Serum Cryptococcal Antigen Research Articles

Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study

Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible. We prospectively followed 101 ART-naïve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1-5.1, p = 0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p = 0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p≤0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level >32 mg/l (highest quartile). Pre-ART CRP level >32 mg/l alone was associated with future death (OR = 8.3, 95% CI 2.7-25.6, p<0.001). Pre-ART increases in Th(17) and Th(2) responses (e.g., IL-17, IL-4) and lack of proinflammatory cytokine responses (e.g., TNF-α, G-CSF, GM-CSF, VEGF) predispose individuals to subsequent IRIS, perhaps as biomarkers of immune dysfunction and poor initial clearance of CRAG. Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start ART or use prophylactic interventions.

A Case of Cryptococcal Lymphadenitis in an HIV-Infected Child

An 8-year-old HIV-positive antiretroviral therapy-naive child developed severe headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG) test was positive, the histology on the lymph node biopsy revealed budding yeast cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal fluid. He was treated with intravenous amphotericin B followed by oral fluconazole with a good response. Therefore cryptococcal lymphadenitis should be considered in the differential diagnosis of children presenting with lymphadenopathy and a positive serum CRAG.

Cost-Effectiveness of Primary Prophylaxis of AIDS Associated Cryptococcosis in Cambodia

BackgroundCryptococcal infection is a frequent cause of mortality in Cambodian HIV-infected patients with CD4+ count ≤100 cells/µl. This study assessed the cost-effectiveness of three strategies for cryptococcosis prevention in HIV-infected patients.MethodsA Markov decision tree was used to compare the following strategies at the time of HIV diagnosis: no intervention, one time systematic serum cryptococcal antigen (CRAG) screening and treatment of positive patients, and systematic primary prophylaxis with fluconazole. The trajectory of a hypothetical cohort of HIV-infected patients with CD4+ count ≤100 cells/µl initiating care was simulated over a 1-year period (cotrimoxazole initiation at enrollment; antiretroviral therapy within 3 months). Natural history and cost data (US$ 2009) were from Cambodia. Efficacy data were from international literature.ResultsIn a population in which 81% of patients had a CD4+ count ≤50 cells/ µl and 19% a CD4+ count between 51–100 cells/µl, the proportion alive 1 year after enrolment was 61% (cost $ 472) with no intervention, 70% (cost $ 483) with screening, and 72% (cost $ 492) with prophylaxis. After one year of follow-up, the cost-effectiveness of screening vs. no intervention was US$ 180/life year gained (LYG). The cost-effectiveness of prophylaxis vs. screening was $ 511/LYG. The cost-effectiveness of prophylaxis vs. screening was estimated at $1538/LYG if the proportion of patients with CD4+ count ≤50 cells/µl decreased by 75%.ConclusionIn a high endemic area of cryptococcosis and HIV infection, serum CRAG screening and prophylaxis are two cost effective strategies to prevent AIDS associated cryptococcosis in patients with CD4+ count ≤100 cells/µl, at a short-term horizon, screening being more cost-effective but less effective than prophylaxis. Systematic primary prophylaxis may be preferred in patients with CD4+ below 50 cells/µl while systematic serum CRAG screening for early targeted treatment may be preferred in patients with CD4+ between 51–100 cells/µl.

