (4.5%) were molecular type VNII. Of 17 C.gattii isolates, 13 (76.5%) were molecular type VGI, and 4 (23.5%) were molecular type VGII. A difference was noted when comparing the molecular types of cryptococcal isolates in the earlier and recent cases of cryptococcosis. While both molecular types VNI and VGI were equally predominant in the earlier cases of cryptococcosis, VNI was the most predominant molecular type isolated from the recent cases. VNII was a new molecular type, isolated from 5.1% of the recent cases. All the bird dropping isolates were molecular type VNI. The genetic heterogeneity of the two predominant molecular types, i.e., VNI, VGI clinical isolates and bird dropping isolates of C. neoformans were further determined by polymerase chain reaction (PCR) fingerprinting method, using (GTG)5 as single primer. Two clusters of cryptococcal isolates were distinguished at 68.5% of similarity, with cluster I consisting of VNI isolates and cluster II consisting of VGI isolates. Each cluster was further subdivided into three subtypes at >/=80% of similarity. Fourteen bird dropping isolates were grouped into a subtype within VN1, sharing 82.7% of similarity with the clinical isolates. A higher degree of similarities, ranging from 93.4-97.6% was noted between 3 bird dropping isolates with the clinical isolates in another subtype. This study demonstrated the existence of various molecular types of C. neoformans isolates in Malaysia and the genetic heterogeneity within the predominant molecular types. The study also provides evidence for genetic relatedness of clinical isolates with bird dropping isolates in the environment.

Matched MeSH terms: Cryptococcosis/microbiology; Cryptococcosis/epidemiology*
The isolation, characterization and antifungal susceptibilities of Cryptococcus neoformans from bird excreta in Klang Valley, Malaysia

Tay ST, Chai HC, Na SL, Hamimah H, Rohani MY, Soo-Hoo TS

Mycopathologia, 2005 Jun;159(4):509-13.
PMID: 15983736

The occurrence of Cryptococcus neoformans in bird excreta in Klang valley, Malaysia was determined in this study. Of 544 samples of bird excreta collected from a local zoo, pet shops and public areas, 20 strains of C. neoformans were isolated. All C. neoformans strains were serotype A and thus identified as C. neoformans variety grubii. All did not produce color changes on canavanine-glycine-bromothymol blue agar. All were of alpha-mating types, as determined by a pheromone-specific PCR assay. The antifungal susceptibility testing using agar diffusion method Neo-sensitabs showed that all were susceptible to amphotericin B, fluconazole and itraconazole.

Matched MeSH terms: Cryptococcosis/epidemiology; Cryptococcosis/parasitology; Cryptococcosis/veterinary*
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*
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
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

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