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Year : 2007  |  Volume : 25  |  Issue : 2  |  Page : 146-149
 

Prevalence of central nervous system cryptococcosis in human immunodeficiency virus reactive hospitalized patients


Department of Microbiology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082, India

Correspondence Address:
V Lakshmi
Department of Microbiology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.32723

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 ~ Abstract 

Central nervous system cryptococcosis is an important cause of mortality among human immunodeficiency virus (HIV) reactive patients. A retrospective study was conducted on a total of 1,863 HIV reactive hospitalized patients suspected of cryptococcal meningitis. Three hundred and fifty-nine cerebrospinal fluid specimens of these cases were screened for various cryptococcal investigations. Thirty-nine out of 359 (10.86%) showed a definite diagnosis of cryptococcosis with a mortality rate of 25.64%. Prevalence of cryptococcal meningitis in the total HIV reactive cohort was 2.09%. Concurrent cryptococcal meningitis and tuberculosis was seen in 33.3% cases. A high index of clinical suspicion and routine mycological surveillance is required to help an early diagnosis and appropriate therapy, as majority of patients respond well to therapy if treated early.


Keywords: Cryptococcal meningitis, CD4 cell counts, latex antigen test


How to cite this article:
Lakshmi V, Sudha T, Teja V D, Umabala P. Prevalence of central nervous system cryptococcosis in human immunodeficiency virus reactive hospitalized patients. Indian J Med Microbiol 2007;25:146-9

How to cite this URL:
Lakshmi V, Sudha T, Teja V D, Umabala P. Prevalence of central nervous system cryptococcosis in human immunodeficiency virus reactive hospitalized patients. Indian J Med Microbiol [serial online] 2007 [cited 2019 Aug 23];25:146-9. Available from: http://www.ijmm.org/text.asp?2007/25/2/146/32723


Since the first reported case in the early 1980s, human immunodeficiency virus (HIV) infection has emerged as the fifth leading cause of death infecting approximately 40.3 million people worldwide. [1] Cryptococcal meningitis, caused by the environmental encapsulated fungus Cryptococcus neoformans , has become the most common lethal fungal infection in patients with acquired immunodeficiency syndrome (AIDS) worldwide. [2],[3],[4] Cryptococcus neoformans is the second most common fungal opportunist after C. albicans , causing symptomatic cryptococcosis in up to 8.5% of HIV-infected individuals. [3],[5],[6] Cryptococcus is the commonest central nervous system (CNS) fungal pathogen in immunocompromized patients, particularly among those with AIDS. [7],[8],[9]

Infection with HIV is widespread in India and cryptococcal meningitis is a common problem in those with AIDS. Recent data indicate that incidence of C. neoformans infection is high in developing countries like in India. [5],[7],[8],[10],[11],[12] A retrospective study was undertaken in our institute with the purpose of describing the clinical and laboratory characteristics of CNS cryptococcosis in HIV reactive patients hospitalized with meningeal signs.


 ~ Materials and Methods Top


Study population constituted 1,863 HIV-1 reactive cases, hospitalized between 1997 and August 2005 at our institute. Of the 487 cases suspected of cryptococcal infection, cerebrospinal fluid (CSF) of 359 cases was screened for various cryptococcal investigations. Medical records of these were reviewed and all the demographic, clinical, diagnostic and immunologic data were recorded.

The definite diagnosis of cryptococcal infection was based on clinical features of chronic meningitis with laboratory findings such as positive India ink preparation or positive fungal culture of cryptococci or demonstration of cryptococcal antigen in the CSF by latex agglutination test. Whenever sufficient amount of sample was available, a cytospin preparation was made for smear examination. Fungal cultures of all samples were performed on Sabouraud dextrose agar, brain heart infusion agar and Mueller Hinton agar and cultures were incubated at both 37°C and 25-27°C. Latex agglutination test on serum sample was performed by using Fumouze Crypto-antigen detection kit. All serum samples were earlier evaluated by enzyme-linked immunoassay for HIV antibodies. All of these were repeatedly HIV reactive and most of them were also confirmed by Western blot test. CD4 enumeration was commenced from August 1999 using FACS Count (Beckton and Dickinson) system.

The demographic and clinical data of all the cases was analyzed by reviewing the case records and was entered into the Epi-info version 5 - 2002, downloaded from the CDC website, www.cdc.gov/epiinfo. Statistical analysis of data was done using Chi-square test and a P -value <0.05 was considered statistically significant.


 ~ Results Top


Thirty-nine out of 359 (10.86%) cases suspected of cryptococcal meningitis showed a definite diagnosis [Table - 1]. Prevalence of cryptococcal infection in the total HIV cohort was 2.09%. Prevalence of CNS cryptococcosis was seen in 33 men (84.62%) and 6 women (15.38%). The incidence was highest among persons 20 to 40 years old (92.31%) ranging from 12-42 years of age with a mean of 31 years.

All the patients suspected of cryptococcal infection were started on amphotericin B and fluconazole during their hospitalization. An improved response was noticed in 21 patients, eight patients were lost to follow-up and 10 patients (25.64%) had expired during the hospital stay. The median duration of hospitalization stay was six days (range 3-9 days). Only two of the 39 cases were aware of their HIV status prior to the admission and the rest 98.47% were diagnosed only after their admission in the hospital. Concurrent cryptococcal meningitis and tuberculosis was reported in 33.33% cases.

The clinical presentations were varied, the most common signs and symptoms being headache (92.31%), fever (79.49%), altered sensorium (71.79%) and neck stiffness (66.67%) [Figure - 1]. CSF WBC counts, glucose and protein concentrations were non-specific with CT/MRI showing basilar inflammation and frequent alterations. CD4+ lymphocyte counts of 30 cases of cryptococcal cases were performed. All cases had their CD4 counts < 100 cells/µL and presented with WHO clinical stage 4 [Table - 1]. The CD4 + /CD8 + ratio was < 0.3 in all patients.