Mediastinal cryptococcosis masquerading as therapy-refractory lymphoma

Dear Editor, A 58-year-old woman presented with a 1-month history of abdominal pain and weight loss. Positron emission tomography computerized tomography (PET-CT) showed markedly thickened and hypermetabolic small bowel (standardized uptake value maximum, SUVmax: 8.7) associated with multiple abdominal and pelvic lymphadenopathy (Fig. 1a). Intestinal obstruction soon developed, necessitating small bowel resection. Histologic examination showed enteropathy-associated T-cell lymphoma. She was treated with three cycles of chemotherapy comprising steroid, methotrexate, ifosphamide, l-asparaginase, and etoposide [1]. Interim reassessment PET-CT showed complete resolution of the abdominal and pelvic lesions (Fig. 1b). However, new pretracheal, precarinal, subcarinal, and left hilar lymphadenopathy (SUVmax, 7.4; Fig. 1b, arrows) developed. The patient was afebrile with no respiratory symptoms. Owing to discrepant responses of lymphadenopathy to chemotherapy, further diagnostic evaluation was pursued. To avoid general anesthesia necessary for mediastinoscopy, endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) was performed under local anesthesia with conscious sedation. Multiple mediastinal lymph nodes located in the upper, lower paratracheal, and subcarinal area were aspirated. Conventional fiberoptic bronchoscopy was also performed with no endobronchial abnormality detected. Both cytologic and histologic specimens obtained from all sampled lymph nodes demonstrated epithelioid-like cells and multinucleated giant cells, with no atypical lymphoid cells found. Roundish spore-like organisms were indentified (Fig. 2a, arrows). These organisms were positive for the fungal mucicarmine (Fig. 2b, arrows) and Grocott stains. The histopathologic features were consistent with cryptococcal lymphadenitis. Serum cryptococcal antigen was also positive at 1:16. The cerebrospinal fluid was normal. She was treated with oral fluconazole (400 mg daily). A PET-CT scan after 6 weeks of fluconazole showed that the mediastinal lymphadenopathy had largely resolved. Fig. 1 Positron emission tomography. a Before treatment, showing massive bowel and pelvic involvement (arrows). b After chemotherapy, showing resolution of all previous lesions, but matted mediastinal lymphadenopathy of similar metabolic activity as the original ... Fig. 2 Lymph node findings. a Histologic examination showed numerous spore-like organisms (arrows). b The organisms were positive for the fungal stain mucicarmine (arrows) Cryptococcal infection usually results from inhalation of fungal spores, and may be confined to the lungs or disseminate systemically. Radiologically, pulmonary cryptococcosis may present as a single well-defined consolidation or mass, diffusely scattered nodules or reticulonodules [2]. Cryptococcal lymphadenopathy, especially affecting the mediastinum, is infrequent and mainly reported in patients infected with the human immunodeficiency virus (HIV) [3, 4]. Radiologically, in HIV-negative patients, pulmonary cryptococcal infection usually presents as large nodular lesions or alveolar infiltrates. In HIV-infected patients, lymphadenopathy and interstitial infiltrates are instead the common findings [5]. In cryptococcal lymphadenitis, lymph nodes are generally <1.5 cm and accompanied by pulmonary parenchymal changes [6]. Hence, the extensive multifocal mediastinal lymphadenopathy without parenchymal lesions in our patient was more consistent radiologically with lymphoma progression. However, suitable investigations finally revealed the correct diagnosis. Conventional transbronchial needle aspiration with a histology needle in immunocompromised patients with intrathoracic lymphadenopathy has a poor diagnostic yield [7]. EBUS-TBNA with a designated 22-gauge needle has significant advantages. In addition to a high diagnostic yield for mediastinal lymphadenopathy, both histologic and cytologic specimens can be obtained. A histological specimen aids in the diagnosis of non-malignant mediastinal lymphadenopathy such as sarcoidosis, as well as eliminates the possibility of false-positive microbiologic results from contamination by airway colonization. Our case illustrated well the utility of EBUS-TBNA as a minimally invasive technique in clinching the diagnosis.

Cost‐Effectiveness of Serum Cryptococcal Antigen Screening to Prevent Deaths among HIV‐Infected Persons with a CD4+Cell Count ⩽100 Cells/μL Who Start HIV Therapy in Resource‐Limited Settings

Cryptococcal meningitis (CM) remains a common AIDS-defining illness in Africa and Asia. Subclinical cryptococcal antigenemia is frequently unmasked with antiretroviral therapy (ART). We sought to define the cost-effectiveness of serum cryptococcal antigen (CRAG) screening to identify persons with subclinical cryptococcosis and the efficacy of preemptive fluconazole therapy. There were 609 ART-naive adults with AIDS who started ART in Kampala, Uganda, and who had a serum CRAG prospectively measured during 2004-2006. The number needed to test and treat with a positive CRAG was assessed for > or = 30-month outcomes. In the overall cohort, 50 persons (8.2%) were serum CRAG positive when starting ART. Of 295 people with a CD4(+) cell count < or = 100 cells/microL and without prior CM, 26 (8.8%; 95% confidence interval [CI], 5.8%-12.6%) were CRAG positive, of whom 21 were promptly treated with fluconazole (200-400 mg) for 2-4 weeks. Clinical CM developed in 3 fluconazole-treated persons, and 30-month survival was 71% (95% CI, 48%-89%). In the 5 CRAG-positive persons with a CD4(+) cell count < or = 100 cells/microL treated with ART but not fluconazole, all died within 2 months of ART initiation. The number needed to test and treat with CRAG screening and fluconazole to prevent 1 CM case is 11.3 (95% CI, 7.9-17.1) at costs of $190 (95% CI, $132-$287). The number needed to test and treat to save 1 life is 15.9 (95% CI, 11.1-24.0) at costs of $266 (95% CI, $185-$402). The cost per disability-adjusted life year saved is $21 (95% CI, $15-$32). Integrating CRAG screening into HIV care, specifically targeting people with severe immunosuppression (CD4(+) cell count < or = 100 cells/microL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.

