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  Table of Contents  
Year : 2012  |  Volume : 30  |  Issue : 2  |  Page : 245-248

Vertebro-cerebral cryptococcosis mimicking tuberculosis: A diagnostic dilemma in countries with high burden of tuberculosis

1 Department of Microbiology, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi 110 095, India
2 Department of Neurology, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi 110 095, India

Date of Submission08-Nov-2011
Date of Acceptance24-Feb-2012
Date of Web Publication28-May-2012

Correspondence Address:
R Gupta
Department of Microbiology, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi 110 095
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.96715

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 ~ Abstract 

We report a case of a 30-year-old immunocompetent man with disseminated cryptococcosis who was initially treated with antitubercular therapy due to clinical and radiological diagnosis of vertebro-cerebral tuberculosis. The diagnosis of Cryptococcus infection was made due to incidental isolation of this fungus from blood culture with negative cerebrospinal fluid culture results. Though disseminated cryptococcosis with central nervous system, skeletal, and skin involvement is an uncommon manifestation of Cryptococcus neoformans infection, a high clinical suspicion and early initiation of therapy is needed to recognise and treat such patients efficiently.

Keywords: Cryptococcus, disseminated cryptococcosis, vertebral tuberculosis

How to cite this article:
Gupta R, Kushwaha S, Behera S, Jaiswal A, Thakur R. Vertebro-cerebral cryptococcosis mimicking tuberculosis: A diagnostic dilemma in countries with high burden of tuberculosis. Indian J Med Microbiol 2012;30:245-8

How to cite this URL:
Gupta R, Kushwaha S, Behera S, Jaiswal A, Thakur R. Vertebro-cerebral cryptococcosis mimicking tuberculosis: A diagnostic dilemma in countries with high burden of tuberculosis. Indian J Med Microbiol [serial online] 2012 [cited 2020 Jul 13];30:245-8. Available from:

 ~ Introduction Top

In a tuberculosis-endemic country with very high burden of brain and spinal cord complications due to tuberculosis, clinicians rarely suspect skeletal cryptococcosis in a young patient with clinical and magnetic resonance imaging (MRI) findings supporting tuberculosis, without any evidence of immunodeficiency and an obvious exposure to Cryptococcus. [1] Though cryptococcosis is a rare event in the absence of impaired cell-mediated immunity or concurrent HIV disease, there has been an increase in incidence of Cryptococcus infection in immunocompetent individuals. [2],[3],[4]

Most of the infections due to Cryptococcus are either pulmonary or cerebromeningeal. Vertebral cryptococcosis presenting as cord compression has been very rarely reported in literature. [5],[6] We report a case of disseminated cryptococcosis with central nervous system, skeletal, and skin involvement in a patient without immunosuppression who was treated on antitubercular therapy (ATT) for 4 months before he was started on antifungal therapy.

 ~ Case Report Top

A 30-year-old man presented to the neurology emergency with history of backache and weakness of lower limbs of 1 month duration. He had continuous low-grade fever for 7 days, along with few episodes of vomiting. He was diagnosed as a case of Pott's spine from a secondary level hospital and was on ATT (Rifampicin 600 mg, Isoniazide 300 mg, Pyrazinamide 1500 mg, Ethambutol 1000 mg) since 1 month.

On examination, the patient was conscious and oriented with stable vital signs. Neurological examination revealed grade 3/5 power in bilateral lower limbs. Deep tendon reflexes were not elicitable. Plantars were equivocal. Upper limbs were normal. There was no bladder or bowel involvement. Signs of meningeal irritation were absent on admission. Local examination of spine had diffuse tenderness over the thoracic spine. He had multiple pustules and umbilicated vesicular eruptions over face and other parts of the body. Other systemic examination was found to be normal.

