Abstract
Cryptococcal meningitis (CM) remains as common life-threatening AIDS-defining illness mainly in resource-limited settings. Previous reports suggested that baseline cytokine profiles can be associated to fungal burden and clinical outcome. This study aimed to evaluate the baseline cytokine profiles in AIDS patients with CM and its relation with the outcome at weeks 2 and 10. Thirty AIDS patients with CM diagnosed by cerebrospinal fluid (CSF) Cryptococcus neoformans positive culture, India ink stain and cryptococcal antigen test were prospectively evaluated. As controls, 56 HIV-infected patients without CM and 48 non-HIV individuals were included. Baseline CSF and sera levels of IL-2, IL-4, IL-8, IL-10, IL-12p40, IL-17A, INF-γ and TNF-α were measured by ELISA. Of 30 CM patients, 24 (80%) were male, median age of 38.1. The baseline CSF high fungal burden and positive blood culture were associated with a positive CSF culture at week 2 (p = 0.043 and 0.029). Most CSF and sera cytokines presented higher levels in CM patients than control subjects (p < 0.05). CSF levels of IL-8, IL-12p40, IL-17A, TNF-α, INF-γ and sera TNF-α were significantly higher among survivors at weeks 2 and 10 (p < 0.05). Patients with increased intracranial pression exhibited CSF IL-10 high levels and poor outcome at week 10 (p = 0.032). Otherwise, baseline CSF log10 IFN-γ and IL-17A were negatively correlated with fungal burden (r = -0.47 and -0.50; p = 0.0175 and 0.0094, respectively). The mortality rate was 33% (10/30) at week 2 and 57% (17/30) at week 10. The severity of CM and the advanced immunodeficiency at admission were related to a poor outcome in these patients. Otherwise, the predominant Th1 cytokines profile among survivors confirms its pivotal role to infection control and would be a prognostic marker in cryptococcal meningitis.
Highlights
Cryptococcal meningitis (CM) is a common life-threatening fungal infection in AIDS patients and represents a medical, social and economic high burden due to its unacceptable 60% mortality rate [1,2]
In order to understand the poor outcome of CM patients, several clinical and laboratory features have been evaluated as prognostic markers such as: to be naive to ART, altered consciousness, abnormal brain imaging at computerized tomography (CT) scan and/or magnetic resonance imaging (MRI), elevated intracranial pressure (ICP) and disseminated infection at admission [3,10,11,12,13]
This study aimed to evaluate the baseline cerebrospinal fluid (CSF) and sera cytokines and their relation with clinical and laboratory features and outcome in AIDS patients with cryptococcal meningitis
Summary
Cryptococcal meningitis (CM) is a common life-threatening fungal infection in AIDS patients and represents a medical, social and economic high burden due to its unacceptable 60% mortality rate [1,2]. This occurs in poor-resources settings where most individuals present late HIV diagnosis and severe fungal disease at admission together with a limited access to anti-retroviral (ART) and ideal antifungal therapy [1,2,3]. CD4+ T count < 100 cells/mm, CSF white blood cell (WBC) count 20 cells/μL, CSF culture >106 CFU/mL with positive India ink stain, paucity of Th1 pattern cytokine release and infection with C. neoformans var. grubii (serotype A) have been considered [14,15,16]
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