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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 2  |  Page : 212-214
Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center


Department of Microbiology, IHBAS, Delhi, India

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   Abstract 

Context: Human immunodeficiency virus (HIV) infection continues to be the most important risk factor for the development of central nervous system (CNS) cryptococcosis, which in turn is an important contributor to morbidity and mortality in HIV-infected patients. Early diagnosis of such patients is the key to their therapeutic success. Aims: This study was undertaken to find out the prevalence of CNS cryptococcosis and to assess the role of microbiological parameters for its specific diagnosis in HIV-reactive hospitalized patients admitted with meningeal signs in a tertiary care setting. Materials and Methods: A total of 104 patients suspected to be suffering from meningitis/meningoencephalitis were subjected to cerebrospinal fluid (CSF) analysis (including India ink preparation, culture by conventional methods and Bactec MGIT 960 system, antigen detection) and tests for HIV antibodies by standard laboratory operating procedures. Results: The prevalence of HIV infection in our study group was 12.5% (13/104), while the prevalence of cryptococcal CNS infection in HIV-reactive cohort was 46% (6/13). Additionally, 15.3% (2/13) of the patients from this cohort were positive for Mycobacterium tuberculosis. Conclusions: High prevalence of cryptococcal CNS infections in HIV-infected patients underscores the importance of precise and early microbiological diagnosis for better management of such patients

Keywords: Central nervous system (CNS) cryptococcosis, cryptococcal CNS infection, human immunodeficiency virus

How to cite this article:
Thakur R, Sarma S, Kushwaha S. Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center. Indian J Pathol Microbiol 2008;51:212-4

How to cite this URL:
Thakur R, Sarma S, Kushwaha S. Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center. Indian J Pathol Microbiol [serial online] 2008 [cited 2019 Oct 14];51:212-4. Available from: http://www.ijpmonline.org/text.asp?2008/51/2/212/41689



   Introduction Top


With the advent of acquired immunodeficiency syndrome (AIDS) pandemic, there has been a dramatic increase in the incidence of cryptococcal infections. Human immunodeficiency virus (HIV) infection continues to be the most important risk factor for the development of central nervous system (CNS) cryptococcosis and it is an important contributor to morbidity and mortality in these patients. [1] Cryptococcal meningitis is one of the AIDS-defining illnesses in patients with CD4 count less than 100/mL and it is caused by the encapsulated yeast Cryptococcus neoformans . [2] A definitive etiological diagnosis of cryptococcosis in the early stages is often missed due to nonspecific clinical and radiological picture. This study was done to determine the prevalence of CNS cryptococcosis and to assess the role of microbiological parameters for its diagnosis in HIV-reactive hospitalized patients admitted with meningitis or meningoencephalitis.


   Materials And Methods Top


A total of 104 patients suspected to be suffering from meningitis/meningoencephalitis were subjected to cerebrospinal fluid (CSF) analysis by biochemical tests, cytological examination and microbiological evaluation. Sera from these patients were tested for HIV by standard laboratory operating procedures. The details of the demographic profile of the patients, their clinical features, predisposing factors and relevant laboratory and radiological findings were recorded.

Microbiological methods included Gram stain; Ziehl Neelsen (Z-N) stain; India ink preparation; Latex antigen test (LAT) [Remel Apogent, USA]; culture by conventional methods for pyogenic, fungal and tuberculosis; and culture in Bactec MGIT (Mycobacterium growth indicator tubes) 960 system for Mycobacterium tuberculosis . Bacteriological media for pyogenic culture included blood agar, chocolate agar, MacConkey agar and brain-heart infusion (BHI) broth, which were incubated at 37°C for up to 48 hours and processed according to a predetermined protocol based on the presence of any visible growth. Sabourauds dextrose agar was used for fungal culture and the tubes were inoculated in duplicate and incubated at 30°C and 37°C. The tubes were inspected after 24 hours; and if found negative, they were further incubated for 4 weeks with inspections for growth at regular intervals. Lowenstein-Jensen's media and MGIT tubes were incubated for 8 weeks at 37°C.

Cryptococcal isolates were identified according to their typical appearance under microscope, of narrow-based budding capsulated yeasts; cultural characteristics; melanin production on Niger seed agar; and hydrolysis of urea.

Testing for HIV status was done using three different tests, namely, Microlisa (J. Mitra), tri-dot test (J. Mitra) and Western Blot (HIV W. Blot, J. Mitra).


   Results Top


A total of 104 patients suspected of having meningitis or meningoencephalitis were evaluated in this study, of which 72 were males and 32 were females. Majority (53%) of the cases were in the age group of 21 to 40 years; 17% in 10 to 20 years; 15% in 41 to 50 years; and the rest were in the age group of more than 50 years. Of the 104 patients who were evaluated, 13 (12.5%) patients were found to be reactive for HIV 1 antibodies. Among the HIV-reactive cohort, 6 (46%) were found to be positive for Cryptococcus neoformans on CSF analysis and 2 patients among the HIV-positive cases were positive for Mycobacterium tuberculosis in CSF culture. Two of the patients who were diagnosed as having cryptococcal meningitis also had associated pulmonary Koch's and they were already on ATT (antitubercular therapy) at the time of presentation to this hospital.