On admission, the liver functions were deranged with raised total bilirubin 8.55 mg/dL, serum glutamate oxaloacetate transaminase (SGOT) 32 U/L, serum glutamate pyruvate transaminase (SGPT) 28 U/L and gamma glutamyltranferase 157 mg/dL. The MRI spine was done which showed collapse of D10 vertebral body and associated pre-paraspinal and dorsal epidural collection at D6-D11 level [Figure 1]. These findings were suggestive of tubercular spondylodiscitis. Serology for HIV was found to be negative, and complement level, CD4/CD8 ratio and serum immunofixation electrophoresis were found to be within normal limits. Routine laboratory investigations revealed mild leucocytosis [white blood cell (WBC) count of 12 × 10 3 cells/mm 3 , with 73% polymorphonucleated cells] with a normal platelet count of 102 × 10 3 per mm 3 . Serum electrolytes were within normal limits.
Figure 1: Magnetic resonance imaging (MRI) of spinal cord showing collapse of D10 vertebra and associated pre-paraspinal and dorsal collections

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The diagnosis of Pott's spine with drug-induced hepatitis was made and patient was kept on modified ATT. Rifampicin, Isoniazide and Pyrazinamide were withheld and Moxiflox 400 mg once a day and Linizolid 600 mg twice a day were added.

After 1 month of hospital stay, he developed high-grade fever and had two episodes of generalised tonic clonic seizures followed by altered sensorium. In view of this, involvement of the brain was considered and MRI brain was done which revealed enhancing basal exudates, diffuse prominent leptomeningeal enhancement, obstructive hydrocephalus along with vasculitic infarcts in basal ganglion and left superior cerebellum, suggesting sequelae of tubercular meningitis [Figure 2]. The possibility of disseminated tuberculosis to brain in the form of meningoencephalitis with tubercular vasculitis along with Pott's paraparesis was considered and Cycloserine 250 mg twice a day and Ethionamide 250 mg thrice a day were added.
Figure 2: MRI brain showing hydrocephalus and vasculitic infarct in left basal ganglion

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Cisternal puncture was done as lumbar puncture could not be done because of spine involvement and difficulty in positioning, and a blood culture was performed in view of continuous high-grade fever for last 7 days.

Examination of cerebrospinal fluid (CSF) showed an opalescent fluid, with mild pleocytosis (40 WBCs per mm 3 with 100% lymphocytes), very low glucose (17 mg/dL) and increased protein level (254 mg/dL). No bacteria, yeast cells or acid-fast bacilli were seen on microscopy by Gram and Ziehl Neelsen staining. India ink preparation showed no capsulated organism. CSF culture was sterile after 48 hr of incubation. CSF culture on conventional and automated BACTEC MGIT 960 system did not isolate Mycobacterium. Real-time polymerase chain reaction (PCR) for the gene coding for 16S rRNA using Mycobacterium genus-specific primers was found to be negative.

Blood culture grew circular grey, mucoid, glistening colonies on blood agar after 48 h of incubation, which were identified as Cryptococcus by colony morphology, microscopic appearance (Gram stain and India ink), antigen detection [latex agglutination test (LAT)] and biochemical properties (rapid urease test positive). The isolate was identified to species level (Cryptococcus neoformans) by observing black colonies on bird seed agar. At this time, antigen detection for Cryptococcus was done on preserved CSF specimen and fresh serum. Both CSF and serum samples were found to be positive for Cryptococcus antigen. Aspirate taken from skin lesions did not show any yeast cell suggestive of Cryptococcus on India ink preparation.

The diagnosis of disseminated cryptococcosis with spinal, cerebral and skin involvement in an immunocompetent patient was made and the patient was treated by intravenous amphotericin B (0.7 mg/kg/day) followed by fluconazole (400 mg/day). Unfortunately, the patient succumbed to infection on 5 th treatment day.

 ~ Discussion Top

The present case report describes the occurrence of disseminated cryptococcosis in an immunocompetent patient who was clinically and radiologically diagnosed as vertebro-cerebral tuberculosis. In a country endemic for tuberculosis with a large number of patients presenting with cerebrospinal tuberculosis, vertebral cryptococcosis is generally not suspected in an immunocompetent patient.