Pulmonary cryptococcosis misdiagnosed as smear-negative pulmonary tuberculosis with fatal consequences

HIV-associated pulmonary cryptococcosis is under diagnosed, and may progress to fatal meningoencephalitis. We present a case of HIV-associated pulmonary Cryptococcus neoformans infection, initially mis-diagnosed as smear-negative pulmonary TB, which progressed to fatal cryptococcal meningitis. Autopsy series suggest that pulmonary cryptococcosis is common in African AIDS patients, and, due to limited diagnostic capacity, often mis-diagnosed as smear negative TB. Serum cryptococcal antigen testing may facilitate diagnosis in such cases.

The role of serum cryptococcal antigen screening for the early diagnosis of cryptococcosis in HIV-infected patients with different ranges of CD4 cell counts

To determine the role of serum cryptococcal antigen (SCA) for the screening of cryptococcosis in HIV-infected patients with different ranges of CD4 cell counts. A retrospective cohort study was conducted in antiretroviral-naïve HIV-infected patients who had no symptom and had been screened with SCA in a tertiary-care hospital. Prevalence of positive SCA at different ranges of CD4 cell counts, risk factor of positive SCA, and incidence of cryptococcosis during one-year follow-up period after negative SCA were determined. There were 131 patients with a mean age of 38.5 years; 61.8% were male. Median (range) CD4 was 62 (3-590) cells/mm(3). The overall prevalence of positive SCA was 9.2%. This prevalence in patients with CD4 < 100, 100-199, and >or=200 cells/mm(3) were 12.9%, 3.6%, and 0%, respectively (P = 0.041). In multivariate analysis, CD4 < 100 cells/mm(3) was associated with positive SCA (OR = 6.69; 95% CI, 1.03-23.56). Four (33.3%) of 12 patients with positive SCA had cryptococcosis whereas one (0.8%) of 119 patients with negative SCA developed meningitis at one-year follow-up. SCA screening has a substantial role for the early detection of cryptococcal infection in HIV-infected patients with low CD4 cell counts. Routine screening with SCA should be performed in patients with CD4 < 100 cells/mm(3).

Identifying Predictors of Central Nervous System Disease in Solid Organ Transplant RecipientsWith Cryptococcosis

Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed. Patients comprised a multicenter cohort of SOT recipients with cryptococcosis. Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (chi for trend P<0.001). CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.

Utility of clinical assessment, imaging, and cryptococcal antigen titer to predict AIDS-related complicated forms of cryptococcal meningitis

BackgroundThis study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. The outcome was complicated cryptococcal meningitis: prolonged (≥ 14 days) altered mental status, persistent (≥ 14 days) focal neurologic findings, cerebrospinal fluid (CSF) shunt placement or death. Predictor variable operating characteristics were estimated using receiver operating characteristic curve (ROC) analysis. Multivariate analysis identified independent predictors of the outcome.ResultsFrom 1990-2009, 82 patients with first episode of cryptococcal meningitis were identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal meningitis (prolonged altered mental status 6, persistent focal neurologic findings 7, CSF surgical shunt placement 8, and death 5). Patients with complicated cryptococcal meningitis had higher frequency of baseline focal neurological findings, head computed tomography (CT) abnormalities, mean CSF opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC area of log2 serum and CSF CRAG titers to predict complicated forms of cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95% CI: 0.67 to 0.89), respectively (χ2, p = 0.95). The ROC areas to predict the outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple logistic regression model, the following were significant predictors of the outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF CRAG titer.ConclusionsDuring initial clinical evaluation, a focal neurologic exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are associated with the outcome of complicated cryptococcal meningitis following 2 weeks from antifungal therapy initiation.

