Fatal Cryptococcus gattii meningitis with negative cryptococcal antigen test in a HIV-non-infected patient

Cryptococcus gattii predominantly causes central nervous system and pulmonary infection in both immunocompromised and immunocompetent patients with substantial morbidity. We report a case of rapidly fatal meningitis by C. gattii in an HIV–non-infected man with CD4 lymphopenia who tested negative for cryptococcal antigen. This case may serve as an alert to its wider occurrence and less explored risk factors.

Extent of Lung Involvement and Serum Cryptococcal Antigen Test in Non-Human Immunodeficiency Virus Adult Patients with Pulmonary Cryptococcosis / 中华医学杂志(英文版)

<p><b>Background</b>Serum cryptococcal antigen (CrAg) test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus (HIV) adult patients with pulmonary cryptococcosis and its clinical features.</p><p><b>Methods</b>One hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative (CrAg- group). It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio (OR) was used to measure correlation. Student's t- test was obtained to analyze continuous variable.</p><p><b>Results</b>No difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups (P > 0.05 in all). Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg- group (χ = 40.34, P < 0.001; OR = 39.87).</p><p><b>Conclusions</b>Among patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation.</p>

Diagnostic and therapeutic strategies in cryptococcosis: impact on outcome

Cryptococcosis diagnosis has been recently improved by the use of rapid cryptococcal antigen testing with lateral flow assays, which have proved sensitive and specific. Using "test and treat" screening strategies for cryptococcal disease with these tests has been showed effective in reducing cryptococcal meningitis (CM) in HIV-infected patients. Recommended induction, consolidation, and maintenance therapeutic strategy for CM is widely unavailable and/or expensive in low and middle-income settings. New therapeutic strategies, mostly using reduced duration, have recently shown acceptable outcome or are currently tested. Diagnostic and therapeutic guidelines for cryptococcal disease in limited resources countries are undergoing a paradigmatic shift.

Early onset primary pulmonary cryptococcosis in a renal transplant patient.

We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB). Broncho-alveolar fluid (BAL) shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold) in serum and was negative in cerebrospinal fluid (CSF). The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.

Histopathology, serology and cultures in the diagnosis of cryptococcosis / Histopatologia, sorologia e cultivo no diagnóstico da criptococose

Cryptococcosis is one of the most common opportunistic fungal infections in patients with acquired immunodeficiency syndrome (AIDS). We report 13 cases of cryptococcal infection based on histopathology, serology and cultures. Epidemiological analysis, histochemical techniques of hematoxilin and eosin (HE) and Grocot's silver (GMS), as well special histochemical techniques such as Mayer's mucicarmine (MM) and Fontana-Masson (FM), cryptococcal antigen test (CrAg) and isolation on fungal media: Sabouraud's (SAB), brain-heart infusion agar (BHI) and canavanine-glycine-bromothymol blue (CGB) agar were analyzed. Unsatisfactory staining results by MM stain associated to negative titers by CrAg test, which FM stain confirmed that capsule-deficient Cryptococcus infections were observed in four cases. Eight isolated cases were identified as follows: six cases were infection with Cryptococcus neoformans and two cases were Cryptococcus gattii.

A criptococose é a mais comum infecção fúngica oportunística observada em pacientes com síndrome da imunodeficiência adquirida (AIDS). Relatamos 13 casos da infecção baseados no diagnóstico histopatológico, sorológico e cultivo. Foram analisadas: a epidemiologia, as técnicas histoquímicas básicas de hematoxilina-eosina (HE) e coloração pela prata (GMS), bem como as técnicas histoquímicas especiais de mucicarmim de Mayer (MM) e Fontana-Masson (FM), o teste do antígeno criptocóccico (CrAg) e o isolamento em cultivos em ágar-Sabouraud (SAB), ágar infusão de cérebro-coração (BHI) e meio com canavanina azul de bromotimol (CGB). Em quatro casos, resultados tintoriais insatisfatórios pela coloração de MM associados a títulos negativos pelo teste do CrAg, a coloração de FM confirmou a infecção pelo Cryptococcus deficiente de cápsula. Oito isolados foram identificados: seis casos apresentaram a infecção por Cryptococcus neoformans e dois casos apresentaram a infecção por Cryptococcus gattii.

Clinical Features of Cryptococcosis Patients and Evaluation of the Diagnostic Tests / 감염

BACKGROUND: Cryptococcus neoformans is an increasingly important pathogen in the immunosuppressed hosts. The aim of this study was to determine any change of the clinical features and to evaluate the laboratory diagnosis in cryptococcosis patients. METHODS: The clinical features of cryptococcsis patients who were diagnosed in Severance Hospital during the 1983~1995 were reviewed retrospectively and various diagnostic laboratory tests, especially latex cryptococcal antigen test were evaluated. RESULTS: The number of crytococcosis patients increased over the years. Twenty-six patients had various underlying diseases including two AIDS patients. Of the 43 patients, 41(95%) had CNS infections, while the patients with non-CNS infections were 10(23%). Latex antigen test, culture, India ink preparation, and Gram stain were positive in 100%, 87 %, 60% and 51%, respectively. Positivity of latex antigen test, India ink preparation, and culture persisted in average 69 days, 26 days, and 12 days, respectively in recovered patients. CONCLUSION: The number of cryptococcosis patients is an increasing trend in the Severance Hospital probably due to the increase of immunocompromised patients, and latex antigen test is a highly sensitive and reliable screening test for the laboratory diagnosis.