Cryptococcal meningitis may be the presenting manifestation of AIDS. The most common sites of occurrence of this infection are the central nervous system and the lungs [
A reduction in the rate of opportunistic infections and hospitalizations in adults infected with AIDS after HAART intervention is well documented in countries with universal access to antiretrovirals [
This retrospective analysis of epidemiological and clinical data from patients with meningeal cryptococcosis was performed during the period of January 2009 to December 2016 in a tertiary care hospital in southern Brazil. Cryptococcal meningitis was confirmed by a positive CSF cryptococcal culture and/or cryptococcal antigen test. The medical records of all eligible patients were reviewed, and data regarding demographics, medical history, clinical and laboratory characteristics, treatment regimens, and clinical outcomes were collected. Patients were evaluated for risk factors and mortality.
Data were analyzed using SPSS software, version 18 or superior. Results were expressed in mean and standard deviation or median and interquartile range for variables in numeric scale and number and percentage for variables in nominal scale. Qualitative variables were compared by the chi-square test, Fisher’s exact test, or McNemar test, when indicated. For determination of the factors associated with overall, 30- and 60-day mortalities, multivariate logistic regression models were constructed using a stepwise regression. A predictive modeling strategy was used in which variables were selected based on the association with mortality in univariate analysis (using a
As shown in Table
Baseline characteristics of 79 patients with cryptococcal meningitis.
Variable | |
---|---|
Age, years; mean (range) | 37 (5–67) |
Age ≥50 years; |
17 (21.5) |
Sex, male |
45 (56.9) |
Time of hospitalization,days; mean (range) | 28 (1–149) |
|
|
HIV | 65 (82.3) |
SOTR | 8 (10.1) |
NHNT | 6 (7.6) |
|
|
Dx during hospitalizationa | 14 (17.7) |
Vertical transmission of HIV | 3 (3.7) |
Receiving HAART at Dx | 34 (43.0) |
CD4, cells/mm³ mean (range) | 34 (3–428) |
HIV viral load, log; mean (range) | 5.01 (2.18–6.16) |
|
|
Kidney | 5 (10.1) |
Liver | 3 (10.1) |
|
|
General; mean (range) | 2.12 (0–7.35) |
Kidney; mean (range) | 3.58 (0.25–7.36) |
Liver; mean (range) | 2.12 (0–7.35) |
|
|
Use of corticosteroids | 8 (10.1) |
Chronic kidney disease | 2 (2.5) |
Cancer | 4 (5.1) |
Rheumatic disease | 2 (2.5) |
Diabetes mellitus | 3 (3.8) |
Cirrhosis | 2 (2.5) |
|
|
|
76 (96.2) |
|
3 (3.8) |
Duration of symptoms, days; mean (range) | 10 (1–120) |
Rehospitalization | 6 (7.5) |
30-day mortality | 15 (19.1) |
60-day mortality | 19 (24.4) |
SOTR, solid organ transplant recipients; NHNT, non-HIV nontransplant; ESRD, end-stage renal disease. aDiagnosis of HIV concomitant with neurocryptococcosis.
Clinical manifestations of 79 patients with cryptococcal meningitis.
Variable |
|
---|---|
Fever | 43 (54.4) |
Malaise | 22 (27.8) |
Headache | 58 (73.4) |
Nausea and vomiting | 33 (41.8) |
Altered mental status | 34 (43.0) |
Visual disturbances | 8 (10.1) |
Behavior changes | 7 (8.9) |
Seizures | 11 (13.9) |
Nuchal rigidity | 15 (18.9) |
Cranial nerve palsy | 8 (10.1) |
Motor deficit | 8 (10.1) |
Cough | 19 (24.1) |
Dyspnea | 9 (11.4) |
Constitutional symptoms | 21 (26.6) |
Laboratory findings of 79 patients with cryptococcal meningitis.
Variable | Initial | aAfter treatment |
|
---|---|---|---|
Mean (range) | Mean (range) | ||
Opening pressure (cm H2O) | 30 (10–130) | 22 (10–50) | 0.387 |
CSF glucose (mg/dL) | 36.5 (1–145) | 43 (2–154) | 0.278 |
CSF leukocytes (cells/ |
25 (1–853) | 8 (0–300) | <0.05 |
CSF proteins (mg/dL) | 82 (0–882) | 59 (0–1866) | 0.228 |
|
|||
(%) |
|
||
|
|||
CSF antigenb ≥1 : 1000 | (55.6) | 7 (8.8) | 0.642 |
CSF positive culture | (93.6) | 6 (7.5) | 1.00 |
Blood culture positivec | (45.5) | — | — |
Blood antigen ≥1 : 1000b | (40.5) | — | — |
Bronchoalveolar lavage positive | (7.5) | — | — |
CSF, cerebrospinal fluid. aAfter 2-week course of induction therapy. bCryptococcus antigen. cCollected within 14-day period of induction therapy.
Comparison between induction treatment schemes of 79 patients with cryptococcal meningitis.
Variable | AmB + 5-FC | AmB + flu |
|
---|---|---|---|
Mean (range) | Mean (range) | ||
Time, weeks | 2.65 (0.57–14.4) | 2.6 (1–5.43) | — |
AmBd dosea | 50 (20.6–69.1) | 52.4 (50–90) | — |
LFAmB dose | 200 (100–371) | 275 (200–375) | — |
5-FC dose | 6000 (1280–9800) | — | — |
Flu dose | — | 800 (300–1000) | — |
(%) | (%) | ||
Hypokalemia | (67.0) | (15.1) | — |
Hypomagnesemia | (67.0) | (8.8) | — |
Acute renal injury | (67.0) | (10.1) | — |
Anemia | (67.0) | (12.6) | — |
Flu-consolidation | (51.8) | (15.1) | — |
Time of consolidation, weeks | 8 (1.5–8) | 7.8 (2–8) | — |
30-day mortality | (11.4) | (26.7) | 0.210 |
60-day mortality | (17.4) | (26.7) | 0.462 |
AmB, amphotericin B; 5-FC, flucytosine (mg/day); Flu, fluconazole (mg/day); IQR, interquartile range; AmBd, amphotericin deoxycholate; LFAmb, lipid formulations of amphotericin B. aDose reported in mg/day.
The incidence of cryptococcal meningitis has increased after the pandemic of AIDS and despite availability of HAART continues to be the most common cause of opportunistic meningitis in many countries [
As expected,
Despite availability of universal HAART, appropriate antifungal treatment including amphotericin B and flucytosine/fluconazole, and management of intracranial hypertension in a reference tertiary care hospital according to the IDSA guidelines, our mortality was high (60-day mortality of 25%) [
Cerebrospinal fluid high opening pressure occurred in the majority of our patients and persisted despite adequate antifungal treatment. In fact, the kinetics of release of a pivotal cytokine like TNF-a in immune responses induced by cryptococcal cell envelope components will reflect on the course of the infection, its containment, and ultimately its elimination by phagocytes [
In summary, the present study highlights important characteristics of a recent cohort of patients with cryptococcal meningitis attending a tertiary care hospital in Brazil after 23 years of the institution of universal HAART. Cryptococcal meningitis continues to be a prevalent opportunistic infection in HIV-infected patients. In addition, mortality and adverse neurologic sequelae from HIV-associated cryptococcal meningitis remain high due to raised intracranial pressure complications despite appropriate treatment. Identification of risk factors and additional treatment modalities, especially for intracranial hypertension, are necessary to improve care for patients with cryptococcal meningitis. Although cryptococcal disease rates are decreasing over time, the associated mortality and costs remain concerning.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.
This study was supported in part by CNPq.