Cryptococcal Meningitis Patients Research Articles

A Case Report of Cryptococcal Meningitis Presenting with Psychiatric Abnormalities

Introduction: Cryptococcal infection is a significant pathogen causing meningitis, often manifesting early with psychiatric abnormalities. Due to the lack of other specific symptoms, these behavioral changes are frequently misattributed to other mental disorders or overlooked, leading to delays in diagnosis. This article reports on the diagnosis and treatment process of a patient with cryptococcal meningitis and summarizes the abnormal behavior in terms of mental and behavioral aspects of cryptococcal meningitis patients, providing a reference for the diagnosis and treatment of cryptococcal meningitis. Case Presentation: We present a case of cryptococcal meningitis where the initial abnormal behaviors were attributed to stress, resulting in a lack of emphasis on cryptococcal treatment and subsequent failure of standard anti-infective therapy. Ultimately, we discovered abnormalities through cerebrospinal fluid examination and conducted targeted tests for Cryptococcus, resulting in a clear diagnosis and timely adoption of appropriate treatment measures. The patient's condition improved, and they were discharged. Conclusions: It is crucial for clinicians to deepen their understanding of cryptococcal meningitis. When encountering patients with unexplained fever accompanied by psychiatric and behavioral changes, a high suspicion for cryptococcal infection should be maintained.

Antifungal susceptibility and multilocus sequence typing (MLST) of Cryptococcus neoformans complex from HIV-associated cryptococcal meningitis patients in Manaus, Amazonas, Brazil.

Cryptococcus neoformans is primarily responsible for cases of cryptococcal meningitis in individuals with HIV/AIDS. This study evaluated the susceptibility of C. neoformans obtained from individuals with cryptococcal meningitis associated with HIV/AIDS in Manaus, Amazonas, Brazil, against the action of the antifungals amphotericin B, flucytosine, fluconazole, itraconazole and posaconazole and analyzed it using Multilocus Sequence Typing (MLST) in order to identify the Sequence Types (STs). We analyzed 30 isolates of C. neoformans, from 24 HIV/AIDS patients diagnosed with cryptococcosis from 2017 to 2019 in a reference hospital, in addition to 3 environmental isolates: 1 isolate obtained in the home of a patient and 2 isolates obtained from neighboring homes of patients. 86.6% (n = 26/30) of the clinical isolates were identified as C. neoformans VNI ST93, 6.6% (n = 2/30) as C. neoformans VNI ST5, 3.3% (n = 1/30) as C. neoformans VNI ST32 and 3.3% (n = 1/30) as C. neoformans VNB ST232. The environmental isolates were identified as C. neoformans VNI ST93 (n = 3/3). 96.6% (n = 29/30) isolates were sensitive to amphotericin B, though there was variation in the MIC. 60% (n = 18/30) presented a MIC above the proposed epidemiological cutoff values for one or more antifungals. All environmental isolates were sensitive to the tested antifungals. The MLST showed that there is an important relationship between C. neoformans VNI ST93 and individuals with HIV/AIDS, including in the environmental isolates analyzed. C. neoformans VNB ST232 was observed for the first time in Amazonas. Amphotericin B was proven to be the best drug, but fluconazole and posaconazole also showed relevant action.

Cryptococcal meningitis patients associated with HIV co-infection admitted in tertiary care hospital–A Case Series

Meningitis is a significant infection of the central nervous system that is followed by inflammation of the meninges, resulting in catastrophic neurologic consequences. The inflammation may be caused by infection with viruses, bacteria, fungi, or other microorganisms and less commonly by certain drugs. Meningitis can be life-threatening because of the inflammation’s proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency. In the present case series, we encompass patient demographics, initial clinical symptoms, physical examinations, laboratory results, cerebrospinal fluid examination findings, treatment side effects, the occurrence of complications, and hospital outcomes. Furthermore, documented were any instances of recurrent cryptococcal meningitis (CM) during follow-up, along with the potential causes of recurrence, the treatment modalities administered, any complications that arose, and the ultimate outcomes. This series reveals CM can manifest alongside HIV co-infection in male patients. Therefore, it is essential to consider the possibility of CM when an immune-compromised patient presents with symptoms such as headaches and other indications of central nervous system involvement. These cases reveal cryptococcosis with HIV-infected patients for rapid and early diagnosis and appropriate treatment of opportunistic infections.

