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We evaluated the prevalence of serum and meningeal cryptococcosis in asymptomatic outpatients with advanced HIV disease (CD4 < 200 cells/mm3) in a cross-sectional screening context in Kinshasa clinics (DRC). Lumbar puncture (LP) was performed in patients with positive serum cryptococcal antigen (CrAg) test, and Cryptococcus spp. isolated from cerebrospinal fluid (CSF) were identified by MALDI-TOF-MS, and characterized using serotyping-PCR, ITS-sequencing and multilocus sequence typing (MLST). The genetic profiles obtained were then compared with those of isolates previously described in symptomatic patients in the same clinics. Forty-seven patients with advanced HIV disease out of 262 included were positive for serum CrAg (18%, 95% CI: 14.2-24.3). The prevalence of asymptomatic cryptococcal meningitis (CM) was then measured at 50% among patients with positive serum CrAg test who consented to LP (19/38). Only four CSF samples were culture positive and all were characterized as Cryptococcus neoformans, molecular type VNI and belonging to two different sequence types (ST): ST93 (3/4) and ST63 (1/4). While ST93 is also the main genomic profile described in advanced HIV disease patients with symptomatic CM in Kinshasa clinics, ST63 has not yet been identified in DRC before. It is likely that future studies involving a large number of strains will be necessary before any definitive conclusions can be drawn on the involved strains in asymptomatic patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Follow-up of previously healthy patients surviving cryptococcal meningitis found that cryptococcal antigen could be detected for >1 year in serum from 38 of 44 (86%) patients and in cerebrospinal fluid (CSF) from 20 of 31 patients (67%), far beyond the time of culture conversion. The speed of titer decline, measured as the number of days for a 2-fold drop in titer to occur, was slower in serum than in CSF. The speed of decline of antigen titers was much slower in serum and CSF for patients infected with Cryptococcus gattii than Cryptococcus neoformans. The speed of decline in CSF and serum titers was also much slower in patients who had received a ventriculoperitoneal shunt for increased intracranial pressure. The variable and extraordinarily slow rate of clearance in our patients did not appear to reflect differences in disease control but rather differences in species and shunting for increased intracranial pressure., Competing Interests: Potential conflicts of interest. Both authors: No reported conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Objectives: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease. However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections., Methods: Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA)., Results: A total of 4,453 PLHIV with clinical suspicion of histoplasmosis (n = 1,343) or cryptococcosis (n = 3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive. Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive. Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay (n = 201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay (n = 170)., Conclusion: Here, we show how the implementation of rapid diagnostics assays impacted case detection and was useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Primary fungal infection of the central nervous system (CNS) is rare but often associated with severe prognosis. Diagnosis is complicated since cerebrospinal fluid (CSF) samples obtained from lumbar puncture usually remain sterile. Testing for fungal antigens in CSF could be a complementary diagnostic tool. We conducted such measurements in CSF from patients with CNS fungal infection and now discuss the usefulness of ventricular puncture. Mannan and (1→3)ß-D-glucan (BDG) testing were retrospectively performed in CSF samples from three patients with proven chronic CNS fungal infection (excluding Cryptococcus), and subsequently compared to 16 controls. Results from lumbar punctures and those from cerebral ventricles were confronted. BDG detection was positive in all the CSF samples (from lumbar and/or ventricular puncture) from the three confirmed cases. In case of Candida infection, mannan antigen measurement was positive in 75% of the CSF samples. In the control group, all antigen detections were negative (n = 15), except for one false positive. Faced with suspected chronic CNS fungal infection, measurement of BDG levels appears to be a complementary diagnostic tool to circumvent the limitations of mycological cultures from lumbar punctures. In the event of negative results, more invasive procedures should be considered, such as ventricular puncture., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objectives: Cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among immunocompromised patients. Laboratory diagnostics for CM includes antigen detection, staining and culture. Data on the performance of the Biofire® FilmArray® meningitis/encephalitis (ME) panel for detecting Cryptococcus neoformans/gattii is limited, with several reports describing false negativity for this target., Methods: A retrospective analysis of 1384 physician-ordered ME panel tests ordered between January 2017 to October 2018 was performed. ME panel results were compared to cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) and CSF culture testing and clinical significance of cryptococcal detection was determined., Results: There were 34 patients positive for cryptococcal detection by either ME panel, CSF CrAg or CSF culture in 2.7% of CSF specimens tested (38/1384). Of the 34 patients positive for cryptococcal detection, 85.3% were human immunodeficiency virus positive (29/34). The ME panel detected 32/38 (84.2%) cryptococcal-positive specimens, culture detected 28/38 (73.7%) and CSF CrAg was positive in 37/38 specimens (97.4%). The ME panel had a sensitivity and specificity of 96.4% (95% CI 81.7-99.9%) and 99.6% (95% CI 99.2-99.9%) compared with culture, and 83.8% (95% CI 68.0-93.8%) and 99.9% (95% CI 99.6-100.0%) compared to CSF CrAg testing, respectively. CrAg titres were lower among ME panel-negative, culture-negative specimens compared with ME panel-positive, culture-negative specimens (reciprocal median end-point titres of 128 ± 60 vs. 1920 ± 1730, p 0.04). All five CrAg-positive, ME panel- and culture-negative specimens were obtained from previously treated CM patients., Discussion: The ME panel had high correlation with CSF culture and a somewhat lower correlation with CSF CrAg testing. The potential utility of using negative ME panel test results to predict culture sterility among patients undergoing treatment for CM warrants further study., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Cryptococcus is a conditional pathogenic fungus causing cryptococcosis, which is one of the most serious fungal diseases faced by humans. Lateral flow immunochromatographic assay (LFA) is successfully applied to the rapid detection of cryptococcal antigens., Methods: Studies were retrieved systematically from the Embase, PubMed, Web of Science, and Cochrane Library before July 2019. The quality of the studies was assessed by Review Manager 5.0 based on the Quality Assessment of Diagnostic Accuracy Study guidelines. The extracted data from the included studies were analyzed by Meta-DiSc 1.4. Stata 12.0 software was used to detect the publication bias., Results: A total of 15 articles with 31 fourfold tables were adopted by inclusion and exclusion criteria. The merged sensitivity and specificity in serum were 0.98 and 0.98, respectively, and those in the cerebrospinal fluid were 0.99 and 0.99, respectively., Conclusions: Compared to the urine and other samples, LFA in serum and cerebrospinal fluid is favorable evidence for the diagnosis of cryptococcosis with high specificity and sensitivity.

