Antigen titers in cryptococcal meningitis: what determines how fast they fall?

Follow-up of previously healthy patients surviving cryptococcal meningitis found that cryptococcal antigen could be detected for more than one year in serum from 38 of 44 (86%) patients and in 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 two fold drop in titer to occur, was slower in serum than in CSF. Speed of decline of antigen titers was much slower in serum and CSF for patients infected with C. gattii than C. 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.

Adjunctive Single-Dose Liposomal Amphotericin to Prevent Cryptococcal Meningitis in People With Human Immunodeficiency Virus (HIV)-Associated Cryptococcal Antigenemia and Low Plasma Cryptococcal Antigen (CrAg) Titers.

BACKGROUND: Cryptococcal meningitis is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) predicts the development of meningitis. Historically, despite standard- of-care fluconazole, 25%-30% of asymptomatic CrAg-positive persons develop breakthrough meningitis or death. We evaluated whether adding single high-dose liposomal amphotericin B to standard pre-emptive fluconazole therapy could improve meningitis-free survival. METHODS: Participants with human immunodeficiency virus (HIV) and asymptomatic cryptococcal antigenemia in Uganda were randomized to liposomal amphotericin B (10 mg/kg once) with fluconazole or fluconazole alone through 24 weeks. We compared 24-week, meningitis-free survival time between treatment groups. After the second interim review, the Data Safety and Monitoring Board recommended no further enrollment of participants with low plasma CrAg lateral flow assay titers (≤1:80) due to futility. Herein, we present the results of participants with low plasma CrAg titers. RESULTS: 168 participants enrolled into the ACACIA trial had low plasma CrAg titers (≤1:80). During 24 weeks of follow-up, meningitis or death occurred in 14.5% (12/83) of participants randomized to liposomal amphotericin B with fluconazole versus 10.6% (9/85) assigned to fluconazole alone (hazard ratio, 1.42; 95% CI, .60-3.36; P = .431). Adverse events were more frequent in participants assigned to the intervention versus standard-of-care (28% vs 12%; P = .011). CONCLUSIONS: Among CrAg-positive persons with low titers (≤1:80), the addition of single-dose liposomal amphotericin B to fluconazole as pre-emptive therapy provided no additional clinical benefit. This trial provides supportive evidence that, in asymptomatic populations with low plasma CrAg titers, lumbar punctures are likely unnecessary as administration of meningitis treatment did not improve outcomes. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT03945448).

Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

Survival after cryptococcosis in Germany: A retrospective multicenter cohort study of patients diagnosed between 2004 and 2021.

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis.

Complex Decisions in HIV-Related Cryptococcosis: Addressing Second Episodes of Cryptococcal Meningitis.

PURPOSE OF REVIEW: This review highlights the difficulties in diagnosing and treating persons with a prior history of cryptococcal meningitis who improve but suffer from a recurrence of symptoms. This scenario is well known to those who frequently care for patients with cryptococcal meningitis but is not well understood. We highlight major gaps in knowledge. RECENT FINDINGS: We recently summarized our experience with 28 persons with paradoxical immune reconstitution inflammatory syndrome (IRIS) and 81 persons with microbiological relapse. CD4 count and cerebrospinal fluid white blood cell count were higher in IRIS than relapse but neither was reliable enough to routinely differentiate these conditions. Second-episode cryptococcal meningitis remains a difficult clinical scenario as cryptococcal antigen, while excellent for initial diagnosis has no value in differentiating relapse of infection from other causes of recurrent symptoms. Updated research definitions are proposed and rapid, accurate diagnostic tests are urgently needed.

Cryptococcosis-a systematic review to inform the World Health Organization Fungal Priority Pathogens List.

Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization's first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%-61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16-32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%-33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%-23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%-27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25-0.5 mg/l), 5-flucytosine (MIC range: 0.5-2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06-0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden.

Successful Treatment of Cryptococcus gattii in an Immunocompetent Adult Rhesus Macaque (Macaca mulatta).