A nomogram to predict cryptococcal meningitis in patients with pulmonary cryptococcosis

BackgroundThe most serious manifestation of pulmonary cryptococcosis is complicated with cryptococcal meningitis, while its clinical manifestations lack specificity with delayed diagnosis and high mortality. The early prediction of this complication can assist doctors to carry out clinical interventions in time, thus improving the cure rate. This study aimed to construct a nomogram to predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis through a scoring system. MethodsThe clinical data of 525 patients with pulmonary cryptococcosis were retrospectively analyzed, including 317 cases (60.38 %) with cryptococcal meningitis and 208 cases (39.62 %) without cryptococcal meningitis. The risk factors of cryptococcal meningitis were screened by univariate analysis, LASSO regression analysis and multivariate logistic regression analysis. Then the risk factors were incorporated into the nomogram scoring system to establish a prediction model. The model was validated by receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve. ResultsFourteen risk factors for cryptococcal meningitis in patients with pulmonary cryptococcosis were screened out by statistical method, including 6 clinical manifestations (fever, headache, nausea, psychiatric symptoms, tuberculosis, hematologic malignancy) and 8 clinical indicators (neutrophils, lymphocytes, glutamic oxaloacetic transaminase, T cells, helper T cells, killer T cells, NK cells and B cells). The AUC value was 0.978 (CI 96.2 %∼98.9 %), indicating the nomogram was well verified. ConclusionThe nomogram scoring system constructed in this study can accurately predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis, which may provide a reference for clinical diagnosis and treatment of patients with cryptococcal meningitis.

Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study

ObjectivesTo explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. MethodsThis is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. ResultsA total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34–5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23–24.10; p 0.026 and HR, 5.09; 95% CI, 1.95–13.26; p 0.001). DiscussionPresence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.

Development and validation of a machine learning model to predict prognosis in HIV-negative cryptococcal meningitis patients: a multicenter study.

To predict prognosis in HIV-negative cryptococcal meningitis (CM)patients by developing and validating a machine learning (ML)model. This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10weeks after the initiation of antifungal therapy. The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid(CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence(AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.

Neurological worsening during treatment ofHIV-negative cryptococcal meningitis in apatient with Evans syndrome.

A 49-year-old woman with a rare autoimmune hematological disease, Evans syndrome, was admitted tothe authors' hospital with immune reconstitution inflammatory syndrome-like reconstitution syndrome after effective antifungal therapy for cryptococcal meningitis. She initially improved after receiving corticosteroid treatment; after prednisone was tapered, herclinical presentation and brain imaging deteriorated but finally improved with the addition of thalidomide. Immune reconstitution inflammatory syndrome-like reconstitution syndrome is a rare complication in cryptococcal meningitis patients receiving immunosuppressive therapy. Thalidomide can be given in addition to corticosteroid therapy to effectively control the paradoxical inflammatory response and improve clinical outcomes.

Neuroimaging of Cryptococcal Meningitis in Patients without Human Immunodeficiency Virus: Data from a Multi-Center Cohort Study

A clearer understanding is needed about the use of brain MRI in non-HIV patients with cryptococcal meningitis. Cerebral CT and MRI were studied in 62 patients in a multicenter study of cryptococcal meningitis in non-HIV patients. CT was performed in 51 and MRI in 44. MRI results are reported for the images read at NIH for 29 of the 44 patients. CT reports obtained from the original REDCap database were added to calculate the incidence of normal findings. CTs were read as normal in 24 of 51 (47%), MRIs were normal in 10% (three of 29). The most characteristic lesions of cryptococcal meningitis on MRI were small basal ganglia lesions representing dilated perivascular spaces in 24% and basal ganglia lesions with restricted diffusion (infarcts) in 38%. In the 18 patients who received contrast, contrast-enhancing lesions, likely representing masses of cryptococci and inflammatory cells, were found in the basal ganglia in 22% and elsewhere in the brain in 22%. Meningeal enhancement was seen in 56%, ependymal enhancement in 24%, and choroid plexus enhancement in 11%. Hydrocephalus was found in five (18%), though increased intacranial pressure was not detected. Suboptimal imaging (n = 6), lack of contrast administration (n = 11) and lack of follow-up, however, markedly limited the accurate assessment of abnormalities in multiple cases. MRI characteristics of non-HIV cryptococcal meningitis include hydrocephalus, meningeal and ependymal enhancement and basal ganglia lesions. Optimal imaging is, however, necessary to maximize the diagnostic and prognostic usefulness of MRI.