Background: Cerebral cryptococcomas is a rare form of central nervous system cryptococcosis. Most previous cases were mistaken for neoplasm before surgery. We present a case of cerebral cryptococcomas whose radiological profiles resembled demyelinating disease, especially tumefactive demyelinating lesion., Case Presentation: A 40-year-old male was admitted for 1-week-long unconsciousness. Brain MRI revealed a rim-enhanced mass within the corpus callosum body. Central nervous system demyelinating disease was suspected. Empirical corticosteroid treatment led to some improvement, but his condition deteriorated 2 months later. Brain MRI revealed punctate new foci. Cryptococcus neoformans was detected in cerebrospinal fluid. Cryptococcus antigen test was positive in his current and previous cerebrospinal fluid samples. The patient died despite standard antifungal treatment., Conclusion: Diagnosis of cerebral cryptococcomas is challenging. It may mimic demyelinating diseases.

Central nervous system aspergillosis is relatively rare and difficult to diagnose. Here, we report a case of 90-year-old man with chronic lymphocytic leukemia who presented with a month-long gradually worsening headache followed by 3 days of low-grade fever associated with altered mental status. Aspergillus meningitis diagnosed using Aspergillus galactomannan antigen in the cerebrospinal fluid and treated with voriconazole. Delayed diagnosis and treatment of Aspergillus meningitis is typically associated with high mortality; therefore, it is imperative to include this disease in the differential diagnoses of subacute meningitis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Cryptococcal meningitis is most commonly found in HIV-infected patients. In HIV-negative patients, its low incidence can lead to prolonged time to diagnosis. Detailed case reports of chronic cryptococcal meningitis are scarce, but could provide clues for earlier diagnosis in this patient category., Case Presentation: A 60-year old man presented June 2015 with intermittent headaches for several months without any fever. Initial work-up showed a leukocytosis, raised CSF opening pressure and raised leukocytes and protein in the CSF. An MRI revealed leptomeningeal contrast enhancement and cerebellar oedema. While malignancy and various infectious causes were excluded, the patient had a spontaneous clinical and radiological recovery. One year later, the patient returned with complaints of headaches. Also, cerebellar oedema and leptomeningeal contrast enhancement had recurred. Eventually in March 2017, the novel cryptococcal antigen lateral flow assay (CrAg LFA) was positive on CSF, and one colony of Cryptococcus neoformans was cultured from CSF. The patient was treated with the standard antifungal regimen which resulted in resolution of his headaches. In retrospect, the cryptococcal antigen test was already positive on a serum sample from June 2015. Interestingly, post-treatment immunological analysis revealed both a low mannose-binding lectin (MBL) concentration and low naïve CD4 counts., Conclusions: We present a patient with cryptococcal meningitis in an HIV-negative patient with low MBL and low naïve CD4 count suffering a chronic relapsing meningo-encephalitis with relatively mild symptoms for around 2 years. In patients with an unexplained meningo-encephalitis such as this case, early performance of CrAg LFA on serum and/or CSF is an inexpensive and rapid method to reduce time-to diagnosis.

