Blastomyces Antigen Detection for Monitoring Progression of Blastomycosis in a Pregnant Adolescent

Although disseminated blastomycosis is a rare complication in pregnancy, delay in diagnosis and treatment can be fatal. We investigate the use of the Blastomyces urine antigen in diagnosis following disease progression in the intrapartum, postpartum, and neonatal periods. We describe a case of disseminated blastomycosis in a pregnant adolescent and review the pertinent literature regarding treatment and monitoring blastomycosis in pregnancy and the neonatal periods. This is the first reported case in which the Blastomyces urine antigen is utilized as a method of following disease activity during pregnancy confirming absence of clinically evident disease in a neonate. Urine antigen detection for blastomycosis can be useful for following progression of disease in patients with disseminated blastomycosis in both the intrapartum and postpartum periods

False-negative Histoplasma antigen in acute pulmonary histoplasmosis: the value of urinary concentration by ultrafiltration and heat denaturation of serum proteins in detection of Histoplasma antigen

We report an infant with localized pulmonary histoplasmosis in whom Histoplasma antibody assays, quantitative Histoplasma urine and serum antigen concentrations, and histopathologic findings of a mediastinal mass were nondiagnostic. A provisional diagnosis of histoplasmosis was established by using laboratory methods that increase the sensitivity of the antigen assay using ultrafiltration of urine and ethylenediaminetetraacetic acid/heat denaturation of serum proteins

Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis

Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow–Based Immunoassay: A Multicenter Study

Background: Accurate and timely methods for the diagnosis of histoplasmosis in resource-limited countries are lacking. Histoplasma antigen detection by enzyme immunoassay (EIA) is widely used in the United States (US) but not in resource-limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFAs) can be used in this setting. Methods: Frozen urine specimens were submitted to MiraVista diagnostics for antigen testing from 3 medical centers in endemic areas of the US. They were blinded and tested for the MVista Histoplasma LFA. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable; pulmonary or disseminated; immunocompetent or immunosuppressed; and mild, moderate, or severe. Results: Three hundred fifty-two subjects were enrolled, including 66 cases (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (71%), and 46 had disseminated and 20 had pulmonary histoplasmosis. Four cases were mild, 42 moderate, and 20 severe. LFA and EIA were highly concordant (κ = 0.84). Sensitivity and specificity of the LFA were 78.8% and 99.3%, respectively. LFA sensitivity was higher in proven cases (93.2%), patients with disseminated (91.3%), moderate (78.6%), and severe disease (80%), and those with galactomannan levels >1.8 ng/mL (97.8%). Specificity was 99.3% in proven cases, 99.3% in patients with moderate or severe disease, and 96.8% in those with galactomannan levels >1.8 ng/mL. Cross-reactivity was noted with other endemic mycoses. Conclusions: The MVista Histoplasma LFA meets the need for accurate rapid diagnosis of histoplasmosis in resource-limited countries, especially in patients with high disease burden, potentially reducing morbidity and mortality

Detection of Histoplasma capsulatum Antigen in Panamanian Patients with Disseminated Histoplasmosis and AIDS ᰔ