The effect of serum uric acid, bilirubin and albumin levels on antioxidant status in HIV-negative immunocompetent cryptococcal meningitis patients with post-infectious inflammatory response syndrome.

Oxidative imbalances have been observed in various neurological diseases. Despite the microbiological control in cryptococcal meningitis (CM), a proportion of previously healthy patients experience a clinical deterioration known as post-infectious inflammatory response syndrome (PIIRS). However, the antioxidant status in PIIRS remains unclear. In this study, we found that the serum antioxidant status of HIV-negative immunocompetent CM patients during PIIRS episodes was lower than that of healthy controls. There was a relationship between baseline serum indirect bilirubin levels and the development of PIIRS, and serum uric acid levels may indicate the severity of the disease during PIIRS episodes. Oxidative stress may play a role in the development of PIIRS.

Diagnostic accuracy of cryptococcal antigen test in pulmonary cryptococcosis: a protocol for a systematic review and meta-analysis

BackgroundThe cryptococcal antigen (CrAg) test was proposed as a rapid diagnostic tool to identify cryptococcal meningitis in patients suffering from AIDS. Several studies have demonstrated its diagnostic performance in cryptococcal...

Efficacy and safety of lenalidomide in HIV-associated cryptococcal meningitis patients with persistent intracranial inflammation: an open-label, single-arm, prospective interventional study

BackgroundPatients with human immunodeficiency virus-associated cryptococcal meningitis (HIV-CM) have persistent intracranial inflammation despite negative cerebrospinal fluid (CSF) fungal cultures after optimal treatment for CM, which could be devastating for the central nervous system. However, a definitive treatment strategy for persistent intracranial inflammation despite optimal antifungal therapies is undefined.MethodsWe identified 14 HIV-CM patients with persistent intracranial inflammation and conducted a 24-week, prospective, interventional study. All participants received lenalidomide (25 mg, p.o.) on days 1 to 21 of a 28-day cycle. Follow-up lasted for 24 weeks with visits at baseline and weeks 4, 8, 12, and 24. The primary endpoint was the change in clinical manifestations, routine CSF parameters, and MRI findings after lenalidomide treatment. An exploratory analysis was made on changes in cytokine levels in CSF. Safety and efficacy analyses were undertaken in patients who received at least one dose of lenalidomide.ResultsOf 14 participants, 11 patients completed the 24 weeks of follow-up. Rapid clinical remission following lenalidomide therapy was observed. Clinical manifestations (fever, headache, altered mentation) were reversed fully by week-4 and remained stable during follow-up. A significant reduction in white blood cell (WBC) count in CSF was noted occurred at week-4 (P = 0.009). The median protein concentration in CSF decreased from 1.4 (0.7–3.2) g/L at baseline to 0.9 (0.6–1.4) at week-4 (P = 0.004). The median albumin concentration in CSF decreased from 79.2 (48.4–149.8) mg/L at baseline to 55.3 (38.3–89.0) mg/L at week-4 (P = 0.011). The WBC count, protein level, and albumin level in CSF remained stable and approached a normal range through week-24. There was no significant change in immunoglobulin-G, intracranial pressure (ICP), or chloride-ion concentration at each visit. Brain MRI demonstrated multiple lesions to be absorbed post-therapy. Levels of tumor necrosis factor-α granulocyte colony stimulating factor, interleukin (IL)-6, and IL-17A decreased significantly during 24-week follow-up. Two (14.3%) patients had mild skin rash, which resolved spontaneously. Lenalidomide-related serious adverse events were not observed.ConclusionLenalidomide could improve persistent intracranial inflammation in HIV-CM patients significantly and was well tolerated without serious adverse events observed. And the additional randomized controlled study is required to further validate the finding.