A 68-year-old man presented for outpatient evaluation of dyspnea and new-onset atrial fibrillation 9 months after undergoing bilateral lung transplantation. Echocardiography prior to cardioversion raised concern for tamponade. Therapeutic pericardiocentesis returned fluid containing 1875 wbc/mcl (68% pmn) and yielded Cryptococcus neoformans in culture. Cryptococcal antigen was detected in serum at a titer of 1:20. Cerebrospinal (CSF) fluid was without evidence of inflammation and without detectable cryptococcal antigen. There was no radiographic evidence of pulmonary cryptococcosis. Cultures of blood and CSF were without growth. Liposomal amphotericin B (3 mg/kg/day) was administered for 15 days. Oral fluconazole was added on day seven of amphotericin, and the patient was discharged to home 3 days later. Daily dosages of prednisone (10 mg), mycophenolate (500 mg), and tacrolimus (3 mg) at discharge were the same as at hospital admission. He was readmitted 12 days later with dyspnea and with re-accumulation and loculation of pericardial fluid. A pericardial window was created. Pericardial fluid contained 722 wbc/mcl (35% pmn); Cryptococcus was not identified on direct examinations or cultures of pericardial fluid or tissue. Cryptococcus antigen was present in serum at 1:160. Liposomal amphotericin B was resumed and continued for 2 weeks followed by resumption of fluconazole. Mycophenolate was stopped. Prednisone and tacrolimus were continued. Restrictive pericarditis was evident 3 weeks after window creation. Colchicine was initiated, prednisone increased to 15 mg daily and pericardiectomy planned. We aim to raise awareness to Cryptococcus as a potential etiology for pericarditis in solid organ transplant recipients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies., Methods: We evaluated 1201 human immunodeficiency virus-seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif., Results: We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91)., Conclusions: Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity., Clinical Trials Registration: NCT01802385., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The case was a 29-year-old male with no previous history of serious disease. He developed headache and fever, which then worsened and he was admitted to our hospital. His temperature was 38.3°C and he had a stiff neck. In cerebrospinal fluid (CSF) tests, the opening pressure was high, the cell count was increased, and the CSF/serum glucose ratio was decreased. In addition, he was positive for cryptococcal antigen. According to these findings, he was diagnosed with cryptococcal meningoencephalitis and antifungal treatment was initiated. His symptoms then improved, but on day 18 after admission, he developed convulsions, and on day 28, right visual field defects appeared. Brain MRI showed disseminated lesions in the bilateral cerebral cortex. Despite a decrease of the cryptococcal antigenic value in the CSF, the IgG index was elevated. IL-6, 8 and 10 in CSF were high levels on Day 1, then gradually reduced as the symptoms improved. But on Day 28, worsening of symptoms, IL-10 was significantly increased dispite IL-6 and 8 reducing. Therefore, the exacerbation of his symptoms and expansion of the lesions were not caused by the Cryptococcus itself, and it was considered that they were due to the late deterioration of cryptococcosis, which responded to steroid treatment.

Background: For definitive diagnosis of cryptococcal meningitis, Cryptococcus neoformans and/or C. gattii must be identified within cerebral spinal fluid from the patients. The traditional methods for detecting Cryptococcus spp. such as India ink staining and culture are not ideal. Although sensitive and specific enough, detection of cryptococcal antigen polysaccharide has a high dose hook effect. Therefore, the aim of this study was to introduce a new rapid and simple detection method of Cryptococcus neoformans and C. gattii in cerebral spinal fluid., Methods: The lateral flow strips combined with recombinase polymerase amplification (LF-RPA) assay was constructed to detect the specific DNA sequences of C. neoformans and C. gattii. The detection limit was evaluated using serial dilutions of C. neoformans and C. gattii genomic DNA. The specificity was assessed by excessive amount of other pathogens genomic DNA. The optimal detection time and amplification temperature were also analyzed. The diagnostic parameters were first calculated using 114 clinical specimens and then compared with that of other diagnostic method. A brief analysis and comparison of different DNA extraction methods was discussed, too., Results: The LF-RPA assay could detect 0.64 pg of genomic DNA of C. neoformans per reaction within 10 min and was highly specific for Cryptococcus spp.. The system could work well at a wide range of temperature from 25 to 45 °C. The overall sensitivity and specificity were 95.2 and 95.8% respectively. As amplification template for LF-RPA assay, both cell lysates and genomic DNA produce similar experimental results., Conclusions: The LF-RPA system described here is shown to be a sensitive and specific method for the visible, rapid, and accurate detection of Cryptococcus spp. in cerebral spinal fluid and might be useful for clinical preliminary screening of cryptococcal meningitis.

Objectives: Cryptococcal meningoencephalitis is the most common fungal infection of the central nervous system diagnosed by cerebrospinal fluid cytology (CSF) studies. Existing literature suggests that routine CSF cytomorphologic evaluations are exquisitely specific; however, less is known about their sensitivity., Methods: An electronic record review of the cytopathology and microbiology files was conducted for the 21-year interval from January 1, 1995, through December 31, 2015., Results: In 21 years, 12,584 CSF samples were processed in the laboratory. Of these, 24 (0.2%) were reported positive for cryptococcal organisms by light microscopy, and 129 CSF fungal cultures were positive for Cryptococcus species. All cotested specimens with positive cytology results were positive on culture (15 specimens, 100% specificity). Twenty-four samples with positive culture results were negative by CSF cytology (sensitivity 39%)., Conclusions: When culture is used as a gold standard, CSF cytology is 100% specific and 39% sensitive, with a positive predictive value of 100% and a negative predictive value of 99.8%.

Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection., (Copyright © 2019 American Society for Microbiology.)

A 71-year-old Japanese man with travel history to the Vancouver Island, Canada was diagnosed the pulmonary and central nervous system infections caused by Cryptococcus gattii genotype VGIIa. This is the first imported case of Cryptococcus gattii genotype VGIIa infection from endemic area of North America to Japan. He was recovery with no residual neurological dysfunction by early resection of brain mass and antifungal therapy. Early surgical resection of cerebellar cryptococcoma may shorten the length of induction therapy with antifungal drugs., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Blastomyces dermatitidis is a thermally dimorphic fungus that is capable of causing pulmonary and extra-pulmonary disease, including infections of the central nervous system (CNS). Diagnosis of CNS blastomycosis with non-invasive testing can be difficult, and a surgical biopsy may ultimately be required for microbiological and/or histopathological confirmation. A case of B. dermatitidis meningitis is presented where the diagnosis was made by testing cerebrospinal fluid (CSF) using the MVista® Blastomyces Quantitative Antigen Enzyme Immunoassay test. The utility of performing this test on CSF for diagnosis of CNS mass lesions/abscesses caused by B. dermatitidis in the absence of associated meningitis remains unclear. Cross reaction of the Blastomyces antigen test with other dimorphic fungi is a concern, necessitating that positive test results are interpreted in the context of the patient's exposure and travel history., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis., Methods: Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics., Results: A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases., Conclusions: Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: HIV-associated cryptococcal meningitis is the leading cause of adult meningitis in Sub-Saharan Africa, accounting for 15%-20% of AIDS-attributable mortality. The development of point-of-care assays has greatly improved the screening and diagnosis of cryptococcal disease. We evaluated a point-of-care immunoassay, StrongStep (Liming Bio, Nanjing, Jiangsu, China) lateral flow assay (LFA), for cryptococcal antigen (CrAg) detection in cerebrospinal fluid (CSF) and plasma., Methods: We retrospectively tested 143 CSF and 77 plasma samples collected from HIV-seropositive individuals with suspected meningitis from 2012-2016 in Uganda. We prospectively tested 90 plasma samples collected from HIV-seropositive individuals with CD4 cell count <100 cells/μL from 2016-2017 as part of a cryptococcal antigenemia screening program. The StrongStep CrAg was tested against a composite reference standard of positive Immy CrAg LFA (Immy, Norman, OK, USA) or CSF culture with statistical comparison by McNemar's test., Results: StrongStep CrAg had a 98% (54/55) sensitivity and 90% (101/112) specificity in plasma (P = 0.009, versus reference standard). In CSF, the StrongStep CrAg had 100% (101/101) sensitivity and 98% (41/42) specificity (P = 0.99). Adjusting for the cryptococcal antigenemia prevalence of 9% in Uganda and average cryptococcal meningitis prevalence of 37% in Sub-Saharan Africa, the positive predictive value of the StrongStep CrAg was 50% in plasma and 96% in CSF., Conclusions: We found the StrongStep CrAg LFA to be a sensitive assay, which unfortunately lacked specificity in plasma. In lower prevalence settings, a majority of positive results from blood would be expected to be false positives.

A Lateral Flow Assay to detect cryptococcal antigen (CrAg® LFA) in serum and cerebrospinal fluid for the rapid diagnosis of cryptococcosis was evaluated. A retrospective validation was performed. Sensitivity and specificity of the CrAg® LFA was 100%. High concordance (kappa index=1.0) between Cryptococcal Antigen Latex Agglutination System (CALAS®) and CrAg® LFA was observed. CrAg® LFA showed higher analytical sensitivity for detecting low concentrations of cryptococcal antigen.