An adult female rhesus macaque presented during routine annual physical examination for evaluation of a 2.5-cm diameter superficial ulcerated dermal lesion that was subsequently diagnosed as a systemic fungal infection caused by Cryptococcus gattii. Cryptococcus gattii is one of several basidiomycetic yeasts responsible for pulmonary, neurologic, and disseminated infections in humans and animals. This report describes the diagnosis, management, and clinical resolution of a C. gattii infection in an immunocompetent 5-year-old female rhesus macaque.

Postpartum cryptococcosis in an HIV-negative patient.

PURPOSE AND METHODS: We present an unusual case of an HIV-negative patient with postpartum pulmonary cryptococcosis and cryptococcemia. RESULTS: The diagnostic methods and treatment of cryptococcosis in a postpartum patient are presented in this case report. Due to anaphylaxis to liposomal amphotericin B, desensitisation to the drug was performed. CONCLUSION: We would like to raise awareness about rare infections such as cryptococcosis in pregnancy and the postpartum period. In addition, we were able to document a successful desensitisation to liposomal amphotericin B.

Comprehensive risk factor predictions for 3-year survival among HIV-associated and disseminated cryptococcosis involving lungs and central nervous system.

BACKGROUND: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. METHODS: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. RESULTS: Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). CONCLUSIONS: IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted.

Cryptococcal invasion: a comprehensive case of adrenal and systemic infection amid immunosuppression.

We report a case of disseminated cryptococcosis, an uncommon fungal infection predominantly affecting the lungs and central nervous system, with the rare involvement of adrenal cryptococcosis, compounded by meningitis and pneumonia. The patient, previously diagnosed with primary myelofibrosis and undergoing oral Ruxolitinib treatment, exhibited immunosuppression. Imaging via chest and abdominal CT scans revealed inflammation in the right lung's middle lobe, splenomegaly, a splenic lesion, and a left adrenal mass, initially prompting considerations of pheochromocytoma. However, unilateral adrenalectomy and subsequent pathological examination disclosed extensive infiltration by inflammatory and multinucleate giant cells, with Periodic acid-Schiff (PAS) staining confirming the diagnosis. The identification of adrenal cryptococcosis was further supported by positive adrenal pus culture and significantly elevated capsular antigens in both serum and cerebrospinal fluid, at titers of 1:2560. Following a month of oral antifungal treatment, marked reductions in capsular antigen levels were noted, to 1:640 and 1:160 in serum and cerebrospinal fluid, respectively. The patient was discharged on a regimen of oral amphotericin B, flucytosine, and fluconazole, with regular outpatient follow-ups showing no signs of recurrence or dissemination.

A case of primary cutaneous Cryptococcus neoformans infection.

BACKGROUND: Cryptococcosis is an infectious disease caused by encapsulated heterobasidiomycete yeasts. As an opportunistic pathogen, cryptococcal inhalation infection is the most common. While Primary cutaneous cryptococcosis is extremely uncommon. CASE PRESENTATION: A 61-year-old woman with a history of rheumatoid arthritis on long-term prednisone developed a red plaque on her left thigh. Despite initial antibiotic treatment, the erythema worsened, leading to rupture and fever. Microbiological analysis of the lesion's secretion revealed Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus epidermidis. Skin biopsy showed thick-walled spores, and culture confirmed primary cutaneous infection with Cryptococcus neoformans. Histopathological stains were positive, and mass spectrometry identified serotype A of the pathogen. The patient was treated with oral fluconazole and topical nystatin, resulting in significant improvement and near-complete healing of the skin lesion within 2.5 months. CONCLUSIONS: Primary cutaneous cryptococcosis was a primary skin infection exclusively located on the skin. It has no typical clinical manifestation of cutaneous infection of Cryptococcus, and culture and histopathology remain the gold standard for diagnosing. The recommended medication for Primary cutaneous cryptococcosis is fluconazole. When patients at risk for opportunistic infections develop skin ulcers that are unresponsive to antibiotic, the possibility of primary cutaneous cryptococcosis needs to be considered.

Cryptococcosis with pulmonary cavitation in an immunocompetent child: a case report and literature review.

BACKGROUND: Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children. CASE PRESENTATION: A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive. CONCLUSION: PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.

Pulmonary cryptococcosis complicated with pulmonary aspergillosis: a series of studies and a literature review.