Disseminated Cryptococcosis Causes Adrenal Insufficiency in an Immunocompetent Individual

Disseminated cryptococcosis infection occurs mainly in the immunocompromised host. There are only a few reports describing disseminated cryptococcosis in immunocompetent patients. Here, we describe the case of a 46-year-old healthy man who presented with primary adrenal insufficiency with hyponatremia, hyperkalemia and skin pigmentation. Contrast-enhanced adrenal computed tomography (CT) revealed bilaterally enlarged adrenal glands without enhancement. CT-guided percutaneous adrenal gland biopsy showed caseous-like necrosis and embedded cryptococcosis. The serum cryptococcal antigen titer was 1:512. After ten months of fluconazole treatment, the serum cryptococcal antigen titer remained elevated at 1:256 and contrast-enhanced adrenal magnetic resonance imaging revealed continued enlargement of bilateral adrenal glands without enhancement. The patient is currently on a therapeutic regimen of prednisolone, fludrocortisone and fluconazole and is scheduled for regular outpatient follow-up.

Cryptococcal immune reconstitution inflammatory syndrome presenting with erosive bone lesions, arthritis and subcutaneous abscesses

Cryptococcal immune reconstitution inflammatory syndrome presenting with erosive bone lesions, arthritis and subcutaneous abscesses

Treatment of cryptococcal meningitis in resource limited settings.

Cryptococcal meningitis most commonly occurs in advanced HIV. Although diminishing in the developed world with antiretroviral therapy (ART), it remains a major problem in resource-limited settings. ART rollout will improve long-term HIV survival if opportunistic infections are effectively treated. Considering cryptococcal meningitis in that context, this review addresses excess morbidity and mortality in developing countries, treatment in areas of limited drug availability and challenges posed by combined anticryptococcal and HIV therapy. From Early Fungicidal Activity (EFA) studies, amphotericin B-flucytosine is best induction therapy but often unavailable; high dose amphotericin B monotherapy may be feasible in some settings. Where fluconazole is the only option, higher doses are more fungicidal. Serum cryptococcal antigen testing may identify patients at highest disease risk and primary prophylaxis is effective; the clinical role of such interventions needs to be established. Timing of ART introduction remains controversial; early initiation risks Immune Reconstitution Disease (IRD) delays may increase mortality. Amphotericin B based treatment is appropriate where possible. More studies are needed to optimize fluconazole monotherapy doses. Other research priorities include management of raised intracranial pressure, appropriate ART initiation and IRD treatment. Studies should focus on developing countries where problems are greatest.

Cryptococcal Immune Reconstitution Inflammatory Syndrome after Antiretroviral Therapy in AIDS Patients with Cryptococcal Meningitis: A Prospective Multicenter Study

A prospective multicenter study of cryptococcal immune reconstitution inflammatory syndrome (IRIS) was conducted as a substudy of the Bacteriology and Mycology Study Group 3-01. Of 101 AIDS patients with cryptococcal meningitis who received highly active antiretroviral therapy (HAART), 13 experienced cryptococcal IRIS. No association between the timing of HAART initiation and the diagnosis of IRIS was identified. Increased baseline serum cryptococcal antigen (CrAg) titer was a risk factor for cryptococcal IRIS.

Disseminated Mycobacterium avium-intracellulare Infection Presenting as Multiple Ring-Enhancing Lesions on Brain MRI