A total of 817 human immunodeficiency virus-infected Ethiopians with CD4 <150 cells/mL underwent plasma cryptococcal antigen (CRAG) screening. CRAG prevalence was 6.2%. Of participants with plasma CRAG titers >1:640, 96% (27 of 28) had cryptococcal meningitis (cerebrospinal fluid CRAG-positive) whereas 50% (7 of 14) with 1:160-1:320 titers had meningitis. With fluconazole 1200 mg/d therapy, 68% of meningitis patients (23 of 34) died within 3 months. Plasma CRAG titers >1:160 predict meningitis, requiring more intensive antifungal therapy., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The incidence of cryptococcal meningitis (CM) and tuberculous meningitis (TBM) have gradually increased in recent years. These two types of meningitis are easily misdiagnosed which leads to a poor prognosis. In this study we compared differences of clinical features and prognostic factors in non-HIV adults with CM and TBM., Methods: We retrospectively reviewed the medical records of CM and TBM patients from January 2008 to December 2015 in our university hospital in China. The data included demographic characteristics, laboratory results, imaging findings, clinical outcomes., Results: A total of 126 CM and 105 TBM patients were included. CM patients were more likely to present with headache, abnormal vision and hearing, and they might be less prone to fever and cough than TBM patients (P < 0.05). Higher percentage of CM patients presented with cerebral ischemia/infarction and demyelination in brain MRI than TBM patients (P < 0.05). CM patients had lower counts of WBC in CSF, lower total protein in CSF and serum CD4/CD8 ratio than TBM patients (P < 0.05). After three months of treatment, CM group have worse outcome than TBM group (P < 0.05). Multivariate analysis showed that age more than 60y (OR = 4.981, 95% CI: 1.955-12.692, P = 0.001), altered mentation (OR = 5.054, 95% CI: 1.592-16.046, P = 0.006), CD4/CD8 ratios < 1 (OR = 8.782, 95% CI: 2.436-31.661, P = 0.001) and CSF CrAg ≥ 1:1024 (OR = 4.853, 95% CI: 1.377-17.098, P = 0.014) were independent risk factors for poor prognosis for CM patients. For TBM patients, hydrocephalus (OR = 7.290, 95% CI: 1.630-32.606, P = 0.009) and no less than three underlying diseases (OR = 6.899, 95% CI: 1.766-26.949, P = 0.005) were independent risk factors, headache was a protective factor of prognosis., Conclusions: Our study provided some helpful clues in the differential diagnosis of non-HIV patients with CM or TBM and identified some risk factors for the poor prognosis of these two meningitis which could help to improve the treatment outcome. Further studies are worth to be done.

Background: Cryptococcus meningoencephalitis is a serious opportunistic infection associated with high morbidity and mortality in immunocompromised hosts, particularly patients with advanced AIDS disease. The diagnosis is established through cerebrospinal fluid (CSF) cryptococcus antigen detection and cultures. Cryptococcus antigen testing is usually the initial test of choice due its high sensitivity and specificity along with the quick availability of the results., Case Report: We hereby report a case of a false-positive CSF cryptococcus antigen assay in a patient with systemic lupus erythematosus presenting with acute confusion. While initial CSF evaluation revealed a positive cryptococcus antigen assay, the patient's symptoms were inconsistent with cryptococcus meningoencephalitis. A repeat CSF evaluation, done 3 days later, revealed a negative CSF cryptococcus antigen assay., Conclusion: Given the patient's active lupus disease and the elevated antinuclear antibody titers, we believe that the initial positive result was a false positive caused by interference from autoantibodies.

Cryptococcal meningitis is a devastating HIV-related opportunistic infection, affecting nearly 1 million individuals and causing over 500 000 deaths each year. The burden of disease is greatest in sub-Saharan Africa and Southeast Asia, where cryptococcal disease is the most common cause of meningitis. Rapid, accurate and affordable diagnosis of cryptococcal disease has been lacking in many of the most heavily affected areas. Here, we review a point-of-care assay for cryptococcal disease, the dipstick-formatted cryptococcal antigen lateral flow assay (LFA) (IMMY, Norman, OK). In comparison to culture, the assay is 99.5% sensitive and 98% specific. In comparison to other commercially available tests for cryptococcal antigen, the LFA has equal or superior sensitivity and specificity in CSF, plasma and serum samples. We discuss potential applications for the use of the assay in resource-limited settings, including what is likely to be an important role of the LFA in screening for early cryptococcal infection before clinical disease and in evaluating pre-emptive treatment.

Invasive cerebral aspergillosis always developed in immunocompromised host. Early diagnosis may save life in this critical condition; however, it is difficult to reach. Herein, we presented an unusual case of invasive cerebral aspergillosis in a cirrhotic patient. A 47-year-old man presented with progressive deterioration of consciousness for three days. The patient had a history of alcoholic liver cirrhosis, Child-Pugh class C. Magnetic resonance imaging (MRI) of brain showed multi-focal parenchymal lesions, which was consistent with multiple brain abscesses. The diagnosis of invasive cerebral aspergillosis was made by molecular based laboratory methods including Aspergillus galactomannan antigen assay and oligonucleotide array. Despite treatment with the antifungal agent, Amphotericin B, the patient died at the ninth day of hospitalization. Our findings suggest that liver cirrhosis can be one of risk factors of invasive cerebral aspergillosis, and support the diagnosing usefulness of MRI, Aspergillus galactomannan antigen assay, and oligonucleotide array.