In the present case, the diagnosis of disseminated cryptococcosis was made due to incidental isolation of the yeast from blood culture, which was done in view of continuous fever and deteriorating clinical condition of the patient. Need for blood culture was not considered at the time of admission as the clinical and radiological findings were clearly suggestive of Pott's spine. The fungus was neither seen in India ink preparation of CSF nor isolated from CSF culture, but antigen for Cryptococcus was detected from both CSF and serum sample by LAT. The negative CSF culture could have been due to low fungal load in CNS due to normal immune status of the patient or the practice of non-enrichment of CSF samples before plating them onto culture media. [7] Though India ink preparation from skin lesions turned out to be negative for Cryptococcus, the clinical picture on reexamination was found to be the same as described in the literature and skin cryptococcosis was considered as nothing else was explaining these skin lesions. [8] The skin lesions were not initially suspected to be due to Cryptococcus as differential diagnosis of cryptococcosis was not considered before.

Though fungal culture is still considered the gold standard for diagnosing Cryptococcus infection, C. neoformans is isolated from blood in only 10-30% of patients with cryptococcal disease. [9] The detection of polysaccharide antigen by LAT has emerged as a very rapid, sensitive and specific method for diagnosing infection and monitoring response to therapy. [9] As the test is quite cheap and does not require high technical expertise, it is recommended that this test should always be done whenever CSF indices show mononuclear pleocytosis, decreased glucose and increased protein level. However, a negative LAT alone does not exclude the diagnosis as false negatives have been reported due to low antigen load. [9] This test should be always be used in conjunction with direct microscopy and fungal culture. This study also emphasises that parallel processing of blood along with CSF is a must in a patient with CNS infections, as it increases the chances of isolation of pathogens.

On extensive literature search, we could find a few case reports citing dual infection of tuberculosis and cryptococcosis in immunocompromised as well as immunocompetent hosts. [2],[10] Though the possibility of dual infection cannot be completely ruled out in the present case, no response to ATT, negative culture/PCR results for Mycobacterium tuberculosis and continuous worsening of patient condition on ATT suggest the diagnosis of disseminated Cryptococcus infection.

As clinical, radiological and MRI findings of vertebral cryptococcosis can mimic tuberculosis, it is strongly recommended that a high index of clinical suspicion is made and those who deteriorate clinically and neurologically should be investigated thoroughly by microscopy, culture and antigen detection for Cryptococcus from multiple sites.

 ~ References Top

1.Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS-100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 1995;8:515-48.  Back to cited text no. 1
2.Manfredi R, Calza L. Severe brain co-infection with Cryptococcus neoformans and Mycobacterium tuberculosis in a young, otherwise healthy student recently immigrated from china. Int J Infect Dis 2008;12:438-41.  Back to cited text no. 2
3.Zaharatos GJ, Behr MA, Libman MD. Profound T-lymphocytopenia and cryptococcemia in a human immunodeficiency virus seronegative patient with disseminated tuberculosis. Clin Infect Dis 2001;33:e125-8.  Back to cited text no. 3
4.Qadir F, Manzoor K, Ahmed E. Disseminated Cryptococcosis in a patient with nephrotic syndrome. Indian J Med Microbiol 2006;24:141-3.  Back to cited text no. 4
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5.Houda B, Wafa A, Zoubida TM, Mohamed A, Mohamed A, Hicham H. Vertebral cryptococcosis in an immunocompetent patient - a case report. Pan Afr Med J 2011;8:42.  Back to cited text no. 5
6.Gupta SK, Chhabra R, Sharma BS, Das A, Khosla VK. Vertabral Cryptococcosis simulating tuberculosis. Br J Neurosurg 2003;17:556-9.  Back to cited text no. 6
7.Sivasangeetha K, Harish BN, Sujatha S, Parija SC, Dutta TK. Cryptococcal meningoencephalitis diagnosed by blood culture. Ind J Med Microbiol2007;25:282-4.  Back to cited text no. 7
8.Lee JJ, Hsia RY. Cutaneous cryptococcal infection as a manifestation of disseminated disease. Ann Emerg Med 2011;57:100-3.  Back to cited text no. 8
9.Khanna N, Chandramuki A, Desai A, Ravi V. Cryptococcal infections of the central nervous system: An analysis of predisposing factors, laboratory findings and outcome in patients from south India with special reference to HIV infection. J Med Microbiol 1996;45:376-9.  Back to cited text no. 9
10.Huang CT, Tsai YJ, Fan JY, Ku SC, Yu CJ. Cryptococcosis and tuberculosis co-infection at a university hospital in Taiwan, 1993-2006. Infection 2010;38:373-9.  Back to cited text no. 10


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