Клиническое наблюдение криптококкового менингита у пациента с системной красной волчанкой

The risk of serious infectious diseases is significantly increased in individuals with systemic lupus erythematosus (SLE). The article describes a clinical case of meningoencephalitis caused by Cryptococcus neoformans, in a 33-year-old female patient with SLE. The diagnosis was based on the results of cerebrospinal fluid analysis, brain magnetic resonance imaging scans, and retrospective analysis of chest computed tomography features. The antifungal therapy comprising liposomal amphotericin B and fluconazole was used successfully. Distinctive features of this clinical case include a delayed diagnosis due to the slow development and the presence of non-specific neurological symptoms, as well as the onset of acute renal disorders amid the use of antifungal therapy. The authors discuss the issues of diagnosing infectious complications in patients with SLE, particularly fungal infections, and the up-to-date approaches to therapy of cryptococcal meningitis. The presented clinical report could help therapists and rheumatologists to improve timely recognition of cryptococcal infections in SLE patients. The authors emphasized that CSF examination plays the key role in diagnosing cryptococcal meningitis. KEYWORDS: cerebral cryptococcosis, opportunistic infection, meningoencephalitis in patients with systemic lupus erythematosus, clinical case, fungal infection, systemic lupus erythematosus. FOR CITATION: Kuzminykh D.A., Eliseev Yu.V., Matrosova M.S. et al. A clinical case of cryptococcal meningitis in patient with systemic lupus erythematosus. Russian Medical Inquiry. 2023;7(3):174–180 (in Russ.). DOI: 10.32364/2587-6821-2023-7-3-174-180.

Ocular Findings of Cryptococcal Meningitis in Previously Healthy Adults.

Patients with cryptococcal meningitis (CM) often have ocular manifestations; although data are describing these findings in nonimmunosuppressed, previously healthy individuals are scarce. A retrospective chart review was performed for previously healthy patients with CM who underwent a complete ophthalmological examination within a 5-year period at the National Institutes of Health. Demographics, CSF parameters, findings on initial ophthalmological examination, and MRI abnormalities were analyzed. Forty-four patients within a median of 12 weeks after CM diagnosis were included in our study; 27 patients (61%) reported abnormal vision on presentation. Seventy-one percent of patients were not shunted at the time of their initial eye examination. The most common ocular abnormalities were visual field defects in 21 (66%), decreased visual acuity in 14 (38%), and papilledema in 8 (26%) patients. Intraocular pressure was within normal range in all patients. Cranial nerve defects were identified in 5 patients and optic neuropathy in 2 patients. Patients who had hydrocephalus or did not receive a ventriculoperitoneal shunt were not noted to have worse ocular abnormalities. The most common ocular findings in our cohort of nontransplant, non-HIV cryptococcal meningitis patients were visual field defects, decreased visual acuity, and papilledema. Our results emphasize the need for a comprehensive eye examination in patients with CM who may not always report a change in vision on presentation.

Induction therapy with high-dose fluconazole plus flucytosine for human immunodeficiency virus-uninfected cryptococcal meningitis patients: Feasible or not?

Cryptococcal meningitis (CM) is increasingly recognised in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high-dose fluconazole plus flucytosine remain unclear. HIV-uninfected CM patients who received high-dose fluconazole (800 mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated. Twenty-seven (71.1%) patients who received high-dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titre >1:1280 (OR 9.56; 95% CI 1.40-103.65; p=.010) and CSF culture of Cryptococcus >3.9 log10 CFU/ml (OR 19.20; 95% CI 1.60-920.54; p=.011), and decreased to 8.6% at 4 weeks. One-year mortality was 15.8% (6/38), and low serum albumin (35 g/L) was found as an independent risk factor for 1-year mortality (HR 6.31; 95% CI 1.150-34.632; p=.034). Induction therapy with high-dose fluconazole (800 mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection.