Testing cerebrospinal fluid (CSF) for the presence of galactomannan (GM) antigen may help in diagnosing cerebral aspergillosis (CA). However, the use of the CSF GM test as a diagnostic test has been little studied. We evaluated its diagnostic performance by comparing the CSF GM optical density indexes (ODI) at different cutoffs in patients with probable and proven CA to those in patients without CA. Patients from 2 tertiary referral hospitals with suspected CA between 2004 and 2014 and in whom CSF GM ODI had been determined were selected. European Organization for Research and Treatment of Cancer/Invasive Infectious Diseases Study Mycoses Group (EORTC/MSG) definitions of invasive aspergillosis and CA were used, but with the exclusion of the test to be validated (i.e., the CSF GM test) as a microbiological EORTC/MSG criterion. The study population consisted of 44 patients (4 with proven CA, 13 with probable CA, and 27 with no CA). Of the 17 patients with CA, 15 had a CSF GM ODI of ≥2.0. Of 27 patients without CA, 26 had a CSF GM ODI of <0.5 and 1 had a CSF GM ODI of 8.2. When a GM CSF ODI cutoff of 1.0 was used, the sensitivity, specificity, and positive and negative predictive values were 88.2%, 96.3%, 93.8%, and 92.9%, respectively. The same results were found when a CSF GM ODI cutoff of 0.5 or 2.0 was used. Testing GM in CSF has a high diagnostic performance for diagnosing CA and may be useful to diagnose or virtually rule out the infection without the need for a cerebral biopsy., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The goal of this study was to report on the potential utility of cerebrospinal fluid (CSF) Coccidioides antigen testing in the diagnosis and management of Coccidioides meningitis. We retrospectively reviewed medical records of seven patients with Coccidioides meningitis who had Coccidioides antigen tests performed on CSF. In two severely immunocompromised patients, CSF Coccidioides antigen testing was helpful in the diagnosis when other testing modalities were negative. Coccidioides antigen testing was also useful in the management of patients who had progression of disease due to non-adherence, development of resistance, failure of therapy and the presence of vasculitis. Changing antigen levels helped identify disease complications in three patients that led to alterations in therapy or management. On the basis of our review of these seven patients with Coccidioides meningitis, we concluded that the Coccidioides antigen test contributed to the diagnosis and management of patients with Coccidioides meningitis., (© 2015 Blackwell Verlag GmbH.)

Background: Cryptococcus neoformans is the most common cause of adult meningitis in sub-Saharan Africa. The cryptococcal antigen (CRAG) lateral flow assay (LFA) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (CSF). We evaluated the accuracy of the CRAG LFA using fingerstick whole blood compared with serum/plasma and CSF for diagnosing meningitis., Methods: From August 2013 to August 2014, CRAG LFA (IMMY, Norman, Oklahoma) tests were performed on fingerstick whole blood, plasma/serum, and CSF in 207 HIV-infected adults with suspected meningitis in Kampala, Uganda. Venous blood was also collected and centrifuged to obtain serum and/or plasma. CSF was tested after lumbar puncture., Results: Of 207 participants, 149 (72%) had fingerstick CRAG-positive results. There was 100% agreement between fingerstick whole blood and serum/plasma. Of the 149 fingerstick CRAG-positive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG. Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and culture, of whom 8 had CSF abnormalities (n = 3 lymphocytic pleocytosis, n = 5 elevated protein, n = 4 increased opening pressure). No persons with cryptococcal meningitis had negative fingersticks., Conclusions: The 100% agreement between whole blood, serum, and plasma CRAG LFA results demonstrates that fingerstick CRAG is a reliable bedside diagnostic test. Using point-of-care CRAG testing simplifies screening large numbers of patients and enables physicians to prioritize on whom to measure CSF opening pressure using manometers., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Cryptococcus gattii was recognized as an emerging infection in the Pacific Northwest in 2004. Out of 62 total infections in Oregon since the outbreak, 11 were in solid organ transplant (SOT) recipients. SOT recipients were more likely to have disseminated disease and higher mortality than normal hosts, who mostly had isolated mass lesions. The median time from transplantation to C. gattii diagnosis was 17.8 months. The primary sites of infection were lung (n = 4), central nervous system (n = 3), or both (n = 4). The Oregon-endemic strain, VGII (subtypes IIa and IIc) was present in 10 of 11 patients; the median fluconazole minimum inhibitory concentration (MIC) was 12 μg/mL (range 2-32 μg/mL) for this strain. We found C. gattii infection among organ transplant recipients was disseminated at diagnosis, had low cerebrospinal fluid cryptococcal antigen titers, and was associated with an elevated fluconazole MIC and high attributable mortality., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: A new lateral flow immunoassay (LFA) for the detection of cryptococcal antigen was developed., Objective: We aimed to systematically review all relevant studies to evaluate the diagnostic accuracy of the cryptococcal antigen LFA on serum, CSF and urine specimens., Methods: We searched public databases including PubMed, Web of Science, Elsevier Science Direct and Cochrane Library for the English-language literature published up to September 2014. We conducted meta-analyses of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratios (DOR) and SROC of LFA in serum and CSF, respectively. The sensitivity of LFA in urine was also analyzed. Subgroup analyses were carried out to analyze the potential heterogeneity., Results: 12 studies were included in this study. The pooled sensitivity and specificity values of LFA in serum were 97.6% (95% CI, 95.6% to 98.9%) and 98.1% (95% CI, 97.4% to 98.6%), respectively. The average PLR of LFA in serum was 43.787 (95% CI, 22.60-84.81) and the NLR was 0.03 (95% CI, 0.01-0.09). The pooled DOR was 2180.30 (95% CI, 868.92-5471.00) and the AUC was 0.9968. The pooled sensitivity and specificity values of LFA in CSF were 98.9% (95% CI, 97.9% to 99.5%) and 98.9% (95% CI, 98.0% to 99.5%), respectively. The average PLR of LFA in serum was 48.83 (95% CI, 21.59-110.40) and the NLR was 0.02 (95% CI, 0.01-0.04). The pooled DOR was 2931.10 (95% CI, 1149.20-7475.90) and the AUC was 0.9974. The pooled sensitivity value of LFA in urine was 85.0% (95% CI, 78.7% to 90.1%)., Conclusions: The study demonstrates a very high accuracy of LFA in serum and CSF for the diagnosis of cryptococcosis in patients at risk. LFA in urine can be a promising sample screening tool for early diagnosis of cryptococcosis.

