Indian Journal of Medical Microbiology Medknow Publications on behalf of Indian Association of Medical Microbiology ISSN: 0255-0857 EISSN: 1998-3646 Vol. 25, Num. 2, 2007, pp. 146-149

Indian Journal of Medical Microbiology, Vol. 25, No. 2, April-June, 2007, pp. 146-149

Brief Communications

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

V Lakshmi, T Sudha, VD Teja, P Umabala

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

Correspondence Address: Department of Microbiology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082, Andhra Pradesh, India (email: lgorthi@hotmail.com)

Date of Submission: 19-Nov-2006
Date of Acceptance: 07-Dec-2006

Code Number: mb07041

Abstract

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

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

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

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

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

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