P325 Trend of cryptococcal meningitis in patients attending a teaching hospital in north-east india — a single center study

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectiveTo determine the changing trend of Cryptococcal meningitis in patients attending Regional Institute of Medical Sciences Hospital, Imphal.MethodsA total of 142 cerebrospinal fluid (CSF) samples collected from patients with suspected meningitis from January 2013 to January 2022 were analyzed in the department of Microbiology, Regional Institute of Medical Sciences, Imphal. The samples were subjected to India ink preparation (IIP), Gram stain, Cryptococcal antigen (CrAg) testing, fungal culture in Sabouraud Dextrose agar (SDA) medium, and Bird Seed Agar.ResultsOut of 142 CSF samples received, direct examination by IIP revealed Cryptococcus in 28 cases (19.7%) whereas, capsular polysaccharide antigen testing using lateral flow immunochromatography kit (CRYPTO-PS) detected a total of 40 cases (28.2%). Culture showed growth of fungus in 22 samples and all were from CrAg positive samples. Maximum number of cases were detected in the year 2019 followed by 2018. Immunosuppression (AIDS) was an important underlying factor. Recurrence was seen in three patients and two cases who were on Cycloserine succumbed while undergoing treatment.ConclusionCryptococcosis continues to be a serious fungal infection among AIDS patients in spite of HAART. High index of clinical suspicion and microbiological examination is necessary to improve clinical outcomes. Whenever immunosuppressive drugs are administered in HIV patients treated earlier for cryptococcosis, monitoring the patient for likely recurrence is to be borne in mind to improve the overall clinical outcome. CrAg testing is an additional armamentarium for the diagnosis of cryptococcosis in the absence of culture positivity.

P449 Semi-quantitative cryptococcal antigen rapid test (CryptoPS, Biosynex®) for cryptococcal meningitis in patients living with HIV in Sub-Saharan Africa: prospective multicenter diagnostic accuracy study (DREAMM)

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMBackgroundCryptococcal meningitis (CM) remains a leading cause of HIV-related meningoencephalitis in African low- and middle-income countries (LMICs), causing 15%-20% of HIV-related deaths. Rapid Diagnostic Tests (RDTs) are powerful tools and key to speeding-up the diagnosis at the bedside, allowing for rapid and targeted treatment, especially in LMICs. For the past 10 years, Cryptococcal Antigen (CrAg) RDTs have a major role in CM management.Driving Reduced AIDS Meningo-Encephalitis Mortality (DREAMM) was a multicenter implementation science study and a capacity-building project to reduce the mortality of HIV-related central nervous system infections (CNS). One of the main DREAMM approaches was to improve the diagnosis of CNS infections at the bedside and in parallel in local laboratories. Within DREAMM, HIV-infected, adult people living with HIV (>18 years old) with suspected CNS infections were recruited in five hospital sites in Cameroon, Malawi, and Tanzania.ObjectivesOur objective was to evaluate the implementation of CrAg CryptoPS (Biosynex, Illkirch Graffenstaden, France), a new semi-quantitative RDT, in routine care settings in Sub-Saharan Africa.MethodsAll CrAg CryptoPS performed were compared to the reference CrAg lateral flow assay (Immy®). The evaluation was done by the local research teams in four DREAMM laboratories sites. CrAg CryptoPS's implementation was evaluated in 301 plasma samples and 258 cerebrospinal fluid (CSF) samples from 320 participants (patients diagnosed with cerebral toxoplasmosis did not have a lumbar puncture). In this analysis, the results will be considered in a binary way (positive/negative).ResultsBetween January 2018 and March 2021, 356 participants were prospectively enrolled with suspected HIV-related CNS infections, including CM, tuberculous meningitis, cerebral toxoplasmosis, and bacterial meningitis cases. Cryptococcal meningitis was the leading cause of CNS infections in Malawi and Tanzania with 66.3% (53/80) and 59.6% (59/99) cases respectively, and the second cause in Cameroon with 40.0% (39/90) cases after cerebral toxoplasmosis.In plasma, CryptoPS's sensitivity was 99.23% (95% CI, 0.98-1.01) and specificity was 94.15% (95% CI, 0.91-0.98); positive and negative predictive values were 92.8% and 99.4%, respectively. In CSF, the sensitivity and specificity of CryptoPS were 100% (95% CI, 0.0-0.0), and 99.26% (95% CI, 0.98-1.01), respectively; positive and negative predictive values were both 100%. A low number of false-positives were observed (<4% in plasma and <0.5% in CSF).ConclusionCryptoPS was evaluated in a context of hospitalized patients within a project including all causes of HIV-related CNS infection, not only CM. The sensitivity and specificity of CryptoPS calculated in these preliminary results are promising. Semi-quantitative CryptoPS has the potential to be used to tailor antifungal therapy but further optimizations need to be done prior to large-scale implementation in African LMICs. In addition, future work to determine CrAg antigen titres is planned, in the perspective to optimize treatment of CrAg positive cases who decline lumbar puncture.

Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells.

Cryptococcus neoformans infection in the central nervous system is a severe infectious disease with poor outcomes and high mortality. It has been estimated that there are 220,000 new cases each year. Over 90% of C. neoformans meningitis cases were diagnosed in AIDS patients with CD4+ T cell count <100 cells/μl; however, the mechanism of cryptococcal meningitis in patients with normal immune functions remains unclear. IL-17 is a pro-inflammatory cytokine and plays an important role in anti-fungal immunity. Here we report that significantly high levels of IL-17 were predominantly detected in the cerebrospinal fluid of patients with either AIDS- or non-AIDS-associated C. neoformans meningitis but not in patients with tuberculous meningitis or non-neurosyphilis. Antifungal therapy minimized the IL-17 level in the cerebrospinal fluid. An in vitro mechanistic study showed that C. neoformans stimulation of healthy peripheral blood mononuclear cells prompted IL-17 production, and CD4+ T cells were the predominant IL-17-producing cells. IL-17 production by C. neoformans stimulation was STAT3 signaling dependent. Inhibition of STAT3 phosphorylation attenuated the C. neoformans-mediated IL-17 expression. Our data highlighted the significance of CD4+ T cells in antifungal immunity and suggested IL-17 as a diagnostic biomarker of C. neoformans infection and STAT3 as a checkpoint for antifungal targeted therapies.

Ventriculoperitoneal shunt is associated with increased cerebrospinal fluid protein level in HIV-infected cryptococcal meningitis patients

BackgroundThe impact of ventriculoperitoneal shunt on cerebrospinal fluid (CSF) biochemical profiles in HIV-associated cryptococcal meningitis (HCM) patients remains unclear.MethodsTwenty-nine HCM patients who underwent ventriculoperitoneal shunt (the VPS group) and 57 HCM patients who did not undergo ventriculoperitoneal shunt (the non-VPS group) were enrolled in this propensity score matching analysis. Demographic characteristics, symptoms, CSF biochemical profiles, and adverse events were compared between the two groups. The Kaplan–Meier method was used to analyze the survival rate. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for increased CSF protein levels.ResultsAfter 24 weeks of treatment, the intracranial pressure was significantly lower in the VPS group than in the non-VPS group (mmH2O; 155.0 [120.0–190.0] vs. 200.0 [142.5–290.0]; P = 0.025), and the rate of neuroimaging improvement was significantly higher in the VPS group (16/17 [94.1%] vs. 2/10 [20%]; P < 0.001). Furthermore, the 24-week cumulative survival rates were also significantly higher in the VPS group (96.6% vs. 83.5%, P = 0.025). Notably, the CSF protein levels were higher in the VPS group than in the non-VPS group at each examination time, and the CSF glucose was lower in the VPS group than in the non-VPS group even at the 12-week follow-up. In the multivariate analysis, we found that VPS placement was an independent risk factor for increased CSF protein (odds ratio [OR]: 27.8, 95% confidence interval [95% CI] 2.2–348.7; P = 0.010).ConclusionsVPS decreased the intracranial pressure, improved neuroimaging radiology and reduced the 24-week mortality in HCM patients. However, VPS significantly altered the CSF profiles, which could lead to misdiagnosis of tuberculous meningitis and some of them were diagnosed with immune reconstitution inflammatory syndrome. Physicians should be aware of these changes in the CSF profiles of patients with HCM undergoing VPS.

Development and Validation of a Machine Learning Model to Predict Prognosis in HIV-Negative Cryptococcal Meningitis Patients: A Multicentre Retrospective Study

Development and Validation of a Machine Learning Model to Predict Prognosis in HIV-Negative Cryptococcal Meningitis Patients: A Multicentre Retrospective Study

Cryptococcal meningitis in patients with and without acquired immunodeficiency

• Cryptococcal meningitis in immunocompromised and non-immunocompromised patients. • Mortality from cryptococcal meningitis in patients immunocompromised or not remains high, even on early diagnosis. • Antifungals used in combination in the treatment of cryptococcal meningitis, contribute to a better prognosis. • Cryptococcal meningitis can evolve with motor, language, auditory and visual sequelae in patients immunocompromised or not.