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Different presentations and outcomes between HIV-infected and HIV-uninfected patients with Cryptococcal meningitis

Chia-Hung Liao¹, Chih-Yu Chi, Yi-Jen Wang

¹Section of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung City, Taiwan.

Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi

|May 22, 2012

Abstract

Background And Purpose:

Cryptococcus species are the most common causative agents of fungal meningitis. Different populations may show different clinical manifestations and outcomes. In this retrospective study, we investigated these differences in patients with and without HIV infection.

Methods:

From 1995 to 2009, we collected data from HIV-infected or HIV-uninfected patients aged 18 years or over who had cryptococcal meningitis (CM) in a medical center in Taiwan. We reviewed and analyzed their demographic data, clinical manifestations, therapeutic strategies and outcomes.

Results:

Among the 72 patients with CM, 19 HIV-infected patients were predominantly younger males, and all of them had AIDS status when CM was diagnosed. In contrast, the 53 HIV-uninfected patients were mostly older males with underlying diseases. The time from initial symptoms to diagnosis was shorter in HIV-infected patients (median 10 vs. 18 days, p = 0.048). The HIV-infected patients presented with less pleocytosis (p = 0.003) and lower protein levels in the cerebrospinal fluid (CSF), but a higher proportion had positive results for cryptococci in the CSF (90% vs. 60%, p = 0.02) and blood (53% vs. 21%, p = 0.009) cultures. Surgical drains and repeated lumbar punctures for the management of increased intracranial pressure were performed in 47% of the HIV-infected patients and 38% of the HIV-uninfected patients. A lower mortality rate was observed in the HIV-infected patients (p = 0.038). On multivariate analysis, initial CD4 count ≤20/mm(3) was an indicator of death or relapse in HIV-infected patients. In the HIV-uninfected group, the initial high cryptococcal antigen titer in the CSF (≥1:512) and hydrocephalus were related to unsatisfactory outcomes.

Conclusion:

In addition to well-known differences, we found a lower mortality in HIV-infected patients than in HIV-uninfected patients. Cryptococci and inflammation in the central nervous system may play important roles in the pathogenesis of CM. Low intensity of inflammation and effective surgical CSF drains for increased intracranial pressure and cryptococci removal may contribute to lower mortality in HIV-infected patients.

Insights

HIV-infected patients with cryptococcal meningitis (CM) had a shorter diagnosis time and lower mortality than HIV-uninfected patients. Lower inflammation and surgical drains may contribute to better outcomes in the HIV-infected group.

Area of Science:

Infectious Diseases
Neurology
Immunology

Background:

Cryptococcus species are leading causes of fungal meningitis.
Clinical presentations and outcomes of cryptococcal meningitis (CM) can vary between different patient populations.
Human Immunodeficiency Virus (HIV) infection is a significant factor influencing CM.

Purpose of the Study:

To investigate the differences in clinical manifestations and outcomes of CM between patients with and without HIV infection.
To analyze demographic data, clinical features, treatment strategies, and outcomes in HIV-infected and HIV-uninfected CM patients.
To identify factors associated with mortality and relapse in different patient groups.

Main Methods:

Retrospective study of 72 patients (19 HIV-infected, 53 HIV-uninfected) diagnosed with CM between 1995 and 2009.
Analysis of demographic data, clinical presentations, cerebrospinal fluid (CSF) findings, and therapeutic interventions.
Multivariate analysis to identify predictors of mortality and relapse.

Main Results:

HIV-infected patients were younger, predominantly male, and diagnosed with AIDS; HIV-uninfected patients were older with underlying diseases.
Diagnosis time was shorter in HIV-infected patients (10 vs. 18 days).
HIV-infected patients showed less pleocytosis, lower CSF protein, higher rates of positive CSF and blood cryptococcal cultures, and lower mortality (p=0.038).
Low CD4 count (≤20/mm³) predicted death/relapse in HIV-infected patients; high CSF cryptococcal antigen (≥1:512) and hydrocephalus predicted poor outcomes in HIV-uninfected patients.

Conclusions:

HIV-infected patients with CM exhibited a lower mortality rate compared to HIV-uninfected patients.
Pathogenesis of CM involves Cryptococci and central nervous system inflammation.
Reduced inflammation intensity and effective surgical management of increased intracranial pressure may contribute to lower mortality in HIV-infected individuals.

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