A 33-year-old man in whom AIDS had been diagnosed in 2003 presented with a 6-week history of progressive generalized weakness, lethargy, dysphagia, slowing of speech, and left-sided weakness. Highly active antiretroviral therapy was initiated, but the patient was not adherent to this regimen. Disseminated Mycobacterium avium-intracellulare infection in the lungs and supraclavicular lymph nodes had been diagnosed 3 to 4 weeks before presentation. Magnetic resonance imaging (MRI) of the brain revealed multiple ring-enhancing lesions. A presumptive diagnosis of central nervous system toxoplasmosis was made, and an extensive work-up for ruling out other causes of multiple ring-enhancing lesions was initiated. Laboratory studies yielded a serum CD4 cell count of 2/μL and a human immunodeficiency virus RNA count of 6100 copies/μL. Results of the following were negative: serum cryptococcal antigen, Bartonella henselae IgM and IgG, cytomegalovirus antigen, rapid plasma reagin, and Toxoplasma IgM and IgG. The following cerebrospinal fluid (CSF) results were negative: Toxoplasma IgM, IgG, Toxoplasma by polymerase chain reaction and staining, acid-fast bacilli (AFB) stain, cryptococcal antigen, venereal disease research laboratory test, Gram stain, and bacterial and fungal cultures. Cytologic examination of the CSF showed numerous neutrophils but no malignant cells. Laboratory studies of the CSF yielded a protein value of 52 mg/dL (to convert to mg/L, multiply by 10) (reference range, 15-45 mg/dL) and a glucose value of 26 mg/dL (to convert to mmol/L, multiply by 0.0555) (reference range, 40-70 mg/dL); the CSF was clear, colorless with 5 red blood cells and 42 white blood cells (77% polymorphonuclear and 23% mononuclear cells). Brain biopsy with AFB stain revealed 3+ AFB (M avium) but showed no Nocardia-like organisms. A modified Kinyoun stain for Nocardia species was negative, as was a wetmount preparation for amebae. A liquid-based biopsy culture grew M avium after 10 days of incubation. A confirmatory DNA probe was performed to verify the diagnosis of central nervous system toxoplasmosis. Therapy with ethambutol, rifampin, and amikacin was initiated; however, the patient chose palliative care after talking with his family.

Pulmonary cryptococcosis: A rare but emerging disease

Pulmonary cryptococcosis occurs primarily in immunocompromised hosts as an isolated infection or as a precursor to disseminated disease. Recent studies indicate that patients with isolated pulmonary cryptococcosis may be asymptomatic or, if symptomatic, will often have very low serum cryptococcal antigen, distinguishing them from patients with disseminated disease. Amphotericin B plus flucytosine is the initial treatment for disseminated cryptococcosis or severe symptomatic pulmonary cryptococcosis, followed by fluconazole once symptoms have improved. Fluconazole is recommended for asymptomatic or mild disease. Targeted immunotherapies and vaccines are being studied and offer exciting new prevention and treatment strategies.

Evaluation of three commercial latex agglutination kits and a commercial enzyme immunoassay for the detection of cryptococcal antigen

We compared the performance of the Meridian CALAS, Wampole Crypto-LA, Murex Cryptococcus latex agglutination assay, and the Meridian Premier EIA for the detection of cryptococcal antigen in serum and CSF. The assays demonstrated similar performance characteristics based on concordance values > or = 93% but important differences were noted in endpoint titers.

Pulmonary Cryptococcosis in Late Pregnancy and Review of Published Literature

Naturally occurring maternal immunosuppression increases the risk of infection by a variety of pathogens during pregnancy and the postpartum period. Pulmonary cryptococcosis during pregnancy is relatively rare. Here, we report on two cases of pulmonary cryptococcosis during pregnancy and puerperium. Both cases were successfully treated using oral fluconazole after parturition to avoid fetal toxicity. For the two patients, the placentas were checked and found to be pathologically normal, and the cryptococcal serum antigen in both infants was negative. Pulmonary cryptococcosis should be considered during differential diagnosis as a possible cause of abnormal chest shadow in pregnant patients.

Clinical Presentation, Diagnosis and Management of Cryptococcus gattii Cases: Lessons Learned from British Columbia

The environmental fungus Cryptococcus gattii emerged on Vancouver Island, British Columbia (BC), in 1999. By the end of 2006, it led to 176 cases and eight deaths - one of the highest burdens of C gattii disease worldwide. The present paper describes three cases, and the BC experience in the diagnosis and management of this infection. All three cases presented with pulmonary findings, including cryptococcomas and infiltrates. One also presented with brain cryptococcomas. Cases were diagnosed by chest and brain imaging, and laboratory evidence including serum or cerebrospinal fluid cryptococcal antigen detection and culture of respiratory or cerebrospinal fluid specimens. Genotyping of fungal isolates confirmed infection with C gattii VGIIa. Pulmonary cases were treated with fluconazole. One patient with central nervous system disease was treated with amphotericin B followed by fluconazole. Although this infection remains rare, clinicians should be aware of it in patients with a compatible clinical presentation who are either living in or returning from a trip to BC.

Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.

Trichosporon asahii infection in an advanced AIDS patient and literature review

Trichosporon asahii infection in an advanced AIDS patient and literature review