Diagnosis of progressive disseminated histoplasmosis in advanced HIV: A meta-analysis of assay analytical performance

Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. Here we describe the results of a systematic literature review, followed by ameta-analysis of the analytical performances of the diagnostic laboratory assays employed. Our initial search identified 1631 references, of which 1559 references were excluded after title and abstract screening, leaving 72 references identified as studies relevant to the validation of histoplasmosis diagnostic assays. After evaluating the full text, 30 studies were selected for final review, including one paper not identified in the initial search. The meta-analysis for assay analytical performance shows the following results for the overall sensitivity (Sen) and specificity (Spe) of the various methods evaluated: Culture, Sen 77%(no data for specificity calculation); antibody detection assays, Sen 58%/Spe 100%; antigen detection assays, Sen 95%/Spe 97%; and DNA detection assays (molecular), Sen 95%/Spe 99%. Of the 30 studies reviewed, nearly half (n = 13) evaluated Histoplasma antigen assays, which were determined to be the most accurate methodology for diagnosis of progressive disseminated histoplasmosis in advanced HIV (inverse of the negative likelihood ratio was 13.2). Molecular assays appear promising for accurate diagnosis of histoplasmosis, but consensus on exact techniques is needed. Cultures showed variable sensitivity related to sample type and laboratory handling. Finally, antibody assays presented high specificity but low sensitivity. This poor sensitivity is most likely due the highly immunosuppressed state of this patient population. Diagnostic assays are crucial for accurate diagnosis of progressive disseminated histoplasmosis (PDH) with advanced HIV disease. © 2019 by the authors. All rights reserved

A Shape-based Glaucoma Index for Tomographic Images

We examine the use of Confocal Laser Tomographic images for detecting glaucoma. From the clinical aspect, the optic nerve head's (ONH) area contains all the relevant information on glaucoma. The shape of ONH is approximately a skewed cup. We summarize its shape by three biological landmarks on the neural-rim and the fourth landmark as the point of the maximum depth, which is approximately the point where the optic nerve enters this eye cup. These four landmarks are extracted from the images related to some Rhesus monkeys before and after inducing glaucoma. Previous analysis on Bookstein shape coordinates of these four landmarks revealed only marginally significant findings. From clinical experience, it is believed that the ratio depth to diameter of the eye cup provides a useful measure of the shape change. We consider the bootstrap distribution of this normalized 'depth' (G) and give evidence that it provides an appropriate measure of the shape change. This measure G is labelled as the glaucoma index. Further experiments are in progress to validate its use for glaucoma in humans.Glaucoma index, medical imaging, high level image analysis, anatomical landmarks, non- parametric bootstrap,

Sporotrichosis-Associated Hospitalizations, United States, 2000–2013

To determine frequency and risk for sporotrichosis-associated hospitalizations, we analyzed the US 2000–2013 National (Nationwide) Inpatient Sample. An estimated 1,471 hospitalizations occurred (average annual rate 0.35/1 million persons). Hospitalizations were associated with HIV/AIDS, immune-mediated inflammatory diseases, and chronic obstructive pulmonary disease. Although rare, severe sporotrichosis should be considered for at-risk patients

Diagnosis of progressive disseminated histoplasmosis in advanced HIV: A meta-analysis of assay analytical performance

Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. Here we describe the results of a systematic literature review, followed by ameta-analysis of the analytical performances of the diagnostic laboratory assays employed. Our initial search identified 1631 references, of which 1559 references were excluded after title and abstract screening, leaving 72 references identified as studies relevant to the validation of histoplasmosis diagnostic assays. After evaluating the full text, 30 studies were selected for final review, including one paper not identified in the initial search. The meta-analysis for assay analytical performance shows the following results for the overall sensitivity (Sen) and specificity (Spe) of the various methods evaluated: Culture, Sen 77%(no data for specificity calculation); antibody detection assays, Sen 58%/Spe 100%; antigen detection assays, Sen 95%/Spe 97%; and DNA detection assays (molecular), Sen 95%/Spe 99%. Of the 30 studies reviewed, nearly half (n = 13) evaluated Histoplasma antigen assays, which were determined to be the most accurate methodology for diagnosis of progressive disseminated histoplasmosis in advanced HIV (inverse of the negative likelihood ratio was 13.2). Molecular assays appear promising for accurate diagnosis of histoplasmosis, but consensus on exact techniques is needed. Cultures showed variable sensitivity related to sample type and laboratory handling. Finally, antibody assays presented high specificity but low sensitivity. This poor sensitivity is most likely due the highly immunosuppressed state of this patient population. Diagnostic assays are crucial for accurate diagnosis of progressive disseminated histoplasmosis (PDH) with advanced HIV disease. © 2019 by the authors. All rights reserved

Wavelet Image Interpolation (WII): A Wavelet-Based Approach to Enhancement of Digital Mammography Images

Cancer detection using mammography focuses on characteristics of tiny microcalcifications, including the number, size, and spatial arrangement of microcalcification clusters as well as morphological features of individual microcalcifications. We developed state-of-the-art wavelet-based methods to enhance the resolution of microcalcifications visible in digital mammograms, thereby improving the specificity of breast cancer diagnoses. In our research, we develop, refine, and evaluate a Wavelet Image Interpolation (WII) procedure and create accompanying software to implement it. WII involves the application of an inverse wavelet transformation to a coarse or degraded image and constructed detail coefficients to produce an enhanced higher resolution image. The construction of detail coefficients is supervised by the observed image and innate regular scaling assessed by a statistical model. Methodology we propose was tested by an experienced radiologist in a blind study using 40 images from the University of South Florida Digital Database for Screening Mammography (DDSM) (Heat et. al. [10])