Histoplasmosis is a common endemic mycosis in the Americas, often causing severe disease in patients with AIDS. Antigen detection has become an important method for rapid diagnosis of histoplasmosis in the United States but not in Central or South America. Isolates from patients in the United States are predominantly found to be class 2 isolates when typed using the nuclear gene YPS3, while isolates from Latin America are predominantly typed as class 5 or class 6. Whether infection with these Latin American genotypes produces positive results in the Histoplasma antigen assay has not been reported. In this study, we have compared the sensitivity of antigen detection for AIDS patients from Panama who had progressive disseminated histoplasmosis to that for those in the United States. Antigenuria was detected in the MVista Histoplasma antigen enzyme immunoassay (EIA) in 95.2% of Panamanian cases versus 100% of U.S. cases. Antigenemia was detected in 94.7% of the Panamanian cases versus 92% of the U.S. cases. Two clinical isolates from Panama were typed using YPS3 and were found to be restriction fragment length polymorphism class 6. We conclude that the MVista Histoplasma antigen EIA is a sensitive method for diagnosis of histoplasmosis in Panama. Progressive disseminated histoplasmosis (PDH) is a common and serious opportunistic disease among patients with AIDS in the United States and Latin America. In Panama, PDH occurred in 8% of hospitalized patients from 1997 to 2003 and was fatal in 12% of cases (6). The clinical picture was similar to that reported elsewhere and usually included fever, weight loss, and respiratory symptoms, often in association with diarrhea, as well as hepatosplenomegaly, hepatic enzyme elevation, and pancytopenia. Skin lesions were noted in 17% of the Panamanian cases (6), lower than the observed rate for cases from Brazil (66%) but higher than that for cases from the United States (ϳ3%) (7). Disease in patients in Mexico and Latin America has been described as being caused by isolates of Histoplasma capsulatum var. capsulatum that exhibit distinct genetic profiles in comparison to those from the United States (3, 8, 9). Keath et al. (9) first described typing based upon restriction fragment length polymorphism (RFLP) in the YPS3 gene. They showed that Panamanian strains were typed as YPS3 class 3, 5, or 6, while the North American strains were predominantly class 2. Later, Kasuga et al. used the DNA sequence substitution rates in four independent protein-coding genes to identify at least eight different genotypes, or clades (8). North American class 2 was the predominant genotype in the United States and Latin American group A in Latin America. Latin American group B was found only in Columbia and Argentina. Based on only four isolates from Panama included in the study by Kasuga et al., Panamanian strains included Latin American group A and a lone lineage, designated H81. The diagnosis of PDH relies on demonstration of the organism in clinical specimens or detection of antigen in body fluids (2). Histopathology may be falsely negative in up to 50% of patients, caused by sampling error, paucity of organisms, or inexperience of the pathologist. Culture may require several weeks to isolate and identify the organism and may be falsely negative for 15% of patients (13). Antigenuria can be detected in 95% of cases in patients with AIDS in the United States (4, 13) but has not been evaluated in Latin America. Whether genetic differences in Latin American isolates would affect the sensitivity for diagnosis by antigen detection is unknown. The prevalence of PDH in AIDS patients from Panama offered the opportunity to address this question. MATERIALS AND METHODS Case definition. The definition included the presence of AIDS based upon a serologic test positive for human immunodeficiency virus infection, a CD4 cell count below 200 cells/l and/or a previous AIDS defining condition according to CDC classification, and PDH proven by culture or histopathology. Methods. We collected samples of serum and urine from Panamanian patients with AIDS and clinical suspicion of PDH who were admitted to the AIDS ward of the Arnulfo Arias Madrid Hospital in Panama City, Panama, from December 2005 through November 2006. All of the samples were taken before the start of antifungal therapy, referred to as baseline, and then stored frozen at Ϫ20°C. Samples were shipped in batches to MiraVista Diagnostics on three occasions during the course of the study, according to International Air Transport Association regulations. We included 21 patients with PDH in the study. The study was approved by the institution&apos;s review board and followed guidelines for clinical research. All patients read and signed an informed-consent form before the samples were taken. The investigators also completed a case report form for each patient with demographic and clinically relevant data. For comparison, paired serum and urine specimens collected at enrollment or week 1 or 2 of treatment from 65 AIDS patients in the United States with PD

Detection of (1,3)-\u3cem\u3eβ\u3c/em\u3e-D-Glucan in Cerebrospinal Fluid in \u3cem\u3eHistoplasma\u3c/em\u3e Meningitis

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to \u3c 31 pg/ml for all controls (P \u3c 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥ 80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis

Improvement in Diagnosis of \u3cem\u3eHistoplasma\u3c/em\u3e Meningitis by Combined Testing for \u3cem\u3eHistoplasma\u3c/em\u3e Antigen and Immunoglobulin G and Immunoglobulin M Anti-\u3cem\u3eHistoplasma\u3c/em\u3e Antibody in Cerebrospinal Fluid

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

NMR metabolomics of cerebrospinal fluid differentiates inflammatory diseases of the central nervous system

BACKGROUND: Myriad infectious and noninfectious causes of encephalomyelitis (EM) have similar clinical manifestations, presenting serious challenges to diagnosis and treatment. Metabolomics of cerebrospinal fluid (CSF) was explored as a method of differentiating among neurological diseases causing EM using a single CSF sample. METHODOLOGY/PRINCIPAL FINDINGS: 1H NMR metabolomics was applied to CSF samples from 27 patients with a laboratory-confirmed disease, including Lyme disease or West Nile Virus meningoencephalitis, multiple sclerosis, rabies, or Histoplasma meningitis, and 25 controls. Cluster analyses distinguished samples by infection status and moderately by pathogen, with shared and differentiating metabolite patterns observed among diseases. CART analysis predicted infection status with 100% sensitivity and 93% specificity. CONCLUSIONS/SIGNIFICANCE: These preliminary results suggest the potential utility of CSF metabolomics as a rapid screening test to enhance diagnostic accuracies and improve patient outcomes

Physical, Psychological and Emotional Benefits of Green Physical Activity: An Ecological Dynamics Perspective

© 2015 Springer International Publishing Switzerland Increasing evidence supports the multiple benefits to physical, psychological and emotional wellbeing of green physical activity, a topic of increasing interest in the past decade. Research has revealed a synergistic benefit of green physical activity, which includes all aspects of exercise and physical activity in the presence of nature. Our theoretical analysis suggests there are three distinct levels of engagement in green physical activity, with each level reported to have a positive effect on human behaviours. However, the extent to which each level of green physical activity benefits health and wellbeing is assumed to differ, requiring confirmation in future research. This elucidation of understanding is needed because previous literature has tended to focus on recording empirical evidence rather than developing a sound theoretical framework to understand green physical activity effects. Here we propose an ecological dynamics rationale to explain how and why green physical activity might influence health and wellbeing of different population groups. This framework suggests a number of unexplored, interacting constraints related to types of environment and population groups, which shape reported levels of benefit of green physical activity. Further analysis is needed to clarify the explicit relationship between green physical activity and health and wellbeing, including levels of engagement, types of environmental constraints, levels of physical activity, adventure effects, skill effects and sampling of different populations