 ~ Discussion Top


In India, HIV infection is widespread and it was estimated that about 5.1 million people in India were living with HIV infection in the year 2005 [1] and the estimation of new HIV infections for India in 2001 was 0.11 million. Cryptococcal meningitis is an emerging opportunistic infection as documented in various Indian studies, especially among HIV infected patients and an important cause of mortality among these patients. The cryptococcal meningitis prevalence of 2.09% among HIV reactive hospitalized patients, in our study, was lower compared to other studies done in India.

Though fall-winter seasonality in the occurrence of cryptococcosis is generally expected, prevalence of cryptococcal meningitis in our study was evenly distributed throughout the year. There was neither any significant increase in the prevalence of cryptococcal meningitis over the years nor the male/female ratio declined, as was observed in similar studies. [2],[5],[13] The number of cryptococcal meningitis cases paralleled the number of HIV infected cases. Even though highly active antiretroviral therapy (HAART) was introduced in 1999 at our Institute, it could not be initiated on 37 cases (94.87%) with unknown HIV status. The other two patients who were aware of their HIV reactive status were not willing to take HAART, as they could not afford the cost. Thus, on the whole, no patient was on any antiretroviral (ARV) therapy prior to admission.

Detection of antigen in spinal fluid is a sensitive and specific test. [12],[13],[14] It was started in 2000 in our department and as the latex test is a fast, easy to perform and quite reliable test for the diagnosis of cryptococcosis, it was employed for 211 suspected cases and 25 of them were positive in various dilutions as shown in the Table.

As tuberculosis has been reported to be the commonest secondary infection in AIDS patients in India, [8],[12] it was not surprising to find high incidence of concurrent cryptococcal meningitis and tuberculosis in our study (33.33%). CD4 + counts and age continued to be strongly associated with the occurrence of cryptococcosis. Cryptococcosis prevalence increased with declining CD4 + lymphocyte count, with risk being greatest at CD4 + cell counts below 50 cells/µL but was inversely proportionate to age.

Infection with HIV continues to be the most important risk factor for development of CNS cryptococcosis and is an important contributor to morbidity and mortality in HIV-infected patients. A high index of clinical suspicion and routine mycological surveillance is required to help in an early diagnosis and appropriate therapy as majority of patients respond to therapy.



 
 ~ References Top

1.UNAIDS/WHO 2006 Report on the global AIDS epidemic.   Back to cited text no. 1    
2.Arora VK, Tumbanatham A, Amarnath S. Cryptococcal meningitis associated with tuberculosis in a HIV infected person. Indian J Tuberculosis 1997; 44 :39-41.  Back to cited text no. 2    
3.Currie BP, Casadevall A. Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin Infect Dis 1994; 19 :1029-33.   Back to cited text no. 3  [PUBMED]  
4.Thomas CJ, Lee JY, Conn LA, Bradley ME, Gillespie RW, Dill SR, et al. Surveillance of cryptococcosis in Alabama, 1992-1994. Ann Epidemiol 1998; 8 :212-6.   Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Chakrabarti A, Sharma A, Sood A, Grover R, Sakhuja V, Prabhakar S, et al . Changing scenario of cryptococcosis in a tertiary care hospital in north India. Indian J Med Res 2000; 112 :56-60.   Back to cited text no. 5  [PUBMED]  
6.Prasad KN, Agarwal J, Nag VL, Verma AK, Dixit AK, Ayyagari A. Cryptococcal infection in patients with clinically diagnosed meningitis in a tertiary care center. Neurol India 2003; 51 :364-6.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.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. 7  [PUBMED]  
8.Khanna N, Chandramuki A, Desai A, Ravi V, Santosh V, Shankar SK, et al . Cryptococcosis in the Immunocompromized Host With Special Reference to AIDS. Indian J Chest Dis Allied Sci 2000; 42 :311-5.   Back to cited text no. 8  [PUBMED]  
9.Oursler KA, Moore RD, Chaisson RE. Risk factors for cryptococcal meningitis in HIV-infected patients. AIDS Res Hum Retroviruses 1999; 15 :625-31.   Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Kalra SP, Chadha DS, Singh AP, Sanchetee PC, Mohapatra AK. Cryptococcal meningitis in acquired immunodeficiency syndrome. J Assoc Physicians India 1999; 47 :958-61.  Back to cited text no. 10  [PUBMED]  
11.Kaur A, Babu PG, Jacob M, Narasimhan C, Ganesh A, Saraswathi NK, et al . Clinical and laboratory profile of AIDS in India. J Acquir Immune Defic Syndr 1992; 5 :883-9.   Back to cited text no. 11  [PUBMED]  
12.Madan M, Ranjitham M, Chandrasekharan S, Sudhakar. Cryptococcal meningitis in immunocompetent individuals. J Assoc Physicians India 1999; 47 :933-4.  Back to cited text no. 12    
13.Bogaerts J, Rouvroy D, Taelman H, Kagame A, Aziz MA, Swinne D, et al . AIDS-associated cryptococcal meningitis in Rwanda (1983-1992): Epidemiologic and diagnostic features. J Infect Dis 1999; 39: 32-7.  Back to cited text no. 13    
14.Swinne D, Bogaerts J, Van de Perre P, Batungwanayo J, Taelman H. Evaluation of the cryptococcal antigen test as a diagnostic tool of AIDS-associated cryptococcosis in Rwanda. Ann Soc Belg Med Trop 1992; 72 :283-8.  Back to cited text no. 14  [PUBMED]  


    Figures

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    Tables

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