Clinical presentations of patients with cryptococcal meningitis were varied, the most common signs and symptoms being headache (66.7%), fever (66.7%), abnormal behavior (50%), seizure (33.3%), vomiting (33.3%) and double vision (16.7%). Biochemical and cytological evaluation in patients of HIV with cryptococcosis showed sugar <40 mg/dL (range, 20-30 mg/dL), proteins >100 mg/dL (range, 108-240 mg/dL), lymphocyte count >30/mm 3 (range, 30-124/mm 3 ) [Table 1]. Neutrophilic leucocytosis was not seen in any of the cases. On microbiological evaluation, India ink and Grams stain showed positive findings in all the 6 cases, but Z-N stain did not show the presence of acid fast bacilli (AFB) in any of the 6 cases. LAT was positive in all the cases, with a titer >512 (range, 512-2028) [Table 1]. MRI of the brain was done in 4 of the 6 patients and a positive radiological picture associated with an infective etiology was seen in 2 of the cases in the form of early hydrocephalus and inflammatory/infective granuloma.


   Discussion Top


Infection with HIV is widespread in India and cryptococcal meningitis is a common problem with AIDS. Various studies have been conducted in different parts of the world, including India, to find the prevalence of cryptococcosis in HIV-reactive patients and it has been found to range from 2.09% to 68.6%. [1],[3],[4],[5] Prevalence of cryptococcal meningitis in our cohort is 46%, which is higher than that reported by Indian studies but is comparable to reports from outside India. In this study 2 (15.3%) patients also had tubercular meningitis, but no case of concomitant cryptococcal and tubercular meningitis was seen. Concurrent cryptococcal infection with tubercular meningitis has been reported in up to 33% of AIDS patients in India. [1]

In this study, overall positivity of microscopy, culture and LAT in CSF is 100%, which is comparable to that reported in the literature, viz., 70% to 90% for microscopy, 80% to 92% for culture and 95% to 100% for LAT. [6] All the 6 patients having cryptococcal infection were started on Amphotericin B and Fluconazole or Itraconazole according to the standard treatment guidelines and later on transferred for antiretroviral therapy to the nearby HIV referral hospital. On follow-up one of the patients died due to relapse of cryptococcal infection, but the rest of them are surviving and continuing therapy.

This study clearly indicates a high prevalence of cryptococcal CNS infections in HIV-reactive patients in a tertiary care neurology setting. As the clinical and radiological pictures of cryptococcosis are often nonpointing, especially in the early stages, microbiological evaluation remains the gold standard for precise and early diagnosis of cryptococcosis of the CNS, which in turn is of paramount importance for better management of such patients.


   Acknowledgment Top


The authors are thankful to Dr. Sujata Chaturvedi, Head of Pathology; and Dr. Neelam Chillar, Head of Neurochemistry, for providing their laboratory parameters; and to Dr. Rima Kumari, Head of Neuroradiology, for providing MRI inputs

 
   References Top

1.Lakshmi V, Sudha T, Teja VD, Umbala P. Prevalence of central nervous system cryptococcosis in human immunodeficiency virus reactive hospitalized patients. Indian J Med Microbiol 2007;25:146-9.  Back to cited text no. 1    
2.Cox GM, Perfect JR. Cryptococcus neoformans var. neoformans and gattii and Trichosporon species. In : Ajello, Land-May RJ, editors. Topley and Wilson's microbiology and microbial infections. London: Arnold; 1999. p. 461-84.  Back to cited text no. 2    
3.Micol R, Lortholary O, Sar B, Laureillard D, Ngeth C, Dousset JP, et al . Prevalence, determinants of positivity and clinical utility of cryptococcal antigenemia in Combodian HIV infected patients. J Acquir Immune Defic Syndr 2007;45:555-9.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, et al . Cryptococcal infection in a cohort of HIV-1 infected Ugandan adults. AIDS 2002;16:1031-8.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Metta HA, Corti ME, Negroni R, Helous S, Arechavala A, Soto I, et al . Disseminated cryptococcosis in patients with AIDS. Clinical, microbiological and immunological analysis of 51 patients. Rev Argent Microbiol 2002;34:117-23.  Back to cited text no. 5    
6.Khanna N, Chandramukhi 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. 6    

Top
Correspondence Address:
Rajeev Thakur
Department of Microbiology, IHBAS, Dilshad Garden, Delhi - 110 095
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.41689

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    Tables

  [Table 1]

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