Evaluation of an Ultrafiltration-Based Procedure for Simultaneous Recovery of Diverse Microbes in Source Waters

In this study, hollow-fiber ultrafiltration (UF) was assessed for recovery of Escherichia coli, Clostridium perfringens spores, Cryptosporidium parvum oocysts, echovirus 1, and bacteriophages MS2 and ΦX174 from ground and surface waters. Microbes were seeded into twenty-two 50-L water samples that were collected from the Southeastern United States and concentrated to ~500 mL by UF. Secondary concentration was performed for C. parvum by centrifugation followed by immunomagnetic separation. Secondary concentration for viruses was performed using centrifugal ultrafilters or polyethylene glycol precipitation. Nine water quality parameters were measured in each water sample to determine whether water quality data correlated with UF and secondary concentration recovery efficiencies. Average UF recovery efficiencies were 66%–95% for the six enteric microbes. Average recovery efficiencies for the secondary concentration methods were 35%–95% for C. parvum and the viruses. Overall, measured water quality parameters were not significantly associated with UF recovery efficiencies. However, recovery of ΦX174 was negatively correlated with turbidity. The recovery data demonstrate that UF can be an effective method for concentrating diverse microbes from ground and surface waters. This study highlights the utility of tangential-flow hollow fiber ultrafiltration for recovery of bacteria, viruses, and parasites from large volume environmental water samples

Wavelet-based 3-D Multifractal Spectrum with Applications in Breast MRI Images

Breast cancer is the second leading cause of death in women in the United States. Breast Magnetic Resonance Imaging (BMRI) is an emerging tool in breast cancer diagnostics and research, and it is becoming routine in clinical practice. Recently, the American Cancer Society (ACS) recommended that women at very high risk of developing breast cancer have annual BMRI exams, in addition to annual mammograms, to increase the likelihood of early detection. (Saslow et al. [20]). Many medical images demonstrate a certain degree of self-similarity over a range of scales. The multifractal spectrum (MFS) summarizes possibly variable degrees of scaling in one dimensional signals and has been widely used in fractal analysis. In this work, we develop a generalization of MFS to three dimensions and use dynamics of the scaling as discriminatory descriptors for the classification of BMRI images to benign and malignant. Methodology we propose was tested using breast MRI images for four anonymous subjects (two cancer, and two cancer-free cases). The dataset consists of BMRI scans obtained on a 1.5T GE Signa MR (with VIBRANT) scanner at Emory University. We demonstrate that meaningful descriptors show potential for classifying inference

Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study

International audienceBackground Fungal infections remain a major contributor to the opportunistic infections that affect people living withHIV. Among them, histoplasmosis is considered neglected, often being misdiagnosed as tuberculosis, and isresponsible for numerous deaths in Latin America. The objective of this study was to estimate the burden ofHIV-associated histoplasmosis compared with tuberculosis in Latin American countries.Methods For this modelling study, we estimated prevalence of previous exposure to Histoplasma capsulatum, HIVassociatedhistoplasmosis annual incidence, and number of deaths in 2012 in Latin American countries based onhistorical histoplasmin skin test studies in the general population, with an antigen dilution level of more than 1/10.Studies were identified in a literature search. Data on HIV-associated tuberculosis were extracted from the WHOnotifications and outcomes tables and data on people living with HIV were extracted from the UNAIDS report for theyear 2012. We systematically propagated uncertainty throughout all the steps of the estimation process.Findings Among 1310 articles identified as of June 1, 2015, 24 articles were included in the study, representing129 histoplasmin skin test studies led in the general population of Latin American countries. For the year 2012, weestimated a range of 6710 (95% CI 5680–7867) to 15 657 (13 254–18 357) cases of symptomatic HIV-associatedhistoplasmosis in Latin America. Hotspot areas for histoplasmosis prevalence (>30%) and incidence (>1·5 cases per100 people living with HIV) were Central America, the northernmost part of South America, and Argentina. Accordingto realistic scenarios, we estimated a range of 671 (95% CI 568–787) to 9394 (7952–11 014) deaths related tohistoplasmosis, compared with 5062 (3777–6405) deaths related to tuberculosis reported in Latin America.Interpretation Our estimates of histoplasmosis incidence and deaths are high and consistent with published data. Forthe first time, the burden of histoplasmosis is estimated to be equivalent in incidence and even higher in deaths whencompared with tuberculosis among people living with HIV in Latin America

Estimated Deaths and Illnesses Averted During Fungal Meningitis Outbreak Associated with Contaminated Steroid Injections, United States, 2012–2013

During 2012–2013, the US Centers for Disease Control and Prevention and partners responded to a multistate outbreak of fungal infections linked to methylprednisolone acetate (MPA) injections produced by a compounding pharmacy. We evaluated the effects of public health actions on the scope of this outbreak. A comparison of 60-day case-fatality rates and clinical characteristics of patients given a diagnosis on or before October 4, the date the outbreak was widely publicized, with those of patients given a diagnosis after October 4 showed that an estimated 3,150 MPA injections, 153 cases of meningitis or stroke, and 124 deaths were averted. Compared with diagnosis after October 4, diagnosis on or before October 4 was significantly associated with a higher 60-day case-fatality rate (28% vs. 5%; p<0.0001). Aggressive public health action resulted in a substantially reduced estimated number of persons affected by this outbreak and improved survival of affected patients