We compared a lateral flow immunoassay (LFA) to a currently used enzyme immunoassay for detection of cryptococcal antigen in 396 sera and 651 cerebrospinal fluid specimens. We found 97% concordance between the 2 assays. The LFA detected an additional 22 positives. Overall, the LFA had sensitivity of 100% and specificity of 99.6% for the diagnosis of cryptococcosis. The LFA is rapid, accurate, and easy to perform, and it is suitable for routine patient care testing., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Current methods for cryptococcal antigen detection have some limitations. This study aimed at evaluating a lateral flow assay (LFA) for the diagnosis of cryptococcosis in a French University medical center., Methods: A retrospective study was performed on samples collected from patients with a definitive diagnosis of cryptococcosis (group I 66 samples; 28 patients) or with non-Cryptococcus invasive fungal infection (group II 18 samples; 17 patients). In addition, 274 samples from 205 consecutive patients, either suspected of cryptococcal infection or routinely screened during their follow-up, were prospectively tested (group III). Cryptococcal antigen was assayed using LFA and an EIA. A latex-based test was used for confirmation., Results: Sensitivity calculated on group I and specificity on group II, were respectively at 100% and 90.0%. Two false positives were related to Trichosporon fungemia. Per-sample analysis on group III revealed sensitivity, specificity, positive and negative predictive values all at 100% for CSF, and at 100%, 98.9%, 75% and 100%, respectively for serum samples. LFA enabled the diagnosis of two cases of asymptomatic cryptococcosis., Conclusion: The excellent diagnostic value and practicality (visual reading results in 15 min) of LFA make it fully appropriate for the diagnosis of cryptococcosis in this particular setting., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients.

Background: Paracoccidioidomycosis (PCM) is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations., Method/principle Findings: A latex immunoassay using sensitized latex particles (SLPs) with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43) was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF), and bronchoalveolar lavage (BAL) from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0), specificity (93.94%, 95% CI 87.3-97.7), and positive (91.4%) and negative (98.9%) predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6), specificity (88.89%, 95% CI 81.0-94.3), and positive (85.1%) and negative (97.8%) predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924) and mAb17c-SLPs (k = 0.850), which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy., Conclusions/significance: The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure and/or minimally trained community health workers.

Central nervous system (CNS) aspergillosis with stroke has a high mortality and poor prognosis generally. We report a 78-years-old woman with diabetes mellitus, who developed invasive paranasal sinus aspergillosis with the orbital apex syndrome on the right side and cerebral infarction caused by intracranial occlusion of the right internal carotid artery. Based on the presence of a mass lesion in the ethmoid sinus extending to the orbital apex on the right side with cranial CT, the mass lesion was surgically removed and the pathological examination of the surgical specimen revealed aspergillus mold. Immediately after surgery, we initiated treatment with voriconazole 200 mg × 2/day intravenously for 38 days, and then via feeding tube for 86 days until the galactomannan-aspergillus antigen level in the cerebrospinal fluid became negative at 132 days. She is alive now for almost two years without relapse of aspergillosis. There is no definitive guideline for management of patients with CNS aspergillosis concerning the length of drug treatment and the method for monitoring the response for treatment. We believe that measurement of the galactomannan-aspergillus antigen level in the cerebrospinal fluid might be a useful way of monitoring the efficacy of treatment for CNS aspergillosis.

A 54-year-old man was admitted due to progressive gait disturbance and cognitive impairment. On MRI, a hyperintense region was observed in the periventricular white matter on FLAIR imaging, with Gd-enhancement in the choroid plexus and periventricular wall. Cerebrospinal fluid (CSF) examination showed marked abnormalities including a high white blood cell count (WBC, 360 cells/mm(3). 83% lymphocytes), an elevated protein level (1,416 mg/dl), a low glucose level (12 mg/dl), and elevated cryptococcal antigen with positive Indian ink staining. Cryptococcal ventriculitis was diagnosed. The patient was initially treated with liposomal amphotericin B, fluconazole, voriconazole, and flucytosine for 38 weeks, followed by administration of itraconazole and fluconazole with some improvement. The brain MRI after one month showed septum formation in the posterior horn, which was suggestive of ventriculitis. Although ventriculitis is rare, we should pay attention to the presence of ventriculitis due to cryptococcal infection in the central nervous system.