BACKGROUND/OBJECTIVE: With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals. METHODS: A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review. RESULT: The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%). CONCLUSION: Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.

Disseminated cryptococcosis in a patient with idiopathic CD4 + T lymphocytopenia presenting as prostate and adrenal nodules: diagnosis from pathology and mNGS, a case report.

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

Cryptococcal prostatitis in an immunocompromised patient with tocilizumab and glucocorticoid therapy: A case report.

Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease.

Association between neuroimaging and clinical outcomes in individuals with central nervous system cryptococcosis.

BACKGROUND: The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. METHODS: All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. RESULTS: We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). CONCLUSION: In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Temporal trends in antifungal susceptibility of Cryptococcus neoformans isolates from a reference laboratory in the United States, 2011-2021.

BACKGROUND: There are no established clinical breakpoints for antifungal agents against Cryptococcus species; however, epidemiological cut-off values can help distinguish wild-type (WT) isolates without any acquired resistance from non-WT strains, which may harbour resistance mechanisms. PATIENTS/METHODS: We describe the trends of antifungal MICs and percentages of WT C. neoformans species complex (CNSC) isolates processed in our reference laboratory from November 2011 to June 2021. There were only nine isolates in 2011, thus, we included them in the year 2012 for data analysis. Clinical data is also described when available. RESULTS: We identified 632 CNSC, the majority collected from blood (n = 301), cerebrospinal fluid (n = 230), and respiratory (n = 71) sources. The overall percentage of WT isolates for amphotericin B (AMB), 5-flucytosine, and fluconazole was 77%, 98%, and 91%, respectively. We noticed a statistically significant change in the percentage of AMB WT isolates over the years, with 98% of isolates being WT in 2012 compared to 79% in 2021 (p < .01). A similar change was not observed for other antifungal agents. Clinical data was available for 36 patients, primarily non-HIV immunocompromised patients with disseminated cryptococcosis. There were no statistically significant differences in the clinical characteristics and outcomes between patients with WT (58.3%) versus non-WT (41.7%) isolates, but we noticed higher mortality in patients infected with an AMB non-WT CNSC isolate. CONCLUSIONS: We observed an increase in the percentage of AMB non-WT CNSC isolates in the past decade. The clinical implications of this finding warrant further evaluation in larger studies.

Supervised training models with or without manual lesion delineation outperform clinicians in distinguishing pulmonary cryptococcosis from lung adenocarcinoma on chest CT.

BACKGROUND: The role of artificial intelligence (AI) in the discrimination between pulmonary cryptococcosis (PC) and lung adenocarcinoma (LA) warrants further research. OBJECTIVES: To compare the performances of AI models with clinicians in distinguishing PC from LA on chest CT. METHODS: Patients diagnosed with confirmed PC or LA were retrospectively recruited from three tertiary hospitals in Guangzhou. A deep learning framework was employed to develop two models: an undelineated supervised training (UST) model utilising original CT images, and a delineated supervised training (DST) model utilising CT images with manual lesion annotations provided by physicians. A subset of 20 cases was randomly selected from the entire dataset and reviewed by clinicians through a network questionnaire. The sensitivity, specificity and accuracy of the models and the clinicians were calculated. RESULTS: A total of 395 PC cases and 249 LA cases were included in the final analysis. The internal validation results for the UST model showed a sensitivity of 85.3%, specificity of 81.0%, accuracy of 83.6% and an area under the curve (AUC) of 0.93. Similarly, the DST model exhibited a sensitivity of 88.2%, specificity of 88.1%, accuracy of 88.2% and an AUC of 0.94. The external validation of the two models yielded AUC values of 0.74 and 0.77, respectively. The average sensitivity, specificity and accuracy of 102 clinicians were determined to be 63.1%, 53.7% and 59.3%, respectively. CONCLUSIONS: Both models outperformed the clinicians in distinguishing between PC and LA on chest CT, with the UST model exhibiting comparable performance to the DST model.

The relationship between lung CT features and serum cryptococcal antigen titers in localized pulmonary cryptococcosis patients.

BACKGROUND: To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. METHODS: A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. RESULTS: A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (ß, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (ß, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. CONCLUSION: In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.