Indian J Sex Transm Dis Indian J Sex Transm Dis
Official Publication of the Indian Association for the Study of Sexually Transmitted Diseases
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Year : 2007  |  Volume : 28  |  Issue : 1  |  Page : 30-31

Chronic meningitis produced by pseudohyphal forms of Cryptococcus neoformans in HIV-seropositive patient

Department of Microbiology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India

Correspondence Address:
V P Baradkar
Department of Microbiology, Lokmanya Tilak Municipal Medical College, Sion, Mumbai - 400 022
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7184.35709

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Cryptococcus neoformans infection is one of the acquired immunodeficiency syndrome (AIDS)-defining conditions. It can be readily identified by its characteristic capsulated morphology by negative staining. We report a case of chronic meningitis produced by pseudohyphal forms of Cryptococcus neoformans in an AIDS patient who responded to amphotericin B.

Keywords: Cryptococcus neoformans , meningitis, pseudohyphal forms

How to cite this article:
Baradkar V P, Mathur M, Kumar S, Rathi M. Chronic meningitis produced by pseudohyphal forms of Cryptococcus neoformans in HIV-seropositive patient. Indian J Sex Transm Dis 2007;28:30-1

How to cite this URL:
Baradkar V P, Mathur M, Kumar S, Rathi M. Chronic meningitis produced by pseudohyphal forms of Cryptococcus neoformans in HIV-seropositive patient. Indian J Sex Transm Dis [serial online] 2007 [cited 2020 Nov 30];28:30-1. Available from:

   Introduction Top

Cryptococcal meningitis is one of the acquired immunodeficiency syndrome (AIDS)-defining conditions. It is important to recognize the organism in clinical specimen for rapid diagnosis by negative staining of cerebrospinal fluid (CSF) with Nigrosin or India ink. [1] Although Cryptococcus neoformans is usually described as an encapsulated yeast cell 2.5-14 micron in diameter, there are numerous reports of unusual cell shapes, like pseudohyphal or hyphal forms. [1],[2],[3] We have reported pseudohyphal forms of Cryptococcus neoformans causing meningitis in an HIV-seropositive patient.

   Case Report Top

A 42-year-old HIV-seropositive male patient was admitted with complaints of low-grade intermittent fever with chills and moderate headache since the last 15 days. He was treated for tuberculosis 1 year back with a 9-month course of antitubercular treatment (ATT).

There was no history of altered sensorium, seizures and visual defects. On examination, the patient had a temperature of 39C, heart rate of 88 per minute and blood pressure of 120/80 mm of Hg. Respiratory and cardiovascular systems were within normal limits. The abdomen was soft with normal bowel sounds. On central nervous system examination, terminal neck stiffness was present. His renal and liver function tests were within normal limits. He had hemoglobin of 10 gm/dl, WBC count of 3,900 cells/cubic mm with 80% polymorphs and 20% lymphocytes.

CSF obtained by lumbar puncture was received in the laboratory. CSF showed lymphocyte predominance (98%) with glucose 20 mg/dl and proteins 60 mg/dl. Wet mount and Nigrosin-stained smears showed capsulated yeast cells with pseudohyphal forms [Figure - 1], predominantly along with normal forms. Gram-stained smears [Figure - 2] also showed yeast cells with pseudohyphal forms. CSF was cultured on Sabouraud's dextrose agar (SDA) and incubated at 27C in B.O.D. incubator. After 48 h of incubation, typical mucoid colonies appeared on SDA. Wet mount from colony showed yeast cells with pseudohyphal forms, as well as normal yeast cells. The isolate was identified by growth on niger seed agar, positive rapid urease test and positive L-Dopa test.

The patient was started with injection amphotericin B (1 mg/kg) intravenously. A second sample of CSF was received after 10 days, which showed normal CSF biochemistry and normal cell counts and it also showed reduced numbers of capsulated cells, indicating good prognosis. No pseudohyphal forms were observed in the second sample. Patient finally responded to amphotericin B for 2 weeks as induction therapy and was discharged on oral Fluconazole 400 mg daily for 10 weeks.

   Discussion Top

Cryptococcosis, an uncommon disease before the AIDS pandemic, has emerged as an important cause of illness and death in HIV-infected persons.

Cryptococcus neoformans is heterothallic encapsulated yeast. Microscopically, the unicellular cells of fungus are spherical to oval in shape. Individual cells are surrounded by capsule. The diameter of cells may vary from 2-3 mm to 30-80 mm in heavily encapsulated cells. [1] Recognition of variants in morphology of cells is important for early laboratory identification of the disease, but unusual forms may give rise to diagnostic dilemma. [1] Rare different morphological forms, like round form with beak, pseudohyphal forms, leaflike forms, peanut-like forms, were also reported in CSF of a patient suffering from meningitis by Shashikala et al. [1] The patient did not respond to amphotericin B.

Morphological changes are potentially relevant to pathogenesis. Newer cellular forms arising from the changes stimulated by the growth may lead to altered antigenic epitopes, resulting in difficulty for the host to mount an immune response. [1] Nelson et al. , [2] in their experimental studies, considered that probably the pseudohyphal forms afford a biological 'escape hatch,' which ensures survival of species. Fries et al. [3] have suggested that these occasional reports of pseudohyphal forms in clinical specimens originate from phenotypic switching events (microevolution).

Nelson et al. [2] showed that pseudohyphal forms resist phagocytosis by soil amebae, which are natural predators of Cryptococcus neoformans . Hence phenotypic switching may provide Cryptococcus neoformans with a survival advantage in certain environments. This phenotypic switching is linked to several unresolved problems of Cryptococcus neoformans biology and virulence, including variations in capsule size, differences in inflammation during infection, the sporadic pseudohyphal or hyphal strains, heterogeneity in polysaccharide structure and strain microevolution. They proposed that phenotypic switching is a mechanism responsible for the protean inflammatory response observed during infection and organ colonization and one that leads to survival advantage.

Further studies are required to determine whether unusual forms of Cryptococcus neoformans in clinical material are more virulent and whether they alter the infection course in patients.

   References Top

1.Shashikala, Kanugo R, Srinivasan S, Mathew R, Karman M. Unusual morphological forms of Cryptococcus neoformans in cerebrospinal fluid. Indian J Med Microbiol 2004;22:188-90.  Back to cited text no. 1    
2.Nelson JB, Ivery MH, Bulmer GS. Cryptococcus neoformans : Pseudohyphal forms surviving culture with Acanthamoeba polyphagia . Infect Immun 1978;20:262-6.  Back to cited text no. 2    
3.Fries BC, Goldman DL, Cherniak R, Ju R, Casadevall A. Phenotypic switching in Cryptococcus neoformans results in changes in cellular morphology and glucoronoxylomannan structure. Infect Immun 1999;67:6076-83.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]


  [Figure - 1], [Figure - 2]


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