Cryptococcosis is a potentially fatal fungal disease caused by variants of Cryptococcus neoformans species.  The respiratory tract is the usual portal of entry, with a peculiar predilection to invade the central nervous system.  The skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation.  The disease is mostly seen in immunodeficiency states.  The diagnosis is frequently unsuspected in immunocompetent patients. We report a case of disseminated cryptococcal meningitis in an immunocompetent young adult. The cutaneous eruption prompted the accurate diagnosis.  The patient, a 20-year-old female, had fever, cough, headache and intractable vomiting for the past two months and was being managed as a case of tuberculous meningitis. Two weeks after starting antituberculous treatment she developed umbilicated papules on the head and neck region. Necessary laboratory workup identified C. neoformans in cerebrospinal fluid (CSF) and skin specimens.  The titers of cryptococcal antigen were measured in CSF and serum for diagnostic and prognostic purposes.  Anti-fungal treatment resulted in regression of the cutaneous lesions and resolution of systemic complaints. The case highlights the need for high degree of suspicion, especially in healthy young adults, in the diagnosis of cryptococcosis. The cutaneous eruptions can be the first manifestation or a diagnostic clue of enormous significance.

Multiple sclerosis (MS) is the prototypical inflammatory disease of the central nervous system and spinal cord, leading to axonal demyelination of neurons. Recently, we have found a correlation between fungal infection and MS in peripheral blood of patients. The present work provides evidence of fungal infection in the cerebrospinal fluid (CSF) of some MS patients. Thus, fungal antigens can be demonstrated in CSF, as well as antibodies reacting against several Candida species. Comparison was made between CSF and blood serum for the presence of fungal antigens (proteins) and antibodies against different Candida spp. Analyses of both CSF and serum are complementary and serve to better evaluate for the presence of disseminated fungal infection. In addition, PCR analyses indicate the presence of DNA from different fungal species in CSF, depending on the patient analyzed. Overall, these findings support the notion that fungal infection can be demonstrated in CSF from some MS patients. This may constitute a risk factor in this disease and could also help in understanding the pathogenesis of MS.

Cryptococcus spp. commonly causes infection in immunocompromised hosts. Clinical presentation of cryptococcal meningoencephalitis (CM) is variable, but headache, fever and a high intracranial pressure should suggest the diagnosis. The cryptococcal antigen test is a specific and sensitive rapid test that can be performed on blood or cerebrospinal fluid. We report a case of CM in a patient with previously undetected lymphocytopenia. Because cryptococcal antigen test results were negative, diagnosis and treatment were delayed.

Cryptococcosis is a systemic infection caused by the pathogenic yeasts Cryptococcus neoformans and C. gattii. Detection of cryptococcal capsular antigen (CrAg) in serum and cerebrospinal fluid (CSF) plays an important diagnostic role. We prospectively compared the new Immuno-Mycologics Inc. (IMMY) lateral flow assay (LFA) and enzyme immunoassay (EIA) to our current CrAg test (Premier EIA; Meridian Bioscience Inc.). Discordant samples were retested with the latex-Cryptococcus antigen test (IMMY) and using serotype-specific monoclonal antibodies (MAbs). A total of 589 serum and 411 CSF specimens were tested in parallel. Qualitative agreement across assays was 97.7%. In all, 56 (41 serum and 15 CSF) samples were positive and 921 (527 serum and 394 CSF) samples were negative by all three assays. The 23 discrepant specimens were all Meridian EIA negative. Of 23 discordant specimens, 20 (87.0%) were positive by both the IMMY LFA and EIA, 2 were LFA positive only, and 1 was EIA positive only. Eleven discrepant specimens had adequate volume for latex agglutination (LA) testing; 8 were LA positive, and 3 were LA negative. LA-negative samples (2 CSF samples and 1 serum) had low IMMY LFA/EIA titers (≤1:10). Serotype-specific MAb analysis of the LA-positive samples suggested that these specimens contained CrAg epitopes similar to those of serotype C strains. In conclusion, the IMMY assays showed excellent overall concordance with the Meridian EIA. Assay performance differences were related to issues of analytic sensitivity and possible serotype bias. Incomplete access to patient-level data combined with low specimen volumes limited our ability to fully resolve discrepant results.

We compared the performance of four assays for the detection of cryptococcal antigen in serum samples (n = 634) and cerebrospinal fluid (CSF) samples (n = 51). Compared to latex agglutination, the sensitivity and specificity of the Premier enzyme immunoassay (EIA), Alpha CrAg EIA, and CrAg lateral flow assay (LFA) were 55.6 and 100%, 100 and 99.7%, and 100 and 99.8%, respectively, from serum samples. There was 100% agreement among the four tests for CSF samples, with 18 samples testing positive by each of the assays.

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., (Copyright © 2012. Published by Elsevier B.V.)

As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); β-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.